Category Archives: Cell Biology

Cells Inside Cells: The Bacteria That Live in Cancer Cells – Technology Networks

Cancer cells are comfy havens for bacteria. That conclusion arises from a rigorous study of over 1,000 tumor samples of different human cancers. The study, headed by researchers at the Weizmann Institute of Science, found bacteria living inside the cells of all the cancer types from brain to bone to breast cancer and even identified unique populations of bacteria residing in each type of cancer. The research suggests that understanding the relationship between a cancer cell and its mini-microbiome may help predict the potential effectiveness of certain treatments or may point, in the future, to ways of manipulating those bacteria to enhance the actions of anticancer treatments.

Dr. Ravid Straussman of the Institutes Molecular Cell Biology Department had, several years ago, discovered bacteria lurking within human pancreatic tumor cells; these bacteria were shown to protect cancer cells from chemotherapy drugs by digesting and inactivating these drugs. When other studies also found bacteria in tumor cells, Straussman and his team wondered whether such hosting might be the rule, rather than the exception. To find out, Drs. Deborah Nejman and Ilana Livyatan in Straussmans group and Dr. Garold Fuks of the Physics of Complex Systems Department worked together with a team of oncologists and researchers around the world. The work was also led by Dr. Noam Shental of the Mathematics and Computer Science Department of the Open University of Israel.

Ultimately, the team would produce a detailed study describing, in high resolution, the bacteria living in these cancers brain, bone, breast, lung, ovary, pancreas, colorectal and melanoma. They discovered that every single cancer type, from brain to bone, harbored bacteria and that different cancer types harbor different bacteria species. It was the breast cancers, however, that had the largest number and diversity of bacteria. The team demonstrated that many more bacteria can be found in breast tumors compared to the normal breast tissue surrounding these tumors, and that some bacteria were preferentially found in the tumor tissue rather than in the normal tissue surrounding it.

To arrive at these results, the team had to overcome several challenges. For one, the mass of bacteria in a tumor sample is relatively small, and the researchers had to find ways to focus on these tiny cells-within-cells. They also had to eliminate any possible outside contamination. To this end they used hundreds of negative controls and created a series of computational filters to remove the traces of any bacteria that could have come from outside the tumor samples.

The team was able to grow bacteria directly from human breast tumors, and their results proved that the bacteria found in these tumors are alive. Electron microscopy visualization of these bacteria demonstrated that they prefer to nestle up in a specific location inside the cancer cells close to the cell nucleus.

Different cells for different bacteria

The team also reported that bacteria can be found not only in cancer cells, but also in immune cells that reside inside tumors. Some of these bacteria could be enhancing the anticancer immune response, while others could be suppressing it a finding that may be especially relevant to understanding the effectiveness of certain immunotherapies, says Straussman. Indeed, when the team compared the bacteria from groups of melanoma samples, they found that different bacteria were enriched in those melanoma tumors that responded to immunotherapy as compared to those that had a poor response.

Straussman thinks that the study can also begin to explain why some bacteria like cancer cells and why each cancer has its own typical microbiome: The differences apparently come down to the choice of amenities offered in each kind of tumor-cell environment. That is, the bacteria may live off certain metabolites that are overproduced by or stored within the specific tumor types. For example, when the team compared the bacteria found in lung tumors from smokers with those from patients who had never smoked, they found variances. These differences stood out more clearly when the researchers compared the genes of these two groups of bacteria: Those from the smokers lung cancer cells had many more genes for metabolizing nicotine, toluene, phenol and other chemicals that are found in cigarette smoke.

In addition to showing that some of the most common cancers shelter unique populations of bacteria within their cells, the researchers believe that the methods they have developed to identify signature microbiomes with each cancer type can now be used to answer some crucial questions about the roles these bacteria play: Are the bacteria freeloaders on the cancer cells surplus metabolites, or do they provide a service to the cell? At what stage do they take up residence? How do they promote or hinder the cancers growth? What are the effects that they have on response to a wide variety of anticancer treatments?

Tumors are complex ecosystems that are known to contain, in addition to cancer cells, immune cells, stromal cells, blood vessels, nerves, and many more components, all part of what we refer to as the tumor microenvironment. Our studies, as well as studies by other labs, clearly demonstrate that bacteria are also an integral part of the tumor microenvironment. We hope that by finding out how exactly they fit into the general tumor ecology, we can figure out novel ways of treating cancer, Straussman says.

Reference:Nejman, D., Livyatan, I., Fuks, G., Gavert, N., Zwang, Y., Geller, L. T., . . . Straussman, R. (2020). The human tumor microbiome is composed of tumor typespecific intracellular bacteria. Science, 368(6494), 973-980. doi:10.1126/science.aay9189

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Cells Inside Cells: The Bacteria That Live in Cancer Cells - Technology Networks

NASA researcher provides overview of science on the ISS – SpaceFlight Insider

Laurel Kornfeld

May 29th, 2020

ISS as photographed by Expedition 56 astronauts from a Soyuz capsule. Image Credit: NASA

Research conducted on board the International Space Station (ISS) encompasses numerous science fields, such as biology and biotechnology, human research, the physical sciences, technological demonstrations, Earth and space science, and public education, noted Brandon Redell of NASAs ISS Integration Office at the Johnson Space Center.

Redell discussed scientific research currently being conducted on the ISS in a NASA Night Sky Network Webinar livestreamed on Wednesday, May 27, titled International Space Station Research and Technology 101.

The Night Sky Network is a national group of amateur astronomy clubs whose purpose is to inspire the public about NASAs missions and the science and technology that go into them.

The ISS is an orbiting laboratory. Its a space station thats been going around the Earth. Its been a continuous presence with humans for at least 20 years now. We conduct research to aid space exploration and for human benefits here on Earth as well as developing new technologies, Redell said.

Research on the ISS has helped scientists learn about a wide range of subjects, from human health to black holes, he added. Scientific discoveries made there provide benefits for humanity and enable future space exploration.

Four international space agencies have laboratories on the ISSNASA, the European Space Agency (ESA), the Japan Aerospace and Exploration Agency (JAXA), and Roscosmos, Russias space agency.

Close to 3,000 scientific investigations have been conducted on the ISS, resulting in more than 1,800 scientific journal papers published.

In 2005, Congress passed a law designating the ISS as a national laboratory, enabling non-NASA research, including student projects, to be conducted there.

David Saint-Jacques places bubble monitors (inset) in various locations around the International Space Station for the Canadian Radi-N2 experiment. The Radi-N2 experiment is designed to measure the amount of neutron radiation received by astronauts on board the Station, help create a map of the ISS to identify areas that offer the most protection in case of a major solar event, and help develop countermeasures to health risks for future long-duration space explorers. (Credit: Canadian Space Agency/NASA)

Redell outlined several major reasons for conducting scientific research on the ISS. First, the micro-gravity environment removes all conditions driven by gravity, letting scientists understand other factors involved in their studies. Second, being in low-Earth orbit provides a unique vantage point, along with support services for Earth and space science missions.

Third is the extreme environment in space, including vacuum, thermal variations, radiation, atomic oxygen, and micro-meteoroids. Finally, the ISS serves as a unique platform for educating and inspiring the next generation, which is an investment in future scientific exploration and advancement.

Redell cited the example of cell biology research, noting that on Earth, cells live in a fluid environment and respond to the force of gravity. When brought into micro-gravity, cells that have irregular shapes on Earth suddenly become spherical and swell up, much like blobs of water do on the ISS. Cells also alter their gene expressions, structure, and the mechanisms by which they communicate with one another in micro-gravity.

To learn more about health and physiological changes in micro-gravity, worms, insects, fish, and rodents are studied on the ISS. Learning about rodents biological processes in space helps scientists better understand how human space travelers will respond to that environment.

Understanding plant biology in micro-gravity will someday be key for astronauts on long space missions. On Earth, plants roots instinctively move downward due to gravity while their stems and leaves reach upward toward the Sun. In the absence of gravity, they get confused; for example, moss grown in the dark on a space shuttle flight grew in all directions.

Plant Habitat-01 (PH-01: An Integrated Omics Guided Approach to Lignification and Gravitational Responses in Plants) is a multi-omic, multi-growth stage plant experiment designed to compare early versus late gene expression in Arabidopsis using the Advanced Plant Habitat (APH) facility. Credit: NASA

Furthermore, growing plants in space is difficult because soil structure is different in micro-gravity than it is on Earth. Water does not settle down in micro-gravity, often causing plants to drown.

If were trying to grow our own food sources on a long-duration mission, this is something we need to understand for long-duration flights, Redell emphasized.

Especially important to the future of human space travel is a better understanding of the effects micro-gravity has on people. Both during spaceflight and afterwards, astronauts have experienced balance disorders, cardiovascular de-conditioning, decreased immune function, muscle atrophy, and bone loss.

Long duration human performance in space is a big research area, Redell noted.

Through ISS research, scientists learned that 60 percent of astronauts who spend long durations in space experience a decline in eyesight that in some cases is permanent. Some researchers believe this is due to fluid shifts to the head in micro-gravity while others attribute it to a genetic predisposition. Whether one or both are true, scientists will have to resolve this issue in order for long-term human space missions to go forward.

The unique orbit of the ISS enables it to observe all geographic locations between 51.6 degrees North and 51.6 degrees South in latitude. This covers 85 percent of the Earths surface and 95 percent of its populated landmasses. Using high-definition cameras, ISS astronauts take a variety of photos, from still ones to hyper-spectral images.

From the ISS, astronauts can monitor natural disasters and climate change effects. Science instruments use remote sensing to study climate science, hydrology, soil mapping, geomorphology/landscape configuration, hazard assessments, and many other phenomena. One such experiment monitors water content in the worlds rainforests.

In the field of astrophysics, astronauts work with scientists to explore the universes origin, identify and study neutron stars and black holes in X-ray wavelengths, and learn more about cosmic rays, dark matter, and even anti-matter.

Anyone interested in learning more about the many science experiments being conducted on the space station is encouraged to visit an ISS website known as the Space Station Research Explorer.

Tagged: education International Space Station ISS laboratory Science The Range

Laurel Kornfeld is an amateur astronomer and freelance writer from Highland Park, NJ, who enjoys writing about astronomy and planetary science. She studied journalism at Douglass College, Rutgers University, and earned a Graduate Certificate of Science from Swinburne Universitys Astronomy Online program. Her writings have been published online in The Atlantic, Astronomy magazines guest blog section, the UK Space Conference, the 2009 IAU General Assembly newspaper, The Space Reporter, and newsletters of various astronomy clubs. She is a member of the Cranford, NJ-based Amateur Astronomers, Inc. Especially interested in the outer solar system, Laurel gave a brief presentation at the 2008 Great Planet Debate held at the Johns Hopkins University Applied Physics Lab in Laurel, MD.

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Liver Cancer Surgery: Types, Recovery and What’s Next – WTOP

Cancer is an unfortunate fact of biology that arises when cellular mutations lead to unchecked proliferation. Cancer can occur in

Cancer is an unfortunate fact of biology that arises when cellular mutations lead to unchecked proliferation. Cancer can occur in virtually any cell in the body, from blood and brain to skin and lungs.

One particularly dangerous form of cancer is liver cancer. Cancer of this large, wedge-shaped organ located under the right ribs and lung is often diagnosed in later stages, once its started spreading to other organs. Later-stage cancers are more difficult to treat than if the cancer is caught early. Thus, the five-year relative survival rate for all stages of liver cancer is 18%, the American Cancer Society reports. However, that rate rises to 33% in early-stage cases of liver cancer because surgical procedures can help people recover.

[See: 10 Innovations in Cancer Therapy. ]

Types of Liver Cancer

Cancerous tumors can develop on the liver and spread to other parts of the body, and this may occur without the patient realizing it because sometimes symptoms are vague or mild and go undetected.

But liver cancer isnt a singular entity. There are two main types of cancer that can form directly from the liver itself, says Dr. Aslam Ejaz, a surgical oncologist with the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in Columbus.

These two primary types of liver cancer are:

Hepatocellular Carcinoma

The most common type of primary liver cancer, HCC usually occurs in people who have another chronic liver disease such as cirrhosis (scarring of the liver that may be related to alcohol abuse or another issue), hepatitis B or hepatitis C infections.

Dr. James J. Lee, a gastroenterologist with St. Joseph Hospital in Orange, California, says hepatitis B and C infections are dangerous because they cause progressive liver damage, which can result in cirrhosis and liver failure as well as hepatoma, another name for HCC. These diseases are caused by blood-borne viruses that are highly contagious. They cause acute inflammation in the liver that leads to scarring (cirrhosis) and may open the door cancer.

No matter the cause, treatment for HCC may include surgery, liver transplant, chemotherapy, radiation, immunotherapy, targeted drug therapies or ablation (destruction) of cancer cells through the application of heat, cold or electrical current. You may undergo a combination of several treatments depending on your specific diagnosis.

Cholangiocarcinoma

This form of cancerous tumor develops in the bile ducts, the slender tubes that connect the liver to the gallbladder and small intestines. These ducts carry bile, a digestive fluid. Cholangiocarcinoma is also called bile-duct cancer, and its the second most common liver cancer, accounting for about 10% to 20% of primary liver tumors.

Tumors may develop in the bile ducts after small mutations in cells add up to rapid proliferation of malignant cells. Risk factors for developing this kind of cancer include:

Chronic liver disease. Cirrhosis caused by a history of chronic liver disease is a major risk factor for bile-duct cancer.

Primary sclerosing cholangitis. This disease causes the bile ducts to harden and scar.

Malformed bile ducts. Some people have congenital defects to the bile ducts that increase risk of developing cancer there.

Parasites. Infestation with certain organisms, such as liver flukes which are very rare in the U.S. but can be introduced to the body via consumption of undercooked or raw fish can damage the liver and bile ducts and potentially lead to cancer.

Age and lifestyle. This type of cancer is more common in adults over age 50. Its also experienced more commonly among smokers.

Bile-duct cancer tends to be more aggressive than HCC, and thus has a worse prognosis. However, it may be treated with surgery, radiation, chemotherapy or other targeted drug therapies.

[SEE: Alcoholic Hepatitis Symptoms: Heres What You Need to Know.]

Types of Surgery for Liver Cancer

If your doctor suspects you have liver cancer, youll undergo extensive testing to determine what type and stage cancer you have and to determine the location of the tumor or tumors. Ultrasound or CT scans of the liver may be part of that process, Lee says.

If youre diagnosed with liver cancer, your doctor may have the option of a few types of surgical procedures to treat them. The choice of procedure will depend on the general health of the patient as well as the type, size and number of liver tumors there are, Ejaz says.

Surgery for liver cancer generally takes one of the following forms:

Partial Hepatectomy

This procedure, also called a liver resection, removes part of the liver. Its only for patients who have good liver function and have a single tumor that hasnt yet grown into blood vessels.

Surgical removal of liver cancer is performed on patients who are in good health and those that have tumors that, once removed, would leave a healthy amount of liver behind, Ejaz notes.

Its not a good option for someone who has severe cirrhosis, a condition that causes scarring of the liver. The ACS reports that most people who have liver cancer also have cirrhosis, so your doctor will perform some additional imaging tests, such as an MRI or CT scan and blood test to check your liver function and determine the size and location of the liver tumor prior to recommending this form of surgery. If its determined that youll have at least 30% of liver function remaining after surgery, you may get the green light for this procedure.

This surgery can be performed either as open surgery or using a minimally-invasive approach. Minimally-invasive liver surgery is performed through small keyhole incisions whereas an open operation requires a large incision on the abdomen, Ejaz says.

Liver surgery is serious business, and while it can extend your life, there are also risks. The main risks of liver removal include bleeding, infection, leakage of bile and liver failure, although this is a rare occurrence, Ejaz says. Some patients also experience complications of anesthesia or may develop pneumonia.

If youre undergoing a partial hepatectomy for liver cancer, expect to be in the hospital anywhere from one day to one week, Ejaz says. In general, recovery is dependent on how healthy you are going into surgery, as well as the amount of liver removed. In some cases, physical therapy may be indicated, especially if you have other, compounding medical problems or physical limitations. Physical therapy can be used to enhance your recovery after surgery, Ejaz says.

Your doctor will follow up with you regularly to check for recurrence of the cancer and other health issues that could arise. But, if you follow your doctors orders, most patients return to their previous health state and quality of life after surgery for liver cancer, Ejaz says.

A 2016 study in the World Journal of Surgical Oncology found that patients who underwent liver resection surgery had good long-term survival rates. The one-year survival rate was 89.0%, the three-year survival rate was 64.3%, and the five-year survival rate was 53.0%.

Ablation

Ablation procedures use heat, cold or electrical current to kill cancerous liver cells. These procedures are usually best suited for patients who have a few small tumors and when surgery is not a good option because of poor overall health or reduced liver function because of chronic liver disease.

There are several ways that ablation can be conducted, including:

Radio-frequency ablation. This form of ablation uses high-energy radio waves to destroy small tumors on the liver. A 2016 study of 320 patients who had radio-frequency ablation found that the cancer eventually came back in 73 (64%) patients. The five- and 10-year overall survival rates were 38.5% and 23.4%.

Microwave ablation. This approach uses electromagnetic waves to heat up tumor cells and destroy them. A 2015 study found that this procedure also has good long-term survival outcomes, and that local recurrence rates were low for tumors of less than 3 cm in diameter.

Ethanol ablation. Also known as percutaneous ethanol injection, this procedure uses concentrated ethanol, a type of alcohol, which is injected into the tumor. This is one of the least invasive and least expensive ways to treat liver cancer, and its best suited for tumors of 3 cm diameter or smaller. One study noted that among 746 patients with HCC, the 1-, 2-, 3-, 4-, and 5-year survival rates after ethanol ablation were 93%, 77%, 60%, 40% and 33% respectively.

Irreversible electroporation. A recently developed therapy, IRE uses electrical pulses to damage tumor cells. This type of treatment may be best suited for patients who have tumors smaller than 5 cm that are located near blood vessels. Heat ablation techniques can damage those vessels, so low-energy ablation such as can be achieved with IRE may be a better option. However, a 2017 study in the journal Medicine noted that its still not the first choice of ablation procedure for many patients with HCC because it requires general anesthesia and muscle blockers because the electrical current can cause muscle stimulation during the procedure that could become dangerous. Another 2017 study found that the median survival rate for HCC patients was 26.8 months post-procedure. Patients with primary HCC, rather than liver metastases that have spread from another primary cancer, seemed to have better results from IRE according to that study, likely because of a difference in cellular biology between primary and metastatic tumors.

Cryoablation. Cryoablation uses extreme cold produced by liquid nitrogen to freeze cancerous tissue. One-year survival rates range from 82.4% to 94% for cryoablation. The three-year survival rate ranged from 32.3 to 40%, and five-year rates are between 13.4% to 20% depending on the report. Cryoablation may have higher complication rates, but can be used on larger tumors than some of these other approaches.

Ablation techniques use a long needle or probe to penetrate the tumor through the abdomen. As such, its a less invasive procedure than other forms of surgery for liver cancer. Patients can often go home the same day.

You may have some pain in your abdomen or right shoulder a condition called referred pain for a few days after the procedure. Your doctor will follow up with tests soon after the procedure to see how well it worked.

Youll need to take it easy for several days after the procedure and avoid lifting heavy objects and strenuous exercise. You may be advised not to drive or go to work for up to a week or two, depending on your specific situation.

[READ: 5 Ways to Detox Your Liver That Really Work.]

Liver Transplant

In certain cases, a liver transplant might be the best option for tumors that cant be removed or would not leave enough functional liver tissue behind after removal. In this procedure, the surgeon removes your entire liver and replaces it with healthy liver tissue from a donor. Procuring a healthy liver matching the patients blood type in a timely fashion can be a major difficulty.

But, unlike other organs that must be harvested from a recently deceased donor, its possible to transplant a piece of a live donors liver. The liver has a miraculous ability to regenerate, and if a section is removed and implanted in a patient, both the donor and the recipient can regenerate whats missing and return to normal function within several weeks.

Still, a liver transplant is major surgery that carries risks. If youre going to have a liver transplant, expect to remain in the intensive care unit for a few days. You may be in the hospital for up to two weeks in total, and youll need frequent check-ups with your surgical team afterwards to ensure that the transplant is taking and liver function is resuming normal levels. Physical therapy may be part of your recovery plan.

Youll also have to remain on powerful immunosuppressant medications for the rest of your life to subdue the bodys urge to reject the new organ. These medications can cause side effects, including gastrointestinal problems. They may also make you more susceptible to other infections, so these powerful medications must be managed carefully.

Aftercare

After surgery for liver cancer, its important that you take good care of your health. This includes:

Getting plenty of rest. Sleep is a powerful healer. Strive to get plenty of good-quality shut-eye.

Exercising. Once your doctor has cleared you for physical activity, you should aim to move as much as you can. Getting the body moving has been shown to reduce the chances of blood clots forming or developing pneumonia.

Eating right. To support your body as it heals, be sure to provide it with healthy, nutritious food and plenty of water. Within the first few days of surgery, youll likely be on a liquid diet, to put less strain on your body and digestive system. When you can transition back to a more standard diet, be sure to avoid alcohol and high-fat foods that can be difficult for the liver to process.

Managing constipation. Constipation can become a problem for some patients post-surgery. Your surgical team will likely brief you on how to manage this potential problem ahead of time, but speak up if it becomes uncomfortable.

Keeping your incision clean. For those who have open surgery or a transplant, caring for your incision and preventing infection is vitally important. Follow your doctors post-surgical orders carefully.

Communicating with your health care team. If youre having pain or other issues, be sure to let your doctor know right away.

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Bruker Introduces Breakthrough MALDI-2 Source on timsTOF fleX, and Further Innovations in CCS-Enabled 4D Proteomics on timsTOF – Business Wire

BILLERICA, Mass.--(BUSINESS WIRE)--At the virtual ASMS 2020 Reboot conference, Bruker Corporation (Nasdaq: BRKR) today announces a major advance in matrix-assisted laser desorption ionization (MALDI) with the launch of the worlds first commercial MALDI-2 post-ionization (PI) source, which is now available as an option on the timsTOF fleX ESI/MALDI mass spectrometer. The novel MALDI-2 technology can offer one or two orders of magnitude higher sensitivity for many small molecules and lipids. MALDI-2 increases the applications range of MALDI mass spectrometry and imaging even further.

Moreover, Bruker launches additional unique TIMS/PASEF-enabled 4D proteomics methods that leverage the large-scale, real-time availability of accurate collision cross sections (CCS) for tens of thousands of measured peptides per 4D nanoLC-CCS-MS/MS run. These new methods and software include prm-PASEF, short-gradient dia-PASEF, MOMA, and Run and Done proteomics using a novel GPU-based real-time search engine. In addition to further enhanced peptide, protein and PTM identification, these CCS-enabled innovations allow for sustained, ultra-high sensitivity LFQ performance, and for truly high-throughput methods for 4D proteomics, 4D lipidomics and 4D metabolomics on the exceptionally robust timsTOF Pro platform.

A. SpatialOMx and Translational Mass Spectrometry Imaging on timsTOF fleX

The innovative MALDI-2 PI source increases both the sensitivity and range of applications of MALDI very significantly. MALDI-2 requires a second laser (266 nm) fired orthogonally into the expanding MALDI plume that is generated by Brukers proprietary primary SmartBeam 3D (355 nm) laser. An optimized flexMatrix formulation is recommended for MALDI-2. The new MALDI-2 source is now available as an option on the timsTOF flex ESI/MALDI instrument.

Professor Klaus Dreisewerd, Leader Section for Biomedical Mass Spectrometry at the University of Muenster in Germany, and the pioneer of MALDI-2, said: In the last 35 years, MALDI has become a unique and rapid analytical tool for a wide variety of applications. We developed MALDI-2 to significantly extend the technique by providing much higher sensitivity for small molecules, and the inclusion of chemical classes that did not ionize efficiently with MALDI. The MALDI-2 powered timsTOF fleX will take MALDI to new scientific and analytical frontiers.

Dr. Michael Easterling, Global MS Imaging Director at Bruker Daltonics, added: The growing value of MALDI Imaging and SpatialOMx for tissue-specific models in drug development drives demand for even higher sensitivity and versatility. With its dramatically increased sensitivity and accessible range of chemical classes, the novel MALDI-2 source option can now further enhance mass spectrometry-based, non-targeted tissue analysis.

Bruker now also offers a MALDI-2 compound reference library for its MetaboScape metabolomics software, which was created during various academic and pharma collaborations. MetaboScape provides automatic analyte annotation within the SCiLS Lab MALDI imaging software, including CCS-algorithms that improve the confidence of annotation for many metabolites, glycans and lipids directly in tissue images.

B. CCS-Enabled 4D Proteomics Innovations on timsTOF Platform

prm-PASEF for Translational Quantitative 4D Proteomics

Brukers revolutionary timsTOF Pro has been further enhanced by combining PASEF with parallel reaction monitoring (PRM) for label-free quantitative proteomics. This unique mode of prm-PASEF takes advantage of the 4th dimension of separation using TIMS to improve selectivity and sensitivity, combined with the speed of PASEF to increase the number of precursor targets. Working closely with the Skyline team to enable prm-PASEF methods, Skyline software can now analyze the prm-PASEF data and produce quantitative reports.

The group of Prof. Gunnar Dittmar from the Luxembourg Institute of Health and Prof. Antoin Lesur, who both worked on the prm-PASEF workflow development, commented: We have been extremely impressed by the early results from prm-PASEF on the timsTOF Pro in our lab. The sensitivity and speed of prm-PASEF already rivals that of PRM methods that have been developed over many years on other platforms.

Dr. Jarrod Marto, Associate Professor at the Dana-Farber Cancer Institute, Harvard Medical School, and Brigham and Womens Hospital added: We have made tremendous progress since initiating co-development of prm-PASEF with the Bruker Team. The unique combination of acquisition speed and integrated ion mobility on the timsTOF Pro enable us to robustly quantify potential biomarker candidates across clinical cohorts. Moreover, real-time adjustment of acquisition parameters with prm-PASEF LIVE will push usability and throughput even further.

Large-Scale, High-Precision Peptide CCS Measurements for Deep Learning

Peptide collisional cross sections (CCS) measured at large scale and with high precision by the unique TIMS technology deliver added dimensionality for increased confidence of identification in 4D proteomics. A new study by Florian Meier et. al., entitled Deep learning the collisional cross sections of the peptide universe from a million training samples, and submitted to bioRxiv, (2020.05.19.102285; doi: https://doi.org/10.1101/2020.05.19.102285), uses a deep learning training set of 570,000 CCS values measured in 360 LC/MS runs of fractionated digests of five organisms, run on a timsTOF Pro system.

Professor Matthias Mann, Director at the Max Planck Institute of Biochemistry, Germany, commented: The size and shape of peptide ions in the gas phase are an under-explored dimension for mass spectrometry-based proteomics. CCS values can now be predicted for any peptide and organism, forming a basis for advanced proteomics workflows that make full use of the additional information.

Short-gradient dia-PASEF and Mobility Offset Mass Aligned (MOMA) for 4D Proteomics

New short-gradient methods have been developed using the dia-PASEF workflow, which is finding increasing use in many timsTOF Pro labs. Dia-PASEF can provide a meaningful advance in data completeness, and the dia-PASEF workflow is now supported by Bioinformatics Solutions Inc. PEAKS and Biognosys Spectronaut software.

Dr. Lukas Reiter, Chief Technology Officer of Biognosys commented: With the Spectronaut 14 launch, we have complete support for the timsTOF Pro: Fast library generation from PASEF and ion mobility calibration for a more specific targeted extraction in Spectronaut. Furthermore, we have added directDIA support for the timsTOF Pro. We are also excited to have a timsTOF Pro in our lab to further speed up our software development for this new and exciting platform.

Dr. Gary Kruppa, Vice President for Proteomics at Bruker Daltonics, added: With the launch of prm-PASEF, the growing success of dia-PASEF, and the trend towards shorter gradients that take advantage of the robustness, sensitivity and unmatched duty-cycle of PASEF, the timsTOF Pro provides the capabilities to make 4D-proteomics translational reality. Furthermore, the unique MOMA feature of TIMS allows for targeting isobaric precursors at similar retention times for MS/MS acquisition. Having MOMA capability helps improve the depth of coverage using short gradients, and this is important to our translational research proteomics users who are running >50 samples per day per timsTOF Pro.

Run & Done Real-Time Search Developed by Yates Lab for High-Throughput 4D Proteomics

Bruker announces the availability of the proteomic pipeline (IP2) with a GPU-based search engine incorporating the ProLuCID database search tool from the laboratory of Professor John Yates at The Scripps Research Institute based in LaJolla, CA. This unique GPU-based IP2 software has been developed by Dr. Robin Park and allows timsTOF Pro 4D data to be searched in real-time during acquisition, with search results available at the end of the run.

Prof. John Yates III and Dr. Robin Park said: The co-evolution of computational advances with mass spectrometry sensitivity and scan speed have enabled more accurate, large-scale data analysis approaches that help answer many biological questions. GPU-based search engines designed to simultaneously execute many parallel instruction threads can reduce search times to the point where the search results can be converted into real-time input to drive tandem MS acquisition. This becomes an exciting part in our partnership with Bruker, as it will utilize the timsTOF Pro even more intelligently.

Dr. Rohan Thakur, Executive Vice President of Life Sciences Mass Spectrometry at Bruker Daltonics, added: The IP2/GPU solution provides a software infrastructure thats amenable to supporting plug-in applications from our third-party software partners that take advantage of high-performance cluster or cloud capabilities. We are committed to our strategy of open data file formats to facilitate community-driven software development, including our third-party partners through API access for the benefit of the timsTOF user community.

Featured speakers at our eXceed symposia and breakfast events. For more detailed information on our eXceed Symposia and Breakfast Workshops please visit http://www.bruker.com/events/2020/asms-2020-reboot.

Bruker will host a virtual scientific and trade press conference on Monday, June 1st, 2020, at 8:00 am CDT, including Bruker management and guest speaker Professor John Yates.

Customers are invited to visit Brukers ASMS 2020 Reboot virtual hospitality suite throughout the conference.

About Bruker Corporation (Nasdaq: BRKR)

Bruker is enabling scientists to make breakthrough discoveries and develop new applications that improve the quality of human life. Brukers high-performance scientific instruments and high-value analytical and diagnostic solutions enable scientists to explore life and materials at molecular, cellular and microscopic levels.

In close cooperation with our customers, Bruker is enabling innovation, improved productivity and customer success in life science molecular research, in applied and pharma applications, in microscopy and nanoanalysis, and in industrial applications, as well as in cell biology, preclinical imaging, clinical phenomics and proteomics research and clinical microbiology. For more information, please visit: http://www.bruker.com.

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Bruker Introduces Breakthrough MALDI-2 Source on timsTOF fleX, and Further Innovations in CCS-Enabled 4D Proteomics on timsTOF - Business Wire

Some autoimmune diseases are work of overzealous T cells, researchers say – The Times of Israel

Israeli researchers say they have found that autoimmune diseases, such as diabetes or thyroid dysfunctions, are generated by immune cells that become overzealous in their protective mission and end up causing harm and they created a mathematical model that demonstrates this.

In a study published in Immunity, scientists at Rehovots Weizmann Institute of Science, decided to find out why some organs are susceptible to autoimmune diseases while others are not. For example, the thyroid gland is often attacked by the autoimmune disease thyroiditis an inflammation of the thyroid gland that can cause fatigue, weight gain, confusion and depression while other organs, like the parathyroid gland, in charge of regulating the amount of calcium in the blood and bones, are almost never hit by autoimmune diseases.

Our model suggests that immune cells play an important role in healthy people, because they clear away mutant cells that secrete too many hormones, said Yael Korem Kohanim, a research student who led the study. It is when this process goes wrong that people develop an autoimmune disease.

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Korem Kohanim works in the lab of Prof. Uri Alon in the Institutes Molecular Cell Biology Department.

Illustrative image of a woman checking blood sugar levels; type-1 diabetes is an autoimmune disease that affects one organ (Ta Nu; iStock by Getty Images)

Autoimmune diseases can be divided into two types: systemic ones like lupus that attack many organs in the body, and the ones like type-1 diabetes that affect just one organ. One of the biggest questions about this second, organ-specific type of autoimmune disease is why some organs get the diseases while others do not.

These organ-specific autoimmune diseases tend to follow a similar pattern: They are found in children or young adults and they involve the destruction of cells that secrete hormones that are essential to good health. In people with autoimmune disease, immune cells called T cells somehow identify these essential hormone cells as dangerous and eradicate them on contact.

In their study, Korem Kohanim, Alon and other researchers decided to find out why this is and if T cells, in charge of protecting us from diseases by regulating our immune response, are tasked naturally to kill these cells.

Yael Korem Kohanim, research student at the Weizmann Institute (Courtesy)

They hypothesized that T cells may act as an extra layer of protection to make sure that the amounts of essential hormones secreted by the cells stay within narrow limits: both too little and too much of these hormones, such as insulin, thyroid hormones, and cortisol, can be damaging.

When demand for the hormone rises for example, a demand for insulin when glucose is sensed in the blood cells not only increase production of the hormone, they ramp up cell division to help meet that demand.

But cell division carries risks, as a certain percentage of the new cells is likely to carry mutations. Most such mutations are harmless, but if somehow a cell misreads the demand for insulin as high instead of low, the result can be deadly: the cell will continue not only to pump out extra hormones, it will divide again and again to produce new cells with the same mutation, which will then divide again and produce even more of the hormone.

The role of T cells thus could also be to curb the over-secreting cells in healthy organs, by removing cells that threaten to secrete too much hormone. The scientists thus hypothesized that in the case of autoimmune diseases, the T cells might be primed to accomplish the task of curbing the hormones but get overzealous and kill off non-mutant cells as well.

To determine if their hypothesis was reasonable, the researchers created a mathematical model for the functioning of healthy organs in which T cells help to keep hormone levels where they should be.

The model backs up the hypothesis, and shows that the organs stay fit and productive as long as the T cells continue to be highly selective and most of their targets are mutated cells. When they are too active, the organs are stricken by an autoimmune disease, the model shows.

Illustrative image of a weighing scale, balance (artisteer; iStock by Getty Images)

Thus, the researchers say, autoimmune diseases could be the result of a trade-off: on one hand T cells are meant to prevent the overproduction of hormones, but on the other hand they could cause a reduced production in some people, if they become too active.

We think that autoimmune diseases do not come out of nowhere, said Korem Kohanim. They are a malfunction, but one of a physiological system that is already in place.

Some people are more prone to this T cell over-activity, she said, due to a variety of risk factors like viral inflammations or genetics.

The scientists also looked at whether organs that do not develop autoimmune diseases do not have T cell protection. And indeed they dont. That is why these organs dont get autoimmune diseases, but they do suffer from illnesses due to the hyper-secretion of hormones.

The parathyroid gland, for example, explained Korem Kohanim, doesnt get autoimmune diseases but does get a disease called primary hyperparathyroidism in which a benign tumor of parathyroid cells secretes too much of the hyperparathyroid hormone.

Now the scientists want to see via experiments if their claims can be proven.

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Some autoimmune diseases are work of overzealous T cells, researchers say - The Times of Israel

Boundless Bio Presents Data Assessing the Relationship Between Extrachromosomal DNA and Biomarker Signatures Associated with Response to Checkpoint…

SAN DIEGO--(BUSINESS WIRE)--Boundless Bio, a company interrogating and targeting extrachromosomal DNA (ecDNA) in aggressive cancers, today will present data at the 2020 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting that highlight ecDNAs relationship with biomarkers associated with response to immunotherapy in gastric cancer and therefore the importance of identifying ecDNA patient populations.

The poster, Extrachromosomal DNA (ecDNA) carrying amplified oncogenes as a biomarker for insensitivity to checkpoint inhibitor treatment in gastric cancer patients, will be presented on Friday, May 29, in ASCOs Developmental Therapeutics Immunotherapy session. The presentation can be accessed starting at 8:00 a.m. EDT (Abstract 3123, Presentation 187) as part of ASCOs on-demand content; ASCO is being held virtually this year due to COVID-19.

ecDNA are identified with high frequency across many solid tumor types and thought to be one of the key drivers of the most aggressive cancers specifically, those cancers characterized by high copy number amplifications of oncogenes. Tumors enabled by ecDNA have a distinct fitness advantage of producing multiple oncogene copies, which drives tumor aggressiveness, rapid progression, and resistance to standard treatment options.

The analysis being presented today demonstrates that the presence of ecDNA in gastric cancer is negatively associated with biomarkers typically associated with response to checkpoint inhibitor therapies. The implication is that the presence of ecDNA in solid tumors potentially renders these cancers unresponsive to immunotherapy and highlights the importance of creating therapies that directly address cancer cells ability to employ ecDNA to grow and resist standard of care treatments, said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. Boundless Bio is committed to continuing to elucidate the role of ecDNA in cancer biology, oncogene amplification, and tumor adaptability and to bringing the first medicines leveraging these insights to patients with intractable cancers.

Study Details

The analysis examined whether patients with gastric tumors that possess ecDNA represent a subset of patients that lack biomarkers associated with clinical response to anti-PD-1 checkpoint inhibitor therapy. Boundless Bio researchers employed computational analysis to determine the ecDNA status of a cohort of gastric cancer patients (N = 108) whose whole genome sequencing data were publicly available in The Cancer Genome Atlas (TCGA). The cohort was grouped into five molecular subtypes:

Additionally, the relationships among the molecular subtypes above and common biomarker signatures associated with response to checkpoint inhibitors were assessed:

The analysis found that 32% of gastric cancer patients in the cohort were positive for ecDNA signatures, and those ecDNA+ patients were mutually exclusive from the 23% of patients who showed MSI high (MSI-H), which is associated with response to checkpoint inhibitors, such as pembrolizumab, in gastric cancer. Further, it found that the ecDNA-positive subtype had statistically significantly lower TIS than all of the other molecular subtypes (p-value < 0.05), except for the tumors marked by the CIN subtype (p-value = 0.09). The ecDNA-positive subtype also had lower PD-L1 expression than all the other molecular subtypes but the GS and CIN subtypes.

Overall, the analysis demonstrated that patients whose tumors are ecDNA positive are a unique population that displays a signature that lacks the hallmark biomarkers that predict response to checkpoint inhibitor therapy, implying that ecDNA+ patients may not respond to standard of care immunotherapies. Boundless Bio is developing novel therapeutic strategies directed to mechanisms critical for ecDNA function in cancer.

About ecDNA

Extrachromosomal DNA, or ecDNA, are large circles of DNA containing genes that are outside the cells chromosomes and can make many copies of themselves. ecDNA can be rapidly replicated within the cell, causing high numbers of oncogene copies, a trait that can be passed to daughter cells in asymmetric ways during cell division. Cells have the ability to upregulate or downregulate ecDNA and resulting oncogenes to ensure survival under selective pressures, including chemotherapy, targeted therapy, immunotherapy, or radiation, making ecDNA one of cancer cells primary mechanisms of recurrence and treatment evasion. ecDNA are rarely seen in healthy cells but are found in many solid tumor cancers. They are a key driver of the most aggressive and difficult-to-treat cancers, specifically those characterized by high copy number amplification of oncogenes.

About Boundless Bio

Boundless Bio is a biotechnology company focused on interrogating a novel area of cancer biology, extrachromosomal DNA (ecDNA), to deliver transformative therapies to patients with previously intractable cancers. For more information, visit http://www.boundlessbio.com. Follow us on LinkedIn and Twitter.

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Boundless Bio Presents Data Assessing the Relationship Between Extrachromosomal DNA and Biomarker Signatures Associated with Response to Checkpoint...

New liver cancer research targets non-cancer cells to blunt tumor growth – Penn: Office of University Communications

Senotherapy, a treatment that uses small molecule drugs to target senescent cells, or those cells that no longer undergo cell division, blunts liver tumor progression in animal models according to new research from a team led byCeleste Simon, a professor of cell and developmental biology in the Perelman School of Medicine, and scientific director of the Abramson Family Cancer Research Institute. The study was published inNature Cell Biology.

This kind of therapy is not something that has been tried before with liver cancer, Simon says. And in our models, so-called senolytic therapy greatly reduced disease burden, even in cases with advanced disease.

Loss of the enzyme FBP1 in human liver cells significantly increases tumor growth. Previous research has shown FBP1 levels are decreased in stage 1 tumors, and further reduced as the disease progresses. In this study, Simon and her team used RNA-sequencing data to identify FBP1 as universally under-expressed in the most common form of liver cancer, hepatocelluar carcinoma, regardless of underlying causes like obesity, alcoholism, and hepatitis.

This story is by Melissa Moody. Read more at Penn Medicine News.

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New liver cancer research targets non-cancer cells to blunt tumor growth - Penn: Office of University Communications

Tracking the physics of biological cells using nanodevices (video) – Lab News

For the first time, scientists have introduced minuscule tracking devices directly into the interior of mammalian cells, giving an unprecedented peek into the processes that govern the beginning of development. This work on one-cell embryos is set to shift our understanding of the mechanisms that underpin cellular behaviour in general, and may ultimately provide insights into what goes wrong in ageing and disease.

The research, led by Professor Tony Perry from the Department of Biology and Biochemistry at the University of Bath, involved injecting a silicon-based nanodevice together with sperm into the egg cell of a mouse. The result was a healthy, fertilised egg containing a tracking device.

The tiny devices are a little like spiders, complete with eight highly flexible 'legs'. The legs measure the 'pulling and pushing' forces exerted in the cell interior to a very high level of precision, thereby revealing the cellular forces at play and showing how intracellular matter rearranged itself over time.

The nanodevices are incredibly thin - similar to some of the cell's structural components, and measuring 22 nanometres, making them approximately 100,000 times thinner than a pound coin. This means they have the flexibility to register the movement of the cell's cytoplasm as the one-cell embryo embarks on its voyage towards becoming a two-cell embryo.

"This is the first glimpse of the physics of any cell on this scale from within," said Professor Perry. "It's the first time anyone has seen from the inside how cell material moves around and organises itself."

Sorry, video does not exists

Caption: Five mouse embryos, each containing a nanodevice that is 22-millionths of a metre long. The film begins when the embryos are 2-hours old and continues for 5 hours. Each embryo is about 100-millionths of a metre in diameter. via @uniofbath,http://www.bath.ac.uk

Why probe a cells mechanical behaviour?

The activity within a cell determines how that cell functions, explains Professor Perry. "The behaviour of intracellular matter is probably as influential to cell behaviour as gene expression," he said. Until now, however, this complex dance of cellular material has remained largely unstudied. As a result, scientists have been able to identify the elements that make up a cell, but not how the cell interior behaves as a whole.

"From studies in biology and embryology, we know about certain molecules and cellular phenomena, and we have woven this information into a reductionist narrative of how things work, but now this narrative is changing," said Professor Perry. The narrative was written largely by biologists, who brought with them the questions and tools of biology. What was missing was physics. Physics asks about the forces driving a cell's behaviour and provides a top-down approach to finding the answer.

"We can now look at the cell as a whole, not just the nuts and bolts that make it."

Mouse embryos were chosen for the study because of their relatively large size (they measure 100 microns, or 100-millionths of a metre, in diameter, compared to a regular cell which is only 10 microns [10-millionths of a metre] in diameter). This meant that inside each embryo, there was space for a tracking device.

The researchers made their measurements by examining video recordings taken through a microscope as the embryo developed. "Sometimes the devices were pitched and twisted by forces that were even greater than those inside muscle cells," said Professor Perry. "At other times, the devices moved very little, showing the cell interior had become calm. There was nothing random about these processes - from the moment you have a one-cell embryo, everything is done in a predictable way. The physics is programmed."

The results add to an emerging picture of biology that suggests material inside a living cell is not static, but instead changes its properties in a pre-ordained way as the cell performs its function or responds to the environment. The work may one day have implications for our understanding of how cells age or stop working as they should, which is what happens in disease.

The study is titled; Tracking intracellular forces and mechanical property changes in mouse one-cell embryo development was published inNature Materialsand involved a trans-disciplinary partnership between biologists, materials scientists and physicists based in the UK, Spain and the USA.

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Tracking the physics of biological cells using nanodevices (video) - Lab News

On the Origins of Modern Biology and the Fantastic: Part 19 Nalo Hopkinson and Stem Cell Research – tor.com

She just wanted to be somewhere safe, somewhere familiar, where people looked and spoke like her and she could stand to eat the food. Midnight Robber by Nalo Hopkinson

Midnight Robber (2000) is about a woman, divided. Raised on the high-tech utopian planet of Touissant, Tan-Tan grows up on a planet populated by the descendants of a Caribbean diaspora, where all labor is performed by an all-seeing AI. But when she is exiled to Touissants parallel universe twin planet, the no-tech New Half-Way Tree, with her sexually abusive father, she becomes divided between good and evil Tan-Tans. To make herself and New Half-Way Tree whole, she adopts the persona of the legendary Robber Queen and becomes a legend herself. It is a wondrous blend of science fictional tropes and Caribbean mythology written in a Caribbean vernacular which vividly recalls the history of slavery and imperialism that shaped Touissant and its people, published at a time when diverse voices and perspectives within science fiction were blossoming.

Science fiction has long been dominated by white, Western perspectives. Vernes tech-forward adventures and Wells sociological allegories established two distinctive styles, but still centered on white imperialism and class struggle. Subsequent futures depicted in Verne-like pulp and Golden Age stories, where lone white heroes conquered evil powers or alien planets, mirrored colonialist history and the subjugation of non-white races. The civil rights era saw the incorporation of more Wellsian sociological concerns, and an increase in the number of non-white faces in the future, but they were often tokensparts of a dominant white monoculture. Important figures that presaged modern diversity included Star Treks Lieutenant Uhura, played by Nichelle Nichols. Nichols was the first black woman to play a non-servant character on TV; though her glorified secretary role frustrated Nichols, her presence was a political act, showing there was space for black people in the future.

Another key figure was the musician and poet Sun Ra, who laid the aesthetic foundation for what would become known as the Afrofuturist movement (the term coined by Mark Dery in a 1994 essay), which showed pride in black history and imagined the future through a black cultural lens. Within science fiction, the foundational work of Samuel Delany and Octavia Butler painted realistic futures in which the histories and cultural differences of people of color had a place. Finally, an important modern figure in the decentralization of the dominant Western perspective is Nalo Hopkinson.

A similarly long-standing paradigm lies at the heart of biology, extending back to Darwins theoretical and Mendels practical frameworks for the evolution of genetic traits via natural selection. Our natures werent determined by experience, as Lamarck posited, but by genes. Therefore, genes determine our reproductive fitness, and if we can understand genes, we might take our futures into our own hands to better treat disease and ease human suffering. This theory was tragically over-applied, even by Darwin, who in Descent of Man (1871) conflated culture with biology, assuming the Wests conquest of indigenous cultures meant white people were genetically superior. After the Nazis committed genocide in the name of an all-white future, ideas and practices based in eugenics declined, as biological understanding of genes matured. The Central Dogma of the 60s maintained the idea of a mechanistic meaning of life, as advances in genetic engineering and the age of genomics enabled our greatest understanding yet of how genes and disease work. The last major barrier between us and our transhumanist future therefore involved understanding how genes determine cellular identity, and as well see, key figures in answering that question are stem cells.

***

Hopkinson was born December 20, 1960 in Kingston, Jamaica. Her mother was a library technician and her father wrote, taught, and acted. Growing up, Hopkinson was immersed in the Caribbean literary scene, fed on a steady diet of theater, dance, readings, and visual arts exhibitions. She loved to readfrom folklore, to classical literature, to Kurt Vonnegutand loved science fiction, from Spock and Uhura on Star Trek, to Le Guin, James Tiptree Jr., and Delany. Despite being surrounded by a vibrant writing community, it didnt occur to her to become a writer herself. What they were writing was poetry and mimetic fiction, Hopkinson said, whereas I was reading science fiction and fantasy. It wasnt until I was 16 and stumbled upon an anthology of stories written at the Clarion Science Fiction Workshop that I realized there were places where you could be taught how to write fiction. Growing up, her family moved often, from Jamaica to Guyana to Trinidad and back, but in 1977, they moved to Toronto to get treatment for her fathers chronic kidney disease, and Hopkinson suddenly became a minority, thousands of miles from home.

Development can be described as an orderly alienation. In mammals, zygotes divide and subsets of cells become functionally specialized into, say, neurons or liver cells. Following the discovery of DNA as the genetic material in the 1950s, a question arose: did dividing cells retain all genes from the zygote, or were genes lost as it specialized? British embryologist John Gurdon addressed this question in a series of experiments in the 60s using frogs. Gurdon transplanted nuclei from varyingly differentiated cells into oocytes stripped of their genetic material to see if a new frog was made. He found the more differentiated a cell was, the lower the chance of success, but the successes confirmed that no genetic material was lost. Meanwhile, Canadian biologists Ernest McCulloch and James Till were transplanting bone marrow to treat irradiated mice when they noticed it caused lumps in the mices spleens, and the number of lumps correlated with the cellular dosage. Their lab subsequently demonstrated that each lump was a clonal colony from a single donor cell, and a subset of those cells was self-renewing and could form further colonies of any blood cell type. They had discovered hematopoietic stem cells. In 1981 the first embryonic stem cells (ESCs) from mice were successfully propagated in culture by British biologist Martin Evans, winning him the Nobel Prize in 2007. This breakthrough allowed biologists to alter genes in ESCs, then use Gurdons technique to create transgenic mice with that alteration in every cellcreating the first animal models of disease.

In 1982, one year after Evans discovery, Hopkinson graduated with honors from York University. She worked in the arts, as a library clerk, government culture research officer, and grants officer for the Toronto Arts Council, but wouldnt begin publishing her own fiction until she was 34. [I had been] politicized by feminist and Caribbean literature into valuing writing that spoke of particular cultural experiences of living under colonialism/patriarchy, and also of writing in ones own vernacular speech, Hopkinson said. In other words, I had models for strong fiction, and I knew intimately the body of work to which I would be responding. Then I discovered that Delany was a black man, which opened up a space for me in SF/F that I hadnt known I needed. She sought out more science fiction by black authors and found Butler, Charles Saunders, and Steven Barnes. Then the famous feminist science fiction author and editor Judy Merril offered an evening course in writing science fiction through a Toronto college, Hopkinson said. The course never ran, but it prompted me to write my first adult attempt at a science fiction story. Judy met once with the handful of us she would have accepted into the course and showed us how to run our own writing workshop without her. Hopkinsons dream of attending Clarion came true in 1995, with Delany as an instructor. Her early short stories channeled her love of myth and folklore, and her first book, written in Caribbean dialect, married Caribbean myth to the science fictional trappings of black market organ harvesting. Brown Girl in the Ring (1998) follows a young single mother as shes torn between her ancestral culture and modern life in a post-economic collapse Toronto. It won the Aspect and Locus Awards for Best First Novel, and Hopkinson was awarded the John W. Campbell Award for Best New Writer.

In 1996, Dolly the Sheep was created using Gurdons technique to determine if mammalian cells also could revert to more a more primitive, pluripotent state. Widespread animal cloning attempts soon followed, (something Hopkinson used as a science fictional element in Brown Girl) but it was inefficient, and often produced abnormal animals. Ideas of human cloning captured the public imagination as stem cell research exploded onto the scene. One ready source for human ESC (hESC) materials was from embryos which would otherwise be destroyed following in vitro fertilization (IVF) but the U.S. passed the Dickey-Wicker Amendment prohibited federal funding of research that destroyed such embryos. Nevertheless, in 1998 Wisconsin researcher James Thomson, using private funding, successfully isolated and cultured hESCs. Soon after, researchers around the world figured out how to nudge cells down different lineages, with ideas that transplant rejection and genetic disease would soon become things of the past, sliding neatly into the hole that the failure of genetic engineering techniques had left behind. But another blow to the stem cell research community came in 2001, when President Bushs stem cell ban limited research in the U.S. to nineteen existing cell lines.

In the late 1990s, another piece of technology capturing the public imagination was the internet, which promised to bring the world together in unprecedented ways. One such way was through private listservs, the kind used by writer and academic Alondra Nelson to create a space for students and artists to explore Afrofuturist ideas about technology, space, freedom, culture and art with science fiction at the center. It was wonderful, Hopkinson said. It gave me a place to talk and debate with like-minded people about the conjunction of blackness and science fiction without being shouted down by white men or having to teach Racism 101. Connections create communities, which in turn create movements, and in 1999, Delanys essay, Racism and Science Fiction, prompted a call for more meaningful discussions around race in the SF community. In response, Hopkinson became a co-founder of the Carl Brandon society, which works to increase awareness and representation of people of color in the community.

Hopkinsons second novel, Robber, was a breakthrough success and was nominated for Hugo, Nebula, and Tiptree Awards. She would also release Skin Folk (2001), a collection of stories in which mythical figures of West African and Afro-Caribbean culture walk among us, which would win the World Fantasy Award and was selected as one ofThe New York Times Best Books of the Year. Hopkinson also obtained masters degree in fiction writing (which helped alleviate U.S. border hassles when traveling for speaking engagements) during which she wrote The Salt Roads (2003). I knew it would take a level of research, focus and concentration I was struggling to maintain, Hopkinson said. I figured it would help to have a mentor to coach me through it. That turned out to be James Morrow, and he did so admirably. Roads is a masterful work of slipstream literary fantasy that follows the lives of women scattered through time, bound together by the salt uniting all black life. It was nominated for a Nebula and won the Gaylactic Spectrum Award. Hopkinson also edited anthologies centering around different cultures and perspectives, including Whispers from the Cotton Tree Root: Caribbean Fabulist Fiction (2000), Mojo: Conjure Stories (2003), and So Long, Been Dreaming: Postcolonial Science Fiction & Fantasy (2004). She also came out with the award-winning novelThe New Moons Arms in 2007, in which a peri-menopausal woman in a fictional Caribbean town is confronted by her past and the changes she must make to keep her family in her life.

While the stem cell ban hamstrung hESC work, Gurdons research facilitated yet another scientific breakthrough. Researchers began untangling how gene expression changed as stem cells differentiated, and in 2006, Shinya Yamanaka of Kyoto University reported the successful creation of mouse stem cells from differentiated cells. Using a list of 24 pluripotency-associated genes, Yamanaka systematically tested different gene combinations on terminally differentiated cells. He found four genesthereafter known as Yamanaka factorsthat could turn them into induced-pluripotent stem cells (iPSCs), and he and Gurdon would share a 2012 Nobel prize. In 2009, President Obama lifted restrictions on hESC research, and the first clinical trial involving products made using stem cells happened that year. The first human trials using hESCs to treat spinal injuries happened in 2014, and the first iPSC clinical trials for blindness began this past December.

Hopkinson, too, encountered complications and delays at points in her career. For years, Hopkinson suffered escalating symptoms from fibromyalgia, a chronic disease that runs in her family, which interfered with her writing, causing Hopkinson and her partner to struggle with poverty and homelessness. But in 2011, Hopkinson applied to become a professor of Creative Writing at the University of California, Riverside. It seemed in many ways tailor-made for me, Hopkinson said. They specifically wanted a science fiction writer (unheard of in North American Creative Writing departments); they wanted someone with expertise working with a diverse range of people; they were willing to hire someone without a PhD, if their publications were sufficient; they were offering the security of tenure. She got the job, and thanks to a steady paycheck and the benefits of the mild California climate, she got back to writing. Her YA novel, The Chaos (2012), coming-of-age novelSister Mine (2013), and another short story collection, Falling in Love with Hominids (2015) soon followed. Her recent work includes House of Whispers (2018-present), a series in DC Comics Sandman Universe, the final collected volume of which is due out this June. Hopkinson also received an honorary doctorate in 2016 from Anglia Ruskin University in the U.K., and was Guest of Honor at 2017 Worldcon, a year in which women and people of color dominated the historically white, male ballot.

While the Yamanaka factors meant that iPSCs became a standard lab technique, iPSCs are not identical to hESCs. Fascinatingly, two of these factors act together to maintain the silencing of large swaths of DNA. Back in the 1980s, researchers discovered that some regions of DNA are modified by small methyl groups, which can be passed down through cell division. Different cell types have different DNA methylation patterns, and their distribution is far from random; they accumulate in the promoter regions just upstream of genes where their on/off switches are, and the greater the number of methyl groups, the lesser the genes expression. Furthermore, epigenetic modifications, like methylation, can be laid down by our environments (via diet, or stress) which can also be passed down through generations. Even some diseases, like fibromyalgia, have recently been implicated as such an epigenetic disease. Turns out that the long-standing biological paradigm that rejected Lamarck also missed the bigger picture: Nature is, in fact, intimately informed by nurture and environment.

In the past 150 years, we have seen ideas of community grow and expand as the world became more connected, so that they now encompass the globe. The histories of science fiction and biology are full of stories of pioneers opening new doorsbe they doors of greater representation or greater understanding, or bothand others following. If evolution has taught us anything, its that nature abhors a monoculture, and the universe tends towards diversification; healthy communities are ones which understand that we are not apart from the world, but of it, and that diversity of types, be they cells or perspectives, is a strength.

Kelly Lagor is a scientist by day and a science fiction writer by night. Her work has appeared at Tor.com and other places, and you can find her tweeting about all kinds of nonsense @klagor

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On the Origins of Modern Biology and the Fantastic: Part 19 Nalo Hopkinson and Stem Cell Research - tor.com

Campbell First Prof From Undergraduate Institution Elected to ASCB Leadership Post – Davidson News

Campbell was elected treasurer, the No. 2 post, in the American Society for Cell Biology. He is the first faculty member, not just from Davidson, but from any undergraduate institution to serve on the executive council for the organization. The society provides national leadership in science policy and in science advocacy in Washingtona critical need right now. The organization also leads in global research and policy, with a quarter of its members outside the United States. Its newly elected president, Columbia Biology Professor Martin Chalfie, is a Nobel laureate, who visited Davidson at Campbells request in 2015.

Campbell founded the James G. Martin Genomics Program at Davidson, and his influence already extended well beyond campus. He teamed up with Mathematics Professor Laurie Heyer and Environmental Studies Professor Chris Paradiseto write a textbook now used in high schools and colleges across the country that upended conventional teaching of biology. Traditional textbooks present information for students to digest and then repeat on a test. Campbells book presents each topic as a question and offers data sets so student can do what scientists doanalyze, interpret and reach a conclusion.

A Michigan State professor who uses the book saw a dramatic rise in students Medical College Admission Test scores. The National Association of Biology Teachers presented Campbell with its highest teaching honor two years ago.

Campbells election to the national post also helps put Davidson in a position of unprecedented national leadership in the sciences and across all academic professional organizations. Last year, R. Stuart Dickson Professor of Psychology Julio Ramirez wasvoted treasurer-elect for the Society for Neuroscience, the worlds largest and most prestigious organization representing the interests of neuroscientists. He is only the second professor from a liberal arts college to hold a leadership post in the groups 50-year history. Gerardo Marti, professor and chair of sociology, recently waselected president of the Association for the Sociology of Religion, an international organization that publishes the leading journal in the field.

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Campbell First Prof From Undergraduate Institution Elected to ASCB Leadership Post - Davidson News