Category Archives: Biochemistry

Biochemistry

Dr. Nina Schor appointed as the NIH Acting Deputy Director for Intramural Research – National Institutes of Health (.gov)

I am pleased to announce the appointment of Nina F. Schor, M.D., Ph.D., as the NIH Acting Deputy Director for Intramural Research (DDIR) in the NIH Office of the Director. Michael M. Gottesman, M.D., who served as NIH DDIR for 29 years, announced his plans last year to step down to return to the Center for Cancer Research, National Cancer Institute, where he is chief of the Laboratory of Cell Biology. Dr. Schor will begin her new role on August 1, 2022.

As Acting DDIR, Dr. Schor will lead the NIH Intramural Research Program (IRP) and facilitate coordination and collaboration among the 24 NIH institutes and centers that are a part of NIHs distinct research community. She will be responsible for the selection and approval of new NIH principal investigators, human subjects research protection, research integrity, technology transfer, and animal care and use for the IRP. Additionally, Dr. Schor will oversee efforts to train the next generation of biomedical and behavioral researchers at NIH, as well as efforts to foster a diverse and inclusive culture across the IRP.

With a career that has touched all realms of the biomedical research enterprise, Dr. Schor brings substantial experience as an educator, scientist, clinician, and administrator. Dr. Schor joined NIH in January 2018 as Deputy Director of the National Institute of Neurological Disorders and Stroke (NINDS), and in May 2021, she also assumed the role of Acting Scientific Director of NINDS. As Deputy Director, she guided the institutes strategic planning activities, career development programs, maternal and child neurologic health collaborations with other NIH institutes, and the creation and implementation of the Ultra-Rare GENe-based Therapies (URGenT) Network. Prior to joining NIH, Dr. Schor worked at the University of Rochester, where for nearly 12 years she held the positions of Chair of the Department of Pediatrics and Pediatrician-in-Chief of the Golisano Childrens Hospital. Prior to that, she spent 20 years building her academic and scientific career at the University of Pittsburgh, culminating with her roles as Associate Dean for Medical Student Research and Chief of the Division of Child Neurology in the Departments of Pediatrics and Neurology.

Dr. Schor earned her Ph.D. in medical biochemistry from Rockefeller University and her M.D. from Cornell University Medical College. Her residency and postdoctoral fellowship training in pediatrics, child neurology, and molecular biochemistry and pharmacology took place at Harvard University Medical School and Boston Childrens Hospital, where she began her three-decades-long, NIH-funded research efforts focused on targeted therapy for neuroblastoma, a type of pediatric cancer, and neuronal cell death caused by oxidative stress, which occurs when harmful forms of oxygen molecules damage cells.

I am profoundly grateful to Dr. Gottesman for his many years of leadership and service at NIH. With his contagious optimism, adept problem-solving attitude, and wise policymaking, Michael leaves a strong legacy to guide the future DDIR. The programs he developed touch every stage of a scientific career from high school and college internship programs, graduate studies, and postdoctoral training, to recruitment, career development, tenure, and emeritus transition of faculty. His leadership will be remembered in many things, including the remarkable improvements seen in research integrity and the recruitment and subsequent achievements of a diverse scientific workforce over the last three decades. We wish him all the best in this next chapter.

Please join me in welcoming Dr. Schor to the NIH leadership team.

Lawrence A. Tabak, D.D.S., Ph.D.Acting Director, National Institutes of Health

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Dr. Nina Schor appointed as the NIH Acting Deputy Director for Intramural Research - National Institutes of Health (.gov)

Biochemistry

U-M researchers track protein binding, build synthetic proteins to study gene expression – University of Michigan News

How does a nose remember that its a nose? Or an eye remember that its an eye?

As scientists probe the question of how cells remember what kind of cells they are supposed to be, or their genetic lineage, its important to understand how cells express different genes without changing the DNA sequence itself.

But studying this subject is difficult: Researchers can purify the proteins that drive genetic expression, put them in a test tube and watch them bind. But doing so inside the nucleus of cells, their native environment, has been so far impossible.

Study: HP1 oligomerization compensates for low-affinity H3K9me recognition and provides a tunable mechanism for heterochromatin-specific localization (DOI: 10.1126/sciadv.abk0793)

Now, a team of researchers at three University of Michigan labs have been able to track how a protein binds to its chromatin substrate within a living cell by establishing a collaboration that combines state-of-the-art ultra high-resolution imaging, synthetic protein design and computational modeling. Their results are published in Science Advances.

The biological question that were asking is, How do cells actually remember past experiences? And how do these experiences also lead to cells establishing distinct identities, as it happens in the case of the human body where you have lineages of cells that form neurons, or blood cells, or brain cells, and all actually maintain their identities for many generations,' said lead author Kaushik Ragunathan, assistant professor of biological chemistry at the U-M Medical School.

An example I like to think about is that if you chop off your nose, you dont get a hand growing there, even though the genome in your nose and the genome in your hand are exactly the same.

Cells control how and which genes are expressed from a copy of the DNA sequence held within each cell, despite that sequence being the same across all cells in the body. One way they control expression is by changing how tightly the DNA is packaged within the nucleus using proteins called histones. Histones can be modified through the addition of small chemical tags that regulate how tightly the DNA is wound around them and thus whether the genes can be expressed.

Proteins that have the ability to read, write and erase these histone tags explore the DNA within the nucleus of the cell very rapidlyon the order of milliseconds, according to Ragunathan. Ultimately, all this epigenetic information needs to be inherited across generations, but the recognition of these tags is a complicated process that involves chromatin binding and proteins meeting and interacting with each other amidst the chaos of all other possible competing interactions within the cell.

Being able to understand each step of the processand therefore enabling control of how the epigenetic information is inheritedintrigued co-author Julie Biteen, professor of chemistry and biophysics.

Biteen uses single-molecule fluorescence imaging to track individual proteins inside cells. Her lab can see where these proteins are relative to the chromatin, and Ragunathans expertise is in the molecular mechanisms underpinning how histone modifications and histone-binding proteins interact. These two worlds needed to come together so that the biochemistry of what happens in a test tube outside of cells could be tested to figure out what happens inside of them.

The timing of this process is critically important to ensure that the right genes are silenced at the right place and at the right time, Biteen said. What hooked me on this project is that in vitroin a test tubeyou can purify two proteins, watch them bind and see how good that binding is, or what is the affinity for one another. That tells you what can happen in the cells, but not what does happen in the cells.

Biteen and Ragunathan worked with Peter Freddolino, associate professor of biological chemistry, and computational medicine and bioinformatics at the U-M Medical School, to combine computer modeling with their experimental results.

This is really where our collaboration becomes really powerful, Biteen said. On one hand, seeing molecules is very helpful and knowing how fast the molecules move helps a lot in terms of understanding what is possible inside the cell, but here we could take a leap forward by perturbing the system even in unnatural ways in order to understand what these different motions of molecules in the cell actually mean.

While epigenetic marks are tremendously important for maintaining different tissues in complex organisms like humans, they also play an important role in regulating genes of single-celled organisms such as yeast. The team focused on a type of HP1 protein in yeast cells called Swi6. This family of proteins binds to a specific type of histone modifications in the cell to enforce gene silencing. By integrating fluorescent labels with Swi6, Bitees lab watched Swi6 move inside the cells nucleus.

While Swi6 searches for the correct binding site on DNA, it moves quickly, Biteen said. When it finds its target, it slows down significantly. The movement of a protein within the cell is akin to gears in a car and things can move at different speeds based on whom proteins interact with.

From these spaghetti tracks that we get inside the cell, we then figure out how much time they are spending searching and how much of the time they are spending bound, Biteen said. The amount of time they spend not moving tells us about how strongly theyre interacting and their biochemical properties.

While Biteens lab can measure movements in the cell on the scale of tens of milliseconds, much of the biochemistry happening in the cell is happening even faster, she said. Freddolino took this experimental information and developed models to estimate the ability of the Swi6 proteins to jump between the binding states that were identified in experiments.

Freddolinos modeling took into account the experimental measurements and the possible biochemical properties, which includes how the Swi6 molecules interact in the cell. These interactions include molecules that freely float in the solution of the cell, molecules that have bound to DNA, and molecules that are holding hands with each other, he said.

My lab wanted to come up with a more fine-grained model that estimated what was the most likely set of molecular states of the proteins and their ability to jump between those states, that would then give rise to the imaging data that Biteens lab created, Freddolino said.

Having this numerical model allows us to do the computational experiments of what happens if the protein binding is twice as fast as we think. What if its 10 times as fast as we think? Or 10 times slower? Could that still give rise to the data? Very happily, in this case, we were able to show that the relevant processes were really being captured in the fluorescence microscopy.

After identifying the binding properties of natural Swi6, the researchers tested their findings by redesigning Swi6 from its components to see whether they could replicate some of its biochemical properties, Ragunathan said. This allowed the researchers to determine that the imaging and modeling conducted in the first part of the paper reflects how the protein was binding in its native environment.

Can we do what nature did over the course of millions of years and make a protein that in many ways has properties similar to that of Swi6 in cells? Ragunathan said. In vivo biochemistry, which is what weve decided to call this, was not something that was ever thought to be possible inside living cells, but we have shown this is entirely feasible by using imaging as a modality. We are using this project as a foundation in order to understand how these epigenetic states can be established and maintained across generations.

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U-M researchers track protein binding, build synthetic proteins to study gene expression - University of Michigan News

Biochemistry

University of Houston researchers snag $1.8M to develop cancer-fighting virus – InnovationMap

Viruses attack human cells, and that's usually a bad thing some Houston researchers have received fresh funding to develop and use the evil powers of viruses for good.

The developing cancer treatment is called oncolytic virotherapy and has risen in popularity among immunotherapy research. The viruses can kill cancer cells while being ineffective to surrounding cells and tissue. Basically, the virus targets the bad guys by "activating an antitumor immune response made of immune cells such as natural killer (NK) cells," according to a news release from the University of Houston.

However exciting this rising OV treatment seems, the early stage development is far from perfect. Shaun Zhang, director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston, is hoping his work will help improve OV treatment and make it more effective.

We have developed a novel strategy that not only can prevent NK cells from clearing the administered oncolytic virus, but also goes one step further by guiding them to attack tumor cells. We took an entirely different approach to create this oncolytic virotherapy by deleting a region of the gene which has been shown to activate the signaling pathway that enables the virus to replicate in normal cells, Zhang says in the release.

Zhang, who is also a M.D. Anderson professor in the Department of Biology & Biochemistry, has received a $1.8 million grant from the National Institutes of Health to continue his work.

Zhang and his team are specifically creating a new OV called FusOn-H2 and based on the Herpes simplex 2 virus.

Our recent studies showed that arming FusOn-H2 with a chimeric NK engager (C-NK-E) that can engage the infiltrated natural killer cells with tumor cells could significantly enhance the effectiveness of this virotherapy, he says. Most importantly, we observed that tumor destruction by the joint effect of the direct oncolysis and the engaged NK cells led to a measurable elicitation of neoantigen-specific antitumor immunity.

Shaun Zhang is the director of the Center for Nuclear Receptors and Cell Signaling at the University of Houston and M.D. Anderson professor in the Department of Biology & Biochemistry. Image via UH.edu

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University of Houston researchers snag $1.8M to develop cancer-fighting virus - InnovationMap

Biochemistry

Far From the Biliary Tree: A Case of Overlapping Autoimmune Liver Disease in a Patient Presenting With Sicca Symptoms – Cureus

Primary biliary cholangitis (PBC) is achronic autoimmune condition with many extrahepatic manifestations that are commonly encountered as a patient's primary presenting complaints. Rarely, PBC co-exists as an overlapping syndrome with other liver-related autoimmune conditions such as autoimmune hepatitis (AIH). Presented is a rare case of PBC with features of AIH diagnosed in a patient who initially presented with hemoptysis and worsened sicca symptoms due to advanced Sjgrens syndrome. The patient had a three-year evolution of abnormal liver biochemistry and was found to be a heterozygous carrier for hereditary hemochromatosis (H63D mutation). Given that patients with PBC-AIH are at an increased risk of complications compared to isolated disease from either disorder, early diagnosis and prompt management can helpspare patients from cirrhosis, liver failure and transplantation, or even death.

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by the progressive destruction of intrahepatic bile ducts. Various genetic and environmental interactions trigger an autoimmune response against biliary epithelial cells, which leads to cholestasis and fibrosisand can ultimately result in liver cirrhosis and failure [1]. The global incidence rate of PBC differs widely among geographic areas, ranging from 40 to 400 per million individuals with a peak incidence in the fifth decade of life and a 10:1 predominance in females compared to males [2]. Symptoms of PBC related to cholestasis typically develop within two to four years of diagnosis and include fatigue, pruritus, dyslipidemia, fat-soluble malabsorption, and osteoporosis, though up to 61% of cases are asymptomatic [2-3]. PBC also has many associations with extrahepatic autoimmune disease, most notably Sjgrens (up to 73%), thyroid dysfunction (up to 23.6%), cutaneous scleroderma (up to 12.3%), and rheumatoid arthritis (RA) (5.6%) [4-6]. The diagnosis of PBC is made if two of the following three criteria are met: (1) biochemical evidence of cholestasis through the elevation of alkaline phosphatase (ALP) to two times the upper limit of normal, (2) presence of antimitochondrial antibody (AMA) with a titer greater than 1:40, (3) histologic evidence of nonsuppurative destructive cholangitis and interlobular bile duct destruction [7-8].

Rarely, PBC can co-exist as an overlapping syndrome with other liver-related autoimmune conditions such as autoimmune hepatitis (AIH). This phenomenon is present in 1-3% of patients with PBC and 7% of patients with AIH [8]. A PBC-AIH overlap syndrome can be diagnosed using the Paris criteria with 92% sensitivity and 97% specificity [9].

For PBC alone, early initiation of ursodeoxycholic acid (UDCA) to slow disease progression is associated with a long-term survival benefit and minimal side effects such as headaches, motility issues, and weight gain. Along with interval monitoring of liver biochemical tests, recommendations for immunizations for hepatitis A and B are given to individuals without serologic evidence of immunity, in addition to abstention from heavy alcohol use. In general, evidence is limited to making treatment recommendations for patients with PBC as well as features of AIH, though it includes UDCA with or without a component of immunosuppression [8].

A 52-year-old female with a history of Sjgrens and rheumatoid arthritis presented to the clinic with worsening sicca symptoms and persistent cough with hemoptysis over the past two weeks. She also reported fatigue and arthralgias. She had been seeing a rheumatologist and had been started on azathioprinetwo years prior, in addition to pilocarpine for dry eyes. She was also taking levothyroxine for hypothyroidism. The patients vital signs were all within normal limits. Her physical exam was notable for a non-tender liver edge palpated six centimeters below the mid-clavicular costal margin with negative shifting dullness or fluid wave. Other pertinent negatives included the absence of icteric sclera,skin hyperpigmentation, gland or lymph node prominence or tenderness, focalizing lung findings, active synovitis or contractures, palmar excoriations, or cutaneous vasculitis.

On review of her medical chart, she had an extensive rheumatologic workup notable for positive antinuclear antibody (ANA), positive anti-SS-A with negative anti-SS-B,positive salivary gland biopsy, and positive rheumatoid factor (RF). She also had a history of consistently elevated gamma-glutamyl transferase (GGT) and alanine (ALT) and aspartate (AST) transaminases with normal alkaline phosphatase (ALP) and normal total and direct bilirubin levels. Labs were obtained at her clinic visit and notable for elevated AST 237 IU/L, ALT 223 IU/L, GGT 169 IU/L, and normal ALP 101 IU/L with otherwise normal complete blood count and mildly elevated values on the lipid panel (Table 1).

Based on her autoimmune history and elevated transaminases, an expandedrheumatologic workup was performed, notable for a positive anti-mitochondrial antibody (AMA) 128.6 U (normal < 20.0 U), negative anti-smooth muscle antibody (ASMA) 11.0 U (normal < 19 U), and immunoglobulin A (IgA) 287 mg/dL (normal 87-352 mg/dL). The patient was referred to a gastroenterologist and found to have a normal esophagogastroduodenoscopy. Upon genetic analysis, the patient was noted to be a carrier for hereditary hemochromatosis (heterozygous carrier for H63D mutation). The rest of her workup was negative, including hepatitis panel, alpha-1-antitrypsin, double-stranded DNAand anti-Smith/ribonucleoprotein antibodies, SCL-70 (scleroderma) antibody, and centromere antibody.

Imaging with ultrasound demonstrated hepatomegaly with fatty infiltration of the liver (Figure 1). The patient was evaluated by a pulmonologist forher cough and hemoptysis and a CT chest was performed. CT imaging demonstrated prominent mucus and debris along the trachea with subpleural reticulations possibly due to respiratory involvement of her Sjgrens syndrome (images were unable to be obtained for inclusion in this article). It also noted questionable hepatic surface lobulation that could represent early cirrhosis morphology. With a positive AMA and biochemical pattern of cholestasis and hepatocellular injury, the patient was referred forliver biopsy, which revealed extensive inflammatory infiltrate consisting of lymphocytes and plasma cells surrounding portal tract structures, with the presence of interface hepatitis into lobular parenchyma (Figure 2). No evidence of malignancy was noted.

The patient met the criteria for diagnosis (Table 2) and was started on UDCA at 15 mg/kg. She was alsocontinued on azathioprine at a therapeutic dose of 2 mg/kg for AIH. At the three-month follow-up, the patient had down-trending transaminases and was reporting subjective improvement in symptoms of fatigue and arthralgias.

Primary biliary cholangitis (PBC) is a rare but potentially life-threatening autoimmune cholestatic disease of the liver that, when left undiagnosed and untreated, can culminate in end-stage liver cirrhosis. Similar to the patient presented in this case report, PBC has a peak prevalence for those between their fourth and sixth decades of life with a predominance for women [2-3]. Diagnostic criteria for primary hepatic autoimmune diseases rely on biochemical evidence of either cholestasis or hepatocellular damage, presence of auto-antibodies, and histopathological features on liver biopsy [7-9]. While present in fewer than 10% of patients with either PBC or AIH, the overlapping syndrome (PBC-AIH) is well-represented in the current case [8]. There are several subtypes and classifications of this condition, though, like other autoimmune disorders, it can be thought to exist on a spectrum of primary tissue involvement. It is hypothesized that patients with underlying bile duct destruction (characteristic of PBC) also possess a genetic predisposition to develop a hepatitic pattern of liver injury (more consistent with AIH), and thus can also be referred to as PBC, hepatitic form [10].

The patient presented in this case report met the Paris criteria for PBC-AIH both on histology as well as an elevated ALT and presence of anti-AMA antibody. Though not meeting diagnostic criteria (5 times upper limit of normal (ULN)), she also had an elevated GGT at 3.1 times ULN. Her past medical history of several extrahepatic autoimmune diseases is consistent with other cases of PBC-AIH. PBC is known to have associations with Sjgrens syndrome in more than half of individualsand to a lesser extent, with thyroid dysfunction, RA, and cutaneous scleroderma[4-6]. Though a majority of patients eventually diagnosed with PBC are asymptomatic, this patient had multiple symptoms on presentation. She presented with cough and hemoptysis along with xerostomia and dry eyes, all potentially attributed to her Sjgrens diagnosis. She was found to have hepatomegaly both on clinical exam and ultrasound imaging, as well as three years of worsening liver transaminases that prompted an expanded autoimmune work-up.

This case highlights the importance of primary care physicians to not only be familiar with the criteria for autoimmune liver diseases but also to not devalue minor changes in liver biochemistry. Though she had been previously followed by a rheumatologist, the patient had been lost to follow-up and her medical record revealed several inconsistencies regarding the interpretation of her autoimmune laboratory findings between specialists and generalists that she had seen in the past. She had also been noted to have an extensive history of alcohol consumption throughout her medical record. While her AST and ALT abnormalities have been attributed to this, her AST:ALT ratio was inconsistent with this assertion.

Interestingly, this patient was also found to be a heterozygous carrier for hereditary hemochromatosis (HH). On discussion with her gastroenterologist, it is difficult to discern the patients elevated ferritin as related to excess collection versus an acute phase reactant given her history of autoimmune disease. In general, HFE H63D heterozygous carriers rarely develop clinically significant iron overload syndromes [11] though may be at increased riskfor breast and colorectal cancers [12-13]. As of the time of this publication, there are no reports in the literature regarding increased rates of PBC or AIH in those with the H63D mutation.

Compared to patients with PBC alone, individuals with PBC-AIH have higher rates of portal hypertension, esophageal varices, gastrointestinal bleeding, ascites, and liver failure [14-15]. Studies have demonstrated death or liver transplantation in PBC-AIH at rates twice as high compared to PBC alone at six-year mean follow-up [14] and nearly four times as high compared to AIH alone at the two-year follow-up [16]. At 10 years following diagnosis, 44-48% of patients with PBC-AIH progress to cirrhosis [8,15], and transplant-free survival ranges from 52-92% [8-9,14].

Goals of management for autoimmune liver disease include suppression of the underlying pathogenic process as well as treatment of acute symptoms that result from chronic cholestasis, including pruritus, fatigue, and xerostomia. Evidence is limited regarding specific treatment recommendations for diseases with overlapping characteristics. The 2018 practice guidelines from the American Association for the Study of Liver Diseases (AASLD) guidelines concede that the clinical benefit and harm of adding immunosuppressive medications require further study, and recommend tailoring pharmacotherapy to the predominant histologic pattern (PBC or AIH) [17-18]. The 2017 practice guidelines from the European Association for the Study of Liver Diseases (EASL) recommend that in addition to UDCA, immunosuppression be given, or considered, in patients with severe to moderate interface hepatitis, respectively [19]. A meta-analysis for the comparative treatment of various overlap syndromes demonstrated that combination therapy with UDCA and immunosuppression may be superior to both UDCA alone and to steroids with or without azathioprine with respect to biochemical improvement and transplant-free survival [8]. The authors concede, however, that these studies are limited by the inclusion ofpatients with a wide range of histologic severity. Additionally, it has been reported that the degree of baseline interface activity on biopsy (pathognomonic of AIH) is a more accurate predictor of failure with UDCA monotherapy compared to the addition of immunosuppressive therapies [19].

Our patient had already been started on azathioprine for her other rheumatological conditions two years prior to her initial presentation to our clinic. Therefore, given her extrahepatic autoimmune diseases that prompted early immunosuppression, she had theoretically been spared from several years of additional damage due to her PBC-AIH. Relapse rates of AIH up to 90% have been demonstrated when discontinuing immunosuppression. Despite this, a withdrawal trial of immunosuppressives can be consideredonce remissionhas been established (normalization of aminotransferases) and maintained for 24 months[19-20]. She was also started on UDCA after confirming the diagnosis with a biopsy and therefore is now on combination UDCA with immunosuppressive therapy. Long-term monitoring for patients with PBC includes liver biochemical and function tests every three to six months in addition to annual screening for thyroid dysfunction and bone mineral densitometry. Of note, our patient did have a degree of long-bone osteopenia on a dual-energy X-ray absorptiometry scan. We also recommended screening for colorectal and breast cancer given her increased risk with HH carrier status.

Primary liver autoimmune conditions are often associated with extrahepatic manifestations, either as a result of chronic cholestatic symptoms or as distinct, laboratory-identifiable syndromes.Therefore, in patients with a significant rheumatological disease history or when a primary autoimmune workup is being performed in the context of abnormal liver biochemistry, PBC and AIH must both be considered. The Paris diagnostic criteria can be used with a high degree of both sensitivity and specificity to either distinguish or correlate these conditions.Based on the current evidence, early initiation of UDCA with immunosuppressive therapies has been shown to help delay cirrhosis, liver failure and transplantation, and even death.

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Far From the Biliary Tree: A Case of Overlapping Autoimmune Liver Disease in a Patient Presenting With Sicca Symptoms - Cureus

Biochemistry

Biochemistry Breakthrough May Soon Have Asthmatics Breathing Easier – SciTechDaily

A breakthrough discovery could result in more effective asthma treatments.

Scientists have discovered differences in the biochemistry of asthmatic and non-asthmatics which could lead to more effective treatments.

An important discovery that could lead to more effective treatments for the worlds 262 million asthma sufferers was recently made in research led by Edith Cowan University (ECU).

It found that severe asthmatics have a distinct biochemical (metabolite) profile detectable in their urine, compared to mild-to-moderate asthmatics and healthy individuals. The study was led by Dr. Stacey Reinke (ECU) and Dr. Craig Wheelock (Karolinska Institute, Sweden).

To identify and better understand different subtypes of severe asthma, researchers analyzed urine samples from more than 600 participants across 11 countries as part of the U-BIOPRED study, a Europe-wide initiative.

The team of researchers discovered a specific type of metabolite, called carnitines, decreased in severe asthmatics.

Carnitines play an important role in cellular energy generation and immune responses.

Further analyses found carnitine metabolism was lower in severe asthmatics.

These new findings will help enable researchers to work towards new, more effective therapies for asthmatics.

Dr. Reinke, from ECUs Centre for Integrative Metabolomics and Computational Biology, said it is vital asthma treatment is improved.

Asthma affects 2.7 million Australians and there were 417 asthma-related deaths in Australia in 2020, she said.

Severe asthma occurs when someones asthma is uncontrolled, despite being treated with high levels of medication and/or multiple medications.

To identify and develop new treatment options, we first need to better understand the underlying mechanisms of the disease.

One way to do this is to examine the bodys chemical profile, or metabolome, which provides a snapshot of a persons current physiological state and gives useful insight into disease processes.

In this case, we were able to use the urinary metabolome of asthmatics to identify fundamental differences in energy metabolism that may represent a target for new interventions in asthma control, Dr. Reinke said.

Dr. Reinke said it can be difficult and invasive to investigate the lungs directly but fortunately, they contain a lot of blood vessels.

Therefore, any biochemical changes in the lungs can enter the bloodstream, and then be excreted through the urine, she said.

These are preliminary results, but we will continue to investigate carnitine metabolism to evaluate its potential as a new asthma treatment target.

Reference: Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study by Stacey N. Reinke, Shama Naz, Romanas Chaleckis, Hector Gallart-Ayala, Johan Kolmert, Nazanin Z. Kermani, Angelica Tiotiu, David I. Broadhurst, Anders Lundqvist, Henric Olsson, Marika Strm, sa M. Wheelock, Cristina Gmez, Magnus Ericsson, Ana R. Sousa, John H. Riley, Stewart Bates, James Scholfield, Matthew Loza, Frdric Baribaud, Per S. Bakke, Massimo Caruso, Pascal Chanez, Stephen J. Fowler, Thomas Geiser, Peter Howarth, Ildik Horvth, Norbert Krug, Paolo Montuschi, Annelie Behndig, Florian Singer, Jacek Musial, Dominick E. Shaw, Barbro Dahln, Sile Hu, Jessica Lasky-Su, Peter J. Sterk, Kian Fan Chung, Ratko Djukanovic, Sven-Erik Dahln, Ian M. Adcock and Craig E. Wheelock on behalf of the U-BIOPRED Study Group, 30 June 2022, European Respiratory Journal.DOI: 10.1183/13993003.01733-2021

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Biochemistry Breakthrough May Soon Have Asthmatics Breathing Easier - SciTechDaily

Biochemistry

Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and…

Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and opportunities for HERV-Kspecific inhibition | Proceedings of the National Academy of Sciences  pnas.org

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Human endogenous retrovirus-K (HERV-K) reverse transcriptase (RT) structure and biochemistry reveals remarkable similarities to HIV-1 RT and...

Biochemistry

UA Researchers Develop Way to Test Water for Metal Pollutants – The University of Alabama

Research involving The University of Alabama created an easier way to detect harmful levels of heavy metals in water, which could help improve human health by boosting detection efforts by regulatory agencies, water utilities and commercial fishing.

Dr. Marco Bonizzoni

The new analytical method for detecting harmful levels of heavy metals such as cadmium, mercury and lead was created by combining chemical array sensing methods developed at UA with polymer synthesis capabilities at the University of Southern Mississippi, according to findings recently published in Advanced Functional Materials.

The work is part of a larger, multiyear collaboration led by the University of Mississippi and supported by the National Science Foundation to develop advanced polymer-based, selective sensing technologies for detecting and analyzing pollutants in the coastal aquatic ecosystems of the Gulf of Mexico, which host important fisheries, aquaculture, trading ports, and off-shore oil exploration and production industries.

The new method proved to be unusually robust and sensitive even in complex and challenging samples, down to the extremely low concentrations relevant for environmental monitoring applications in fresh- and saltwater, said Dr. Marco Bonizzoni, UA associate professor of chemistry and biochemistry.

Our method for these analyses uses less complex instrumentation, yet achieves sensitivity similar to established lab-based standard techniques, Bonizzoni said. Additionally, our system is simpler and more rugged than existing techniques, potentially opening the path towards development of a portable device for and point-of-sampling measurements.

At low levels, heavy metals are ubiquitous in the environment and some are essential nutrients for the ecosystem. At increased levels, mostly from human intervention, they threaten human, animal and ecosystem health. Exposure to heavy metals has been linked to neurological disease, organ failure and cancer.

Methods for their rapid and simple detection are a scientific and technological priority. Water utilities regularly monitor these potential contaminants in municipal water. Government regulatory agencies track heavy metals in waters as a proxy for potential contamination of marine life such as fish sold for consumption.

Bonizzoni, associate professor of chemistry and biochemistry, and his group created a simple method for detecting harmful levels of heavy metals in water.

Current methods require lugging water samples taken on location back to a lab for analysis, which is time consuming and requires additional measures to ensure the sample isnt contaminated. The new method could simplify this process greatly by allowing for direct on-site measurements.

For now, researchers demonstrated they can simplify analysis by testing samples taken from the site of the Deep Water Horizon oil spill in the Gulf, gathered by a group led by Dr. Alan Shillerfrom Southern Mississippi. The site near the destroyed oil rig and subsequent massive oil spill into the ocean in 2010 released heavy metals into the environment.

Former UA graduate student Dr. Michael Ihde, now a faculty member at Williams College, led the Bonizzoni groups efforts to combine their method for using an array of receptors in a chemical sensor with the polymer synthesis capabilities from a group led by Dr. Jason Azoulay at Southern Mississippi and his graduate student Joshua Tropp.

Researchers prepared bright fluorene-based light-emitting charged polymers with appended metal binding groups, and studied their interactions with metal pollutants, developing methods for their ultrasensitive detection and discrimination.

Through the collaboration, we made new polymers, we combined them in a physical sensing system, and we measured complex and challenging samples with it, Bonizzoni said.

After demonstrating this proof of principle, the research team will focus on streamlining the procedure to fit inside a portable sensing system that could be operated by most anyone as a self-contained testing device deployed on a boat or, possibly, on a buoy that passively and continuously monitors the water; however, that future is several steps away.

Contact

Adam Jones, UA communications, 205-348-4328, adam.jones@ua.edu

The University of Alabama, part of The University of Alabama System, is the states flagship university. UA shapes a better world through its teaching, research and service. With a global reputation for excellence, UA provides an inclusive, forward-thinking environment and nearly 200 degree programs on a beautiful, student-centered campus. A leader in cutting-edge research, UA advances discovery, creative inquiry and knowledge through more than 30 research centers. As the states largest higher education institution, UA drives economic growth in Alabama and beyond.

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UA Researchers Develop Way to Test Water for Metal Pollutants - The University of Alabama

Biochemistry

UAPB Alumnus Recommends a UAPB Education in Aquaculture/Fisheries for Research, Job Opportunities – UAPB News

Will Hehemann|School of Agriculture, Fisheries and Human Sciences

Andrew Maina, originally from the east African country of Kenya, says his lifelong interest in science led him to enroll in the University of Arkansas at Pine Bluffs (UAPB) graduate program in aquaculture/fisheries.

My father was a pharmacist, and I also started to get interested in science in elementary school, he said. In high school, I became really interested in biology. My love for the outdoors and wildlife started in Kenya but continues to play a part in my life in my new home of North Carolina. I frequently go hiking and birdwatching.

During his undergraduate studies at the University of Eastern Africa in Baraton, Kenya, Maina took a course on marine biology. This experience made him curious about studying a discipline of science largely new to him.

I became interested in further studying fish because they have unique physiologies compared to other groups of animals, he said. I visited with Dr. Rebecca Lochmann, chair of the UAPB Department of Aquaculture and Fisheries. Our conversation about her research on catfish piqued my interest. I had previously taken a graduate course in chemical separations and biochemistry at the University of Florida, which gave me the theoretical background in the type of tools and techniques used in her lab for research.

In 2012, he enrolled in the graduate program and started conducting research on channel catfish nutrition under the mentorship of Dr. Lochmann.

In the lab, I was able to build an entirely new skill set as we used biochemistry techniques and separation chemistry to investigate the nutritional composition of fish muscle and whole fish, Maina said. Dr. Lochmann was influential in providing guidance throughout my graduate studies and also in giving me opportunities to attend large conferences and present my original research.

After graduating from UAPB in 2016, Maina was employed by Smithers, a company that provides independent testing services for a range of industries and products.

I was hired as a study director for channel catfish nutrient equivalency studies with various genetically modified organisms (GMO) grain varieties meant for export to the Asian market, he said. We were testing catfish feeds formulated to incorporate GMO grains. Our job was to ensure GMO grains used in these feeds were similar enough to non-GMO strains. We also made sure the feeds did not have any negative effects on catfish growth.

Maina currently works for Catalent, Inc., a global pharmaceutical company, where he is responsible for performing drug substance and drug product stability analysis.

Before they hit the market, medicines must be tested to make sure whatever components listed on the label are actually in the tablet in those precise measurements, he said. Our work helps ensure that any drug released to the market is in full compliance with U.S. Food and Drug Administration standards.

Maina said he recommends an education at the UAPB Department of Aquaculture and Fisheries for students looking to gain quality research experience. In addition to the labs on campus, he said students can also pursue collaborative opportunities with organizations such as the Harry K. Dupree Stuttgart National Aquaculture Research Center in Stuttgart, Arkansas.

The research skills I gained at UAPB continue to help me in my career, he said. During my studies, I enjoyed working with professors and students from different backgrounds on research that truly supported Arkansas and the region.

The University of Arkansas at Pine Bluff offers all its Extension and Research programs and services without regard to race, color, sex, gender identity, sexual orientation, national origin, religion, age, disability, marital or veteran status, genetic information, or any other legally protected status, and is an Affirmative Action/Equal Opportunity Employer.

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Biochemistry

28-year-old Becomes First Black Woman to Earn PhD in Biochemistry at Florida International University – YEN.COM.GH – Yen.com.gh

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Student-athlete, Chantrell Frazier, has made history as the first Black woman to earn a doctoral degree in Biochemistry at Florida International University.

Frazier, 28, began her college journey at Historically Black College or University (HBCU), where she earned her bachelor's degree to give her the proper foundation to prepare her for graduate school.

It was also the same reason that inspired her to attend Savannah State University (SSU), according to Atlanta Black Star.

After making history, Frazier looks forward to continuing her studies at a postdoctoral teaching fellowship at Framingham State University in Massachusetts.

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The trailblazer plans to become a chemistry professor and champion the next generation of STEM leaders.

Still on education, YEN.com.gh previously reported that Lerato Jaca triumphed adversity to achieve her goals, becoming the first person in her family to bag a degree in 2020.

She understood what it meant for a Black girl to glean such a feat, more so, make history.

In a post on Twitter, Jaca disclosed that she graduated from the University of Cape Town, UCT, making history as her family's first graduate and doctor.

Meanwhile, YEN.com.gh earlier reported that Ray Curtis Petty Jr, ESQ is the definition of a fighter who overcame cycles of obstacles life threw at him to achieve his goal as a legal brain, becoming the first lawyer in his family.

Undaunted by the mountain of difficulties and childhood inadequacies, he triumphed and made history as his family's first-generation attorney.

Recounting his story on his Instagram account, he recalls being told by his teachers that he should be in special education classes. His coaches also doubted his ability to remember a playbook as a child, he said.

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28-year-old Becomes First Black Woman to Earn PhD in Biochemistry at Florida International University - YEN.COM.GH - Yen.com.gh

Biochemistry

Designing the next generation of nanoscale electronics | Rowan Today | Rowan University – Rowan Today

Amid an ongoing semiconductor shortage delaying the production of cars, phones, computers, and televisions, a new research collaboration between Rowan University and Butler University seeks to develop computational tools for designing the next generation of nanoscale electronics. The $222,559 grant was awarded by the National Science Foundation.

It is becoming increasingly more difficult to create these computer chips.

The classical computing architectures are starting to reach their development potential, said principal investigator Erik Hoy, Ph.D., an assistant professor of chemistry and biochemistry in the College of Science & Mathematics. What we're looking to contribute to is the next generation of computer architectures.

These next-generation devices are incredibly small, but have enormous potential. Hoy and his research team will partner with a team from Butler University to develop new techniques to study these devices on a molecular level more effectively. Previous methods have limitations in their treatment of molecular electronic interactions, and a more comprehensive methodology is needed to ensure that nanoscale architectures deliver their promised performance gains.

Hoys software will treat electronic interactions in these devices to a degree that has not been done before. The software will help determine if nanoelectronics-based computer chips will function as engineers hoped. This tool will then be made publicly available for any researcher to use.

In the long run, it's intended to address a key supply chain problem, Hoy said. Were going to provide new tools, so that when people go to build these devices, they can predict their properties accurately so they know the device will behave as expected.

The grant will support Rowans materials science and engineering program by heavily involving both graduate and undergraduate students throughout the research.

One of my key goals is to help build the next generation of materials science and nanoscience-focused students in the U.S., Hoy said.

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Designing the next generation of nanoscale electronics | Rowan Today | Rowan University - Rowan Today