Arn Anderson Bron Breakker Has Got His Dads Genetics, Will Be A Big Star eWrestlingNews
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Category Archives: Genetics
Genetic research: possibilities and risks Exaudi – Exaudi
The Bioethics Observatory of the Catholic University of Valencia (UCV) invites an in-depth analysis of genetic research at the conference Genetic research: possibilities and risks. An approach from bioethics. This event, which will take place on July 4, 2024, at the UCV San Juan y San Vicente headquarters (18 Jorge Juan Street), will bring together experts from various fields to explore the ethical implications of scientific advances in this area.
In-person attendance at the congress requires prior registration, but the possibility of following it online will also be offered through the following link: https://youtube.com/live/.
The advancement of genetic research constitutes one of the spearheads of biomedical sciences and opens up enormous application possibilities in the fields of bioengineering, editing, and gene therapies. In parallel, with the development of these new tools, new bioethical dilemmas arise related to their fields of application, their safety and effectiveness, and regulation and control needs that urgently need to be addressed.
In our congress we propose a scientific approach to the current state of genetic research, analyzing the most recent evidence, such as that related to epigenetic processes, the therapeutic applications of the editing processes and obtaining mini human organs through bioengineering procedures, the aspects ethics of the heritability of potential changes and the need for ethical and legal regulation of related practices.
A prestigious team of expert researchers in each of these areas will provide us with updated access to this evidence that allows its bioethical assessment based on scientific rigor.
It is aimed at researchers, teachers, students and anyone with an interest in the field of Bioethics, and especially in genetics.
REGISTRATION HERE
PROGRAM
10:00. Institutional inauguration
10:15. Round Table: Epigenetics and genome editing: A scientific update
Ethics and epigenetics.
Luis Franco. Full member of the Royal Academy of Sciences of Spain and the Royal Academy of Medicine of the Valencian Community. University of Valencia.
10:45. Genome editing. Therapeutic advances and bioethical uncertainties.
Nicolas Jouve. Emeritus Professor of Genetics, former member of the Bioethics Committee of Spain.
11:15. Colloquium
Moderator:Luca Gmez Tatay. Professor of cell biology, biochemistry and bioethics. Catholic University of Valencia.
11:30. Coffee Break
12:00. Round Table: Bioengineering and gene therapy
Deciphering the potential of human mini-organs in the laboratory through ethics and bioengineering.
Nria Montserrat. ICREA research professor and principal researcher at the Institute of Bioengineering of Catalonia (IBEC).
12:30. Advances in the therapeutic application of gene editing systems based on CRISPR. Juan Roberto Rodrguez-Madoz. Researcher of the Hemato-Oncology Program. TOP. University of Navarra.
13:00. Colloquium.
Moderator:Jos Miguel Hernndez Andreu. Professor and researcher of biochemistry and molecular biology. Catholic University of Valencia.
16:15. Round Table: Ethical limits in genetic manipulation
Heritable gene editing in humans and future generations.
Vicente Bellver. Professor of Philosophy of Law at the University of Valencia. President of the Bioethics Committee of the Valencian Community.
16:45. Regulating gene editing: principles versus rules.
Federico de Montalvo. Vice Chancellor of Institutional Relations and Secretary General of the Universidad Pontificia Comillas.
17:15. Gene editing: what should really scare us?
igo De Miguel. Research Group of the Chair of Law and Human Genome of the Department of Public Law. University of the Basque Country Euskal Herriko Unibertsitatea.
17:45. Colloquium
Moderator:Mara Jos Salar. Coordinator of the Philosophy Degree. Professor at the Faculty of Economic and Social Legal Sciences of the Catholic University of Valencia.
18:00. Closure. Mr. Julio Tudela. Director of the Bioethics Observatory of the Catholic University of Valencia.
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Genetic research: possibilities and risks Exaudi - Exaudi
Study shows effect of ‘interaction’ on epigenetic marking in… – Parkinson’s News Today
Genetic variations along with exposure to environmental factors, such as pesticides, may increase Parkinsons disease in a sex-dependent manner, a study of French farmworkers suggests.
Most cases of Parkinsons disease dont arise from a single factor, but rather a combination of a persons genes, lifestyle, and what theyre exposed to in the environment, Michael Kobor, PhD, who co-led the study from the University of British Columbia (UBC) in Canada, said in a university press release.
Studies like ours provide building blocks for investigation of personalized risk profiles for Parkinsons disease and biomarkers for earlier diagnosis, said Samantha Schaffner, PhD, a postdoctoral fellow at UBCs Edwin S.H. Leong Centre for Healthy Aging, who noted that, while its too early to know if the findings will hold true when looking at larger pools of data, in the future, [scientists] may be able to estimate someones risk level based on their sex, genetics and lifestyle, and provide tailored guidance on prevention.
The study, Genetic variation and pesticide exposure influence blood DNA methylation signatures in females with early-stage Parkinsons disease, was published in npj Parkinsons disease by Kobors team in collaboration with researchers in France.
How Parkinsons starts is unclear, but growing evidence points to how genetics and a number of environmental factors, such as breathing in or having contact with pesticides, may come together to cause the disease.
While there has been a great deal of research into each of these factors on their own, we have a limited understanding of how they interact with each other, said Kobor, a Canada research chair in social epigenetics, who is leading efforts to establish a link between genetics and pesticide exposure. Were working to bring these pieces of the puzzle together to gain a better understanding of how Parkinsons develops, whos most at risk, and how we can prevent it.
The study included 71 people with early-stage Parkinsons and 147 people without it who were enrolled with TERRE, a health database of French agricultural workers that contains a detailed history of pesticide exposure.
People exposed to pesticides used in farming are at a higher risk for developing Parkinsons and those who live or work near areas with higher levels of certain pesticides are more likely to see their symptoms get worse faster.
Here, the researchers focused on DNA methylation and how its patterns change in women versus men with Parkinsons. In DNA methylation, chemical marks on DNA can indicate whether genes are turned on or off, that is, how the information in genes is used by cells without changing the genetic code itself.
After scanning more than 42,000 regions of DNA from blood samples, the researchers found that DNA methylation linked to early-stage Parkinsons was spread across 69 regions in women and only two in men.
In women, DNA methylation mapped to genes related to cell signaling, protein production, and ion transport. In men, those epigenetic changes mapped to genes related to protein breakdown or recycling and the transport of ions within cells.
To validate their findings in women, the researchers downloaded the PEG1 (GSE111629) and SGPD (GSE145361) datasets from a public database. They found a significant match in DNA methylation between TERRE and PEG1 along with a French database called DIGPD, but not between TERRE and SGPD.
For 48 of the 69 regions targeted by DNA methylation in women, genetics alone provided the best explanation for the epigenetic changes previously attributed to Parkinsons, but pesticide exposure also contributed, especially when it interacted with genetic factors.
These findings highlight the complex interactions between genetic and environmental factors, Schaffner said. Having certain genetic variations may only increase Parkinsons disease risk in the context of an environmental exposure like pesticides, and they might have a sex-dependent effect on risk.
While this study may help lead to a more personalized approach to Parkinsons based on a persons genetic makeup, the findings should be further explored in larger study populations and in experimental systems, preferably with precise measures of exposure, the researchers said.
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Study shows effect of 'interaction' on epigenetic marking in... - Parkinson's News Today
The same genetic mutations behind gorillas’ small penises may hinder fertility in men – Livescience.com
Silverback gorillas are famous for their impressive, bulging physiques and their rather modest genitalia. Now, scientists have uncovered a potential genetic link between these apes' small members and infertility problems in male humans.
Coming in at just 1.1 inches (3 centimeters) long, on average, the penis of the adult male gorilla (Gorilla) is the smallest phallus of all apes. The gorilla's genital size comes with other deficits in its reproductive capacity, such as low sperm count compared to other primates, and sperm with poor motility and a diminished ability to bind to eggs.
Given that these are reproductive issues that can also affect humans, it may seem surprising that all male gorillas share these traits. However, this can be explained by gorillas' mating system, said Jacob Bowman, lead author of the new study and a postdoctoral researcher at the University at Buffalo.
Gorillas operate in a polygynous system, in which a dominant male has near-exclusive access to females in his troop. The silverback's unwieldy physique means it has no problem securing mates, and thus, its sperm doesn't have to compete with that of other males and it can produce offspring without many, highly motile swimmers. The theory is that this lack of sperm competition led to the evolution of gorillas' small genitalia.
Related: Move over, Viagra this spider's boner-inducing venom could treat people let down by the blue pill
This got researchers "wondering if, at a genetic level, we can find genes associated with spermatogenesis [sperm production] or that we see leading to poor-quality sperm," Bowman told Live Science. Gorillas and humans share the vast majority of the same genes so if the researchers could pinpoint suspect genes in gorillas, they could next turn their attention to the human genome.
Roughly 15% of U.S. couples have trouble conceiving, according to Yale Medicine, and more than half of those cases involve male infertility. Around 30% of infertility cases have a genetic basis, said Vincent Straub, a doctoral student in population health at the University of Oxford who was not involved in the new study. However, the genes involved in male infertility are poorly understood.
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To help unravel those genetics, Bowman and colleagues combed through a database of more than 13,000 genes across 261 mammals. This involved looking at genes' underlying sequences, to see how they changed over time in related animals. The aim was to see if certain genes in the gorilla branch of the tree of life were evolving at dramatically reduced rates, Bowman said.
This can happen when there isn't strong pressure to get rid of genetic mutations that could hinder a population's survival such as those related to gorillas' low-quality sperm. This process, called "relaxed purifying selection," can result in seemingly harmful mutations becoming common in a species.
The data turned up 578 genes in the gorilla lineage that underwent this type of selection. An analysis and existing data suggested that many of these genes are involved in making sperm. However, not all the flagged genes had known roles in male fertility.
To better understand these genes' functions, the team turned to the fruit fly (Drosophila melanogaster), a commonly used genetic model in biology. They systematically silenced each of the genes in male flies to see if they affected the insects' ability to reproduce. In this way, they uncovered 41 new genes that hadn't previously been tied to male fertility.
The researchers then connected the dots back to humans using a genetic database with data from 2,100 men with infertility, who either had very low amounts or a lack of sperm in their semen. They also looked at data from fertile men, focusing on the genes they'd flagged in gorillas. They found that, in 109 of relaxed gorilla genes, the infertile men carried more loss-of-function mutations than did fertile men; loss-of-function mutations reduce a gene's ability to make the protein it codes for.
While it's likely these genes are involved in human male fertility, more research is needed to learn exactly how they work in the body. Straub emphasized that infertility is very complex, and that not all of it comes down to genetics. To fully understand it, scientists need to account for how different genes interact with one another and with an organism's environment and its behavior.
The findings drawn from gorillas open the door to future explorations about how these genes, and others closely associated with them, might influence fertility in people, Straub said. The study was published May 9 in the journal eLife.
Ever wonder why some people build muscle more easily than others or why freckles come out in the sun? Send us your questions about how the human body works to community@livescience.com with the subject line "Health Desk Q," and you may see your question answered on the website!
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The same genetic mutations behind gorillas' small penises may hinder fertility in men - Livescience.com
Genetics reveals surprising origin of the German cockroach – Cosmos
The German cockroach lurks in human homes, cities, and structures worldwide. You wont find it crawling through natural habitats its entirely domesticated.
The pest species, Blattella germanica, was first recorded in central Europe about 250 years ago. But its origin and spread has remained a mystery until now.
But a team of researchers has now confirmed the species evolved from the Asian cockroach Blattella asahinaiabout 2,100 years ago and probably did this by adapting to human settlements in India or Myanmar.
We found that the sequence for the German cockroach was almost identical to that of B. asahinai, a species native to the Bay of Bengal, from east India to Bangladesh and into Myanmar, says Theo Evans of the University of Western Australia, who co-authored the study published inProceedings of the National Academy of Sciences.
Genomic analysis of DNA collected from 281 cockroaches, from 17 countries across 6 continents, revealed 2 routes through which the species spread across the globe.
We found an early spread route around 1,200 years ago, which was from eastern India westwards, likely from increasing trade and military activities of the Islamic Umayyad or Abbasid Caliphates, says Evans.
The next spread route was eastwards around 390 years ago into the Indonesia archipelago, likely facilitated by various European East India Companies.These companies traded spices, tea, cotton and other products within South and Southeast Asia, and back to Europe.
We estimated that German cockroaches arrived in Europe about 270 years ago, which matches the historical records from the Seven Years War. From Europe the German cockroach spread to the rest of the world, around 120 years ago, probably from faster transportation on steam ships.
B. germanica grows to about 1.1-1.6 centimetres long and varies in colouration from tan to almost black. They are omnivorous scavengers attracted to meats, starches, sugars and fatty foods.
To survive, cockroaches have to avoid being seen by humans. German cockroaches have evolved to be nocturnal, avoid open spaces, and although it retained its wings it has stopped flying, says Evans.
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Genetics reveals surprising origin of the German cockroach - Cosmos
Genetics Reveals The Mysterious Origins Of The Cockroach – Forbes
Genetics Reveals The Mysterious Origins Of The Cockroach Forbes
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Genetics Reveals The Mysterious Origins Of The Cockroach - Forbes
Optimizing genetics to advance controlled environment agriculture – AgriLife Today – AgriLife Today
Texas A&M AgriLife is adding crucial expertise to help guide future innovations in controlled environment horticulture as the burgeoning field continues to evolve.
Krishna Bhattarai, Ph.D., Texas A&M AgriLife Research plant breeder for controlled environment horticulture and assistant professor, has joined the Texas A&M College of Agriculture and Life Sciences Department of Horticultural Sciences. His research uses genetics and genomics to develop new horticulture crop cultivars specifically for controlled environment production.
Bhattarais research will be performed at the Texas A&M AgriLife Research and Extension Center in Dallas.
Amit Dhingra, Ph.D., head of the Department of Horticultural Sciences, said Bhattarais hiring is a major step forward for the controlled environment horticulture program. He said technological advances have spurred much of the burgeoning fields momentum, and Bhattarais arrival and focus on optimization of plant genetics in these systems comes at a critical time.
Dhingra said he believes the next step in the evolution of controlled environment horticulture is cohesion between plant genetics and the grow systems they support. The idea is not only to optimize yields but also focus on other cultivar characteristics like nutritional density and growth habit as well as aesthetics and flavor.
Daniel Leskovar, Ph.D., director at the Dallas center, said Bhattarais hire resulted from the strategic plan and vision of the controlled environment horticulture program at Texas A&M AgriLife.
His expertise in plant breeding and phenotyping tools will provide very valuable synergy to our growing CEH multidisciplinary programs at Texas A&M University, he said.
Specifically, his expertise in plant breeding and genetics focused on developing new fruits and vegetable cultivars with improved resource use of efficient traits, disease and abiotic stress resistance, and with high nutritional and sensorial quality will ultimately benefit consumers, as well as the controlled environment growers and industry.
The controlled environment program at the Dallas center includes small-acreage/urban horticulturists, Joe Masabni, Ph.D., and Genhua Niu, Ph.D., both professors in the Department of Horticultural Sciences; Azlan Zahid, agriculture engineer from the Department of Biological and Agricultural Engineering and entomologist, Arash Kheirodin, Ph.D., in the Department of Entomology. The team also includes Shuyang Zhen, Ph.D., assistant professor in the Department of Horticultural Sciences, College Station.
Dhingra said Bhattarais arrival provides important expertise for the programs holistic approach, making Texas A&M an innovator and leader in the field.
Researchers in the controlled environment horticulture program are experimenting with plants in a range of technologies that include long-standing methods like high tunnels and greenhouses and aquaponic and hydroponic systems.
They are also engaged in concepts like precision agriculture that rely on innovative technologies such as remote sensors to collect a range of data related to environmental and plant conditions. Sensing technology allows growers to incorporate other cutting-edge advancements like automation, robotics and artificial intelligence to manage plants.
The next frontier in controlled environment production of horticultural crops is plant genetics, Dhingra said. We hope to increase the efficiency, sustainability and profitability for controlled environment growers by harnessing the genetic potential in plant material so that crops perform at optimal levels in these systems.
Bhattarai said he is aware of only one other plant breeder conducting public research dedicated to controlled environment production.
A lot of research has been done on the structural and software programming side of controlled environment horticulture, but plant breeding specifically for those systems is lagging, he said. Cultivar development dedicated to controlled environment production is a field where there is a lot of opportunity to explore and contribute.
Bhattarais previous research covered a broad range of horticultural crops, including flowers, fruits and vegetables.
Bacterial leaf spot resistance was the focal point of his research as a graduate research assistant in the North Carolina State University tomato breeding program. The disease is problematic for open-field tomato production.
In 2014, while a masters student at the University of Florida, his focus shifted to ornamental plants, including the prevention of powdery mildew in cut flowers like Gerbera daisies.
Bhattarais research took another turn as a postdoctorate researcher at the University of California, Davis. Instead of breeding for plant disease resistance, he started analyzing genomic regions of strawberries in search of improved aroma and flavor.
Since I have experience in all three of these important commodities, I thought I could deliver some good research that could impact plant breeding for controlled environment production in Texas, he said. We have seen tremendous growth of controlled environment production in Texas, and that makes Texas A&M an ideal place to be.
Controlled environment horticulture is emerging as a sustainable production method that can supplement traditional field production. As agriculture grapples with the potential impacts of climate change, water scarcity, land fragmentation and other challenges, systems that optimize resources, operate within small footprints and are not subject to the whims of Mother Nature continue to gain momentum.
Bhattarai said Texas is rapidly becoming a leader in controlled environment production, which puts Texas A&M AgriLife in a position to help the industry and producers navigate challenges. Breeding plants to optimize their uptake of water and fertilizer is a focus, but he is also looking at genes that determine plant structure and inflorescence to maximize yields in limited space.
According to grower surveys, he said many of these systems are dedicated to leafy green production, but Bhattarai wants to expand grower options and crop variety.
Producers have to be profitable, and the ability to harness traits in cultivars for these targeted environments will be a critical part of the industrys evolution, he said. The genetic side of innovation in this field will optimize technological innovations in these systems.
Using genetic tools to identify and harness traits for specific growing systems will drive system optimization and industry sustainability, Bhattarai said.
For instance, in hydroponic systems, plants do not need high root biomass because nutrients are readily available. Bhattarai will select for cultivars producing higher volumes of the consumable products, whether fruit, shoots or leaves, for hydroponic growers. Genetics influencing inflorescence could also be chosen to optimize the systems ability to automate the crop harvest.
Identifying and expressing plant genes that open pathways to better flavors, better nutrition and other distinct characteristics will help controlled environment producers grow premium produce, Bhattarai said. Plant breeding programs will also help create high-value fruit and vegetables that are distinct in the marketplace.
The idea is to give controlled environment growers options and to optimize those options, Bhattarai said.
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Optimizing genetics to advance controlled environment agriculture - AgriLife Today - AgriLife Today
Genetics help combat illegal movement of feral swine – The Wildlife Society
May 21, 2024 by Gail Keirn and Tim Smyser, USDA Wildlife Services
Most wild pigs are hybrids, offering clues to distinguish them from domestic pigs
When the gate swings open on a trailer, it doesnt take long for wild pigs to pour out into their new environment. Experts are not sure how often people move wild pigs, but they know it is contributing to the spread of invasive wild pigs (Sus scrofa) across the United States.
The illegal transportation of wild pigs (also known as feral swine) for hunting purposes has contributed to the rapid expansion of this invasive species across to the United States over the past 40 years. They are now reported in at least 35 states. To help curb the spread of these invasive animals, multiple states have passed laws prohibiting their possession or transport. However, the similarities between domestic pigs and invasive wild pigs pose a challenge to enforcing these regulations.
Sometimes it can be difficult to distinguish a domestic pig from an invasive wild pig just by looking at them, said NWRC geneticist Dr. Tim Smyser. But genetic analysis shows that about 97% of invasive wild pigs (Sus scrofa) in the U.S. are hybrids of wild boars and domestic pigs, Smyser said.
That has allowed NWRC researchers and partners to exploit the wild boar ancestry found in most invasive pigs to differentiate them from domestic pigs. Approximately 1,400 samples from 33 domestic breeds and 16 wild boar populations were genotyped and sorted into five genetically cohesive reference groups: mixed-commercial breeds, Durocs, heritage breeds, primitive breeds and wild boars.
Then, researchers used well-established genetic clustering techniques to evaluate the likelihood that some level of wild boar hybridization took place.
The technique we developed basically allows wildlife managers and law enforcement officials to collect a genetic sample from a captured pig, genotype it and determine how likely it is that the pig descended from one of the domestic breed lineages, a pure wild boar lineage or a hybrid of the two, Smyser said.
Researchers evaluated the discriminatory power of this approach using simulated genotypes and real data from an additional 29 breeds of domestic pigs and more than 6,500 invasive wild pig samples. All the simulated and real data from domestic pigs fell within the statistical distribution of the domestic pig reference groups, while 74% of the wild pig data exceeded the maximum threshold for the domestic pig reference groups and could be statistically classified as having wild boar ancestry.
The ability to curtail illegal translocations of invasive wild pigs is an important part of reducing their spread and damage to the economy and the environment, Smyser said. This new genetic and statistical approach will aid in the enforcement of prohibitions on wild pig movement and introduction.
Wildlife Services is a Strategic Partner of TWS.
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Genetics help combat illegal movement of feral swine - The Wildlife Society
Tracking the cellular and genetic roots of neuropsychiatric disease – Yale News
A new analysis has revealed detailed information about genetic variation in brain cells that could open new avenues for the targeted treatment of diseases such as schizophrenia and Alzheimers disease.
The findings, reported May 23 in Science, were the result of a multi-institutional collaboration known as PsychENCODE, founded in 2015 by the National Institutes of Health, which seeks new understandings of genomic influences on neuropsychiatric disease. The study was published alongside related studies in Science, Science Advances, and Science Translational Medicine.
Previous research has established a strong link between a persons genetics and their likelihood of developing neuropsychiatric disease, saysMark Gerstein, the Albert L. Williams Professor of Biomedical Informatics at Yale School of Medicine and senior author of the new study.
The correlations between genetics and your susceptibility to disease are much higher for brain diseases than for cancer or heart disease, said Gerstein. If your parents have schizophrenia, youre much more likely to get it than you are to get heart disease if your parents have the disease. There is a very large heritability for these brain-related conditions.
Whats less clear, however, is how this genetic variation leads to disease.
We want to understand the mechanism, said Gerstein. What is that gene variantdoingin the brain?
For the new study, researchers set out to better understand the genetic variation across individual cell types in the brain. To do so, they performed several types of single-cell experiments on more than 2.8 million cells taken from the brains of 388 people, including healthy individuals and others with schizophrenia, bipolar disorder, autism spectrum disorder, post-traumatic stress disorder, and Alzheimers disease.
From that pool of cells, the researchers identified 28 different cell types. Then they examined gene expression and regulation within those cell types.
In one analysis, the researchers were able to link gene expression to variants in upstream regulatory regions, bits of genetic code situated before the gene in question that can increase or decrease the genes expression.
Thats useful because if you have a variant of interest, you can now link it to a gene, said Gerstein. And thats really powerful because it helps you interpret the variants. It helps you understand what effect theyre having in the brain. And because we looked across cell types, our data also allow you to connect that variant to an individual cell type of action.
The researchers also assessed how particular genes, such as those associated with neurotransmitters, varied across individuals and cell types, finding variability was usually higher across cell types than across individuals. This pattern was even stronger for genes that code for proteins targeted for drug treatment.
And thats generally good for a drug, Gerstein said. It means that those drugs are homing in on particular cell types and not affecting your whole brain or body. It also means those drugs are more likely to be unaffected by genetic variants and work in many people.
Using the data generated by the analysis, the researchers were able to map out within-cell type genetic regulatory networks and between-cell communication networks, and then plug those networks into a machine learning model. Then, using an individuals genetic information, the model could predict whether they had a brain disease.
Because these networks were hard coded in the model, when the model made a prediction we could see which parts of the network contributed to it, said Gerstein. So we could identify which genes and cell types were important for that prediction. And that can suggest candidate drug targets.
In one example, the model predicted an individual with a particular genetic variant might have bipolar disorder, and the researchers could see that prediction was based on two genes in three cell types. In another, the researchers identified six genes in six cell types that contributed to a schizophrenia prediction.
The model also worked in the opposite direction. The researchers could introduce a genetic perturbation and see how that might affect the network and an individuals health. This, Gerstein says, is useful for drug design or previewing how well drugs or drug combinations might fare as treatments.
Together, the findings could help facilitate precision-medicine approaches for neuropsychiatric disease, said the researchers.
To further this work, the consortium hasmade its results and model availableto other researchers.
Our vision is that researchers interested in a particular gene or variant can use our resources to better understand what its doing in the brain or to perhaps identify new candidate drug targets to investigate more, said Gerstein.
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Tracking the cellular and genetic roots of neuropsychiatric disease - Yale News
Seedling root system adaptation to water availability during maize domestication and global expansion – Nature.com
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