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Breakthrough in understanding folding of single stranded viral RNAs could lead to cure for the common cold

February 9, 2015 Leave a comment

Pretty cool stuff, not only is it the primary sequence, but all the secondary structural interacts are absolutely key for folding and assembly into the viral partciel.

Title overstates the case but excerpt from: Scientists have figured out how to stop the common cold in its tracks

“We have understood for decades that the RNA carries the genetic messages that create viral proteins, but we didn’t know that, hidden within the stream of letters we use to denote the genetic information, is a second code governing virus assembly,” one of the team, biophysicist Roman Tuma from the University of Leeds in the UK, told Laura Donnelly at The Telegraph. “It is like finding a secret message within an ordinary news report and then being able to crack the whole coding system behind it.”

Single-stranded RNA viruses are the most simple type of viruses known to science, and it’s thought that they were probably one of the first to evolve. And being around for a long time means they’re super-effective at what they do. Rhinovirus, which is the predominant cause of the common cold, is responsible for 1 billion infections per year – in the US alone.

Revealing the density of encoded functions in a viral RNA

We present direct experimental evidence that assembly of a single-stranded RNA virus occurs via a packaging signal-mediated mechanism. We show that the sequences of coat protein recognition motifs within multiple, dispersed, putative RNA packaging signals, as well as their relative spacing within a genomic fragment, act collectively to influence the fidelity and yield of capsid self-assembly in vitro. These experiments confirm that the selective advantages for viral yield and encapsidation specificity, predicted from previous modeling of packaging signal-mediated assembly, are found in Nature. Regions of the genome that act as packaging signals also function in translational and transcriptional enhancement, as well as directly coding for the coat protein, highlighting the density of encoded functions within the viral RNA. Assembly and gene expression are therefore direct molecular competitors for different functional folds of the same RNA sequence. The strongest packaging signal in the test fragment, encodes a region of the coat protein that undergoes a conformational change upon contact with packaging signals. A similar phenomenon occurs in other RNA viruses for which packaging signals are known. These contacts hint at an even deeper density of encoded functions in viral RNA, which if confirmed, would have profound consequences for the evolution of this class of pathogens.

Findings on new antibiotic Teixobactin published in Nature

January 7, 2015 Leave a comment

Excerpt from “New Antibiotic from Soil Bacteria” by Anna Azvolinsky

That the antibiotic can kill M. tuberclosis “is a major breakthrough because it is virtually certain to be effective for the multi-resistant strains that are now all but impossible to treat,” said Richard Novick, a microbiologist at New York University Langone Medical Center who was not involved in the work.

Although further studies are needed before the antibiotic can be tested in humans, animal efficacy models are often predictive of a drug’s effects in humans, said Gerard Wright, director of the Institute for Infectious Disease Research at McMaster University in Hamilton, Canada, who penned an accompanyingeditorial.

Teixobactin was isolated from a previously unknown Gram-negative bacterium that lives in soil and cannot be cultured in the lab using standard techniques. So the researchers applied an approach called Ichip, developed jointly by Lewis and Slava Epstein’s lab, in which a soil sample is diluted with agar, and a single bacterial cell is suspended in a chamber surrounded with semi-permeable membrane. The researchers pack 96 such chambers into a single device, which they then place in soil—allowing the bacteria access to nutrients and growth factors but not to escape. This cultivation approach is an innovative way to tap into the rich biodiversity that we are currently missing because only 1 percent of microorganisms can be cultured in the lab, said Wright.  “This biodiversity is also hiding a lot of chemical diversity that may include other new antibiotics.”

A new antibiotic kills pathogens without detectable resistance

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

nature14098-sf7

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In loving memory of Nicholas Mahoney, Rest in Peace

December 10, 2014 Leave a comment

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Sadly we are all reminded that life is all too short. We lost one of the best and brightest stars from our BMCDB galaxy. Words fail to express how much he meant, how his presence made us all better, and how much we will miss him.

I am putting this blog post up in the hopes that people will share not just their thoughts and condolences, but also their favorite memories and stories Nick. I know his influence will stay with me for a life time. I can’t think of much else to say other than to talk to those you care about, never take anyone for granted, and share the warmth, love, and compassion that he shared with all of us. RIP Nick

Dear BMCDB faculty and students,

It is with great sorrow that I share with you this sad news.

The graduate group has received word that Nick Mahoney, a  third year Ph.D. candidate, working in Chris Fraser’s lab, passed away Saturday from a heart attack. There is no additional information at this time, but I wanted to let you all know of this tragic event. Our hearts go out to Nick’s family. I will keep you posted as to what arrangements are being made as I become aware of them.

Campus psychological services are also available if you find you or someone you know needs to reach out for confidential support.  The Counseling Center for Psychological Services (CAPS) is available for students. Please call (530) 752-0871.  The Academic & Staff Assistance Program (ASAP) is available to faculty and staff.  Please call (530) 752-2727.

Our thoughts go out to his family, friends and colleagues,

Mitch Singer

Dear BMCDB students and faculty,

Sydney Mahoney has asked that you be informed of services for Nicholas Mahoney. She will have a visitation with family on Saturday, December 13th from 2:00-5:00 p.m. at Wiscombe Funeral Home. A Memorial Service will be at the Unitarian Church on Sunday Dec. 28th at 3:00 p.m.

Both services are open to faculty, students, and staff.

Erin C. Kent, Ph.D

Categories: Recent News

Vampire Ameboas are all around us

November 17, 2014 Leave a comment

Holy hell these things are nifty

vampireameboa

Very cool article from the BBC and Michael Marshall

http://emp.bbc.co.uk/emp/embed/smpEmbed.html?playlist=http%3A%2F%2Fwww.bbc.com%2Ffuture%2Fadpolicy%2Fplaylist%2Fp029rnf2%2Fpc%2F&title=BBC%20Earth%3A%20vampyrellah264.mov&product=news

“Vampire amoebas” were first described in 1865 by the Russian biologist Leon Semenowitj Cienkowski, one of the founders of microbiology. He discovered bright red single-celled creatures, rather like amoebas, which attacked algae by perforating their cell walls and extracting their contents. Evidently conscious of the similarity to vampire folklore, Cienkowski called the microbes Vampyrella.

Their macabre feeding style has fascinated microbiologists for 150 years. A 1926 study describes how Vampyrella lateritia “spreads partly around the doomed cell” and “within a minute or so the transverse walls of the attacked cell begin to bend gradually inward”. When they finally buckle, the vampire amoeba “suddenly swells” due to “the injection of algal cell contents into the animal through an oval opening”.

After they have eaten their fill, vampyrellids build a hard wall around themselves called a cyst. “They stay in an immobile state and digest their food,” says Sebastian Hess of the University of Cologne in Germany. This takes a day or two, and at the same time the cell divides. As a result, when the cyst reopens there may be two vampire amoebas where previously there was just one.

http://emp.bbc.co.uk/emp/embed/smpEmbed.html?playlist=http%3A%2F%2Fwww.bbc.com%2Ffuture%2Fadpolicy%2Fplaylist%2Fp029rtnl%2Fpc%2F&title=BBC%20Earth%3A%20Lvoraxh264_2.mov&product=news

Incredible illustration of breathing in mammals, avians, and bugs

October 27, 2014 Leave a comment

Thanks to Elanor Lutz of tabletopwhale.com

A super cool, and scientifically accurate illustration of gas exchange in three representative organisms.

Ever wonder what the difference is between Ale vs. Lager yeast?

October 22, 2014 2 comments

Despite being a yeast researcher, and supposedly having a pretty good handle on yeast genetics, I have always struggled to fully understand what the underlying genetic differences are between ale and lager yeasts. Thanks to a great article by Martha Harbison from Popsci, and research done by Libkind et al, I have finally figured it out!

Generally ales are fermented warmer with”top fermenting” yeast, and produce more fruity esters as a result. Lagers tend to be fermented cooler with “bottom fermenting” yeast, and produce more “reductive” or sulfur characters.

Ale vs. Larger

This description, while great for brewers was always unsatisfactory to me as someone with an interest in genetics and taxonomy. This was further complicated by the interchangeable use of S. calsbergensis and S. pastorianus. Top fermenting yeast are generally just plain old Saccharomyces cerevisiae. Bottom fermenting yeasts are generally more variable and have allotetraploid chromosomes, i.e. 4 chromosomes made up of mixed up bits and pieces of different yeast genomes.

So, where the hell did lager yeast S. pastorianus come from? And why did it only show up in the 1500s, thousands of years after humans figured out how to brew with S. cerevisiae? The answer came in 2011, with the publication of “Microbe domestication and the identification of the wild genetic stock of lager-brewing yeast” by Libkind et al in Proceedings of the National Academies of Sciences. In it, the researchers analyzed 6 yeast genomes: S. pastorianus, S. cerevisiae, two contaminant Saccharomyces species found in breweries, S. bayanus and S. uvarum, and two wild strains. The scientists knew through prior research that Saccharomyces species thrive on oak trees in Europe. After collecting samples from forests all over the world, they isolated two cold-tolerant yeast strains from the forests of Patagonia in Argentina.

After analyzing the genomes of these cold-tolerant strains, the researchers discovered that they were members of an entirely new species of Saccharomyces yeast, which they namedSaccharomyces eubayanus. The “eubayanus” part is interesting, because what the scientists also determined in this study is that the contaminant strain S. bayanus found in the European brewing environment isn’t, as previously thought, actually its own species. It is a domesticated hybrid strain of this Patagonian yeast. The “eu” part of “eubayanus” is to indicate that the Patagonian strain is the pure progenitor species.

From Eubayanus to Pastorianus Ale yeast and yeast from the forests of Patagonia met in a brewery…and lager was born! 

Microbe domestication and the identification of the wild genetic stock of lager-brewing yeast

Diego LibkindChris Todd HittingerElisabete ValérioCarla GonçalvesJim DoverMark JohnstonPaula GonçalvesJosé Paulo Sampaio

Domestication of plants and animals promoted humanity’s transition from nomadic to sedentary lifestyles, demographic expansion, and the emergence of civilizations. In contrast to the well-documented successes of crop and livestock breeding, processes of microbe domestication remain obscure, despite the importance of microbes to the production of food, beverages, and biofuels. Lager-beer, first brewed in the 15th century, employs an allotetraploid hybrid yeast, Saccharomyces pastorianus (syn. Saccharomyces carlsbergensis), a domesticated species created by the fusion of a Saccharomyces cerevisiae ale-yeast with an unknown cryotolerant Saccharomyces species. We report the isolation of that species and designate itSaccharomyces eubayanus sp. nov. because of its resemblance to Saccharomyces bayanus (a complex hybrid of S. eubayanus, Saccharomyces uvarum, and S. cerevisiae found only in the brewing environment). Individuals from populations of S. eubayanus and its sister species, S. uvarum, exist in apparent sympatry inNothofagus (Southern beech) forests in Patagonia, but are isolated genetically through intrinsic postzygotic barriers, and ecologically through host-preference. The draft genome sequence of S. eubayanus is 99.5% identical to the non-S. cerevisiae portion of the S. pastorianus genome sequence and suggests specific changes in sugar and sulfite metabolism that were crucial for domestication in the lager-brewing environment. This study shows that combining microbial ecology with comparative genomics facilitates the discovery and preservation of wild genetic stocks of domesticated microbes to trace their history, identify genetic changes, and suggest paths to further industrial improvement.

Some of this can be summed up by this figure from:

Saccharomyces diversity and evolution: a budding model genus

Chris Todd Hittinger

Relationships of the seven natural species of Saccharomyces and their key industrial hybrids. Populations and lineages that are not regarded as distinct species are discussed in the text but not shown. Note that the S. bayanus species complex includes two natural species (S. uvarum and S. eubayanus) and two hybrids that had been given species names (Saccharomyces pastorianus and S. bayanus).

Basically it seems like S. pastorianus evolved through the actions of human beings and hybridizations of different Saccharomyces species in the context of brewing.

Here is a spread sheet of compiled strain comparisons from different companies. Mostly beer oriented, and very helpful: YeastBot Database thanks to u/Oginme for posting it.

This leads me to a final question: did we select yeast, or did yeast select us?

-Gordon Walker

Got ugly mug, at least you can take a punch! Males have facial features that were selected to stand up to getting punched

June 9, 2014 Leave a comment

Interesting, if slightly controversial argument that male faces (and other features) were selected through the course of evolution to be more resistant to impacts from violent altercations. Fascinating idea, but I would still cry like a baby if you clocked me right in the face.

Excerpt from “Male faces ‘buttressed against punches’ by evolution” By Jonathan Webb

Fossil records show that the australopiths, immediate predecessors of the human genus Homo, had strikingly robust facial structures.

For many years, this extra strength was seen as an adaptation to a tough diet including nuts, seeds and grasses. But more recent findings, examining the wear pattern and carbon isotopes in australopith teeth, have cast some doubt on this “feeding hypothesis”.

Instead of diet, Prof Carrier and his co-author, physician Dr Michael Morgan, propose that violent competition demanded the development of these facial fortifications: what they call the “protective buttressing hypothesis”.

“Jaws are one of the most frequent bones to break – and it’s not the end of the world now, because we have surgeons, we have modern medicine,” Prof Carrier explained. “But four million years ago, if you broke your jaw, it was probably a fatal injury. You wouldn’t be able to chew food… You’d just starve to death.”

The jaw, cheek, eye and nose structures that most commonly come to grief in modern fist fights were also the most protected by evolutionary changes seen in the australopiths.

Furthermore, these are the bones that show the most differences between men and women, as well as between our male and female forebears. That is how you would expect defensive armour to evolve, Prof Carrier points out.

“In humans and in great apes in general… it’s males that are most likely to get into fights, and it’s also males that are most likely to get injured,” he told BBC News.

 

 

Related articles:

Protective buttressing of the hominin face 

David R. Carrier and Michael H. Morgan

When humans fight hand-to-hand the face is usually the primary target and the bones that suffer the highest rates of fracture are the parts of the skull that exhibit the greatest increase in robusticity during the evolution of basal hominins. These bones are also the most sexually dimorphic parts of the skull in both australopiths and humans. In this review, we suggest that many of the facial features that characterize early hominins evolved to protect the face from injury during fighting with fists. Specifically, the trend towards a more orthognathic face; the bunodont form and expansion of the postcanine teeth; the increased robusticity of the orbit; the increased robusticity of the masticatory system, including the mandibular corpus and condyle, zygoma, and anterior pillars of the maxilla; and the enlarged jaw adductor musculature are traits that may represent protective buttressing of the face. If the protective buttressing hypothesis is correct, the primary differences in the face of robust versus gracile australopiths may be more a function of differences in mating system than differences in diet as is generally assumed. In this scenario, the evolution of reduced facial robusticity in Homo is associated with the evolution of reduced strength of the upper body and, therefore, with reduced striking power. The protective buttressing hypothesis provides a functional explanation for the puzzling observation that although humans do not fight by biting our species exhibits pronounced sexual dimorphism in the strength and power of the jaw and neck musculature. The protective buttressing hypothesis is also consistent with observations that modern humans can accurately assess a male’s strength and fighting ability from facial shape and voice quality.

 

 

Pattern, severity and aetiology of injuries in victims of assault.

Although the incidence of assault and other violent crime is increasing in the UK, the cause and overall pattern of injury, and the need for admission have not been defined in adult victims who attend hospital. In a prospective study, all 539 adult victims of assault attending a major city centre Accident & Emergency department in 1986 were therefore interviewed and examined. Facial injury was extremely common: 83% of all fractures, 66% of all lacerations and 53% of all haematomas were facial. The upper limb was the next most common site of injury (14% of all injuries). Twenty-six per cent of victims sustained at least one fracture and nasal fractures were the most frequently observed skeletal injuries (27%) followed by zygomatic fractures (22%) and mandibular body (12%), angle (12%) and condyle (9%) fractures. Seventeen per cent of victims required hospital admission. Overall, the type of injury observed correlated with the alleged weapon used (P = less than 0.001) though 20% of victims who reported attacks with sharp weapons sustained only haematomas or fractures. Injury most often resulted from punching (72% of assaults) or kicking (42% of assaults). Only 6% of victims reported injury with knives but 11% were injured by broken drinking glasses. Those who were kicked were most likely to need hospital admission.