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Ribosomes Optimized for Autocatalytic Production; Theory Accurately Predicts Large-Scale Features, Revealing Why Ribosomes Are Made of Large Number of Unusually Small, Uniformly Sized Proteins, and a Few Strands of RNA That Vary Greatly in Size

Optimization for self-production may explain key features of ribosomes, the protein production factories of the cell, reported researchers from Harvard Medical School in Nature online on July 19, 2017. The article is titled “Ribosomes Are Optimized for Autocatalytic Production.” In a new study, a team led by Dr. Johan Paulsson, Professor of Systems Biology at Harvard Medical School, mathematically demonstrated that ribosomes are precisely structured to produce additional ribosomes as quickly as possible, in order to support efficient cell growth and division. The study's theoretical predictions accurately reflect observed large-scale features of ribosomes -- revealing why are they made of an unusually large number of small, uniformly sized proteins and a few strands of RNA that vary greatly in size -- and provide perspective on the evolution of an exceptional molecular machine. "The ribosome is one of the most important molecular complexes in all of life, and it's been studied across scientific disciplines for decades," Dr. Paulsson said. "I was always puzzled by the fact that it seemed like we could explain its finer details, but ribosomes have these bizarre features that have not often been addressed, or, if so, in an unsatisfying way." Every living cell, whether a single bacterium or a human neuron, is a biological system as dynamic and complex as any city. Contained within cells are walls, highways, power plants, libraries, recycling centers and much more, all working together in unison to ensure the continuation of life. The vast majority of these myriad structures are made of and made by proteins. And those proteins are made by ribosomes.

Evolutionary History of Salivary Protein (MUC7) Points to Possible Interbreeding Between Humans and a “Ghost” Species of Ancient Human; MUC7 May Also Be Key to Oral Microbiome Composition

In saliva, scientists have found hints that a "ghost" species of archaic humans may have contributed genetic material to ancestors of people living in Sub-Saharan Africa today. The research adds to a growing body of evidence suggesting that sexual rendezvous between different archaic human species may not have been unusual. Past studies have concluded that the forebears of modern humans in Asia and Europe interbred with other early hominin species, including Neanderthals and Denisovans. The new research is among more recent genetic analyses indicating that ancient Africans also had trysts with other early hominins. "It seems that interbreeding between different early hominin species is not the exception -- it's the norm," says Omer Gokcumen, PhD, an Assistant Professor of Biological Sciences in the University at Buffalo (UB) College of Arts and Sciences. "Our research traced the evolution of an important mucin protein called MUC7 that is found in saliva," he says. "When we looked at the history of the gene that codes for the protein, we see the signature of archaic admixture in modern day Sub-Saharan African populations." The research was published online on July 21, 2017 in Molecular Biology and Evolution. The study was led by Dr. Gokcumen and Stefan Ruhl, DDS, PhD, a professor of oral biology in UB's School of Dental Medicine. The open-access article is titled “Archaic Hominin Introgression in Africa Contributes to Functional Salivary MUC7 Genetic Variation.” The scientists came upon their findings while researching the purpose and origins of the MUC7 protein, which helps give spit its slimy consistency and binds to microbes, potentially helping to rid the body of disease-causing bacteria. As part of this investigation, the team examined the MUC7 gene in more than 2,500 modern human genomes.

Elephant Seals Recognize Each Other by Rhythm of Their Calls; Finding Is First for Non-Human Mammals

Every day, humans pick up on idiosyncrasies such as slow drawls, high-pitched squeaks, or hints of accents to put names to voices from afar. This ability may not be as unique as once thought, researchers report on July 20, 2017 in Current Biology. The open-access article is titled "Northern Elephant Seals Memorize the Rhythm and Timbre of Their Rivals' Voices." The scientists find that, unlike all other non-human mammals that have been studied, northern elephant seal males consider the spacing and timing of vocal pulses in addition to vocal tones when identifying the calls of their rivals. "This is the first natural example where on a daily basis, an animal uses the memory and the perception of rhythm to recognize other members of the population," says first author Dr. Nicolas Mathevon, of the Université de Lyon/Saint-Etienne in France. "There have been experiments with other mammals showing that they can detect rhythm, but only with conditioning." Over several years studying an elephant seal colony in Año Nuevo State Park, California, the researchers were able to recognize many of the individual animals just by the rhythm of their voices, he says. To test whether the elephant seals themselves made those distinctions in the same way, the researchers designed an experiment based on the social behavior of the colony's "beta males," who shy away upon hearing the call of a more powerful "alpha male," but ignore or confront other beta males and still-weaker "peripheral males." Upon hearing computer-modified alpha male calls with a sped-up or slowed-down tempo or a shifted pitch range, the beta males fled the scene if the alteration was minute enough to be within the individual variation of a particular alpha male's roar, but stayed put when confronted with more extreme changes.

Patch-Clamp Technique Extended to Intracellular Vesicles

Ion channels in the membrane vesicles that mediate intracellular protein transport play a crucial role in cell physiology. A method developed by a team at Ludwig-Maximilians-Universitaet (LMU) in Munich now allows these vesicles to be studied with greater specificity than ever before. Tiny membrane-bound vesicles known as endosomes and lysosomes serve as vehicles for the transport of protein cargoes within animal cells. Embedded in the vesicle membranes are proteins called ion channels, which control the passage of ions into and out of these intracellular organelles. Defects in these proteins play a central role in the pathogenesis of many diseases, and dissection of their molecular functions is vital for the development of effective therapies for these disorders. PD Christian Grimm and Professor Christian Wahl-Schott of the Department of Pharmacy (Director: Professor Martin Biel) at LMU Munich are among Europe's leading specialists in the use of the so-called “patch-clamp” technique for the study of ion channels in cell membranes. In the July 20, 2017 issue of Nature Protocols, these scientists and colleagues describe how they have adapted the method for use with endolysosomal vesicles. The Nature Protocols article is titled “Patch-Clamp Technique to Characterize Ion Channels in Enlarged Individual Endolysosomes.” In a second study, published in the July 20, 2017 issue of Cell Chemical Biology, the scientists go on to demonstrate how patch clamping can be applied to specific functional classes of transport vesicles. This article is titled “Small Molecules for Early Endosome-Specific Patch Clamping.” The work described in the to articles opens up entirely new perspectives for the characterization of ion channels and the mechanisms that regulate them.

Animal Model for Coffin-Siris Disorder May Provide Insights into Genetic Bases of Some Neuropsychiatric Disorders

A study by scientists at the Children’s Medical Center Research Institute at University of Texas Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation in the arid1b gene was created and then used to show that growth hormone treatments reverse some manifestations of the mutation. The ARID1B gene is one of the most commonly mutated genes in patients with intellectual disability and autism spectrum disorders, but scientists have not yet discerned if and how defects in the ARID1B gene contribute to these clinical manifestations. To understand how reduced levels of the protein product of the gene might cause these disorders, a team of researchers led by Hao Zhu, MD (photo) and including graduate student Cemre Celen genetically modified mice to carry a mutation in one of two copies of the arid1b gene. This mutation replicates the genetics of Coffin-Siris syndrome, a disorder that some patients with defects in the ARID1B gene have that is characterized by speech and social development problems, intellectual disability, and delayed physical growth. The hope is that by understanding the molecular basis of Coffin-Siris syndrome, scientists will gain a deeper understanding of more common diseases involving intellectual and social impairment. Scientists found mice with the mutated arid1b gene exhibited the same type of physical and social changes seen in children with Coffin-Siris syndrome, such as abnormal brain development, muscle weakness, and increased anxiety and fear. The mice also displayed features consistent with autism spectrum disorder, such as social interaction abnormalities, repetitive behaviors, and abnormal “squeaks” or vocalizations.

Unexpected Source of Tuna's Precise Control of Movement: Hydraulic Control of Fins by Lymph System

The precise control that tuna have of their fins for tight turns and movement while swimming is aided by hydraulic activity of the lymphatic system, a new study reveals. Furthermore, the authors found that this specialization of the lymphatic system is associated with other fishes in the family Scombridae, suggesting that it may have evolved in response to the demand for the sophisticated maneuvering control in these high-performance species. The new report was published in the July 21, 2017 issue of Science and is titled “Hydraulic Control of Tuna Fins: A role for the lymphatic system in vertebrate locomotion.” While dissecting tuna fins, Vadim Pavlov, PhD, of the Stanford University Hopkins Marine Station in Pacific Grove, California, and colleagues found a chamber-like compartment, or large vascular sinus (VS), located at the base of both the second dorsal and anal fins. When the scientists pumped fluid into the chamber, this provided finely controlled adjustment of the fin. Close video monitoring of tuna as they swam revealed that the degree of fin erection increases when tuna are engaging in behaviors that require frequent changes in movement direction, such as searching and feeding, compared to when the fish are simply cruising. Next, the researchers injected special fluid into the VS of tuna to trace fluid dynamics throughout the system. The injection was present only in a sub-section of vessels with vein-like morphology, a characteristic of the lymphatic system, which helps distribute immune cells. Analyzing fluid naturally found in the VS of tuna revealed a high portion of lymphatic cells relative to that found in blood, further suggesting that the VS is a part of the lymphatic system.

Methicillin-Resistant Staph aureus (MRSA) Emerged Years Before Methicillin Was Introduced into Clinical Practice

Science Advances article]Methicillin-resistant Staphylococcus aureus (MRSA) emerged long before the introduction of the antibiotic methicillin into clinical practice, according to a study published online on July 20,2017 in the open-access journal Genome Biology. It was the widespread use of earlier antibiotics such as penicillin rather than of methicillin itself that caused MRSA to emerge, researchers at the University of St. Andrews, and the Wellcome Trust Sanger Institute, UK, suggest. The article is titled “Methicillin-Resistant Staphylococcus aureus Emerged Long Before the Introduction of Methicillin into Clinical Practice.” The researchers found that S. aureus acquired the gene that confers methicillin resistance - mecA - as early as the mid-1940s - fourteen years before the first use of methicillin. Professor Matthew Holden, molecular microbiologist at the University of St. Andrews, the corresponding author said: "Our study provides important lessons for future efforts to combat antibiotic resistance. It shows that new drugs which are introduced to circumvent known resistance mechanisms, as methicillin was in 1959, can be rendered ineffective by unrecognized, pre-existing adaptations in the bacterial population. These adaptations happen because - in response to exposure to earlier antibiotics - resistant bacterial strains are selected instead of non-resistant ones as bacteria evolve." The mecA gene confers resistance by producing a protein called PBP2a, which decreases the binding efficiency of antibiotics used against S. aureus to the bacterial cell wall. The introduction of penicillin in the 1940s led to the selection of S. aureus strains that carried the methicillin resistance gene. Dr.

AAAAI Lifetime Achievement Award Will Go to Yale Physician/Scientist, Immunology Giant, & Exosome Pioneer: Philip Askenase

BioQuick News has recently learned that Philiip Askenase, MD, will be honored with a life-time achievement award--Distinguished Scientist Awardee of the AAAAI for 2018—by the American Academy of Allergy, Asthma, and Immunology. This award is presented annually to recognize scientific contributions of a single individual to the field of Allergy and Immunology that have advanced allergy and immunology research, and for leadership contributions to the specialty. Generally, only one such award is given each year. Dr. Askenase, Professor of Medicine (Immunology) at the Yale School of Medicine is the first from Yale ever selected for this prestigious award. The award will be given before a large audience in Orlando, Florida at the Annual AAAAI meeting in early March 2018. The AAAAI has a total of about 7,000 members from all over the world. Dr. Askenase will present a lecture at the time of the award presentation and the provisional title for his address is “The Role of Exosome Delivery of miRNAs in Allergy, Asthma and Immunology.” Working with the well-known models of cutaneous immune hypersensitivity and immunity, Dr. Askenase discovered the series of steps from challenge with antigen, in a sensitized host, to the entry of T cells into the site of challenge. This work uncovered previously unrecognized roles of: B-1a B cells, NKT cells, IL-4, complement, serotonin, and mast cells. These findings are relevant to the diagnosis and therapy of allergic and autoimmune diseases, as well as cancers and transplantation. Current work in the Askenase lab centers on the very exciting newly discovered exosomes that are nanoparticles released by all cells sending RNA functional messages to each other.

Study Demonstrates Use of ACE Technology for Direct Isolation of Exosomes

On July 12, 2017, Biological Dynamics announced the publication of data in ACS Nano demonstrating that the company's proprietary lab-on-a-chip ExoVerita™ system can simplify and streamline the process for isolation and recovery of exosomes. The company is using this technology to develop a portfolio of minimally-invasive diagnostic tests to provide faster answers to critical clinical questions in high-burden diseases, such as cancer, traumatic brain injury, and infectious diseases. The ACS Nano article, published online on July 3, 2017, is titled “Rapid Isolation and Detection of Exosomes and Associated Biomarkers from Plasma.” Exosomes are cell-derived, extracellular vesicles that enable communication between cells. They are secreted from most cell types and released in bodily fluids such as urine, blood plasma, and saliva. Due to their stability and ability to transport information about their origin and the state of their parental cells, exosomes are believed to have great potential to power the next generation of liquid biopsies and cancer biomarkers. "Current exosome isolation methods are generally expensive, complex, and cumbersome, which could limit large-scale diagnostic applications," said Michael Heller, PhD, principal investigator on the paper and scientific advisory board member of Biological Dynamics. "This study describes a relatively simple, rapid, and non-destructive method for the isolation of exosomes, that preserves their valuable biomarker information for direct analysis.

Rare Human Disease (Williams-Beuren Syndrome) May Help Explain Why Dogs Are So Friendly; Study Suggests Dogs Evolved from Wolves Due to Gene-Based Affinity to Associate with Humans

Dogs' ability to communicate and interact with humans is one the most astonishing differences between them and their wild cousins, wolves. A new study published online on July 19, 2017 in the journal Science Advances identifies genetic changes that are linked to dogs' human-directed social behaviors and suggests there is a common underlying genetic basis for hyper-social behavior in both dogs and humans. The open-access article is titled “Structural Variants in Genes Associated with Human Williams-Beuren Syndrome Underlie Stereotypical Hyper-Sociability in Domestic Dogs." In the study, an interdisciplinary team of researchers, including ones from Princeton University, sequenced a region of chromosome 6 in dogs and found multiple sections of canine DNA that were associated with differences in social behavior. In many cases, unique genetic insertions called transposons on the Williams-Beuren syndrome critical region (WBSCR) were strongly associated with the tendency to seek out humans for physical contact, assistance and information. In contrast, in humans, it is the deletion of genes from the counterpart of this region on the human genome, rather than insertions, that causes Williams-Beuren syndrome, a congenital disorder characterized by hyper-social traits such as exceptional gregariousness. "It was the remarkable similarity between the behavioral presentation of Williams-Beuren syndrome and the friendliness of domesticated dogs that suggested to us that there may be similarities in the genetic architecture of the two phenotypes," said Bridgett vonHoldt, PhD, an Assistant Professor in Ecology and Evolutionary Biology at Princeton and the study's lead co-author. Dr. vonHoldt had identified the canine analog of the WBSCR in her publication in Nature in 2010.

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