A conserved domain important for association of eukaryotic J-protein co-chaperones Jjj1 and Zuo1 with the ribosome

AbstractJ-proteins, obligate co-chaperones, provide specialization for Hsp70 function in a variety of cellular processes. Two of the 13 J-proteins of the yeast cytosol/nucleus, Zuo1 and Jjj1, are associated with 60S ribosomal subunits. Abundant Zuo1 facilitates folding of nascent polypeptides; Jjj1, of much lower abundance, functions in ribosome biogenesis. However, overexpression of Jjj1 substantially rescues growth defects of cells lacking Zuo1. We analyzed a region held in common by Zuo1 and Jjj1, outside the signature J-domain found in all J-proteins. This shared “zuotin homology domain” (ZHD) is important for ribosome association of both proteins. An N-terminal segment of Jjj1, containing the J-domain and ZHD, is ribosome-associated and, like full-length Jjj1, is competent to rescue both the cold- and cation-sensitivity of ∆zuo1. However, this fragment, when expressed at normal levels, cannot rescue the cytosolic ribosome biogenesis defect of ∆jjj1. Our results are consistent with a model in which the primary functions of Zuo1 and Jjj1 occur in the cytosol. In addition, our data suggest that Zuo1 and Jjj1 bind overlapping sites on ribosomes due to an interaction via their common ZHDs, but Jjj1 binds primarily to pre-60S particles and Zuo1 to mature subunits. We hypothesize that ZUO1 and JJJ1, which are conserved throughout eukaryotes, arose from an ancient duplication of a progenitor J-protein gene that encoded the ZHD ribosome-binding region; subsequently, specialized roles and additional ribosome interaction sites evolved

Treatment Options for Seasonal Affective Disorder

Many patients who have undiagnosed Seasonal Affective Disorder (SAD) may come into the pharmacy to try to self-treat their symptoms with over-the-counter and herbal drugs. Often, patients don\u27t recognize their symptoms as a true depressive disorder since they are not constant. The pharmacist has the opportunity to talk to these patients, educate them on the disease state and explain that they do have options, both pharmacologic and non-pharmacologic. It also is important for pharmacists to point out any interactions that the herbal or over-the-counter medications may have with other medications and to refer patients to their physician for further treatment. Currently, the Diagnostic and Statistical Manual for Mental Disorders (DSM) IV does not recognize SAD as a separate disorder but rather a specifier of Major Depressive Disorder (MDD). However, there are currently recommendations to include SAD as a distinct disorder in DSM V, which is to be released in May 2013

Vitamin D with Calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials

Introduction: Vitamin D may affect multiple health outcomes. If so, an effect on mortality is to be expected. Using pooled data from randomized controlled trials, we performed individual patient data (IPD) and trial level meta-analyses to assess mortality among participants randomized to either vitamin D alone or vitamin D with calcium. Subjects and Methods: Through a systematic literature search, we identified 24 randomized controlled trials reporting data on mortality in which vitamin D was given either alone or with calcium. From a total of 13 trials with more than 1000 participants each, eight trials were included in our IPD analysis. Using a stratified Cox regression model, we calculated risk of death during 3 yr of treatment in an intention-to-treat analysis. Also, we performed a trial level meta-analysis including data from all studies. Results: The IPD analysis yielded data on 70,528 randomized participants (86.8% females) with a median age of 70 (interquartile range, 62–77) yr. Vitamin D with or without calcium reduced mortality by 7% [hazard ratio, 0.93; 95% confidence interval (CI), 0.88–0.99]. However, vitamin D alone did not affect mortality, but risk of death was reduced if vitamin D was given with calcium (hazard ratio, 0.91; 95% CI, 0.84–0.98). The number needed to treat with vitamin D plus calcium for 3 yr to prevent one death was 151. Trial level meta-analysis (24 trials with 88,097 participants) showed similar results, i.e. mortality was reduced with vitamin D plus calcium (odds ratio, 0.94; 95% CI, 0.88–0.99), but not with vitamin D alone (odds ratio, 0.98; 95% CI, 0.91–1.06). Conclusion: Vitamin D with calcium reduces mortality in the elderly, whereas available data do not support an effect of vitamin D alone

Hachimoji DNA and RNA: A genetic system with eight building blocks

Reported here are DNA and RNA-like systems built from eight (hachi-) nucleotide letters (-moji) that form four orthogonal pairs. This synthetic genetic biopolymer meets the structural requirements needed to support Darwinism, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to double the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos

An evaluation of metrics for assessing maternal exposure to agricultural pesticides

We evaluate the use of three different exposure metrics to estimate maternal agricultural pesticide exposure during pregnancy. Using a geographic information system-based method of pesticide exposure estimation, we combine data on crop density and specific pesticide application amounts/dates to create the three exposure metrics. For illustration purposes, we create each metric for a North Carolina cohort of pregnant women, 2003–2005, and analyze the risk of congenital anomaly development with a focus on metric comparisons. Based on the results, and the need to balance data collection efforts/computational efficiency with accuracy, the metric which estimates total chemical exposure using application dates based on crop-specific earliest planting and latest harvesting information is preferred. Benefits and drawbacks of each metric are discussed and recommendations for extending the analysis to other states are provided

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

Future research directions on the "elusive" white shark

White sharks, Carcharodon carcharias, are often described as elusive, with little information available due to the logistical difficulties of studying large marine predators that make long-distance migrations across ocean basins. Increased understanding of aggregation patterns, combined with recent advances in technology have, however, facilitated a new breadth of studies revealing fresh insights into the biology and ecology of white sharks. Although we may no longer be able to refer to the white shark as a little-known, elusive species, there remain numerous key questions that warrant investigation and research focus. Although white sharks have separate populations, they seemingly share similar biological and ecological traits across their global distribution. Yet, white shark’s behavior and migratory patterns can widely differ, which makes formalizing similarities across its distribution challenging. Prioritization of research questions is important to maximize limited resources because white sharks are naturally low in abundance and play important regulatory roles in the ecosystem. Here, we consulted 43 white shark experts to identify these issues. The questions listed and developed here provide a global road map for future research on white sharks to advance progress toward key goals that are informed by the needs of the research community and resource managers

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13