bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational regulation of non-autonomous mitochondrial stress response promotes longevity
Authors: Lan Jianfeng , Rollins Jarod , Wu Di , Zang Xiao , Zou Lina , Wang Zi , Ye Chang , Wu Zixing , Kapahi Pankaj , Rogers Aric N. , Chen Di 
Published: January 2019

SummaryInhibition of mRNA translation delays aging, but the underlying mechanisms remain underexplored. Mutations in both DAF-2 (IGF-1 receptor) and RSKS-1 (ribosomal S6 kinase/S6K) cause synergistic lifespan extension inC. elegans. To understand the roles of S6K-mediated translational regulation in this process, we performed genome-wide translational profiling and genetic screens to identify genes that are not only regulated at the translational level in thedaf-2 rsks-1mutant, but also affect lifespan. Inhibition of CYC-2.1 (cytochrome c) in the germline significantly extends lifespan through non-autonomous activation of the mitochondrial unfolded protein response (UPRmt) and AMP-activated kinase (AMPK) in the metabolic tissue. Furthermore, the RNA-binding protein GLD-1-mediated translational repression of cytochrome c in the germline is important for the non-autonomous activation of UPRmtand synergistic longevity of thedaf-2 rsks-1mutant. Together, these results illustrate a translationally regulated non-autonomous mitochondrial stress response mechanism in the modulation of lifespan by insulin-like signaling and S6K.HighlightsLongevity of thedaf-2 rsks-1mutant is mediated by translational repression of ribosomal proteins and CYC-2.1/cytochrome c.Germline inhibition ofcyc-2.1non-autonomously activates UPRmtand AMPK to extend lifespan.GLD-1 represses germlinecyc-2.1translation in thedaf-2 rsks-1mutant.Translational regulation ofcyc-2.1and UPRmtcontribute to the synergistic longevity of thedaf-2 rsks-1mutant.
Shared mechanisms between coronary heart disease and depression: findings from a large UK general population-based cohort
Authors: Khandaker Golam M , Zuber Verena , Rees Jessica MB , Carvalho Livia , Mason Amy M , Foley Christopher N , Gkatzionis Apostolos , Jones Peter B , Burgess Stephen 
Published: January 2019

ABSTRACTWhile comorbidity between coronary heart disease (CHD) and depression is evident, it is unclear whether the two diseases have shared underlying mechanisms. We performed a range of analyses in 367,703 unrelated middle-aged participants of European ancestry from UK Biobank, a population based cohort study, to assess whether comorbidity is primarily due to genetic or environmental factors, and to test whether cardiovascular risk factors and CHD are likely to be causally related to depression using Mendelian randomization. We showed family history of heart disease was associated with a 20% increase in depression risk (95% confidence interval [CI] 16% to 24%, p<0.0001), but a genetic risk score that is strongly associated with CHD risk was not associated with depression. An increase of one standard deviation in the CH D genetic risk score was associated with 71% higher CHD risk, but 1% higher depression risk (95% CI 0% to 3%; p=0.11). Mendelian randomization analyses suggested that triglycerides, interleukin-6 (IL-6), and C-reactive protein (CRP) are likely causal risk factors for depression. The odds ratio for depression per standard deviation increase in genetically-predicted triglycerides was 1.18 (95% CI 1.09 to 1.27; p=2×10-5); per unit increase in genetically-predicted log-transformed I L-6 was 0.74 (95% CI 0.62 to 0.89; p=0.0012); and per unit increase in genetically-predicted log-transformed CRP was 1.18 (95% CI 1.07 to 1.29; p=0.0009). Our analyses suggest that comorbidity between depression and CHD arises largely from shared environmental factors. I L-6, CRP and triglycerides, are likely to be causally linked with depression, so could be targets for treatment and prevention of depression.
Water and ion transport across the eversible vesicles in the collophore of a springtailOrchesella cincta
Authors: Konopová Barbora , Kolosov Dennis , O’Donnell Michael J. 
Published: January 2019

ABSTRACTSpringtails (Collembola) are ancient close relatives of the insects. The eversible vesicles are their unique paired transporting organs, which consist of an epithelium located inside a tube-like structure on the first abdominal segment called the collophore. The vesicles can be protruded out of the collophore and several lines of evidence indicate that they have a vital function in water uptake and ion balance. However, the amount of water absorbed by the vesicles and which other ions apart from sodium are transported remain unknown. UsingOrchesella cinctaas a model, we developed protocols for two assays that enabled us to study water and ion movement across the eversible vesicles in whole living springtails. Using an inverse Ramsay assay we demonstrate that the eversible vesicles absorb water from a droplet applied onto their surface. Using the scanning ion-selective electrode technique (SIET) we show that the vesicles absorb Na+and Cl−from the bathing medium, secrete NH4+, and both absorb and secrete K+, H+is secreted at a low level in the anterior part and absorbed at the posterior. We did not detect transport of Ca2+at significant levels. The highest flux was the absorption of Cl−, and the magnitude of ion fluxes were significantly lower in fully hydrated springtails. Our data demonstrate that the eversible vesicles are a transporting epithelium functioning in osmo- and ionoregulation, nitrogenous waste excretion and likely acid-base balance.
Evolutionary Implications of Anoxygenic Phototrophy in the Bacterial PhylumCandidatusPalusbacterota (WPS-2)
Authors: Ward Lewis M. , Cardona Tanai , Holland-Moritz Hannah 
Published: January 2019

AbstractGenome-resolved environmental metagenomic sequencing has uncovered substantial previously unrecognized microbial diversity relevant for understanding the ecology and evolution of the biosphere, providing a more nuanced view of the distribution and ecological significance of traits including phototrophy across diverse niches. Recently, the capacity for bacteriochlorophyll-based anoxygenic photosynthesis has been found in the uncultured bacterial WPS-2 clade that are in close association with boreal moss. Here, we use phylogenomic analysis to investigate the diversity and evolution of phototrophic WPS-2. We demonstrate that phototrophic WPS-2 show significant genetic and metabolic divergence from other phototrophic and non-phototrophic lineages. The genomes of these organisms encode a completely new family of anoxygenic Type II photochemical reaction centers and other phototrophy-related proteins that are both phylogenetically and structurally distinct from those found in previously described phototrophs. We propose the nameCandidatusPalusbacterota for the phylum-level aerobic WPS-2 clade which contains phototrophic lineages, from the Latin for “bog bacteria”, distinguishing it from the anaerobic, non-phototrophic sister phylumCandidatusEremiobacterota for “desert bacteria”, typically found in dry environments.
DNA-guided DNA cleavage at moderate temperatures by Clostridium butyricum Argonaute
Authors: Hegge Jorrit W. , Swarts Daan C. , Chandradoss Stanley D. , Cui Tao Ju , Kneppers Jeroen , Jinek Martin , Joo Chirlmin , van der Oost John 
Published: January 2019

AbstractProkaryotic Argonaute proteins (pAgos) constitute a diverse group of endonucleases of which some mediate host defense by utilizing small interfering DNA guides (siDNA) to cleave complementary invading DNA. This activity can be repurposed for programmable DNA cleavage. However, currently characterized DNA-cleaving pAgos require elevated temperatures (≥65°C) for their activity, making them less suitable for applications that require moderate temperatures, such as genome editing. Here we report the functional and structural characterization of the siDNA-guided DNA-targeting pAgo from the mesophilic bacterium Clostridium butyricum (CbAgo). CbAgo displays a preference for siDNAs that have a deoxyadenosine at the 5’-end and thymidines in the sub-seed segment (siDNA nucleotides 2-4). Furthermore, CbAgo mediates DNA-guided DNA cleavage of AT-rich double stranded DNA at moderate temperatures (37°C). This study demonstrates that certain pAgos are capable of programmable DNA cleavage at moderate temperatures and thereby expands the scope of the potential pAgo–based applications.
Chemogenetic inhibition of the amygdala modulates emotional behavior expression in infant rhesus monkeys
Authors: Raper Jessica , Murphy Lauren , Richardson Rebecca , Romm Zoe , Kovacs-Balint Zsofia , Payne Christa , Galvan Adriana 
Published: January 2019

AbstractManipulation of neuronal activity during the early postnatal period in monkeys has been largely limited to permanent lesion studies, which can be impacted by developmental plasticity leading to reorganization and compensation from other brain structures that can interfere with the interpretations of results. Chemogenetic tools, such as DREADDs (designer receptors exclusively activated by designer drugs), can transiently and reversibly activate or inactivate brain structures, avoiding the pitfalls of permanent lesions to better address important developmental neuroscience questions. We demonstrate that inhibitory DREADDs in the amygdala can be used to manipulate socioemotional behavior in infant monkeys. Two infant rhesus monkeys (1 male, 1 female) received AAV5-hSyn-HA-hM4Di-IRES-mCitrine injections bilaterally in the amygdala at 9 months of age. DREADD activation after systemic administration of either clozapine-N-oxide or low dose clozapine resulted in decreased freezing and anxiety on the human intruder paradigm and changed the looking patterns on a socioemotional attention eyetracking task, compared to vehicle administration. The DREADD-induced behaviors were reminiscent of, but not identical to, those seen after permanent lesions of the amygdala in infant monkeys, such that early amygdala lesions produce a more extensive array of behavioral changes in response to the human intruder task that were not seen with DREADD-evoked inhibition of this region. Our results support the notion that early permanent damage leads to brain reorganization manifesting in a broader impact on behavior. The current study provides a proof-of-principle that DREADDs can be used in young infant monkeys to transiently and reversibly manipulate behavior.Statement of SignificanceMany neurodevelopmental disorders exhibit abnormal structural or functional amygdala development and alterations in socioemotional behavior. To date, developmental neuroscience studies have relied on permanent lesions techniques to investigate how atypical amygdala development impacts socioemotional behaviors, which may not adequately recapitulate the role of amygdala dysfunction in the manifestation of aberrant behavior. The present study sought to demonstrate that the DREADDs (designer receptors exclusively activated by designer drugs) chemogenetic tool could transiently inhibit amygdala activity in infant monkeys resulting in alterations in socioemotional behavior. This proof-of-principle study supports the use of chemogenetics for developmental neuroscience research, providing an opportunity to broaden our understanding of how changes in neuronal activity across early postnatal development influences behavior and clinical symptoms.
3D Ultrastructure of the Cochlear Outer Hair Cell Lateral Wall Revealed By Electron Tomography
Authors: Jeffrey Triffo William , Palsdottir Hildur , Gene Morgan David , McDonald Kent L. , Raphael Robert M. , Auer Manfred 
Published: January 2019

AbstractOuter hair cells in the mammalian cochlea display a unique type of voltage-induced mechanical movement, termed electromotility, which amplifies auditory signals and contributes to the sensitivity and frequency selectivity of mammalian hearing. Electromotility occurs in the outer hair cell (OHC) lateral wall, and it is not fully understood how the supramolecular architecture of the lateral wall enables this unique form of cellular motility. Employing electron tomography of high-pressure frozen and freeze-substituted OHCs, we visualized the 3D structure and organization of the membrane and cytoskeletal components of the OHC lateral wall. The subsurface cisterna (SSC) is a highly prominent feature, and we report that the SSC membranes and lumen possess hexagonally ordered arrays of particles that endow the SSC with a previously unrealized anisotropic structural rigidity. We also find the SSC is tightly connected to adjacent actin filaments by short filamentous protein connections spaced at regular intervals. Pillar proteins that join the plasma membrane to the cytoskeleton appear as variable structures considerably thinner than actin filaments and significantly more flexible than actin-SSC links. The structurally rich organization and rigidity of the SSC coupled with apparently weaker mechanical connections between the plasma membrane and cytoskeleton reveal that the membrane-cytoskeletal architecture of the OHC lateral wall is more complex than previously appreciated. These observations are important for our understanding of OHC mechanics and need to be considered in computational models of OHC electromotility that incorporate subcellular features.
MTF1, a classic metal sensing transcription factor, promotes myogenesis in response to copper
Authors: Tavera-Montañez Cristina , Hainer Sarah J. , Cangussu Daniella , Gordon Shellaina J.V. , Xiao Yao , Reyes-Gutierrez Pablo , Imbalzano Anthony N. , Navea Juan G. , Fazzio Thomas G. , Padilla-Benavides Teresita 
Published: January 2019

AbstractMTF1 is a conserved metal-binding transcription factor in eukaryotes that binds to conserved DNA sequence motifs, termed metal response elements (MREs). MTF1 responds to metal excess and deprivation, protects cells from oxidative and hypoxic stresses, and is required for embryonic development in vertebrates. We used multiple strategies to identify an unappreciated role for MTF1 and copper (Cu) in cell differentiation. Upon initiation of myogenesis from primary myoblasts, MTF1 expression increased, as did nuclear localization.Mtf1knockdown impaired differentiation, while addition of non-toxic concentrations of Cu+enhanced MTF1 expression and promoted myogenesis. Cu+bound stoichiometrically to a C-terminus tetra-cysteine of MTF1. MTF1 bound to chromatin at the promoter regions of myogenic genes and binding was stimulated by copper. MTF1 formed a complex with MyoD at myogenic promoters, the master transcriptional regulator of the myogenic lineage. These studies establish novel mechanisms by which copper and MTF1 regulate gene expression in myoblast differentiation.
The Metabolites NADP+ and NADPH are the Targets of the Circadian Protein Nocturnin (Curled)
Authors: Estrella Michael A. , Du Jin , Chen Li , Rath Sneha , Prangley Eliza , Chitrakar Alisha , Aoki Tsutomu , Schedl Paul , Rabinowitz Joshua , Korennykh Alexei 
Published: January 2019

AbstractNocturnin (NOCT) is a rhythmically expressed protein that regulates metabolism under the control of circadian clock. It has been proposed that NOCT deadenylates and regulates metabolic enzyme mRNAs. However, in contrast to other deadenylases, purified NOCT lacks the deadenylase activity. To identify the substrate of NOCT, we conducted a mass spectrometry screen and report that NOCT specifically and directly converts the dinucleotide NADP+ into NAD+ and NADPH into NADH. Further, we demonstrate that the Drosophila NOCT ortholog, Curled, has the same enzymatic activity. We obtained the 2.7 Å crystal structure of the human NOCT•NADPH complex, which revealed that NOCT recognizes the chemically unique ribose-phosphate backbone of the metabolite, placing the 2’-terminal phosphate productively for removal. We provide evidence for NOCT targeting to mitochondria and propose that NADP(H) regulation, which takes place at least in part in mitochondria, establishes the molecular link between circadian clock and metabolism.
Soybean Haplotype Map (GmHapMap): A Universal Resource for Soybean Translational and Functional Genomics
Authors: Torkamaneh Davoud , Laroche Jérôme , Valliyodan Babu , O’Donoughue Louise , Cober Elroy , Rajcan Istvan , Abdelnoor Ricardo Vilela , Sreedasyam Avinash , Schmutz Jeremy , Nguyen Henry T. , Belzile François 
Published: January 2019

AbstractHere we describe the first worldwide haplotype map for soybean (GmHapMap) constructed using whole-genome sequence data for 1,007Glycine maxaccessions and yielding 15 million variants. The number of unique haplotypes plateaued within this collection (4.3 million tag SNPs) suggesting extensive coverage of diversity within the cultivated germplasm. We imputed GmHapMap variants onto 21,618 previously genotyped (50K array/210K GBS) accessions with up to 96% success for common alleles. A GWAS performed with imputed data enabled us to identify a causal SNP residing in theNPC1gene and to demonstrate its role in controlling seed oil content. We identified 405,101 haplotypes for the 55,589 genes and show that such haplotypes can help define alleles. Finally, we predicted 18,031 putative loss-of-function (LOF) mutations in 10,662 genes and illustrate how such a resource can be used to explore gene function. The GmHapMap provides a unique worldwide resource for soybean genomics and breeding.
Saccharomyces cerevisiae strains display robust phenotypes in the presence of Dyskeratosis congenita mutations in the Cbf5 gene
Authors: Ogailan Abeer Abdullah , Rintala-Dempsey Anne C. , Kothe Ute 
Published: January 2019

AbstractDyskeratosis congenita is a rare, congenital disorder affecting the skin, nails and oral mucosa of patients that often progresses to bone marrow failure and an increased predisposition for a variety of carcinomas. Mutations in the human dyskerin gene have been identified as the most prevalent cause of the disease. Dyskerin is a pseudouridine synthase and the catalytic subunit of H/ACA ribonucleoproteins (RNPs) responsible for the modification of uridines to pseudouridine in ribosomal RNA (rRNA), but dyskerin also binds to the telomerase RNA component (TERC). Accordingly, Dyskeratosis congenita mutations have been reported to affect both telomerase function as well as ribosome biogenesis, but the relative contribution of each pathway to the diseases is under debate. As the yeast homolog of dyskerin, Cbf5, does not interact with telomerase RNA, Saccharomyces cerevisiae is an ideal model to identify the selective impact of Dyskeratosis congenita mutations on ribosome biogenesis. Therefore, chromosomal mutations in the yeast homologue of dyskerin, Cbf5, were introduced at positions corresponding to the mutations in human dyskerin that result in Dyskeratosis congenita. To determine if the mutations affect cellular fitness, we screened for growth defects in yeast. Growth curves at different temperatures and yeast spot assays under several stress conditions revealed that the mutations in cbf5 did not impair growth compared to wild type. These findings suggest that in the yeast cell, Dyskeratosis congenita mutations do not significantly affect ribosome biogenesis, and we discuss the implications for understanding the molecular cause of Dyskeratosis congenita.
Dosimetric Study of Breast Scar Marker in Different Radiotherapy Dose Calculation Algorithms
Authors: Abdullah S. S , Alsadig Ahmed , Sulieman A. , Mattar Isam H. , Ying C. K. , Gokula K. , Azahari A. N. , Abdul Aziz M. Z 
Published: January 2019

AbstractThe purpose to this work is to validate and benchmark the delivered dose accuracy during radiotherapy treatment (without marker at scar site) to the dose calculated by treatment planning that included a marker on scar site. Dose distributions in breast cancer 3-dimensional conformal treatment planning (3D CRT) calculated with Pencil Beam (PB) and Collapsed Cone (CC) algorithms of commercial treatment planning system (Monaco and Oncentra MasterPlan) was compared as photon beam through homogenous and heterogenous media (by placing marker on phantom surface) to evaluate the perturbation of photon beam. Radiochromic film dose distribution value was compared to the dose calculated by CC algorithm of Monaco and Oncentra MasterPlan (OMP) Treatment Planning Systems (TPS) and PB algorithm of OMP TPS. During Computed Tomography (CT) simulation procedure for breast case, a metal-based scar marker (wire) was used to localize the tumour bed during treatment planning procedure which the phantom was considered as heterogeneous medium. In homogenous medium, PB algorithm gave smaller dose deviation compared to CC algorithm. When wire was introduced to the surface of phantom, PB algorithm (6.0 cGy) gave higher dose deviation compared to CC algorithm (2.0 cGy). However, CC algorithm (plasticine: 7.0 cGy and cable: 7.3 cGy) shows higher dose deviation compared to PB algorithm (plasticine: 6.3 cGy and cable: 6.6 cGy) when Plasticine and Cable marker were introduced. The placement of marker in lateral orientation gave smaller perturbation to megavoltage photon beam compared to axial orientation in overall case. Moreover, wire and plasticine are suitable as a scar marker due to its tissue equivalent density with less perturbation to photon beam.
Maturity2, a novel regulator of flowering time in Sorghum bicolor, increases expression of SbPRR37 and SbCO in long days delaying flowering
Authors: Casto Anna L. , Mattison Ashley J. , Olson Sara N. , Thakran Manish , Rooney William L. , Mullet John E. 
Published: January 2019

AbstractSorghum bicolor is a drought-resilient facultative short-day C4 grass that is grown for grain, forage, and biomass. Adaptation of sorghum for grain production in temperate regions resulted in the selection of mutations in Maturity loci (Ma1 – Ma6) that reduced photoperiod sensitivity and resulted in earlier flowering in long days. Prior studies identified the genes associated with Ma1 (PRR37), Ma3 (PHYB), Ma5 (PHYC) and Ma6 (GHD7) and characterized their role in the flowering time regulatory pathway. The current study focused on understanding the function and identity of Ma2. Ma2 delayed flowering in long days by selectively enhancing the expression of SbPRR37 (Ma1) and SbCO, genes that co-repress the expression of SbCN12, a source of florigen. Genetic analysis identified epistatic interactions between Ma2 and Ma4 and located QTL corresponding to Ma2 on SBI02 and Ma4 on SBI10. Positional cloning and whole genome sequencing identified a candidate gene for Ma2, Sobic.002G302700, which encodes a SET and MYND (SYMD) domain lysine methyltransferase. Nine sorghum genotypes previously identified as recessive for Ma2 contained the mutated version of Sobic.002G302700 present in 80M (ma2).