bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laser capture microdissection coupled mass spectrometry (LCM-MS) for spatially resolved analysis of formalin-fixed and stained human lung tissues
Authors: Herrera Jeremy A. , Mallikarjun Venkatesh , Rosini Silvia , Montero Maria Angeles , Warwood Stacey , O’Caulian Ronan , Knight David , Schwartz Martin A. , Swift Joe 
Published: August 2019

ABSTRACTHaematoxylin and eosin (H&E) – which respectively stain nuclei blue and other cellular and stromal material pink – are routinely used for clinical diagnosis based on the identification of morphological features. A richer characterization can be achieved by laser capture microdissection coupled to mass spectrometry (LCM-MS), giving an unbiased assay of the proteins that make up the tissue. However, the process of fixing, and H&E staining of tissues is poorly compatible with standard sample preparation methods for mass spectrometry, resulting in low protein yield. Here we describe a microproteomics technique optimized to analyze H&E-stained, formalin-fixed paraffin-embedded (FFPE) tissues. We advance our methodology by combining 3 techniques shown to individually enhance protein yields (heat extraction, physical disruption, and in column digestion) into one optimized pipeline for the analysis of H&E stained FFPE tissues. Micro-dissected morphologically normal human lung alveoli (0.082 mm3) and human lung blood vessels (0.094 mm3) from FFPE fixed section from Idiopathic Pulmonary Fibrosis (IPF) specimens were then subject to comparative proteomics using this methodology. This approach yielded 1252 differentially expressed proteins including 137 extracellular matrix (ECM) proteins. In addition, we offer proof of principal that MS can identify distinct, characteristic proteomic compositions of anatomical features within complex tissues.
Probability of Change in Life: amino acid changes in single nucleotide substitutions
Authors: Chan Kwok-Fong , Koukouravas Stelios , Yeo Joshua Yi , Koh Darius Wen-Shuo , Gan Samuel Ken-En 
Published: August 2019

ABSTRACTMutations underpin the processes in life, be it beneficial or detrimental. While mutations are assumed to be random in the bereft of selection pressures, the genetic code has underlying computable probabilities in amino acid phenotypic changes. With a wide range of implications including drug resistance, understanding amino acid changes is important. In this study, we calculated the probabilities of substitutions mutations in the genetic code leading to the 20 amino acids and stop codons. Our calculations reveal an enigmatic in-built self-preserving organization of the genetic code that averts disruptive changes at the physicochemical properties level. These changes include changes to start, aromatic, negative charged amino acids and stop codons. Our findings thus reveal a statistical mechanism governing the relationship between amino acids and the universal genetic code.
Peculiar cases of a “sleeping” brain in alert cancer patients
Authors: Benveniste Helene , Vaska Paul , Franceschi Dinko , Salerno Michael , Rizwan Sabeen , Lee Hedok , Logan Jean , Rothman Douglas , Lazebnik Yuri , Volkow Nora D. , Bilfinger Thomas V. 
Published: August 2019

AbstractCognitive and constitutional symptomatology is common in cancer patients but the causes are not well understood. To investigate whether cancers cause these symptoms by changing cerebral metabolism, we measured the cerebral rate of glucose consumption (CMRglc) in patients diagnosed with a lung lesion.MethodsThe CMRglc was quantified in 20 patients undergoing 18F-FDG PET for lesion staging. The cognitive status was assessed by neuropsychological testing.ResultsParadoxically, despite being alert three of the patients had CMRglc typical of people who are in deep sleep or anesthetized. All three had cancers, two died within 2 months of scanning. Remaining patients including four with early stage cancer had CMRglc within normal range.ConclusionsWe speculate that the low CMRglc reflects a switch to an alternative energy source that is mediated by cancers remotely. Identifying the underlying mechanism and the alternative energy sources may help to understand how cancers can change body metabolism.
Demographic history shaped geographical patterns of deleterious mutation load in a broadly distributed Pacific Salmon
Authors: Rougemont Quentin , Moore Jean-Sébastien , Leroy Thibault , Normandeau Eric , Rondeau Eric B. , Withler Ruth E. , Van Doornik Donald M. , Crane Penelope A. , Naish Kerry A. , Garza John Carlos , Beacham Terry D. , Koop Ben F. , Bernatchez Louis 
Published: August 2019

AbstractA thorough reconstruction of historical processes is essential for a comprehensive understanding the mechanisms shaping patterns of genetic diversity. Indeed, past and current conditions influencing effective population size have important evolutionary implications for the efficacy of selection, increased accumulation of deleterious mutations, and loss of adaptive potential. Here, we gather extensive genome-wide data that represent the extant diversity of the Coho salmon (Oncorhynchus kisutch) to address two objectives. We demonstrate that a single glacial refugium is the source of most of the present-day genetic diversity, with detectable inputs from a putative secondary micro-refugium. We found statistical support for a scenario whereby ancestral populations located south of the ice sheets expanded in postglacial time, swamping out most of the diversity from other putative micro-refugia. Demographic inferences revealed that genetic diversity was also affected by linked selection in large parts of the genome. Moreover, we demonstrate that the recent demographic history of this species generated regional differences in the load of deleterious mutations among populations, a finding that mirrors recent results from human populations and provides increased support for models of expansion load. We propose that insights from these historical inferences should be better integrated in conservation planning of wild organisms, which currently focuses largely on neutral genetic diversity and local adaptation, with the role of potentially maladaptive variation being generally ignored.
The quorum sensing transcription factor AphA directly regulates natural competence inVibrio cholerae
Authors: Haycocks James R. J. , Warren Gemma Z. L. , Walker Lucas M. , Chlebek Jennifer L. , Dalia Triana N. , Dalia Ankur B. , Grainger David C. 
Published: August 2019

ABSTRACTMany bacteria use population density to control gene expression via quorum sensing. InVibrio cholerae, quorum sensing coordinates virulence, biofilm formation, and DNA uptake by natural competence. The transcription factors AphA and HapR, expressed at low- and high-cell density respectively, play a key role. In particular, AphA triggers the entire virulence cascade upon host colonisation. In this work we have mapped genome-wide DNA binding by AphA. We show that AphA is versatile, exhibiting distinct modes of DNA binding and promoter regulation. Unexpectedly, whilst HapR is known to induce natural competence, we demonstrate that AphA also intervenes. Most notably, AphA is a direct repressor oftfoX, the master activator of competence. Hence, production of AphA markedly suppressed DNA uptake; an effect largely circumvented by ectopic expression oftfoX. Our observations suggest dual regulation of competence. At low cell density AphA is a master repressor whilst HapR activates the process at high cell density. Thus, we provide deep mechanistic insight into the role of AphA and highlight howV. choleraeutilises this regulator for diverse purposes.AUTHOR SUMMARYCholera remains a devastating diarrhoeal disease responsible for millions of cases, thousands of deaths, and a $3 billion financial burden every year. Although notorious for causing human disease, the microorganism responsible for cholera is predominantly a resident of aquatic environments. Here, the organism survives in densely packed communities on the surfaces of crustaceans. Remarkably, in this situation, the microbe can feast on neighbouring cells and acquire their DNA. This provides a useful food source and an opportunity to obtain new genetic information. In this paper, we have investigated how acquisition of DNA from the local environment is regulated. We show that a “switch” within the microbial cell, known to activate disease processes in the human host, also controls DNA uptake. Our results explain why DNA scavenging only occurs in suitable environments and illustrates how interactions between common regulatory switches affords precise control of microbial behaviours.
Stimulus-specific adaptation to behaviorally-relevant sounds in awake rats
Authors: Yaron A. , Jankowski M. M. , Badrieh R. , Nelken I. 
Published: August 2019

AbstractStimulus-specific adaptation (SSA) is the reduction in responses to a common stimulus that does not generalize, or only partially generalizes, to other stimuli. SSA has been studied mainly with sounds that bear no behavioral meaning. We hypothesized that the acquisition of behavioral meaning by a sound should modify the amount of SSA evoked by that sound. To test this hypothesis, we used fear conditioning in rats, using two word-like stimuli, derived from the English words “danger” and “safety”, as well as pure tones. One stimulus (CS+) was associated with a foot shock whereas the other stimulus (CS-) was presented without a concomitant foot shock. We recorded neural responses to the auditory stimuli using chronically implanted multi-electrode arrays, recording responses telemetrically in freely moving animals before and after conditioning. Consistent with our hypothesis, SSA changed in a way that depended on the behavioral role of the sound: the contrast between standard and deviant responses remained the same or decreased for CS+ stimuli but increased for CS- stimuli, showing that SSA is shaped by experience. In most cases the sensory responses underlying these changes in SSA increased following conditioning. Unexpectedly, the responses to CS+ word-like stimuli showed a specific, substantial decrease, which we interpret as evidence for substantial inhibitory plasticity.
Assignment of frost tolerant coast redwood trees of unknown origin to populations within their natural range using nuclear and chloroplast microsatellite genetic markers
Authors: Breidenbach Natalie , Gailing Oliver , Krutovsky Konstantin V. 
Published: August 2019

AbstractConsidering climate change and expected changes in temperature and precipitation, some introduced timber species are prospective for growing in Germany or Europe to produce valuable wood products and support sustainable forestry. The Californian tree, coast redwood (Sequoia sempervirens[D. Don] Endl.) is one of such species due to its excellent wood properties and high growth rate. It is sensitive to the freezing temperatures, but several trees of unknown origin introduced to Germany decades ago demonstrated high frost tolerance, and their propagated cuttings were planted all over German botanic gardens and arboreta. The knowledge of their origin within the natural distribution range could help us identify the potential genetic resources of frost resistant coast redwood genotypes. Therefore, both trees of unknown origin in Germany (G) and two reference data sets representing the “Kuser provenance test” established in 1990 in France (F) and samples collected in California (C) with known origin were genotyped using 18 microsatellite markers including 12 nuclear and six chloroplast simple sequence repeat (cpSSR) markers. The number of haplotypes found in the data sets based on six cpSSR markers was surprisingly very high. These markers were used to assign the German frost resistant trees (G) to the two reference data sets (F and C). The genetic structure among California samples (C) based on nSSR and cpSSR markers was very weak and mainly due to northern and southern clusters separated by the San Francisco Bay as a geographic barrier between coast redwood populations confirming previously published data. It was impossible to confidently assign frost tolerant trees (G) to single native populations, but rather to either the northern or southern cluster. However, the existing frost tolerant genotypes can already be used to establish commercial coast redwood plantation for future German forestry.
Pseudolesion in the right parafissural liver parenchyma on CT: the base is found in embryology and collagen content
Authors: Klein Willemijn M , Sonnemans Lianne JP , Franckenberg Sabine , Fliss Barbara , Gascho Dominic , Prokop Mathias , Lamers Wouter H , Hikspoors Jill PJM , Thali Michael J , Flach Patricia M 
Published: August 2019

AbstractBackgroundComputed tomography (CT) images of livers may show a hypo-attenuated structure alongside the falciform ligament, which can be a focal fatty pseudolesion and can mimic a malignancy. The preferred location is on the right parafissural site, ventral in segment IVa/b. The etiology is not clear, nor is it known how the histology of this location develops. These are evaluated in this study.Methods40 adult cadavers with autopsy and / or postmortem CT in a university hospital and a forensic center were included. Liver biopsies were taken at the left side of the falciform ligament as control, and at the right side as the possible precursor of a pseudolesion; these were examined for collagen and fat content. Cadavers with steatotic (>5% fat) or fibrotic (>2% collagen) control samples were excluded.ResultsSignificantly more collagen was present in the right parafissural liver parenchyma: median 0.68% (IQR: 0.32 – 1.17%), compared to the left side 0.48% (IQR: 0.21 – 0.75%) (p 0.008), with equal fat content and CT attenuation values. The etiophysiology goes back to the demise of the umbilical venes in the early embryonic and neonatal period.ConclusionsThe right parafissural area contains more collagen and an equal amount of fat compared to the control left side. This supports the hypothesis of delayed, ‘third’ inflow: the postnatal change in blood supply from umbilical to portal leaves the downstream parafissural area hypoperfused leading to hypoxia which in turn results in collagen accumulation and the persistence of paraumbilical veins of Sappey.Key pointsThe typical location for a parafissural hepatic pseudolesion contains increased collagen.A change in histology is caused by physiological demise of the umbilical venes.The suboptimal blood supply of the right parafissural side leads to hypoxia and collagen deposition.Embryologic knowledge and postmortem histology can help resolve issues in radiology.
TRiC activates the unfolded protein response and protects starved stem cells by modulating energy and lipid metabolism during planarian regeneration
Authors: Gutiérrez-Gutiérrez Óscar , Felix Daniel A. , Salvetti Alessandra , Thems Anne , Pietsch Stefan , Koeberle Andreas , Rudolph K. Lenhard , González-Estévez Cristina 
Published: August 2019

SummaryFasting protects stem cells and increases stem cell functionality through mechanisms which are not fully understood. Planarians are not only able to regenerate their bodies, but also to stand long periods of starvation by shrinking in size. This adaptation is possible because of a large population of adult stem cells which indefinitely self-renew even under starved conditions and thus confer planarians with immortality. How starved planarians are able to maintain healthy stem cells and to fuel stem cell proliferation allowing regeneration is unknown. Here we found the TCP-1 ring complex (TRiC) to be upregulated in starved stem cells. Down-regulation of TRiC impairs planarian regenerative response by inducing stem cell genome instability, mitotic defects and stem cell death which translates into stem cell exhaustion. This regulation is specific of starvation since feeding planarians prevents the phenotype. Importantly we found that TRiC activates the unfolded protein response (UPR) which allows a convergent regulation of cellular energy and lipid metabolism in starved planarians thus permitting the high energy demanding regenerative mitotic response. We identified a novel mechanism through which starvation protects the somatic stem cell genome allowing for unlimited stem cell proliferation and regeneration.
Altered auditory feedback induces coupled changes in formant frequencies during speech production
Authors: Tang Ding-lan , Lametti Daniel R. , Watkins Kate E. 
Published: August 2019

AbstractSpeaking is one of the most complicated motor behaviours, involving a large number of articulatory muscles which can move independently to command precise changes in speech acoustics. Here, we used real-time manipulations of speech feedback to test whether the acoustics of speech production (e.g. the formants) reflect independently controlled articulatory movements or combinations of movements. During repetitive productions of “head, bed, dead”, either the first (F1) or the second formant (F2) of vowels was shifted and fed back to participants. We then examined whether changes in production in response to these alterations occurred for only the perturbed formant or both formants. In Experiment 1, our results showed that participants who received increased F1 feedback significantly decreased their F1 productions in compensation, but also significantly increased the frequency of their F2 productions. The combined F1-F2 change moved the utterances closer to a known pattern of speech production (i.e. the vowel category “hid, bid, did”). In Experiment 2, we further showed that a downshift in frequency of F2 feedback also induced significant compensatory changes in both the perturbed (F2) and the unperturbed formant (F1) that were in opposite directions. Taken together, the results demonstrate that a shift in auditory feedback of a single formant drives combined changes in related formants. The results suggest that, although formants can be controlled independently, the speech motor system may favour a strategy in which changes in formant production are coupled to maintain speech production within specific regions of the vowel space corresponding to existing speech-sound categories.New & NoteworthyFindings from previous studies examining responses to altered auditory feedback are inconsistent with respect to the changes speakers make to their production. Speakers can compensate by specifically altering their production to offset the acoustic error in feedback. Alternatively, they may compensate by changing their speech production more globally to produce a speech sound closer to an existing category in their repertoire. Our study shows support for the latter strategy.
Transcriptome computational workbench (TCW): analysis of single and comparative transcriptomes
Authors: Soderlund Carol A. 
Published: August 2019

AbstractDe novo transcriptome sequencing and analysis provides a way for researchers of non-model organisms to explore the differences between various conditions and species. The results are typically not definitive but will lead to new hypotheses to study. Therefore, it is important that the results be reproducible, extensible, queryable, and easily available to all members of the team. Towards this end, the Transcriptome Computational Workbench (TCW) is a software package to perform basic computations for transcriptome analysis (singleTCW) and comparative analysis (multiTCW). It is a Java-based desktop application that uses MySQL for the TCW database. The input to singleTCW is sequence and optional count files; the computations are sequence similarity, gene ontology (GO), open reading frame (ORF), and differential expression (DE). TCW provides support for searching with the super-fast DIAMOND program against UniProt taxonomic databases, though the user can provide other databases to search against. The ORF finder uses hit information, 5th-order Markov models and ORF length. For DE and GO enrichment, TCW interfaces with the R environment and an R script, where R scripts are provided for popular methods. The input to multiTCW is multiple singleTCW databases; the computations are homologous pair assignment, pairwise analysis (e.g. Ka/Ks) from codon-based alignments, clustering (bidirectional best hit, Closure, Best Hit, OrthoMCL, user-supplied), and cluster analysis and annotation. Both singleTCW and multiTCW provide a graphical interface for extensive query and display of the data and results. Example results are presented from two rhizome and one non-rhizome plant, where one of the rhizome plants has replicate count data from four tissues. The supplement describes how to reproduce all tables and figures. The TCW V4 software is freely available at https://github.com/csoderlund/TCW; the package contains the jar files, external software, and demo files.
Reconstructed protein sequence evolution consistent with the evolution of C4 photosynthesis via a C2 ancestor in the Paniceae
Authors: Carvalho Daniel S. , Kenchanmane Raju Sunil Kumar , Zhang Yang , Schnable James C. 
Published: August 2019

AbstractThe grass tribe Paniceae includes a monophyletic subclade of species, the MPC clade, which specialize in each of the three primary C4 sub-pathways NADP-ME, NAD-ME and PCK. The evolutionary history of C4 photosynthesis in this subclade remains ambiguous. Leveraging newly sequenced grass genomes and syntenic orthology data, we estimated rates of protein sequence evolution on ancestral branches for both core enzymes shared across different C4 sub-pathways and enzymes specific to C4 sub-pathways. While core enzymes show elevated rates of protein sequence evolution in ancestral branches consistent with a transition from C3 to C4 photosynthesis in the ancestor for this clade, no subtype specific enzymes showed similar patterns. At least one protein involved in photorespiration also showed elevated rates of protein sequence evolution in the ancestral branch. The set of core C4 enzymes examined here combined with the photorespiratory pathway are necessary for the C2 photosynthetic cycle, a previously proposed intermediate between C3 and C4 photosynthesis. The patterns reported here are consistent with, but not conclusive proof that, C4 photosynthesis in the MPC clade of the Paniceae evolved via a C2 intermediate.
Structured connectivity exploits NMDA non-linearities to enable flexible encoding of multiple memoranda in a PFC circuit model
Authors: Stefanos Stefanou S. , Papoutsi Athanasia , Poirazi Panayiota 
Published: August 2019

SummaryPrefrontal Cortex (PFC) exerts control on action selection and mediates behavioral flexibility during working memory (WM) task execution, when integration and retention of sensory information takes place. We used biophysical circuit modelling to investigate the dendritic, neuronal and circuit mechanisms that underlie these computations, aiming to causally link these three processing levels. Our simulations predict that dendritic NMDA non-linearities drive distinct activity dynamics of the same network, thus enabling adaptive coding in the absence of plasticity mechanisms. Specifically, we find that distinct assemblies of mixed-selectivity neurons emerge and fire in stable trajectories in a stimulus-dependent manner. Synaptic inputs that are spatio-temporally clustered, as provided by the structured connectivity of the PFC, facilitate these activity dynamics, thus further increasing the flexibility of the network. Our study suggests that behavioral flexibility may result from the formation of memoranda-specific assemblies in the PFC which are utilized dynamically in relation to the task at hand.