bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feed restriction in mid-lactation dairy cows. I: Effects on milk production and energy metabolism-related blood metabolites
Authors: Ansia I. , Ohta Y. , Fujieda T. , Drackley J. K. 
Published: June 2020

AbstractThe aim of the study was to describe the metabolic responses on energy metabolism to a period of negative nutrient balance induced by feed restriction (FR). Seven multiparous Holstein cows (93 ± 15 days in milk) were randomly assigned to 7 treatments in a 7 × 4 Youden square design. Daily intake was restricted to provide 60% of energy requirements during 5 d except for one treatment with ad libitum (AL) feeding. While 5 out of 7 experimental treatments involved abomasal supplementation of amino acids or glucose, in this article we evaluated only the effects of a negative nutrient balance by comparing both control treatments (AL and FR). Data of 2 cows within the AL group were removed due to sickness and therefore it had n = 2. Milk and energy corrected milk yield were reduced by FR. Yields of milk protein and lactose were lower during FR than during AL but the yield of milk fat only had a tendency (P> 0.06) to be lower with FR. Milk protein concentration was lower with FR than with AL but concentration of milk lactose and fat were not different between diets. The FR induced a decrease in plasma insulin and glucose concentrations, with quadratic decreasing trends both reaching nadirs on d 3. Simultaneously, non-esterified fatty acids (NEFA) concentration was greater and increased quadratically, peaking at d 3 during FR. There were no differences in daily β-hydroxybutyrate concentration, but it increased linearly until d 4 with FR. Comparison of the variation in concentration after feeding of insulin, NEFA and glucose could indicate a likely increased insulin sensitivity for peripheral NEFA uptake and a resistance for glucose uptake. This mechanism would contribute to decrease NEFA in circulation and sparing of glucose for lactose synthesis, respectively. Metabolic adaptations to a short-term reduction in dry matter intake include lipid mobilization, as well as modulation of peripheral tissue endocrine sensitivity in order to maintain yield of milk components production but prioritizing milk fat and lactose over milk protein.ImplicationsThe short-term feed restriction model described in this article can serve as an alternative to study metabolic adaptations during the transition period. The response of energy metabolism observed sets the baseline to measure the effect of nutrients supplementation and identify those candidates that will improve milk production and overall health after calving.
State-dependent signatures of Anti-NMDA Receptor Encephalitis: a dynamic functional connectivity study
Authors: von Schwanenflug Nina , Krohn Stephan , Heine Josephine , Paul Friedemann , Prüss Harald , Finke Carsten 
Published: June 2020

ABSTRACTObjectiveTraditional static functional connectivity (FC) analyses have shown functional network alterations in patients with anti-NMDA receptor encephalitis (NMDARE). Here, we use a dynamic FC approach that increases the temporal resolution of connectivity analyses from minutes to seconds. We hereby explore the spatiotemporal variability of large-scale brain network activity in NMDARE and assess the discriminatory power of functional brain states in a supervised classification approach.MethodsWe included resting-state fMRI data from 57 patients and 61 controls to extract four discrete connectivity states and assess state-wise group differences in FC, dwell time, transition frequency, fraction time and occurrence rate. Additionally, for each state, logistic regression models with embedded feature selection were trained to predict group status in a leave-one-out cross-validation scheme.ResultsCompared to controls, patients exhibited diverging dynamic FC patterns in three out of four states mainly encompassing the default-mode network and frontal areas. This was accompanied by a characteristic shift in the dwell time pattern and higher volatility of state transitions in patients. Moreover, dynamic FC measures were associated with disease severity, disease duration and positive and negative schizophrenia-like symptoms. Predictive power was highest in dynamic FC models and outperformed static analyses, reaching up to 78.6% classification accuracy.ConclusionsBy applying time-resolved analyses, we disentangle state-specific FC impairments and characteristic changes in temporal dynamics not detected in static analyses, offering new perspectives on functional reorganization underlying NMDARE. Correlation of dynamic FC measures with disease symptoms and severity indicates their clinical relevance and potential as prognostic biomarkers in NMDARE.
Feed restriction in mid-lactation dairy cows. II: Effects on protein metabolism-related blood metabolites
Authors: Ansia I. , Ohta Y. , Fujieda T. , Drackley J. K. 
Published: June 2020

AbstractThe aim of the study was to describe the metabolic responses of protein metabolism to a period of negative nutrient balance induced by feed restriction (FR). Seven multiparous Holstein cows (93 ± 15 days in milk) were randomly assigned to 7 treatments in a 7 × 4 Youden square design. Daily intake was restricted to provide 60% of energy requirements during 5 d except for one treatment with ad libitum (AL) feeding. While 5 out of 7 experimental treatments involved abomasal supplementation of AA or glucose, in this article we evaluated only the effects of FR by comparing both control treatments (AL and FR). Data of 2 cows within the AL group were removed due to sickness and therefore it had n = 2. A rapid decrease of most amino acids in plasma was paired with an increase in blood urea N with its peak on d 2 and decreasing afterwards. On the other hand, Lys, Arg, Gly, Gln, and Cys were greater during FR. Comparing the fluctuation of all the essayed N components in circulation across the 5-d period, protein tissue mobilization may have supplied amino acids for catabolism to provide needs for N and energy precursors.ImplicationsThe short-term feed restriction model described in this article can serve as an alternative to study metabolic adaptations during the transition period. The response observed of the protein metabolism sets the baseline to measure the effect of nutrients supplementation and identify those candidates that will improve milk production and overall health after calving.
A peptide-signal amplification strategy for the detection and validation of neoepitope presentation on cancer biopsies
Authors: Ramarathinam Sri H. , Faridi Pouya , Peng Angela , Szeto Pacman , Wong Nicholas C. , Behren Andreas , Shackleton Mark , Purcell Anthony W. 
Published: June 2020

AbstractTargeting the right cancer-specific peptides presented by Human Leukocyte antigen (HLA) class I and II molecules on the tumor cell surface is a crucial step in cancer immunotherapy. Numerous approaches have been proposed to predict the presentation of potential neoepitopes that may be targeted through immune-based therapies. Often founded on patient specific somatic mutations, the routine validation of their actual appearance on the tumor cell surface is a significant barrier to realising personalized cancer immunotherapy. This can be attributed to the lack of robust and adaptable assays for antigen presentation that offer the required sensitivity to deal with the limited amounts of patient tumor tissue available. Rather than personalize individual assays we propose the use mass spectrometry to identify tumor neoepitopes from HLA-bound peptides directly isolated form the surface of tumor biopsies. We have developed a microscale HLA-peptide complex immunoprecipitation protocol combined with tandem mass tagging (TMT) to directly sequence HLA-bound peptides using mass spectrometry. Using this strategy, we identified HLA-bound peptides from as few as ~1000 cultured cells and from a small piece (~1 mg) of whole melanoma tumour tissue, encompassing epitopes derived from Melanoma-associated antigens and potential neoantigens.
Mapping Connectional Differences between Humans and Macaques in the Nucleus Accumbens Shell-Core Architecture
Authors: Xia Xiaoluan , Fan Lingzhong , Cheng Chen , Cheng Luqi , Cao Long , He Bin , Chen Junjie , Li Haifang , Jiang Tianzi 
Published: June 2020

AbstractTwo nucleus accumbens subregions, the shell and core, differ in the patterns whereby they integrate signals from prefrontal and limbic areas of the brain. In this study, we investigated whether the disproportionate volumetric differences of these brain areas, particularly the prefrontal cortex, between humans and macaques are accompanied by unique modifications of their macroscopic integrative connections with the shell and core. More specifically, we characterized the tractographic connectivity profiles of the human and macaque shell-core architecture and compared them between the two species. To make the cross-species comparisons more viable, we used the same whole-brain voxel-wise tractography-defined shell-like and core-like divisions in the two species as seeds and delineated pairs of interspecies connectionally comparable (ICC) target regions based on the similarity of the resting-state functional connectivity profiles for the two species, and finally used these seeds and ICC targets to establish a fingerprint-based common space for cross-species comparisons. Our results revealed that dissimilar structural connectivity profiles were found in the prefrontal but not the subcortical target group. We further localized this difference to specific targets to infer possible functional modifications between the two species.
Dynamic integration of enteric neural stem cells in ex vivo organotypic colon cultures
Authors: Navoly Georgina , McCann Conor J. 
Published: June 2020

AbstractEnteric neural stem cells (ENSC) have been identified as a possible treatment for enteric neuropathies. Afterin vivotransplantation, ENSC and their derivatives have been shown to engraft within colonic tissue, migrate and populate endogenous ganglia, and functionally integrate with the enteric nervous system. However, the mechanisms underlying the integration of donor ENSC, in recipient tissues, remains unclear. Here, using a modifiedex vivoorganotypic culture system we show that donor ENSC-derived cells integrate across the colonic wall in a dynamic fashion, across a three-week period. We further show that donor cells display two integrative patterns; longitudinal migration and medial invasion which allow donor cells to populate colonic tissue. Moreover, we demonstrate that significant remodelling of the intestinal ECM, and musculature, occurs upon transplantation to facilitate donor cell integration. Thus, our results provide critical evidence on the timescale, and mechanisms, which regulate donor ENSC integration within recipient gut tissue.
Global FAW population genomic signature supports complex introduction events across the Old World
Authors: Tay WT , Rane RV , Padovan A , Walsh TK , Elfekih S , Downes S , Nam K , d’Alençon E , Zhang J , Wu Y , Nègre N , Kunz D , Kriticos DJ , Czepak C , Otim MH , Gordon KHJ 
Published: June 2020

AbstractNative to the Americas, the invasiveSpodoptera frugiperda(fall armyworm; FAW) was reported in West Africa in 2016, followed by chronological order of detections across the Old World and the hypothesis of an eastward Asia expansion. We explored population genomic signatures of American and Old World FAW and identified 12 maternal mitochondrial DNA genome lineages across the invasive range, while from 870 high-quality nuclear single nucleotide polymorphic DNA markers five distinct New World population clusters were identified, broadly reflected their native geographical ranges and absence of host-plant preferences. We identified unique admixed Old World populations, and admixed and non-admixed Asian FAW individuals, all of which suggested multiple introductions underpinned the pest’s global spread. Directional gene flow from the East into eastern Africa was also detected, in contrast to the west-to-east spread hypothesis. Our study demonstrated population genomic approaches via international partnership to address global emerging pest threats and biosecurity challenges.
An Adaptive Detection for Automatic Spike Sorting Based on Mixture of Skew-t distributions
Authors: Toosi Ramin , Akhaee Mohammad Ali , Dehaqani Mohammad-Reza A. 
Published: June 2020

ABSTRACTDeveloping new techniques of simultaneous recoding using thousand electrodes, make the wide variety of spike waveforms across multiple channels. This problem causes spike loss and raise the crucial issue of spike sorting with unstable clusters. While there exist many automatic spike sorting methods, there has been a lack of studies developing robust and adaptive spike detection algorithm. Here, an adaptive procedure is introduced to improve the detection of spikes in different scenarios. This procedure includes a new algorithm which aligns the spike waveforms at the point of extremums. The other part is statistical filtering, which seeks to remove noises that mistakenly detected as true spike. To deal with non-symmetrical clusters, we proposed a new clustering algorithm based on the mixture of skew-t distributions. The proposed method could overcome the spike loss and skewed cells challenges by offering an improvement over automatic detection, alignment, and clustering of spikes. Investigating the sorted spikes, reveals that proposed adaptive algorithm improves the performance of the spike detection in both terms of precision and recall. The adaptive algorithm has been validated on different datasets and demonstrates a general solution to precise spike sorting, in vitro and in vivo.
Gonads or body? Differences in gonadal and somatic photoperiodic growth response in two vole species
Authors: van Rosmalen Laura , van Dalum Jayme , Hazlerigg David G. , Hut Roelof A. 
Published: June 2020

AbstractTo optimally time reproduction, seasonal mammals use a photoperiodic neuroendocrine system (PNES) that measures photoperiod and subsequently drives reproduction. To adapt to late spring arrival at northern latitudes, a lower photoperiodic sensitivity and therefore a higher critical photoperiod for reproductive onset is necessary in northern species to arrest reproductive development until spring onset. Temperature-photoperiod relationships, and hence food availability-photoperiod relationships, are highly latitude dependent. Therefore, we predict PNES sensitivity characteristics to be latitude-dependent. Here, we investigated photoperiodic responses at different times during development in northern- (tundra/root vole,Microtus oeconomus) and southern vole species (common vole,Microtus arvalis) exposed to constant short (SP) or long photoperiod (LP).M. oeconomusgrows faster under LP, whereas no photoperiodic effect on somatic growth is observed inM. arvalis. Contrastingly, gonadal growth is more sensitive to photoperiod inM. arvalis, suggesting that photoperiodic responses in somatic and gonadal growth can be plastic, and might be regulated through different mechanisms. In both species, thyroid-stimulating-hormone-β subunit (Tshβ) and iodothyronine-deiodinase 2 (Dio2) expression is highly increased under LP, whereasTshrandDio3decreases under LP. HighTshrlevels in voles raised under SP may lead to increased sensitivity to increasing photoperiods later in life. The higher photoperiodic inducedTshrresponse inM. oeconomussuggests that the northern vole species might be more sensitive to TSH when raised under SP.Species differences in developmental programming of the PNES, which is dependent on photoperiod early in development, may form part divergent breeding strategies evolving as part of latitudinal adaptation.Summary statementDevelopment of the neuroendocrine system driving photoperiodic responses in gonadal and somatic growth differ between the common and the tundra vole, indicating that they use a different breeding strategy.
Overhauling a faulty control in the CDC-recommended SARS-CoV-2 RT-PCR test panel
Authors: Dekker Rob J. , Ensink Wim A. , van Leeuwen Selina , Rauwerda Han , Breit Timo M. 
Published: June 2020

ABSTRACTTo battle the COVID-19 pandemic, widespread testing for the presence of the SARS-CoV-2 virus is worldwide being employed by specific real-time RT-PCR (rRT-PCR) of viral RNA. The CDC has issued a recommended panel of PCR-based test sets that entail several primer/probe sets that target the SARS-CoV-2 N-gene, but also one that targets the human RNase P gene (h-RP) as a positive control for RNA extraction and/or reverse-transcription (RT) efficacy.We discovered that the CDC-recommended h-RP primer/probe set has a faulty design, because both PCR primers are located in the same exon, which allows for unwanted PCR-amplification of background genomic DNA (gDNA). By removing RNA from nose-swab samples by an RNase treatment, we showed that the presence of gDNA in samples resulted in false-positive signals for the h-RP test control. This is rather serious, because it could lead to false-negative test outcomes, since the CDC interpretation of an absent SARS-CoV-2 rRT-PCR signal plus a positive h-RP rRT-PCR signal is interpreted as “2019-nCoV not detected”, whereas a false-positive h-RP rRT-PCR signal resulting from amplification of gDNA should be interpreted as “Invalid Result” and the procedure should be repeated.In order to overhaul the faulty h-RP rRT-PCR primer/probe set with minimal modification, we designed and tested several new h-RP reverse primers. Replacement of the CDC-recommended PCR reverse primer with our selected exon-exon junction reverse primer corrected the problem of false-positive results with this important SARS-CoV-2 RT-PCR test control and thus eliminated the problem of potential false-negative COVID-19 diagnoses.
CRISPR/Cas “non-target” sites inhibit on-target cutting rates
Authors: Moreb Eirik A. , Hutmacher Mitchell , Lynch Michael D. 
Published: June 2020

AbstractCRISPR/Cas systems have become ubiquitous for genome editing in eukaryotic as well as bacterial systems. Cas9 associated with a guide RNA (gRNA) searches DNA for a matching sequence (target site) next to a protospacer adjacent motif (PAM) and once found, cuts the DNA. The number of PAM sites in the genome are effectively a non-target pool of inhibitory substrates, competing with the target site for the Cas9/gRNA complex. We demonstrate that increasing the number of non-target sites for a given gRNA reduces on-target activity in a dose dependent manner. Furthermore, we show that the use of Cas9 mutants with increased PAM specificity towards a smaller subset of PAMs (or smaller pool of competitive substrates) improves cutting rates. Decreasing the non-target pool by increasing PAM specificity provides a path towards improving on-target activity for slower high fidelity Cas9 variants. These results demonstrate the importance of competitive non-target sites on Cas9 activity and, in part, may help to explain sequence and context dependent activities of gRNAs. Engineering improved PAM specificity to reduce the competitive non-target pool offers an alternative strategy to engineer Cas9 variants with increased specificity and maintained on-target activity.HighlightsThe pool of non-target PAM sites inhibit Cas9/gRNA on-target activitynon-target PAM inhibition is dose dependentnon-target PAM inhibition is a function of gRNA sequencenon-target PAM inhibition is a function of Cas9 levels
Computational studies of drug repurposing targeting P-glycoprotein mediated multidrug-resistance phenotypes in agents of neglected tropical diseases
Authors: Jaishankar Nivedita , Muthamilselvan Sangeetha , Palaniappan Ashok 
Published: June 2020

ABSTRACTMammalian ABCB1P-glycoprotein is an ATP- dependent efflux pump with broad substrate specificity associated with cellular drug resistance. Homologous to this role in mammalian biology, the P-glycoprotein of agents of neglected tropical diseases (NTDs) mediates the emergence of multidrug-resistance phenotypes. The clinical and socioeconomic implications of NTDs are exacerbated by the lack of research interest among Big Pharma for treating such conditions. This work aims to characterise P-gp homologues in certain agents of key NTDs, namelyProtozoa: Leishmania major, Trypanosoma cruzi;Helminths: Onchocerca volvulus, Schistosoma mansoni.PSI-BLAST searches against the genome of each of these organisms confirmed the presence of P-gp homologues. Each homologue was aligned against five P-gp sequences of known structure, to identify the most suitable template based on sequence homology, phylogenetic nearest neighbor, and query coverage. Antibiotics used in the current line of therapy against each of these pathogens were identified using PubChem and their SMILES structures were converted to PDB using BABEL software. Potential antibiotics to test against the set of FDA-approved antibiotics were identified based on similarity to the chemical class of the known drugs and repurposing of the existing drugs. Docking studies of the respective modelled Pgp structures and the set of antibiotic ligands were carried out using AutoDock and the most tenable target-ligand conformations were assessed. The interacting residues within 4.5 Å of the ligand were identified, and the binding pockets were studied. The relative efficacy of the new drugs and the interacting pump residues were identified. Our studies could lay the foundation for the development of effective synergistic or new therapies against key neglected tropical diseases.