bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Pan-Omics Data in Human Interactome Network (APODHIN)
Authors: Biswas Nupur , Kumar Krishna , Bose Sarpita , Bera Raisa , Chakrabarti Saikat 
Published: April 2020

AbstractAnalysis of Pan-Omics Data in Human Interactome Network (APODHIN) is a platform for integrative analysis of transcriptomics, proteomics, genomics, and metabolomics data for identification of key molecular players and their interconnections exemplified in cancer scenario. APODHIN works on a meta-interactome networks consisting of human protein-protein interactions, miRNA-target gene regulatory interactions, and transcription factor-target gene regulatory relationships, respectively. In its first module, APODHIN maps proteins/genes/miRNAs from different omics data in its meta-interactome network and extracts the network of biomolecules that are differentially altered in the given scenario. Using this context specific, filtered interaction network, APODHIN identifies topologically important nodes (TINs) implementing graph theory based network topology analysis and further justifies their role via pathway and disease marker mapping. These TINs could be used as prospective diagnostic and/or prognostic biomarkers and/or potential therapeutic targets. In its second module, APODHIN attempts to identify cross pathway regulatory and protein-protein interaction (PPI) links connecting signaling proteins, transcription factors, and miRNAs to metabolic enzymes via utilization of single-omics and/or pan-omics data and implementation of mathematical modeling. Interconnections between regulatory components such as signaling proteins/TFs/miRNAs and metabolic pathways need to be elucidated more elaborately in order to understand the role of oncogene and tumor suppressors in regulation of metabolic reprogramming during cancer.APODHIN platform contains a web server component where users can upload single/multi omics data to identify TINs and cross-pathway links. Tabular, graphical and 3D network representations of the identified TINs and cross-pathway links are provided for better appreciation. Additionally, this platform also provides a database part where cancer specific, single and/or multi omics dataset centric meta-interactome networks, TINs, and cross-pathway links are provided for cervical, ovarian, and breast cancers, respectively. APODHIN platform is freely available athttp://www.hpppi.iicb.res.in/APODHIN/home.html.
Anthropogenic food enhancement alters the timing of maturational landmarks among wild savanna monkeys (Chlorocebus pygerythrus)
Authors: Schmitt Christopher A. , Rich Alicia M. , Parke Stacy-Anne R. , Blaszczyk Maryjka B. , Cramer Jennifer Danzy , Freimer Nelson B. , Grobler J. Paul , Turner Trudy R. 
Published: April 2020

ABSTRACTAnthropogenic landscapes are rapidly replacing natural nonhuman primate habitats. Yet, the access to anthropogenic resources on primate biology, health, and fitness remain poorly studied. Given their ubiquity across a range of human impacted landscapes, from cities to national parks, savanna monkeys (Chlorocebusspp.) provide an excellent study system in which to test these effects. We compared body condition and reproductive maturation in vervets (Chlorocebus pygerythrus) inhabiting a private farm in !Gariep Dam, with ample access to anthropogenic foods, and wild-foraging vervets in Soetdoring Nature Reserve, South Africa. Overall, vervets in !Gariep show significantly thicker skin folds, and higher BMI and body mass, than those in Soetdoring, suggesting increased fat deposition. Males in !Gariep have larger relative testis volumes at peri-pubescent ages compared to those in Soetdoring, suggesting early reproductive maturation associated with age-specific increases in body mass. Females from !Gariep showed evidence of an earlier onset of reproduction than those in Soetdoring, based on parity status as assessed by nipple length and evidence of lactation. Parity status at sub-adult dental ages was also strongly associated with body mass. These results are consistent with a positive effect of anthropogenic food-enhancement on body fat deposition, potentially linked to an earlier onset of reproductive maturation. Further investigation into primate responses to cultivated resources will inform our understanding of the broader effects of food enhancement on developmental plasticity.
Mycobiome analysis in fungal Infected formalin-fixed and paraffin-embedded tissues for identification of pathogenic fungi: A pilot study
Authors: Lee Taebum , Na Hee Young , Kim Kyoung-Mee , Lee Hey Seung , Park Sung-Hye , Choe Ji-Young , Choi Kyoung Chan , Byeon Sun-ju 
Published: April 2020

ABSTRACTBackgroundFungal organisms are frequently observed in surgical pathological diagnosis. In order to more accurately identify fungi in formalin-fixed and paraffin-embedded (FFPE) tissues, it is necessary to use genomic information. The purpose of our pilot study is to identify the factors to be considered for the identification of pathogenic fungi using mycobiome analysis in FFPE tissues.MethodsWe selected 49 cases in five hospitals. In each case, FFPE tissue was cut into 50 µm and DNA was extracted. Multiplex PCR with four primers (ITS1, ITS2, ITS3 and ITS4) was performed. Multiplex sequencing was performed using MinION device according to the manufacturer’s protocol. Sequences of each case were searched using BLASTN with an ITS database from NCBI RefSeq Targeted Loci Project with default parameter.ResultsA total of 2,526 DNA nucleotides were sequenced. We were able to identify 342 fungal nucleotides in 24 (49.0%, 24/49) cases. The median value of the detected fungal DNA per case was 3 (1Q: 1 and 3Q: 14.25). The 215 (62.87%) fungal DNA contained the entire region of ITS1 or ITS2. The remaining 127 fungal DNAs were identified as fungi using partial sequence of ITS1, ITS2, 5.8S, LSU or SSU.ConclusionIn conclusion, we have identified the possibility of finding pathogenic fungi through mycobiome analysis in fungal infected FFPE tissues using nanopore sequencing method. However, we have also found several limitations to be solved for further studies. If we develop a method to characterize pathogenic fungi in FFPE tissues in a follow-up study, we think it will help patients to use appropriate antifungal agents.
Efficient assessment of nocturnal flying insect communities by combining automatic light traps and DNA metabarcoding
Authors: Mata Vanessa A. , Ferreira Sónia , Campos Rebecca , da Silva Luís P. , Veríssimo Joana , Corley Martin F. V. , Beja Pedro 
Published: April 2020

SummaryIncreasing evidence for global insect declines is prompting a renewed interest in the survey of whole insect communities. DNA metabarcoding can contribute to assessing diverse insect communities over a range of spatial and temporal scales, but efforts are still needed to optimise and standardise procedures, from field sampling, through laboratory analysis, to bioinformatic processing.Here we describe and test a methodological pipeline for surveying nocturnal flying insects, combining a customised automatic light trap and DNA metabarcoding. We optimised laboratory procedures and then tested the methodological pipeline using 12 field samples collected in northern Portugal in 2017. We focused on Lepidoptera to compare metabarcoding results with those from morphological identification, using three types of bulks produced from each sample (individuals, legs and the unsorted mixture).The customised trap was highly efficient at collecting nocturnal flying insects, allowing a small team to operate several traps per night, and a fast field processing of samples for subsequent metabarcoding with low contamination risks. Morphological processing yielded 871 identifiable individuals of 102 Lepidoptera species. Metabarcoding detected a total of 528 taxa, most of which were Lepidoptera (31.1%), Diptera (26.1%) and Coleoptera (14.7%). There was a reasonably high matching in community composition between morphology and metabarcoding when considering the ‘individuals’ and ‘legs’ bulk samples, with few errors mostly associated with morphological misidentification of small microlepidoptera. Regarding the ‘mixture’ bulk sample, metabarcoding identified nearly four times more Lepidoptera species than morphological examination.Our study provides a methodological metabarcoding pipeline that can be used in standardised surveys of nocturnal flying insects, showing that it can overcome limitations and potential shortcomings of traditional methods based on morphological identification. Our approach efficiently collects highly diverse taxonomic groups such as nocturnal Lepidoptera that are poorly represented when using Malaise traps and other widely used field methods. To enhance the potential of this pipeline in ecological studies, efforts are needed to test its effectiveness and potential biases across habitat types and to extend the DNA barcode databases for important groups such as Diptera.
A 29-year retrospective analysis of koala rescues in New South Wales, Australia
Authors: Charalambous Renae , Narayan Edward J. 
Published: April 2020

AbstractThe koala (Phascolactos cinereus) is currently listed by both the IUCN and the Australian Governments’ Threatened Species Scientific Committee as vulnerable to extinction with a decreasing population trend. This listing can be attributed to climate change and its impact on ecosystems, and anthropomorphic environmental change due to extensive land clearing and habitat fragmentation. These have both been proven to induce stress, which influences the onset of disease. This novel study performed a retrospective analysis whereby records for 12,543 wild, rescued koalas in New South Wales (NSW), Australia were studied in order to determine trends in koala sightings, clinical admissions and injury diagnoses over a period of 29 years (1989-2018). Results indicated that between all three study locations (Port Stephens, Port Macquarie and Lismore), the most common reason koalas were admitted into care was because of disease, the most common disease diagnosed was signs of chlamydia, and the most common outcome for koalas admitted into care was released. At Port Stephens, mature and female koalas were diagnosed with a disease more than any other age or sex, while juvenile and male koalas were released (back into the wild) more than any other age or sex. Additionally, there were fewer koalas with a disease and fewer koalas released in Port Stephens as each year progressed. At Port Macquarie, mature and male koalas were diagnosed with a disease more than any other age or sex, while juvenile and female koalas were released more than any other age or sex. Additionally, there were more koalas with a disease and fewer koalas released in Port Macquarie as each year progressed. At Lismore, adult and female koalas were diagnosed with a disease more than any other age or sex, while joey and male koalas were released more than any other age or sex. Additionally, there were more koalas with a disease and fewer koalas released in Lismore as each year progressed. Determining trends in clinical admissions and diagnosis over such a substantial period of time is an important factor in preventing the continuing decline of koalas throughout Australia, and in particular NSW. It is important to note that there are cultural differences between koala rescue groups in the three study locations (Port Stephens, Port Macquarie and Lismore). These differences may be reflected in the outcomes of koala patients as each group are driven by their own management team. It is essential that any further decline of koala populations is prevented, however this can only be achieved through informed recommendations through research studies such as these. These recommendations should lead to government legislation which can provide stronger protection to koala habitat.
Regulations of expressions of rat/human sulfotransferases (SULTs) by anti-cancer drug, nolatrexed and micronutrients
Authors: Maiti Smarajit , MaitiDutta Sangita , Chen Guangping 
Published: April 2020

AbstractCancer is a disease related to cellular proliferative-state. Drastically increase in cell-cycle regulations augments cellular folate-pool and folate-metabolism. So, this pathway is targeted therapeutically. A number of drugs are involved in this metabolism i.e. folic-acid/folinic-acid/nolatrexed(NT)/ methotrexate(MTX) for the research and treatment of cancer. Our previous study showed that MTX significantly modulated rat/human SULTs. Present study was an attempt to study the effect of NT (widely used in different cancers) and these micronutrients on the expressions of rat/human SULTs. Male Sprague-Dawley rats were treated with NT (01,10 or 100 mg/Kg) or both sexes were treated to folic acid (100,200 or 400 mg/kg) for 2-weeks and their AST-IV (2-napthol sulfation) and STa (DHEA-sulfation) activities, protein-expression (Western-Blot) and mRNA-expression (RT-PCR) were tested. In cultured HepG2 cells NT (1nM-1.2mM) or folonic-acid (10nM-10μM) were applied for 10 days. Folic acid (0-10μM) was treated to human hepatocarcinoma (HepG2) cells. PPST (phenol-catalyzing), MPST (dopamine) DHEAST (dehydroepiandrosterone,DHEA) and EST (estradiol-sulfating) protein-expressions (Western-blot) were tested in all HepG2 study. Present results suggest NT significantly increased SULTs expressions in rat (protein/mRNA/activity) and HepG2 cells. Folic acid increased SULTs activity/protein in sex-dependant manner (ASTIV in female/ STa in male). Both folic and folinic acid increased several hSULTs isoforms with varied level of significance (least or no increase at highest-dose) in HepG2 cells pointing its dose-dependent multi-phasic responses. The clinical importance of this study may be furthered in the verification of sulfation-metabolism of several exogenous/endogenous molecules, drug-drug interaction and their influences on the patho-physiological processes. Further studies are necessary in this regard.
Syd/JIP3 Controls Tissue Size by Regulating Diap1 Protein Turnover Downstream of Yorkie/YAP
Authors: Ahmad Vakil , Vadla Gangadhar P. , Chabu Chiswili Y. 
Published: April 2020

AbstractHow organisms control organ size is not fully understood. We found that Syd/JIP3 is required for proper wing size inDrosophila.JIP3mutations are associated with organ size defects in mammals. The underlying mechanisms are not well understood. We discovered that Syd/JIP3 inhibition results in a downregulation of the inhibitor of apoptosis protein1 (Diap1) in theDrosophilawing. Correspondingly, Syd/JIP3 deficient tissues exhibit ectopic cell death and yield smaller wings. Syd/JIP3 inhibition generated similar effects in mammalian cells, indicating a conserved mechanism. We found that Yorkie/YAP stimulates Syd/JIP3 inDrosophilaand mammalian cells. Notably, Syd/JIP3 is required for the full effect of Yorkie-mediated tissue growth. Thus Syd/JIP3 regulation of Diap1 functions downstream of Yorkie/YAP to control growth.This study provides mechanistic insights into the recent and perplexing link betweenJIP3mutations and organ size defects in mammals, including in humans where de novoJIP3variants are associated with microcephaly.HighlightsSyd/JIP3 is required for properDrosophilawing sizeSyd/JIP3 stabilizes Diap1 to inhibit cell death inDrosophilaand in mammalian cellsActivation of Yorkie/YAP stimulates Syd/JIP3Yorkie-mediated tissue growth is highly sensitive to Syd/JIP3 dosage
Dual-level autoregulation of theE. coliDeaD RNA helicase via mRNA stability and Rho-dependent transcription termination
Authors: Ojha Sandeep , Jain Chaitanya 
Published: April 2020

ABSTRACTDEAD-box proteins (DBPs) are RNA remodeling factors associated with RNA helicase activity that are found in nearly all organisms. Despite extensive studies on the mechanisms used by DBPs to regulate RNA function, very little is known about how DBPs themselves are regulated. In this work, we have analyzed the expression and regulation of DeaD/CsdA, the largest of the DBPs inEscherichia coli(E. coli). We show thatdeaDtranscription initiates 838 nts upstream of the start of the coding region. We have also found that DeaD is autoregulated through a negative feedback mechanism that operates both at the level of mRNA stability and Rho-dependent transcription termination, and this regulation is dependent upon the 5’ untranslated region (5’ UTR). These findings suggest that DeaD might be regulating the conformation of its own mRNA through its RNA helicase activity to facilitate ribonuclease and Rho access to its 5’UTR.
In SilicoIdentification of Novel PrfA Inhibitors to Fight Listeriosis: A Virtual Screening and Molecular Dynamics Studies
Authors: Nizami Bilal , Tan Wen , Arias-Moreno Xabier 
Published: April 2020

AbstractListeria monocytogenesis considered to be one of the most dangerous foodborne pathogens as it can cause listeriosis, a life-threatening human disease. While the incidence of listeriosis is very low its fatality rate is exceptionally high. Because many multi-resistanceListeria monocytogenesstrains that do not respond to conventional antibiotic therapy have been recently described, development of new antimicrobials to fight listeriosis is necessary. The positive regulatory factor A (PrfA) is a key homodimeric transcription factor that modulates the transcription of multiple virulence factors which are ultimately responsible ofListeria monocytogenes’pathogenicity. In the present manuscript we describe several new potential PrfA inhibitors that were identified after performing ligand-based virtual screening followed by structure-based virtual screening against the wild-type PrfA structure. The three top-scored drug-likeness inhibitors bound to the wild-type PrfA structure were further assessed by Molecular Dynamics simulations. Besides, the three top-scored inhibitors were docked into a constitutive active apoPrfA mutant structure and the corresponding complexes were also simulated. According to the obtained data, PUBChem 87534955 (P875) and PUBChem 58473762 (P584) may not only bind and inhibit wild-type PrfA but the aforementioned apoPrfA mutant as well. Therefore, P875 and P584 might represent good starting points for the development of a completely new set of antimicrobial agents to treat listeriosis.
Reduction of Nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration
Authors: Tejwani Leon , Kokubu Hiroshi , Lee Paul J. , Xiang Yangfei , Luttik Kimberly , Soriano Armand , Yoon Jennifer , Park Junhyun , Ro Hannah , Ju Hyoungseok , Liao Clara , Tieze Sofia M. , Rigo Frank , Jafar-Nejad Paymaan , Lim Janghoo 
Published: April 2020

AbstractProtein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in TARDBP, encoding TDP-43, account for less than 1% of all ALS cases, TDP-43-positive aggregates are present in nearly all ALS patients, including patients with sporadic ALS (sALS) or carrying other familial ALS (fALS)-causing mutations. Interestingly, TDP-43 inclusions are also present in subsets of patients with frontotemporal dementia, Alzheimer’s disease, and Parkinson’s disease; therefore, methods of activating intracellular protein quality control machinery capable of clearing toxic cytoplasmic TDP-43 species may alleviate disease-related phenotypes. Here, we identify a novel function of Nemo-like kinase (Nlk) as a negative regulator of lysosome biogenesis. Genetic or pharmacological reduction of Nlk increased lysosome formation and improved clearance of aggregated TDP-43. Furthermore, Nlk reduction ameliorated pathological, behavioral, and lifespan deficits in two distinct mouse models of TDP-43 proteinopathy. Because many toxic proteins can be cleared along the autophagy-lysosome axis, targeted reduction of Nlk represents a viable approach to therapy development for multiple neurodegenerative disorders.
Shape Analysis of the Human Association Pathways
Authors: Yeh Fang-Cheng 
Published: April 2020

AbstractShape analysis has been widely used in digital image processing and computer vision, but they have not been utilized to compare the structural characteristics of the human association pathways. Here we used shape analysis to derive length, area, volume, and shape metrics from diffusion MRI tractography and utilized them to study the morphology of human association pathways. The reliability analysis showed that shape descriptors achieved moderate to good test-retest reliability. Further analysis on association pathways showed left dominance in the arcuate fasciculus, cingulum, uncinate fasciculus, frontal aslant tract, and right dominance in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The superior longitudinal fasciculus has a mixed lateralization profile with different metrics showing either left or right dominance. The analysis of between-subject variations shows that the overall layout of the association pathways does not variate a lot across subjects, as shown by low between-subject variation in length, span, diameter, and radius. In contrast, the area of the pathway innervation region has a considerable between-subject variation. A follow-up analysis is warranted to thoroughly investigate the nature of population variations and their structure-function correlation.
TRIP6 is required for tension at adherens junctions
Authors: Venkatramanan Srividya , Ibar Consuelo , Irvine Kenneth D. 
Published: April 2020

ABSTRACTHippo signaling mediates influences of cytoskeletal tension on organ growth. TRIP6 and LIMD1 have each been identified as being required for tension-dependent inhibition of the Hippo pathway LATS kinases and their recruitment to adherens junctions, but the relationship between TRIP6 and LIMD1 was unknown. Using siRNA-mediated gene knockdown we show that TRIP6 is required for LIMD1 localization to adherens junctions, whereas LIMD1 is not required for TRIP6 localization. TRIP6, but not LIMD1, is also required for recruitment of Vinculin and VASP to adherens junctions. Knockdown of TRIP6 or Vinculin, but not of LIMD1, also influences the localization of phosphorylated myosin light chain and F-actin. In TRIP6 knockdown cells actin stress fibers are lost apically but increased basally, and there is a corresponding increase in recruitment of Vinculin and VASP to basal focal adhesions. These observations identify a role for TRIP6 in organizing F-actin and maintaining tension at adherens junctions that could account for its influence on LIMD1 and LATS. They also suggest that focal adhesions and adherens junctions compete for key proteins needed to maintain attachments to contractile F-actin.
Targeting subtype-specific metabolic preferences in nucleotide biosynthesis inhibits tumor growth in a breast cancer model
Authors: Ogrodzinski Martin P. , Teoh Shao Thing , Lunt Sophia Y. 
Published: April 2020

AbstractInvestigating metabolic rewiring in cancer can lead to the discovery of new treatment strategies for breast cancer subtypes that currently lack targeted therapies. Using MMTV-Myc driven tumors to model breast cancer heterogeneity, we investigated metabolic differences between two histological subtypes, the epithelial-mesenchymal transition (EMT) and the papillary subtypes, using a combination of genomic and metabolomic techniques. We identified differences in nucleotide metabolism between EMT and papillary subtypes: EMT tumors preferentially use the nucleotide salvage pathway, while papillary tumors preferde novonucleotide biosynthesis. Using CRISPR/Cas9 gene editing and mass spectrometry-based methods, we determined that targeting the preferred pathway in each subtype resulted in greater metabolic impact than targeting the non-preferred pathway. We further show that knocking out the preferred nucleotide pathway in each subtype has a deleterious effect onin vivotumor growth. In contrast, knocking out the non-preferred pathway has a lesser effect or results in increased tumor growth.