bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique features of Plasmids among different Citrobacter species
Authors: Sanmukh Swapnil , Paunikar Waman 
Published: July 2019

AbstractThe Citrobacter plasmids are supposed to represent the host genetic association within the living bacterial cell. The plasmids impart various beneficial characteristics to the host, helping it to retain suitable characteristics for adaptation as well as evolution. The study aims at understanding the role of prophage in influencing host functional characteristics by horizontal gene transfer or as whole plasmids. The Citrobacter plasmid can be understood by analyzing many hypothetical protein sequences within its genome. Our study included 82 hypothetical proteins in 5 Citrobacter plasmids genomes. The function predictions in 31 hypothetical proteins and 3-D structures were predicted for 11 protein sequences using PS2 server. The probable function prediction was done by using Bioinformatics web tools like CDD-BLAST, INTERPROSCAN, PFAM and COGs by searching sequence databases for the presence of orthologous enzymatic conserved domains in the hypothetical sequences. This study identified many uncharacterized proteins, whose roles are yet to be discovered in Citrobacter plasmids. These results for unknown proteins within plasmids can be used in linking the genetic interactions of Citrobacter species and their functions in different environmental conditions.
Beyond the fuzzy lock-and-key: spontaneous symmetry shifts and glycan/lectin logic gates
Authors: Wallace Rodrick 
Published: July 2019

AbstractChanges in the molecular topology of glycan/lectin interaction may explain observed reaction punctuation driven by experimental gradients in reactant concentration. Adoption of a 'biological renormalization' perspective from statistical physics for the analysis of such phase transitions suggests, in marked contrast to conventional physical systems, a broad spectrum of possible universality class behaviors. This spectrum may, in typical perverse biological manner, be of central scientific interest. Generalization, via formalism abducted from coevolutionary theory, suggests that glycan/lectin molecular switches instantiate logic gates that may be as sophisticated as those characterizing basic neural process, if on a different scale.
Trichoderma pseudokoningii Rifai isolation from Egyptian immunocompromised cattle with Mycobacterium bovis infection
Authors: Torky Helmy , Khalifa Eman 
Published: July 2019

AbstractRecently, Trichoderma species have emerged as potent fungal pathogens in immunocompromised humans. We report the first three cases of Trichoderma pseudokoningii Rifai pulmonary infection in the Egyptian tuberculous dairy cattle with Mycobacterium bovis, from the heart of a generalized bovine TB in a cow over 5 years old, a mediastinal lymph node of pulmonary TB in a cow of 3 years old, and a lung of mixed pulmonary and digestive BTB in a cow of 4 years old. We have also developed a pathogenisity test technique for Trichoderma pseudokoningii Rifai infection in 3 G. pigs by intraperitoneal injection of 2 G. pigs with mixed infection of Mycobacterium bovis and Trichoderma pseudokoningii Rifai; death of both animals 14 days, thereafter, and by injection of 1 G. pig with single infection of Trichoderma pseudokoningii Rifai; death of animal 21 days, thereafter. We did not report any animal case along review of literature.
Inference of population splits and mixtures from genome-wide allele frequency data
Authors: Pickrell Joseph , Pritchard Jonathan 
Published: July 2019

AbstractMany aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In this model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication, and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and ``ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at "http://treemix.googlecode.com":http://treemix.googlecode.com.
Translational neuroscience requires better design and analysis of preclinical studies
Authors: Lazic Stanley 
Published: July 2019

AbstractAnimal models are often used to obtain a better understanding of psychiatric, neurodegenerative, and neurodevelopmental disorders. Despite many years of research, these models have not led to many novel therapies or treatments. Translating results between species will always be difficult, and it is argued that inappropriate statistical analyses, failure to identify the experimental unit, lack of random assignment to treatment conditions, and unblinded assessment of outcomes contribute to the low rate of translating preclinical in vivo studies into successful therapies. It is known that these shortcomings can generate biased estimates, too many false positives and false negatives, and unreproducible results. These issues have been raised repeatedly, but have largely gone unheeded by scientists. Two recommendations are made to improve the situation.
Using causal models to distinguish between neurogenesis-dependent and -independent effects on behaviour
Authors: Lazic Stanley 
Published: July 2019

AbstractThere has been a substantial amount of research on the relationship between hippocampal neurogenesis and behaviour over the past fifteen years, but the causal role that new neurons have on cognitive and affective behavioural tasks is still far from clear. This is partly due to the difficulty of manipulating levels of neurogenesis without inducing off-target effects, which might also influence behaviour. In addition, the analytical methods typically used do not directly test whether neurogenesis mediates the effect of an intervention on behaviour. Previous studies may have incorrectly attributed changes in behavioural performance to neurogenesis because the role of known (or unknown) neurogenesis-independent mechanisms were not formally taken into consideration during the analysis. Causal models can tease apart complex causal relationships and were used to demonstrate that the effect of exercise on pattern separation is via neurogenesis-independent mechanisms. Many studies in the neurogenesis literature would benefit from the use of statistical methods that can separate neurogenesis-dependent from neurogenesis-independent effects on behaviour.
HTRIdb: an open-access database for experimentally verified human transcriptional regulation interactions
Authors: Bovolenta Luiz , Acencio Marcio , Lemke Ney 
Published: July 2019

Abstract
Background:
The modeling of interactions among transcription factors (TFs) and their respective target genes (TGs) into transcriptional regulatory networks is important for the complete understanding of regulation of biological processes. In the case of human TF-TG interactions, there is no database at present that explicitly provides such information even though many databases containing human TF-TG interaction data have been available. In an effort to provide researchers with a repository of TF-TG interactions from which such interactions can be directly extracted, we present here the Human Transcriptional Regulation Interactions database (HTRIdb).Description: The HTRIdb is an open-access database of experimentally validated interactions among human TFs and their TGs. HTRIdb can be searched via a user-friendly web interface and the retrieved TF-TG interactions data and the associated protein-protein interactions can be downloaded or interactively visualized as a network using the Cytoscape Web software. Moreover, users can improve the database quality by uploading their own interactions and indicating inconsistencies in the data. So far, HTRIdb has been populated with 283 TFs that regulate 11886 genes, totaling 18160 TF-TG interactions. HTRIdb is freely available at http://www.lbbc.ibb.unesp.br/htri.

Conclusions:
HTRIdb is a powerful user-friendly tool from which human experimentally validated TF-TG interactions can be easily extracted and used to construct transcriptional regulation interaction networks enabling researchers to decipher the regulation of biological processes.
A potential diagnostic biomarker: Proteasome LMP2/b1i-differential expression in human uterus neoplasm
Authors: Hayashi Takuma , Horiuchi Akiko , Aburatani Hiroyuki , Yaegashi Nobuo , Tonegawa Susumu , Konishi Ikuo 
Published: July 2019

AbstractUterine leiomyosarcoma (ULMS) develops more often in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of uterine ULMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Importantly, a diagnostic-biomarker which distinguishes malignant ULMS from benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine ULMS, to establish a treatment method. Proteasome low-molecular mass polypeptide 2(LMP2)/b1i-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. We found LMP2/b1i expression to be absent in human LMS, but present in human LMA. Therefore, defective-LMP2/b1i expression may be one of the risk factors for ULMS. LMP2/b1i is a potential diagnostic-biomarker for uterine ULMS, and may be a targeted-molecule for a new therapeutic approach.
A unified mechanistic model of niche, neutrality and violation of the competitive exclusion principle
Authors: Kalmykov Lev , Kalmykov Vyacheslav 
Published: July 2019

AbstractThe origin of species richness is one of the most widely discussed questions in ecology. The absence of unified mechanistic model of competition makes difficult our deep understanding of this subject. Here we show such a two-species competition model that unifies (i) a mechanistic niche model, (ii) a mechanistic neutral (null) model and (iii) a mechanistic violation of the competitive exclusion principle. Our model is an individual-based cellular automaton. We demonstrate how two trophically identical and aggressively propagating species can stably coexist in one stable homogeneous habitat without any trade-offs in spite of their 10% difference in fitness. Competitive exclusion occurs if the fitness difference is significant (approximately more than 30%). If the species have one and the same fitness they stably coexist and have similar numbers. We conclude that this model shows diffusion-like and half-soliton-like mechanisms of interactions of colliding population waves. The revealed mechanisms eliminate the existing contradictions between ideas of niche, neutrality and cases of violation of the competitive exclusion principle.
Fundamental Principles of Neural Organization of Cognition
Authors: Perlovsky Leonid 
Published: July 2019

AbstractThe manuscript advances a hypothesis that there are few fundamental principles of neural organization of cognition, which explain several wide areas of the cognitive functioning. We summarize the fundamental principles, experimental, theoretical, and modeling evidence for these principles, relate them to hypothetical neural mechanisms, and made a number of predictions. We consider cognitive functioning including concepts, emotions, drives-instincts, learning, “higher” cognitive functions of language, interaction of language and cognition, role of emotions in this interaction, the beautiful, sublime, and music. Among mechanisms of behavior we concentrate on internal actions in the brain, learning and decision making. A number of predictions are made, some of which have been previously formulated and experimentally confirmed, and a number of new predictions are made that can be experimentally tested. Is it possible to explain a significant part of workings of the mind from a few basic principles, similar to how Newton explained motions of planets? This manuscript summarizes a part of contemporary knowledge toward this goal.
Complex Systems Analysis of Arrested Neural Cell Differentiation during Development and Analogous Cell Cycling Models in Carcinogenesis
Authors: Baianu I , Prisecaru V. 
Published: July 2019

AbstractA new approach to the modular, complex systems analysis of nonlinear dynamics of arrested neural cell Differentiation--induced cell proliferation during organismic development and the analogous cell cycling network transformations involved in carcinogenesis is proposed. Neural tissue arrested differentiation that induces cell proliferation during perturbed development and Carcinogenesis are complex processes that involve dynamically inter-connected biomolecules in the intercellular, membrane, cytosolic, nuclear and nucleolar compartments. Such 'dynamically inter-connected' biomolecules form numerous inter-related pathways referred to as 'molecular networks'. One such family of signaling pathways contains the cell cyclins. Cyclins are proteins that link several critical pro-apoptotic and other cell cycling/division components, including the tumor suppressor gene TP53 and its product, the Thomsen-Friedenreich antigen (T antigen), Rb, mdm2, c-Myc, p21, p27, Bax, Bad and Bcl-2, which play major roles in various neoplastic transformations of many tissues.The novel theoretical analysis presented here is based on recently published studies of arrested cell differentiation that normally leads to neural system formation during early developmental stages; the perturbed development may involve cyclin signaling and cell cycling responsible for rapidly induced cell proliferation without differentiation into neural cells in such experimental studies.
A MEMS ultrasound stimulation system for modulation of neural circuits with high spatial resolution in vitro
Authors: Lee Jungpyo , Ko Kyungmin , Shin Hyogeun , Oh Soo-Jin , Lee C. Justin , Chou Namsun , Choi Nakwon , Tack Oh Min , Chul Lee Byung , Chan Jun Seong , Cho Il-Joo 
Published: July 2019

AbstractNeuromodulation by ultrasound has recently received attention due to its noninvasive stimulation capability for treating brain diseases. Although there have been several studies related to ultrasonic neuromodulation, these studies have suffered from poor spatial resolution of the ultrasound and low repeatability with a fixed condition caused by conventional and commercialized ultrasound transducers. In addition, the underlying physics and mechanisms of ultrasonic neuromodulation are still unknown. To determine these mechanisms and accurately modulate neural circuits, researchers must have a precisely controllable ultrasound transducer to conduct experiments at the cellular level. Herein, we introduce a new MEMS ultrasound stimulation system for modulating neurons or brain slices with high spatial resolution. The piezoelectric micromachined ultrasonic transducers (pMUTs) with small membranes (sub-mm membranes) generate enough power to stimulate neurons and enable precise modulation of neural circuits. We designed the ultrasound transducer as an array structure to enable localized modulation in the target region. In addition, we integrated a cell culture chamber with the system to make it compatible with conventional cell-based experiments, such as in vitro cell cultures and brain slices. In this work, we successfully demonstrated the functionality of the system by showing that the number of responding cells is proportional to the acoustic intensity of the applied ultrasound. We also demonstrated localized stimulation capability with high spatial resolution by conducting experiments in which cocultured cells responded only around a working transducer.
Development of a delayed-release nutrient for appetite control in adults with obesity and type 2 diabetes and initial clinical testing in a single dose randomized controlled trial
Authors: Beale E. , Lim E. , Yassine H. , Azen C. , Christopher C. 
Published: July 2019

Abstract
Background and objectives
Delivery of nutrients directly to the small intestine, either via enteral feeding tube or by gastric bypass surgery, is associated with increased levels of appetite-suppressing and glucoregulatory hormones, including GLP-1, and reduced appetite. Achieving these changes non-invasively using formulated foods may be of therapeutic benefit in individuals with obesity and related comorbidities. The aim of this pilot study was to determine the effect of a single dose of a novel delayed-release nutrient (DRN) on glucose, GLP-1, c-peptide, insulin, and appetite in adults with obesity and type 2 diabetes.

Subjects and methods
We formulated an all-natural, generally recognized as safe (‘GRAS”) DRN and conducted a randomized prospective crossover trial. Nineteen adults with obesity and type 2 diabetes underwent paired 3-h meal tolerance tests (MTT) in randomized order 1–4 weeks apart. Subjects ingested a single dose of DRN and the same nutrients as unformulated powders (UN).

Results
For DRN compared with UN, the maximal concentration (Cmax) was significantly lower for glucose, c-peptide, and insulin, and the time of maximal concentration (Tmax) was significantly delayed. While Tmax for GLP-1 was also significantly delayed following DRN compared with UN (45 min later; p = 0.26), Cmax did not differ significantly. GLP-1 rose significantly during the last 90 min of the 3-h MTT (β1 = 0.16 pg/mL/min, p = 0.025), while following UN it decreased (β1 = −0.21 pg/mL/min, p = 0.0026) (p difference = 0.0003). There were minimal differences in seven measures of appetite and adverse symptoms between DRN and UN.

Conclusions
We conclude that nutrient can be formulated using all-natural ingredients to induce a delayed rise in GLP-1. Further testing is needed to determine the amount and site of nutrient release, when maximum GLP-1 levels occur, and if modification of the formulation specifications and dose are associated with appetite and glucose control.
Clinical update on head and neck cancer: molecular biology and ongoing challenges
Authors: Alsahafi Elham , Begg Katheryn , Amelio Ivano , Raulf Nina , Lucarelli Philippe , Sauter Thomas , Tavassoli Mahvash 
Published: July 2019

AbstractHead and neck squamous cell carcinomas (HNSCCs) are an aggressive, genetically complex and difficult to treat group of cancers. In lieu of truly effective targeted therapies, surgery and radiotherapy represent the primary treatment options for most patients. But these treatments are associated with significant morbidity and a reduction in quality of life. Resistance to both radiotherapy and the only available targeted therapy, and subsequent relapse are common. Research has therefore focussed on identifying biomarkers to stratify patients into clinically meaningful groups and to develop more effective targeted therapies. However, as we are now discovering, the poor response to therapy and aggressive nature of HNSCCs is not only affected by the complex alterations in intracellular signalling pathways but is also heavily influenced by the behaviour of the extracellular microenvironment. The HNSCC tumour landscape is an environment permissive of these tumours’ aggressive nature, fostered by the actions of the immune system, the response to tumour hypoxia and the influence of the microbiome. Solving these challenges now rests on expanding our knowledge of these areas, in parallel with a greater understanding of the molecular biology of HNSCC subtypes. This update aims to build on our earlier 2014 review by bringing up to date our understanding of the molecular biology of HNSCCs and provide insights into areas of ongoing research and perspectives for the future.
Association of imputed prostate cancer transcriptome with disease risk reveals novel mechanisms
Authors: Emami Nima C. , Kachuri Linda , Meyers Travis J. , Das Rajdeep , Hoffman Joshua D. , Hoffmann Thomas J. , Hu Donglei , Shan Jun , Feng Felix Y. , Ziv Elad , Van Den Eeden Stephen K. , Witte John S. 
Published: July 2019

AbstractHere we train cis-regulatory models of prostate tissue gene expression and impute expression transcriptome-wide for 233,955 European ancestry men (14,616 prostate cancer (PrCa) cases, 219,339 controls) from two large cohorts. Among 12,014 genes evaluated in the UK Biobank, we identify 38 associated with PrCa, many replicating in the Kaiser Permanente RPGEH. We report the association of elevated TMPRSS2 expression with increased PrCa risk (independent of a previously-reported risk variant) and with increased tumoral expression of the TMPRSS2:ERG fusion-oncogene in The Cancer Genome Atlas, suggesting a novel germline-somatic interaction mechanism. Three novel genes, HOXA4, KLK1, and TIMM23, additionally replicate in the RPGEH cohort. Furthermore, 4 genes, MSMB, NCOA4, PCAT1, and PPP1R14A, are associated with PrCa in a trans-ethnic meta-analysis (N = 9117). Many genes exhibit evidence for allele-specific transcriptional activation by PrCa master-regulators (including androgen receptor) in Position Weight Matrix, Chip-Seq, and Hi-C experimental data, suggesting common regulatory mechanisms for the associated genes.
Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis
Authors: Serwas Nina K. , Hoeger Birgit , Ardy Rico C. , Stulz Sigrun V. , Sui Zhenhua , Memaran Nima , Meeths Marie , Krolo Ana , Yüce Petronczki Özlem , Pfajfer Laurène , Hou Tie Z. , Halliday Neil , Santos-Valente Elisangela , Kalinichenko Artem , Kennedy Alan , Mace Emily M. , Mukherjee Malini , Tesi Bianca , Schrempf Anna , Pickl Winfried F. , Loizou Joanna I. , Kain Renate , Bidmon-Fliegenschnee Bettina , Schickel Jean-Nicolas , Glauzy Salomé , Huemer Jakob , Garncarz Wojciech , Salzer Elisabeth , Pierides Iro , Bilic Ivan , Thiel Jens , Priftakis Peter , Banerjee Pinaki P. , Förster-Waldl Elisabeth , Medgyesi David , Huber Wolf-Dietrich , Orange Jordan S. , Meffre Eric , Sansom David M. , Bryceson Yenan T. , Altman Amnon , Boztug Kaan 
Published: July 2019

AbstractImmune responses need to be controlled tightly to prevent autoimmune diseases, yet underlying molecular mechanisms remain partially understood. Here, we identify biallelic mutations in three patients from two unrelated families indifferentially expressed in FDCP6 homolog (DEF6)as the molecular cause of an inborn error of immunity with systemic autoimmunity. Patient T cells exhibit impaired regulation of CTLA-4 surface trafficking associated with reduced functional CTLA-4 availability, which is replicated inDEF6-knockout Jurkat cells. Mechanistically, we identify the small GTPase RAB11 as an interactor of the guanine nucleotide exchange factor DEF6, and find disrupted binding of mutant DEF6 to RAB11 as well as reduced RAB11+CTLA-4+vesicles inDEF6-mutated cells. One of the patients has been treated with CTLA-4-Ig and achieved sustained remission. Collectively, we uncover DEF6 as player in immune homeostasis ensuring availability of the checkpoint protein CTLA-4 at T-cell surface, identifying a potential target for autoimmune and/or cancer therapy.