bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Staphylococcal Superantigens and their association among bacteremic and Infective Endocarditis patients in Egypt
Authors: Elsherif Heba M. , Helal Zeinab H. , El-Ansary Mona R. , Fahmy Zeinab A. , Eltayeb Wafaa N. , Radwan Sahar , Aboshanab Khaled M. 
Published: February 2020

AbstractAimInfective endocarditis (IE) is a major complication ofStaphylococcus (S.) aureusinfection in humans particularly those with bacteremia. AlthoughStaphylococcusspecies are commensal on or in different parts of the human body, it is also known to be a serious pathogen causing bacteremia and sepsis that could lead to IE. Therefore, our aim was to assess the prevalence as well as phenotypic and genotypic association of the Staphylococcal superantigens (SAgs) among bacteremic and IE patients.MethodsThis study was conducted onStaphylococcusisolates recovered from bacteremic and IE patients. The isolates were screened phenotypically for the detection of SAgs including Staphylococcal enterotoxins (SEs) and toxic shock syndrome toxin-1 (TSST-1). Molecular detection and analysis ofsea, seb, sec, sed, seeand tsst-1, the major SAgs coding genes were performed using PCR and agarose gel electrophoresis, respectively. The obtained findings were statistically analyzed using standard methods.ResultsDetection of SAgs using ELISA revealed that 12 (46%) isolates were positive for enterotoxin production. However, the PCR revealed that 19 (73%) isolates were positive for enterotoxin genes with the highest prevalence of theseagene (79%), followed by theseb(63%), tsst-1 (21%). The least frequent gene was thesed(5.3%). Accordingly, phenotypic and genotypic screening for prevalence of SAgs among Staphylococcal isolates showed significant difference(P value=0.046703), however, no significant correlation could be observed among the coagulase negative Staphylococci (CoNS) isolates (Pvalue=0.248213). Statistical correlations between bacteremic and IE isolates with respect to prevalence of SAgs, showed no significant difference (P-value = 0.139, Effect size = 0.572) indicating no specific association between any of the detected SAgs and IE.Conclusionno significant difference has been found between Staphylococcal IE and bacteremia isolates regarding both phenotypic and genotypic detection of the most commonly SAgs. Therefore, all Staphylococcal bacteremic patients are suspected for IE. Also, future work should be conducted for analysis of SAgs gene expression.
Twist, Snail, and Sox9 form an allosterically regulated complex, the EMTosome, on a bipartite E-box site
Authors: McCracken Daniel S , Peng Hongzhuang , Ayyanathan Kasirajan , Jiang Yike Lindy , Welsh Sarah , Yang Jing , Kennedy Eileen , Rauscher Frank J. , Gardini Alessandro , Rauscher Frank J 
Published: February 2020

AbstractEpithelial-Mesenchymal transition (EMT) of primary tumor cells is a critical trans-differentiation event that contributes to dissemination and metastasis. The process of EMT is controlled by specific DNA-binding transcription factors (TFs) that reprogram the tumor transcriptome. In particular, the canonical EMT-TFs Twist and Snail can induce an EMT program when overexpressed in cancer cells, and both are found upregulated in metastatic cancers. Twist and Snail bind DNA directly, by recognition to variants of the E-Box sequence CANNTG. However, it is unclear how this binding is regulated. We have used a biochemical approach to dissect DNA binding and protein-protein interactions that occur amongst these proteins. We find that Twist preferentially recognizes a dyad repeat of E-boxes that are not directly bound by Snail. Our data suggest that Twist use its WR domain to recruit Snail into a binding complex through the Snail zinc-finger motifs. We analyzed Twist-Snail complexes in the breast carcinoma cell line SUM1315 and found evidence that it contains an additional protein partner, Sox9. Notably, we report that a native Twist complex can be displaced from its dyad binding site by consensus DNA binding sites for Snail and Sox9 even though these proteins do not contact the Twist dyad site. Taken together, our findings suggest that Snail and Sox9 interact with Twist to regulate its DNA binding ability via protein-protein interactions, thereby allosterically regulating Twist DNA binding. We designate this ternary complex EMTosome. These results may inform efforts to therapeutically target the EMT program in order to target cancer metastasis.
A genome engineering resource to uncover principles of cellular organization and tissue architecture by lipid signalling
Authors: Trivedi Deepti , CM Vinitha , Bisht Karishma , Janardan Vishnu , Pandit Awadhesh , Basak Bishal , Raghu Padinjat 
Published: February 2020

SummaryPhosphoinositides (PI) are key regulators of cellular organization in eukaryotes and genes that tune PI signalling are implicated in human disease mechanisms. Biochemical analyses and studies in cultured cells have identified a large number of proteins that can mediate PI signalling. However, the role of such proteins in regulating cellular processesin vivoand development in metazoans remains to be understood. Here we describe a set of CRISPR based genome engineering tools that allow the manipulation of each of these proteins with spatial and temporal control during metazoan development. We demonstrate the use of these reagents to deplete a set of 103 proteins individually in theDrosophilaeye and identify several new molecules that control eye development. Our work demonstrates the power of this resource in uncovering the molecular basis of tissue homeostasis during normal development and in human disease biology.
Sharp tuning of head direction by somatosensory fast-spiking interneurons
Authors: Long Xiaoyang , Young Calvin K. , Zhang Sheng-Jia 
Published: February 2020

AbstractHead direction (HD) information is intricately linked to spatial navigation and cognition. We recently reported the co-existence of all currently recognized spatial cell types can be found in the hindlimb primary somatosensory cortex (S1HL). In this study, we carried out an in-depth characterization of HD cells in S1HL. We show fast-spiking (FS), putative inhibitory neurons are over-represented in and sharply tuned to HD compared to regular-spiking (RS), putative excitatory neurons. These FS HD cells are non-conjunctive, rarely theta modulated, not locally connected and are enriched in layer 4/5a. Their co-existence with RS HD cells and angular head velocity (AHV) cells in a layer-specific fashion through the S1HL presents a previously unreported organization of spatial circuits. These findings challenge the notion that FS, putative inhibitory interneurons are weakly tuned to external stimuli in general and present a novel local network configuration not reported in other parts of the brain.
A Bayesian Generative Model of Vestibular Afferent Neuron Spiking
Authors: Paulin Michael , Pullar Kiri , Hoffman Larry 
Published: February 2020

AbstractUsing an information criterion to evaluate models fitted to spike train data from chinchilla semicircular canal afferent neurons, we found that the superficially complex functional organization of the canal nerve branch can be accurately quantified in an elegant mathematical model with only three free parameters. Spontaneous spike trains are samples from stationary renewal processes whose interval distributions are Exwald distributions, convolutions of Inverse Gaussian and Exponential distributions. We show that a neuronal membrane compartment is a natural computer for calculating parameter likelihoods given samples from a point process with such a distribution, which may facilitate fast, accurate, efficient Bayesian neural computation for estimating the kinematic state of the head. The model suggests that Bayesian neural computation is an aspect of a more general principle that has driven the evolution of nervous system design, the energy efficiency of biological information processing.Significance StatementNervous systems ought to have evolved to be Bayesian, because Bayesian inference allows statistically optimal evidence-based decisions and actions. A variety of circumstantial evidence suggests that animal nervous systems are indeed capable of Bayesian inference, but it is unclear how they could do this. We have identified a simple, accurate generative model of vestibular semicircular canal afferent neuron spike trains. If the brain is a Bayesian observer and a Bayes-optimal decision maker, then the initial stage of processing vestibular information must be to compute the posterior density of head kinematic state given sense data of this form. The model suggests how neurons could do this. Head kinematic state estimation given point-process inertial data is a well-defined dynamical inference problem whose solution formed a foundation for vertebrate brain evolution. The new model provides a foundation for developing realistic, testable spiking neuron models of dynamical state estimation in the vestibulo-cerebellum, and other parts of the Bayesian brain.
Forecasting the Wuhan coronavirus (2019-nCoV) epidemics using a simple (simplistic) model
Authors: Hermanowicz Slav W. 
Published: February 2020

Abstract and FindingsConfirmed infection cases in mainland China were analyzed using the data up to January 28, 2020 (first13 daysof reliable confirmed cases). In addition, all available data up to February 3 were processed the same way. For the first period the cumulative number of cases followed an exponential function. However, from January 28, we discerned a downward deviation from the exponential growth. This slower-than-exponential growth was also confirmed by a steady decline of the effective reproduction number. A backtrend analysis suggested the original basic reproduction numberR0to be about 2.4 – 2.5. We used a simple logistic growth model that fitted very well withalldatareported until the time of writing. Using this model and the first set of data, we estimate thatthe maximum caseswill be about 21,000 reaching this level in mid-February. Using all available data the maximum number of cases is somewhat higher at 29,000 but its dynamics does not change. These predictions do not account for any possible other secondary sources of infection.
Assessing spread risk of Wuhan novel coronavirus within and beyond China, January-April 2020: a travel network-based modelling study
Authors: Lai Shengjie , Bogoch Isaac I. , Ruktanonchai Nick W , Watts Alexander , Lu Xin , Yang Weizhong , Yu Hongjie , Khan Kamran , Tatem Andrew J 
Published: February 2020

AbstractBackgroundA novel coronavirus (2019-nCoV) emerged in Wuhan City, China, at the end of 2019 and has caused an outbreak of human-to-human transmission with a Public Health Emergency of International Concern declared by the World Health Organization on January 30, 2020.AimWe aimed to estimate the potential risk and geographic range of Wuhan novel coronavirus (2019-nCoV) spread within and beyond China from January through to April, 2020.MethodsA series of domestic and international travel network-based connectivity and risk analyses were performed, by using de-identified and aggregated mobile phone data, air passenger itinerary data, and case reports.ResultsThe cordon sanitaire of Wuhan is likely to have occurred during the latter stages of peak population numbers leaving the city before Lunar New Year (LNY), with travellers departing into neighbouring cities and other megacities in China. We estimated that 59,912 air passengers, of which 834 (95% UI: 478 - 1349) had 2019-nCoV infection, travelled from Wuhan to 382 cities outside of mainland China during the two weeks prior to Wuhan’s lockdown. The majority of these cities were in Asia, but major hubs in Europe, the US and Australia were also prominent, with strong correlation seen between predicted importation risks and reported cases. Because significant spread has already occurred, a large number of airline travellers (3.3 million under the scenario of 75% travel reduction from normal volumes) may be required to be screened at origin high-risk cities in China and destinations across the globe for the following three months of February to April, 2020 to effectively limit spread beyond its current extent.ConclusionFurther spread of 2019-nCoV within China and international exportation is likely to occur. All countries, especially vulnerable regions, should be prepared for efforts to contain the 2019-nCoV infection.
A novel mutation inKCNK16causing a gain-of-function in the TALK-1 potassium channel: a new cause of maturity onset diabetes of the young
Authors: Graff Sarah M , Johnson Stephanie R , Leo Paul J , Dadi Prasanna K , Nakhe Arya Y , McInerney-Leo Aideen M , Marshall Mhairi , Brown Matthew A , Jacobson David A , Duncan Emma L 
Published: February 2020

ABSTRACTBackgroundMaturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders of impaired glucose-stimulated insulin secretion (GSIS). Mechanisms include β-cell KATPchannel dysfunction (e.g.,KCNJ11(MODY13) orABCC8(MODY12) mutations); however, no other β-cell channelopathies have been identified in MODY.MethodsA four-generation family with autosomal dominant non-obese, non-ketotic antibody-negative diabetes, without mutations in known MODY genes, underwent exome sequencing. Whole-cell and single-channel K+currents, Ca2+handling, and GSIS were determined in cells expressing either mutated or wild-type (WT) protein.ResultsWe identified a novel non-synonymous genetic mutation inKCNK16(NM_001135105: c.341T>C, p.Leu114Pro) segregating with MODY.KCNK16is the most abundant and β-cell-restricted K+channel transcript and encodes the two-pore-domain K+channel TALK-1. Whole-cell K+currents in transfected HEK293 cells demonstrated drastic (312-fold increase) gain-of-function with TALK-1 Leu144Pro vs. WT, due to greater single channel activity. Glucose-stimulated cytosolic Ca2+influx was inhibited in mouse islets expressing TALK-1 Leu114Pro (area under the curve [AUC] at 20mM glucose: Leu114Pro 60.1 vs. WT 89.1;P=0.030) and less endoplasmic reticulum calcium storage (cyclopiazonic acid-induced release AUC: Leu114Pro 17.5 vs. WT 46.8;P=0.008). TALK-1 Leu114Pro significantly blunted GSIS compared to TALK-1 WT in both mouse (52% decrease,P=0.039) and human (38% decrease,P=0.019) islets.ConclusionsOur data identify a novel MODY-associated gene,KCNK16; with a gain-of-function mutation limiting Ca2+influx and GSIS. A gain-of-function common polymorphism inKCNK16is associated with type 2 diabetes (T2DM); thus, our findings have therapeutic implications not only forKCNK16-associated MODY but also for T2DM.
Methylome-based cell-of-origin modeling (Methyl-COOM) identifies aberrant expression of immune regulatory molecules in CLL
Authors: Wierzbinska Justyna A. , Toth Reka , Ishaque Naveed , Rippe Karsten , Mallm Jan-Philipp , Klett Lara , Mertens Daniel , Zenz Thorsten , Hielscher Thomas , Seifert Marc , Küppers Ralf , Assenov Yassen , Lutsik Pavlo , Stilgenbauer Stephan , Roessner Philipp M. , Seiffert Martina , Byrd John , Oakes Christopher C. , Plass Christoph , Lipka Daniel B. 
Published: February 2020

ABSTRACTBackgroundIn cancer, normal epigenetic patterns are disturbed and contribute to gene expression changes, disease onset and progression. The cancer epigenome is composed of the epigenetic patterns present in the tumor-initiating cell at the time of transformation, and the tumor-specific epigenetic alterations that are acquired during tumor initiation and progression. The precise dissection of these two components of the tumor epigenome will facilitate a better understanding of the biological mechanisms underlying malignant transformation. Chronic lymphocytic leukemia (CLL) originates from differentiating B cells, which undergo extensive epigenetic programming. This poses the challenge to precisely determine the epigenomic ground-state of the cell-of-origin in order to identify CLL-specific epigenetic aberrations.MethodsWe developed a linear regression model, methylome-based cell-of-origin modeling (Methyl-COOM), to map the cell-of-origin for individual CLL patients based on the continuum of epigenomic changes during normal B cell differentiation.ResultsMethyl-COOM accurately maps the cell-of-origin of CLL and identifies CLL-specific aberrant DNA methylation events that are not confounded by physiologic epigenetic B cell programming. Furthermore, Methyl-COOM unmasks abnormal action of transcription factors, altered super-enhancer activities, and aberrant transcript expression in CLL. Among the aberrantly regulated transcripts were many genes that have previously been implicated in T cell biology. Flow cytometry analysis of these markers confirmed their aberrant expression on malignant B cells at the protein level.ConclusionsMethyl-COOM analysis of CLL identified disease-specific aberrant gene regulation. The aberrantly expressed genes identified in this study might play a role in immune-evasion in CLL and might serve as novel targets for immunotherapy approaches. In summary, we propose a novel framework forin silicomodeling of reference DNA methylomes and for the identification of cancer-specific epigenetic changes, a concept that can be broadly applied to other human malignancies.
Florigen family chromatin recruitment, competition and target genes
Authors: Zhu Yang , Klasfeld Samantha , Jeong Cheol Woong , Jin Run , Goto Koji , Yamaguchi Nobutoshi , Wagner Doris 
Published: February 2020

AbstractPlants monitor seasonal cues, such as day-length, to optimize life history traits including onset of reproduction and inflorescence architecture1–3. Florigen family transcriptional co-regulators TERMINAL FLOWER 1 (TFL1) and FLOWERING LOCUS T (FT) antagonistically regulate these vital processes4–6yet how TFL1 and FT execute their roles and what the mechanism is for their antagonism remains poorly understood. We show genome-wide, that TFL1 is recruited to the chromatin by the bZIP transcription factor FLOWERING LOCUS D (FD) inArabidopsis. We find that seasonal cue-mediated upregulation of FT competes TFL1 from chromatin-bound FD at key target loci. We identify the master regulator of floral fate,LEAFY(LFY) as a target under dual opposite regulation by TFL1 and FT. Exonic bZIP motifs inLFYare critical for repression by TFL1, upregulation by FT and adoption of floral fate. Transcriptomic identification of target genes directly repressed by the TFL1-FD complex not only identifies key regulators of onset of reproduction and floral fate, but reveals that TFL1-FD repress sugar and hormone signalling pathways and chromatin regulators. Our data provide mechanistic insight into how florigen family member sculpt inflorescence architecture, a trait important for reproductive success and yield.
Small heat shock proteins determine synapse number and neuronal activity during development
Authors: de los Reyes Teresa , Santana Elena , Casas-Tintó Sergio 
Published: February 2020

AbstractEnvironmental changes cause stress, Reactive Oxygen Species and unfolded protein accumulation which hamper synaptic activity and trigger cell death. Heat shock proteins (HSPs) assist protein refolding to maintain proteostasis and cellular integrity. Mechanisms regulating the activity of HSPs include transcription factors and posttranslational modifications that ensure a rapid response. HSPs preserve synaptic function in the nervous system upon environmental insults or pathological factors and contribute to the coupling between environmental cues and neuron control of development. We have performed a biased screening inDrosophilamelanogastersearching for synaptogenic modulators among HSPs during development. We explore the role of two small-HSPs (sHSPs), sHSP23 and sHSP26 in synaptogenesis and neuronal activity. Both sHSPs immunoprecipitate together and the equilibrium between both chaperones is required for neuronal development and activity. The molecular mechanism controlling HSP23 and HSP26 accumulation in neurons relies on a novel gene (CG1561), which we namePinkman(pkm). We propose that sHSPs and Pkm are targets to modulate the impact of stress in neurons and to prevent synapse loss.
Molecular characterization of differences between the tomato immune receptors Fls3 and Fls2
Authors: Roberts Robyn , Liu Alexander E. , Wan Lingwei , Geiger Annie M. , Hind Sarah R. , Rosli Hernan G. , Martin Gregory B. 
Published: February 2020

AbstractPlants mount defense responses by recognizing indications of pathogen invasion, including microbe-associated molecular patterns (MAMPs). Flagellin from the bacterial pathogenPseudomonas syringaepv. tomato (Pst) contains two MAMPs, flg22 and flgII-28, that are recognized by tomato receptors Flagellin sensing 2 (Fls2) and Flagellin sensing 3 (Fls3), respectively. It is unknown to what degree each receptor contributes to immunity and if they promote immune responses using the same molecular mechanisms. Characterization of CRISPR/Cas9-generatedFls2andFls3tomato mutants revealed that the two receptors contribute equally to disease resistance both on the leaf surface and in the apoplast. However, striking differences were observed in certain host responses mediated by the two receptors. Compared to Fls2, Fls3 mediated a more sustained production of reactive oxygen species (ROS) and an increase in transcript abundance of 44 tomato genes, with two genes serving as reporters for Fls3. Fls3 had greaterin vitrokinase activity and interacted differently with thePsteffector AvrPtoB as compared to Fls2. Using chimeric Fls2/Fls3 proteins, we found that no receptor domain was solely responsible for the Fls3 sustained ROS, suggesting involvement of multiple structural features. This work reveals differences in the immunity outputs between Fls2 and Fls3, suggesting they use distinct molecular mechanisms to activate pattern-triggered immunity in response to flagellin-derived MAMPs.
Progesterone shapes medial temporal lobe volume across the human menstrual cycle
Authors: Taylor Caitlin M. , Pritschet Laura , Olsen Rosanna , Layher Evan , Santander Tyler , Grafton Scott T. , Jacobs Emily G. 
Published: February 2020

AbstractThe rhythmic production of sex steroid hormones is a central feature of the mammalian endocrine system. In rodents and nonhuman primates, sex hormones are powerful regulators of hippocampal subfield morphology. However, it remains unknown whether intrinsic fluctuations in sex hormones alter hippocampal morphology in the human brain. In a series of dense-sampling studies, we used high-resolution imaging of the medial temporal lobe (MTL) to determine whether endogenous fluctuations (Study 1) and exogenous manipulation (Study 2) of sex hormones alter MTL volume over time. Across the menstrual cycle, intrinsic fluctuations in progesterone were associated with volumetric changes in CA2/3, entorhinal, perirhinal, and parahippocampal cortex. Chronic progesterone suppression abolished these cycle-dependent effects and led to pronounced volumetric changes in entorhinal cortex and CA2/3 relative to freely cycling conditions. No associations with estradiol were observed. These results establish progesterone’s ability to rapidly and dynamically shape MTL morphology across the human menstrual cycle.HighlightsSex hormones are powerful regulators of hippocampal plasticity in mammals.The impact of hormone fluctuations on hippocampal morphology in humans is unknown.High resolution imaging of the MTL was conducted across two 30-day periods.Progesterone dynamically shapes MTL volume across the human menstrual cycle.Chronic progesterone suppression abolishes cycle-dependent changes.