bluuebunny/crossref_metadata_2025_split huggingface dataset:
A GO catalogue of human DNA-binding transcription factors
Authors: Lovering Ruth C. , Gaudet Pascale , Acencio Marcio L. , Ignatchenko Alex , Jolma Arttu , Fornes Oriol , Kuiper Martin , Kulakovskiy Ivan V. , Lægreid Astrid , Martin Maria J. , Logie Colin 
Published: October 2020

AbstractDNA-binding transcription factors recognise genomic addresses, specific sequence motifs in gene regulatory regions, to control gene transcription. A complete and reliable catalogue of all DNA-binding transcription factors is key to investigating the delicate balance of gene regulation in response to environmental and developmental stimuli. The need for such a catalogue of proteins is demonstrated by the many lists of DNA-binding transcription factors that have been produced over the past decade.The COST Action Gene Regulation Ensemble Effort for the Knowledge Commons (GREEKC) Consortium brought together experts in the field of transcription with the aim of providing high quality and interoperable gene regulatory data. The Gene Ontology (GO) Consortium provides strict definitions for gene product function, including factors that regulate transcription. The collaboration between the GREEKC and GO Consortia has enabled the application of those definitions to produce a new curated catalogue of human DNA-binding transcription factors, that can be accessed athttps://www.ebi.ac.uk/QuickGO/targetset/dbTF.In addition, this curation effort has led to the GO annotation of almost sixty thousand DNA-binding transcription factors in over a hundred species. Thus, this work will aid researchers investigating the regulation of transcription in both biomedical and basic science.
Production of HPV16 capsid proteins in suspension cultures of human epithelial cells
Authors: Sakauchi Dirce , Sasaki Erica Akemi Kavati , de Oliveira Bou Anni Fernanda , Cianciarullo Aurora Marques 
Published: October 2020

AbstractHuman papillomavirus (HPV) infection is a leading cause of morbidity and mortality in women worldwide. The virus is associated with benign warts and a broad spectrum of malignancies, including cervical cancer, considered a disease of high clinical relevance, especially in developing countries. In this study we developed the production of recombinant proteins HPV16 L1 and HPV16 L2 in human cells in suspension (293-F), which were transiently co-transfected with the pUF3/L1h and pUF3/L2h vectors. Expressions of recombinant HPV16 L1 and L2 capsid proteins was detected by laser scanning confocal microscopy and flow cytometry. Both proteins were identified intracellularly in the nucleus and cytoplasm of cells. The presence of these heterologous proteins and VLPs formation were detected by transmission electron microscopy (TEM) through colloidal gold immunolabeling and negative staining. Cell extracts containing recombinant proteins were purified by affinity chromatography and immunization of Balb/c mice with the formulation HPV16 L1/L2 VLPs containing adjuvant was able to induce higher titer of anti-HPV16 L1, when compared to HPV16 L2 antibodies by indirect ELISA assay. These data indicate that transient expression in 293-F cells was efficiently established. The results are promising for obtain recombinant proteins of the HPV capsid for future studies involving human papillomavirus, as well as to contribute for the development of other vaccine strategies for prevention against HPV.
High-human acuity of speed asymmetry during walking
Authors: Iturralde Pablo A. , Gonzalez-Rubio Marcela , Torres-Oviedo Gelsy 
Published: October 2020

1AbstractDespite its central role in the proper functioning of the motor system, sensation has been less studied than motor output in sensorimotor adaptation paradigms. This deficit is probably due to the difficulty of measuring sensation: while motor output has easily observable consequences, sensation is by definition an internal variable of the motor system. In this study we asked how well can subjects estimate relevant environmental changes inducing motor adaptation. We addressed this question in the context of walking on a split-belt treadmill, which allows subjects to experience distinct belt speeds for each leg. We used a two-alternative forced-choice perceptual task (2AFC) in which subjects report which belt they thought to be moving slower. We characterized baseline accuracy in this task for healthy human subjects, and found 75% accuracy for 75 mm/s speed differences. Additionally, we used a drift-diffusion model of the task that could account for both accuracy and reaction times. We conclude that 2AFC tasks can be used to probe subjects’ estimates of the environment and that this approach opens an avenue for investigating perceptual deficits and its relation to motor impairments in clinical populations.
Apical PAR complex proteins protect against epithelial assaults to create a continuous and functional intestinal lumen
Authors: Sallee Maria D. , Pickett Melissa A. , Feldman Jessica L. 
Published: October 2020

ABSTRACTSustained polarity and adhesion of epithelial cells is essential for the protection of our organs and bodies, and this epithelial integrity emerges during organ development amidst numerous morphogenetic assaults. Using the developingC. elegansintestine as anin vivomodel, we investigated how epithelial cells maintain integrity through cell division and elongation to build a functional tube. Live-imaging revealed that apical PAR complex proteins PAR-6/Par6 and PKC-3/aPkc remained apical during mitosis while apical microtubules and microtubule-organizing center (MTOC) proteins were transiently removed. Intestine-specific depletion of PAR-6, PKC-3, and the aPkc regulator CDC-42/Cdc42 caused persistent gaps in the apical MTOC as well as in other apical and junctional proteins after cell division and in non-dividing cells that elongated. Upon hatching, gaps coincided with luminal constrictions that blocked food, and larvae arrested and died. Thus, the apical PAR complex maintains apical and junctional continuity to construct a functional intestinal tube.
Propofol Anesthesia Concentration Rather Than Abrupt Behavioral Unresponsiveness Linearly Degrades Responses in the Rat Primary Auditory Cortex
Authors: Bergman Lottem , Krom Aaron J , Sela Yaniv , Marmelshtein Amit , Hayat Hanna , Regev Noa , Nir Yuval 
Published: October 2020

AbstractDespite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration vs. behavioral unresponsiveness, since these are typically confounded. Here, we employed slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural EEG, and neuronal spiking activity in the primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, post-onset neuronal silence duration, and late-locking to 40Hz click-trains, gradually deteriorated in a dose- dependent manner with increasing anesthesia levels without showing abrupt changes around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences.
Waffle Method: A general and flexible approach for improving throughput in FIB-milling
Authors: Kelley Kotaro , Raczkowski Ashleigh M. , Klykov Oleg , Jaroenlak Pattana , Bobe Daija , Kopylov Mykhailo , Eng Edward T. , Bhabha Gira , Potter Clinton S. , Carragher Bridget , Noble Alex J. 
Published: October 2020

AbstractCryo-FIB/SEM combined with cryo-ET has emerged from within the field of cryo-EM as the method for obtaining the highest resolution structural information of complex biological samplesin-situin native and non-native environments. However, challenges remain in conventional cryo-FIB/SEM workflows, including milling thick specimens that do not vitrify well, specimens with preferred orientation, low-throughput when milling small and/or low concentration specimens, and cellular specimens that distribute poorly across grid squares. Here we present a general approach we call the ‘Waffle Method’ which leverages high-pressure freezing to address these challenges. We illustrate the mitigation of these challenges by applying the Waffle Method and cryo-ET to reveal the macrostructure of the polar tube in microsporidian spores in multiple complementary orientations, which was previously not possible due to preferred orientation of the spores on the grid. We demonstrate the broadness of the Waffle Method by applying it to three additional cellular samples and a single particle sample using a variety of cryo-FIB-milling hardware, with both manual and automated approaches. We also present a unique and critical stress-relief gap designed specifically for waffled lamellae. Additionally, we describe applications of the Waffle Method which are currently being explored. We propose the Waffle Method as a way to achieve many of the advantages of cryo-liftout on the specimen grid while avoiding the long, challenging, and technically-demanding process required for cryo-liftout.
IFN-λ4 may contribute to HCV persistence by increasing ER stress and enhancing IRF1 signaling
Authors: Onabajo Olusegun O. , Wang Fang , Lee Mei-Hsuan , Florez-Vargas Oscar , Obajemu Adeola , Castro Mauro A. A. , Tanikawa Chizu , Vargas Joselin , Liao Shu-Fen , Song Ci , Huang Yu-Han , Shen Chen-Yang , Banday A. Rouf , O’Brien Thomas R. , Hu Zhibin , Matsuda Koichi , Robertson A. Gordon , Prokunina-Olsson Ludmila 
Published: October 2020

ABSTRACTChronic hepatitis C virus (HCV) infection and cirrhosis are major risk factors for developing hepatocellular carcinoma (HCC). Genetic polymorphisms in theIFNL3/IFNL4locus have been associated both with impaired clearance of HCV and protection from liver fibrosis, an early stage of cirrhosis. Here, we aimed to address the genetic and functional relationships betweenIFNL3/IFNL4polymorphisms, HCV-related cirrhosis, and HCC risk. We evaluated associations betweenIFNL4genotype, defined as the presence of rs368234815-dG or rs12979860-T alleles, with cirrhosis and HCC risk in patients with chronic HCV - 2,931 from Taiwan and 3,566 from Japan. We detected associations betweenIFNL4genotype and decreased risk of cirrhosis (OR=0.66, 95%CI=0.46-0.93, P=0.018, in Taiwan), but increased risk of HCC (OR=1.28, 95%CI=1.07-1.52, P=0.0058, in Japan).In-vitro, IFN-λ4 expression increased ER stress, and enhanced positive regulation of IFN responses via IRF1 induction, which mediated antiproliferative effects in hepatic cells. Our data present novel IFN-λ4-associated pathways that may be contributing to HCV persistence and development of HCC.
Live-dead assay on unlabeled cells using phase imaging with computational specificity
Authors: Hu Chenfei , He Shenghua , Lee Young Jae , He Yuchen , Kong Edward M. , Li Hua , Anastasio Mark A. , Popescu Gabriel 
Published: October 2020

AbstractExisting approaches to evaluate cell viability involve cell staining with chemical reagents. However, this step of exogenous staining makes these methods undesirable for rapid, nondestructive and long-term investigation. Here, we present instantaneous viability assessment ofunlabeledcells using phase imaging with computation specificity (PICS). This new concept utilizes deep learning techniques to compute viability markers associated with the specimen measured by label-free quantitative phase imaging. Demonstrated on different live cell cultures, the proposed method reports approximately 95% accuracy in identifying live and dead cells. The evolution of the cell dry mass and projected area for the labelled and unlabeled populations reveal that the viability reagents decrease viability. The nondestructive approach presented here may find a broad range of applications, from monitoring the production of biopharmaceuticals, to assessing the effectiveness of cancer treatments.
A novel family of secreted insect proteins linked to plant gall development
Authors: Korgaonkar Aishwarya , Han Clair , Lemire Andrew L. , Siwanowicz Igor , Bennouna Djawed , Kopec Rachel , Andolfatto Peter , Shigenobu Shuji , Stern David L. 
Published: October 2020

AbstractIn an elaborate form of inter-species exploitation, many insects hijack plant development to induce novel plant organs called galls that provide the insect with a source of nutrition and a temporary home. Galls result from dramatic reprogramming of plant cell biology driven by insect molecules, but the roles of specific insect molecules in gall development have not yet been determined. Here we study the aphidHormaphis cornu, which makes distinctive “cone” galls on leaves of witch hazelHamamelis virginiana. We found that derived genetic variants in the aphid genedeterminant of gall color(dgc) are associated with strong downregulation ofdgctranscription in aphid salivary glands, upregulation in galls of seven genes involved in anthocyanin synthesis, and deposition of two red anthocyanins in galls. We hypothesize that aphids inject DGC protein into galls, and that this results in differential expression of a small number of plant genes.Dgcis a member of a large, diverse family of novel predicted secreted proteins characterized by a pair of widely spaced cysteine-tyrosine-cysteine (CYC) residues, which we named BICYCLE proteins.Bicyclegenes are most strongly expressed in the salivary glands specifically of galling aphid generations, suggesting that they may regulate many aspects of gall development.Bicyclegenes have experienced unusually frequent diversifying selection, consistent with their potential role controlling gall development in a molecular arms race between aphids and their host plants.One Sentence SummaryAphidbicyclegenes, which encode diverse secreted proteins, contribute to plant gall development.
Detecting Insulitis in Type 1 Diabetes with Ultrasound Phase-change Contrast Agents
Authors: Ramirez David G. , Upadhyay Awaneesh K. , Pham Vinh T. , Ciccaglione Mark , Borden Mark A , Benninger Richard K.P. 
Published: October 2020

AbstractType 1 diabetes (T1D) results from immune infiltration and destruction of insulin-producing β-cells within the pancreatic islets of Langerhans (insulitis), resulting in loss of glucose homeostasis. Early diagnosis during pre-symptomatic T1D would allow for therapeutic intervention prior to substantial loss of β-cell mass at T1D onset. There are limited methods to track the progression of insulitis and β-cell mass decline in pre-symptomatic T1D. During insulitis, the islet microvasculature increases permeability, such that sub-micron sized particles can extravasate and accumulate within the islet microenvironment. Ultrasound is a widely deployable and cost-effective clinical imaging modality. However, conventional microbubble contrast agents are restricted to the vasculature. Sub-micron sized nanodroplet (ND) phasechange agents can be vaporized into micron-sized bubbles; serving as a circulating microbubble precursor. We tested if NDs extravasate into the immune-infiltrated islet microenvironment. We performed ultrasound contrast-imaging following ND infusion in NOD mice and NOD;Rag1ko controls, and tracked diabetes development. We measured the biodistribution of fluorescently labeled NDs, with histological analysis of insulitis. Ultrasound contrast signal was elevated in the pancreas of 10w NOD mice following ND infusion and vaporization, but was absent in both the non-infiltrated kidney of NOD mice and pancreas of Rag1ko controls. High contrast elevation also correlated with rapid diabetes onset. In pancreata of NOD mice, infiltrated islets and nearby exocrine tissue were selectively labeled with fluorescent NDs. Thus, contrast ultrasound imaging with ND phase-change agents can detect insulitis prior to diabetes onset. This will be important for monitoring disease progression to guide and assess preventative therapeutic interventions for T1D.SignificanceThere is a need for imaging methods to detect type1 diabetes (T1D) progression prior to clinical diagnosis. T1D is a chronic disease that results from autoreactive T cells infiltrating the islet of Langerhans and destroying insulin-producing β-cells. Overt disease takes years to present and is only diagnosed after significant β-cells loss. As such, the possibility of therapeutic intervention to preserve β-cell mass is hampered by an inability to follow pre-symptomatic T1D progression. There are immunotherapies that can delay T1D development. However identifying ‘at risk’ individuals, and tracking whether therapeutic interventions are impacting disease progression, prior to T1D onset, is lacking. A method to detect insulitis and β-cell mass decline would present an opportunity to guide therapeutic treatments to prevent T1D.
ViMIC: A Database of Human Disease-related Virus Mutations, Integration Sites and Cis-effects
Authors: Wang Ying , Tong Yuantao , Zhang Zeyu , Zheng Rongbin , Huang Danqi , Yang Jinxuan , Zong Hui , Tan Fanglin , Zhang Xiaoyan 
Published: October 2020

ABSTRACTMolecular mechanisms of virus-related diseases involve multiple factors, including viral mutation accumulation and integration of a viral genome into the host DNA. With increasing attention being paid to virus-mediated pathogenesis and the development of many useful technologies to identify virus mutations (VMs) and viral integration sites (VISs), abundant literatures on these topics are available in PubMed. However, knowledge of VMs and VISs is widely scattered in numerous published papers, and the association of VMs with VISs in the viral genome or the functional annotation of VISs still lacks integration and curation. To address these challenges, we built a database of human disease-related Virus Mutations, Integration sites and Cis-effects (ViMIC), which specialize in three features: virus mutation sites, viral integration sites and target genes. In total, the ViMIC provides information on 6,461 VMs, 79,089 VISs, and 15,056 viral target genes of 8 viruses in 65 human diseases obtained from literatures. Furthermore, in ViMIC, users are allowed to explore the cis-effects of virus-host interactions by surveying 78 histone modifications, binding of 1,358 transcription regulators, and chromatin accessibility on these VISs. We believe ViMIC will become a valuable resource for the virus research community. The database is available at http://bmtongji.cn/ViMIC/index.php.
HEXOKINASE1 interferes with cytokinin synthesis and strigolactone perception during sugar-induced shoot branching
Authors: Barbier Francois F. , Cao Da , Fichtner Franziska , Weiste Christoph , Perez-Garcia Maria-Dolores , Caradeuc Mathieu , Le gourrierec José , Sakr Soulaiman , Beveridge Christine A. 
Published: October 2020

ABSTRACT-Plant architecture is controlled by several endogenous signals including hormones and sugars. However, only little is known about the nature and roles of the sugar signalling pathways in this process. Here we test whether the sugar pathway mediated by HEXOKINASE1 (HXK1) is involved in the control of shoot branching.-To test the involvement of HXK1 in the control of shoot architecture we modulated the HXK1 pathway using physiological and genetic approaches in diverse plants, rose, arabidopsis and pea and evaluated impacts of hormonal pathways.-We show that triggering a hexokinase-dependent pathway was able to promote bud outgrowth in pea and rose. In arabidopsis, both HXK1 deficiency and defoliation led to decreased shoot branching and conferred hypersensitivity to auxin.HXK1expression was positively correlated with sugar availability. HXK1-deficient plants displayed decreased cytokinin levels and increased expression ofMAX2which is required for strigolactone signalling. The branching phenotype of HXK1-deficient plants could be partly restored by cytokinin treatment and strigolactone deficiency could override the negative impact ofHXK1deficiency on shoot branching.-Our observations demonstrate that a HXK1-dependent pathway contributes to the regulation of shoot branching and interact with hormones to modulate plant architecture.
Dynamical consequences of regional heterogeneity in the brain’s transcriptional landscape
Authors: Deco Gustavo , Aquino Kevin , Arnatkevičiūtė Aurina , Oldham Stuart , Sabaroedin Kristina , Rogasch Nigel C. , Kringelbach Morten L. , Fornito Alex 
Published: October 2020

AbstractBrain regions vary in their molecular and cellular composition, but how this heterogeneity shapes neuronal dynamics is unclear. Here, we investigate the dynamical consequences of regional heterogeneity using a biophysical model of whole-brain functional magnetic resonance imaging (MRI) dynamics in humans. We show that models in which transcriptional variations in excitatory and inhibitory receptor (E:I) gene expression constrain regional heterogeneity more accurately reproduce the spatiotemporal structure of empirical functional connectivity estimates than do models constrained by global gene expression profiles and MRI-derived estimates of myeloarchitecture. We further show that regional heterogeneity is essential for yielding both ignition-like dynamics, which are thought to support conscious processing, and a wide variance of regional activity timescales, which supports a broad dynamical range. We thus identify a key role for E:I heterogeneity in generating complex neuronal dynamics and demonstrate the viability of using transcriptional data to constrain models of large-scale brain function.
An embryonic zebrafish model to screen disruption of gut-vascular-barriers upon exposure to ambient ultrafine particles
Authors: Baek Kyung In , Qian Yi , Chang Chih-Chiang , O’Donnell Ryan , Soleimanian Ehsan , Sioutas Constantinos , Li Rongsong , Hsiai Tzung K. 
Published: October 2020

AbstractEpidemiological studies have linked exposure to ambient particulate matter (PM) with gastrointestinal (GI) diseases. Ambient ultrafine particle (UFP) are the redox-active sub-fraction of PM2.5, harboring elemental and polycyclic aromatic hydrocarbons from urban environmental sources including diesel and gasoline exhausts. The gut vascular barrier (GVB) regulates paracellular trafficking and systemic disseminations of ingested microbes and toxins. Here, we posit that acute UFP ingestion disrupts the integrity of the intestinal barrier by modulating intestinal Notch activation. Using zebrafish embryos, we performed micro-gavage with the FITC-conjugated dextran (FD10, 10 kDa) to assess the disruption of GVB integrity upon UFP exposure. Following micro-gavage, FD10 retained in the embryonic GI system, migrated through the cloaca. Conversely, co-gavaging UFP increased transmigration of FD10 across the intestinal barrier, and FD10 fluorescence occurred in the venous capillary plexus. Ingestion of UFP further impaired the mid-intestine morphology. We performed micro-angiogram of FD10 to corroborate acute UFP-mediated disruption of GVB. Transient genetic and pharmacologic manipulations of global Notch activity suggested Notch regulation of the GVB. Overall, our integration of a genetically tractable embryonic zebrafish and micro-gavage technique provided epigenetic insights underlying ambient UFP ingestion disrupts the GVB.Graphic Abstract