bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exposure to Zika and chikungunya viruses impacts aspects of the vectorial capacity ofAedes aegyptiandCulex quinquefasciatus
Authors: Crespo Mônica , Guedes Duschinka , Paiva Marcelo , Sobral Mariana , Helvecio Elisama , Alves Rafael , Tadeu George , Oliveira Claudia , Melo-Santos Maria Alice Varjal , Barbosa Rosângela , Ayres Constância 
Published: February 2023

AbstractZika (ZIKV) and chikungunya (CHIKV) are arboviruses that cause infections in humans and can causeclinical complications, representing a worldwide public health problem.Aedes aegyptiis the primary vector of these pathogens andCulex quinquefasciatusmay be a potential ZIKV vector. This study aimed to evaluate fecundity, fertility, survival, longevity, and blood feeding activity inAe. aegyptiafter exposure to ZIKV and CHIKV and, inCx. quinquefasciatusexposed to ZIKV.Three colonies were evaluated: AeCamp(Ae. aegypti -field),RecL (Ae. aegypti -laboratory)and CqSLab (Cx. quinquefasciatus -laboratory). Seven to 10 days-old females from these colonies were exposed to artificial blood feeding with CHIKV or ZIKV. CHIKV caused reduction in fecundity and fertilityinthe natural population, AeCamp and reduction in survival and fertility in RecL.ZIKV impacted survival in RecL, fertility in AeCamp. and fecundity and fertility in CqSLab. Both viruses had no effect on blood feeding activity. These results show that CHIKV produces a higher biological cost inAe. aegypti, compared to ZIKV, and ZIKV differently alters the biological performance in colonies ofAe. aegyptiandCx. quinquefasciatus. These results provide a better understanding over the processes of virus-vector interaction and can shed light on the complexity of arbovirus transmission.
Neurovascular coupling conversely modulates emotion
Authors: Ruan Jiayu , Quan Xinghua , Zhang Yiyi , Xie Huiqi , Zhang Dongdong , Wang Wentao , Zhao Bingrui , Lu Danping , Jia Jie-Min 
Published: February 2023

SummaryEmotion induces changes in regional cerebral blood flow (rCBF), a manifestation of neurovascular coupling (NVC). However, whether rCBF changes during NVC might, in turn, influence emotion is unclear. Here, by establishing arteriolar-optogenetic control of rCBF in free-moving mice, we demonstrate rCBF changes themselves induce emotional changes, and NVC actively modulates emotion. NVC deficiency impairs emotional flexibility, leading to contextually inappropriate emotional rigidity. Conversely, enhancing NVC counteracts this rigidity. To categorize inappropriate responses, we developed a predictive platform based on neural-activity patterns of the basolateral amygdala (BLA) in the mice exposed to a range of contexts. This platform revealed that NVC deficiency leads to BLA activations in a bipolar form, whereby predicting context-dependent hyper-reactivity and hypo-reactivity. Notably, this prediction was verified by actual physiological and behavioral responses. Mechanistically, neuronal mechanosensory receptor Piezo2 is essential for NVC-modulated emotion flexibility. Our findings establish NVC as an allostatic program for shaping emotion flexibility.
A multi-omics integrative approach unravels novel genes and pathways associated with senescence escape after targeted therapy in NRAS mutant melanoma
Authors: Gureghian Vincent , Herbst Hailee , Kozar Ines , Mihajlovic Katarina , Malod-Dognin Noël , Ceddia Gaia , Angeli Cristian , Margue Christiane , Randic Tijana , Philippidou Demetra , Tetsi Nomigni Milène , Hemedan Ahmed , Tranchevent Leon-Charles , Longworth Joseph , Bauer Mark , Badkas Apurva , Gaigneaux Anthoula , Muller Arnaud , Ostaszewski Marek , Tolle Fabrice , Pržulj Nataša , Kreis Stephanie 
Published: February 2023

AbstractTherapy Induced Senescence (TIS) leads to sustained growth arrest of cancer cells. The associated cytostasis has been shown to be reversible and cells escaping senescence further enhance the aggressiveness of cancers. Together with targeted therapeutics, senolytics, specifically targeting senescent cancer cells, constitute a promising avenue for improved cancer treatments. Understanding how cancer cells evade senescence is needed to optimise the clinical benefits of this therapeutic approach. Here we characterised the response of three different NRAS mutant melanoma cell lines to a combination of CDK4/6 and MEK inhibitors over 33 days. Transcriptomic data show that all cell lines trigger a senescence programme coupled with strong induction of interferons. Kinome profiling revealed the activation of Receptor Tyrosine Kinases (RTKs) and enriched downstream signaling of neurotrophin, ErbB and insulin pathways. Characterisation of the miRNA interactome associates miR-211-5p with resistant phenotypes. Finally, iCELL-based integration of bulk and single-cell RNA-seq data identified biological processes perturbed during senescence, and predicts new genes involved in its escape. Overall, our data associate insulin signaling with persistence of a senescent phenotype and suggest a new role for interferon gamma in senescence escape through the induction of EMT and the activation of ERK5 signaling.
Systematic Nature Positive Markets
Authors: Bush Alex , Simpson Katherine , Hanley Nick 
Published: February 2023

AbstractDespite decades of global commitments, and increasingly urgent warning of environmental instability, the demand for land to support economic production is still increasing. Isolated and disorganized actions will not be enough to avert ecosystem failures. As many developers are already required to compensate for their ecological impacts through restoration, many see markets trading biodiversity credits as a financial mechanism to counteract degradation and drive investment in conservation. The challenge stems from a desire to recognize the multidimensional nature of biodiversity that contributes to ecosystem integrity without making suitable offsets intractable to supply. Instead, most regulators have opted to streamline ecological assessment, and undermine ecological rigour, in favour of promoting offset supply and economic efficiency. As a result, all evidence suggests offset trading programs have so far failed to mitigate losses, let alone support “nature positive” outcomes. To overcome this disconnect, and support more effective and equitable biodiversity markets, we propose credits be defined by theirreplaceabilityof a site, a metric long-established in the domain of systematic conservation planning. Irreplaceability avoids the limitations of like-for-like trading, reduces costs of offsetting to developers and society, ensures farmers willing to sell are fairly rewarded for loss of earnings, and that sites critical to achieving conservation goals are safeguarded. We developed an ecological-economic model of a biodiversity offset market to demonstrate irreplaceability guarantees no net loss of biodiversity and is the most efficient metric for guiding investment toward the recovery of Nature.
Cell-type deconvolution of bulk RNA-Seq from kidney using opensource bioinformatic tools
Authors: Riojas Angelica M. , Spradling-Reeves Kimberly D. , Christensen Clinton L. , Hall-Ursone Shannan , Cox Laura A. 
Published: February 2023

AbstractTraditional bulk RNA-Seq pipelines do not assess cell-type composition within heterogeneous tissues. Therefore, it is difficult to determine whether conflicting findings among samples or datasets are the result of biological differences or technical differences due to variation in sample collections. This report provides a user-friendly, open source method to assess cell-type composition in bulk RNA-Seq datasets for heterogeneous tissues using published single cell (sc)RNA-Seq data as a reference. As an example, we apply the method to analysis of kidney cortex bulk RNA-Seq data from female (N=8) and male (N=9) baboons to assess whether observed transcriptome sex differences are biological or technical, i.e., variation due to ultrasound guided biopsy collections. We found cell-type composition was not statistically different in female versus male transcriptomes based on expression of 274 kidney cell-type specific transcripts, indicating differences in gene expression are not due to sampling differences. This method of cell-type composition analysis is recommended for providing rigor in analysis of bulk RNA-Seq datasets from complex tissues. It is clear that with reduced costs, more analyses will be done using scRNA-Seq; however, the approach described here is relevant for data mining and meta analyses of the thousands of bulk RNA-Seq data archived in the NCBI GEO public database.Author SummaryThis method, which provides a simple method for assessing sampling biases in bulk RNA-Seq datasets with evaluation of cell-type composition, will aid researchers in assessing whether bulk RNA-Seq from different studies of the same heterogeneous tissue are comparable. The additional layer of information can help determine if differential gene expression observed is biological or technical, i.e., cell composition variation among study samples. The described method uses publicly available bioinformatics resources and does not require coding expertise or high-capacity computational processing. Development of tools accessible to scientists without computing expertise will contribute to greater rigor and reproducibility for bioinformatic analyses of transcriptome data.
Rab7 dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis
Authors: Gaur Preksha , Rajendran Yesheswini , Srivastava Bhagyashree , Markandey Manasvini , Fishbain-Yoskovitz Vered , Mohapatra Gayatree , Suhail Aamir , Chaudhary Shikha , Tyagi Shaifali , Yadav Subhash C , Pandey Amit K , Merbl Yifat , Bajaj Avinash , Ahuja Vineet , Srikanth Chittur V 
Published: February 2023

AbstractInflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier coupled with microbial dysbiosis has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis.In vivoRab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease Chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7 dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.
High-gamma activity is coupled to low-gamma oscillations in precentral cortices and modulates with movement and speech
Authors: Nie Jeffrey Z. , Flint Robert D. , Prakash Prashanth , Hsieh Jason K. , Mugler Emily M. , Tate Matthew C. , Rosenow Joshua M. , Slutzky Marc W. 
Published: February 2023

AbstractPlanning and executing motor behaviors requires coordinated neural activity among multiple cortical and subcortical regions of the brain. Phase-amplitude coupling between the high-gamma band amplitude and the phase of low frequency oscillations (theta, alpha, beta) has been proposed to reflect neural communication, as has synchronization of low-gamma oscillations. However, coupling between low-gamma and high-gamma bands has not been investigated. Here, we measured phase-amplitude coupling between low- and high-gamma in monkeys performing a reaching task and in humans either performing finger movements or speaking words aloud. We found significant coupling between low-gamma phase and high-gamma amplitude in multiple sensorimotor and premotor cortices of both species during all tasks. This coupling modulated with the onset of movement. These findings suggest that interactions between the low and high gamma bands are markers of network dynamics related to movement and speech generation.
A non-canonical Hippo pathway represses the expression of ΔNp63
Authors: Low-Calle Ana Maria , Ghoneima Hana , Ortega Nicholas , Cuibus Adriana M. , Katz Chen , Tong David , Prives Carol , Prywes Ron 
Published: February 2023

AbstractThe p63 transcription factor, a member of the p53 family, plays an oncogenic role in squamous cancers, while in breast cancers its expression is often repressed. In the canonical conserved Hippo pathway, known to play a complex role in regulating growth of cancer cells, the protein kinases MST1/2 and LATS1/2 act sequentially to phosphorylate and inhibit the YAP/TAZ transcription factors. We found that in the MCF10A mammary epithelial cell line as well as in squamous and breast cancer cell lines, expression of ΔNp63 RNA and protein is strongly repressed by inhibition of the Hippo pathway protein kinases in a manner that is independent of p53. While MST1/2 and LATS1 are required for p63 expression, the next step of the pathway, namely phosphorylation and degradation of the YAP/TAZ transcriptional activators is not required for repression of p63. This suggests that regulation of p63 expression occurs by a non-canonical version of the Hippo pathway. We additionally identified additional genes that were similarly regulated suggesting the broader importance of this pathway. Interestingly, we observed that experimentally lowering p63 expression leads to increased YAP protein levels, thereby constituting a feedback loop. These results, which reveal the intersection of the Hippo and p63 pathways, may prove useful for the control of their activities in cancer cells.One Sentence SummaryRegulation of p63 expression occurs by a non-canonical version of the Hippo pathway in mammary epithelial, breast carcinoma and head and neck squamous carcinoma cells
Comparative membrane proteomics reveals diverse cell regulators concentrated at the nuclear envelope
Authors: Cheng Li-Chun , Zhang Xi , Baboo Sabyasachi , Nguyen Julie A , Martinez-Bartolomé Salvador , Loose Esther , Diedrich Jolene , Yates John R , Gerace Larry 
Published: February 2023

AbstractThe nuclear envelope (NE) is a subdomain of the ER with prominent roles in nuclear organization, largely mediated by its distinctive protein composition. We developed methods to reveal novel, low abundance transmembrane (TM) proteins concentrated at the NE relative to the peripheral ER. Using label-free proteomics that compared isolated NEs to cytoplasmic membranes, we first identified proteins with apparent NE enrichment. In subsequent authentication, ectopically expressed candidates were analyzed by immunofluorescence microscopy to quantify their targeting to the NE in cultured cells. Ten proteins from a validation set were found to associate preferentially with the NE, including oxidoreductases, enzymes for lipid biosynthesis and regulators of cell growth and survival. We determined that one of the validated candidates, the palmitoyltransferase Zdhhc6, modifies the NE oxidoreductase Tmx4 and thereby modulates its NE levels. This provides a functional rationale for the NE concentration of Zdhhc6. Overall, our methodology has revealed a group of previously unrecognized proteins concentrated at the NE and additional candidates. Future analysis of these can potentially unveil new mechanistic pathways associated with the NE.
Laurasian legacies in the Gondwanan tree fern order Cyatheales
Authors: Ramírez-Barahona Santiago 
Published: February 2023

AbstractPresent-day geographic and phylogentic patterns often reflect the Gondwana–Laurasia separation and subsequent history of continental drift. However, some lineages show non-overlapping fossil distributions relative to extant species and in some cases extant ‘Gondwanan’ lineages have ‘Laurasian’ extinct relatives. Here, I combined distribution data for 101 fossils and 442 extant species of tree ferns (Cyatheales) to reconstruct their biogeographic history over the last 220 million years. The time calibrated tree showed most tree ferns families originating during the Jurassic and the onset of crown group diversification beginning during the Cretaceous; a major shift in diversification rates occurred in the largest tree fern family (Cyatheaceae) that comprises ~90% of extant diversity in the group. Biogeographical reconstructions based on extant distributions alone supported a Gondwanan origin for the group; the most probable ancestral range encompassed Australasia and South America. Alternatively, incorporating fossil distribution data into reconstructions showed a Laurasian origin and a most probable ancestral range in Eurasia. These results evince the Laurasian legacies of the Cyatheales spanning the Triassic–Cretaceous, which otherwise remain hidden from biogeographic inferences. These results show that extant-only biogeographic analyses are limited when fossils distribution are more wide spread than in the present-day, highlighting the need to directly incorporate fossils into biogeographical analyses and improve the reliability of ancestral geographic range estimation.
Gene regulatory dynamics during craniofacial development in a carnivorous marsupial
Authors: Cook Laura E. , Feigin Charles Y. , Hills John , Vespasiani Davide M. , Pask Andrew J. , Gallego Romero Irene 
Published: February 2023

AbstractMarsupials and placental mammals exhibit significant differences in reproductive and life history strategies. Marsupials are born highly underdeveloped after an extremely short period of gestation, leading to prioritization of the development of structures critical for post-birth survival in the pouch. Critically, they must undergo accelerated development of the oro-facial region compared to placentals. Previously we described the accelerated development of the oro-facial region in the carnivorous Australian marsupial, the fat-tailed dunnartSminthopsis crassicaudatathat has one of the shortest gestations of any mammal. By combining genome comparisons of the mouse and dunnart with functional data for the enhancer-associated chromatin modifications, H3K4me3 and H3K27ac, we investigated divergence of craniofacial regulatory landscapes between these species. This is the first description of genome-wide face regulatory elements in a marsupial, with 60,626 putative enhancers and 12,295 putative promoters described. We also generated craniofacial RNA-seq data for the dunnart to investigate expression dynamics of genes near predicted active regulatory elements. While genes involved in regulating facial development were largely conserved in mouse and dunnart, the regulatory landscape varied significantly. Additionally, a subset of dunnart-specific enhancers were associated with genes highly expressed only in dunnart relating to cranial neural crest proliferation, embryonic myogenesis and epidermis development. Comparative RNA-seq analyses of facial tissue revealed dunnart-specific expression of genes involved in the development of the mechanosensory system. Accelerated development of the dunnart sensory system likely relates to the sensory cues received by the nasal-oral region during the postnatal journey to the pouch. Together these data suggest that accelerated face development in the dunnart may be driven by dunnart-specific enhancer activity. Our study highlights the power of marsupial-placental comparative genomics for understanding the role of enhancers in driving temporal shifts in development.
BOLD response is more than just magnitude: improving detection sensitivity through capturing hemodynamic profiles
Authors: Chen Gang , Taylor Paul A. , Reynolds Richard C. , Leibenluft Ellen , Pine Daniel S. , Brotman Melissa A. , Pagliaccio David , Haller Simone P. 
Published: February 2023

AbstractTypical FMRI analyses assume a canonical hemodynamic response function (HRF) with a focus on the overshoot peak height, while other morphological aspects are largely ignored. Thus, in most reported analyses, the overall effect is reduced from a curve to a single scalar. Here, we adopt a data-driven approach to HRF estimation at the whole-brain voxel level, without assuming a response profile at the individual level. Then, we estimate the response in its entirety with a roughness penalty at the population level to improve predictive accuracy, inferential efficiency, and cross-study reproducibility. Using a fast event-related FMRI dataset, we demonstrate the extent of under-fitting and information loss that occurs when adopting the canonical approach. We also address the following questions:How much does the HRF shape vary across regions, conditions, and groups?Does an agnostic approach improve sensitivity to detect an effect compared to an assumed HRF?Can examining HRF shape help validate the presence of an effect complementing statistical evidence?Could the HRF shape provide evidence for whole-brain BOLD response during a simple task?
Histone variant H2B.Z acetylation is necessary for maintenance ofToxoplasma gondiibiological fitness
Authors: Vanagas Laura , Muñoz Daniela , Cristaldi Constanza , Ganuza Agustina , Nájera Rosario , Bonardi Mabel C. , Turowski Valeria R. , Guzman Fanny , Deng Bin , Kim Kami , Sullivan William J. , Angel Sergio O. 
Published: February 2023

AbstractThrough regulation of DNA packaging, histone proteins are fundamental to a wide array of biological processes. A variety of post-translational modifications (PTMs), including acetylation, constitute a proposed histone code that is interpreted by “reader” proteins to modulate chromatin structure. Canonical histones can be replaced with variant versions that add an additional layer of regulatory complexity. The protozoan parasiteToxoplasma gondiiis unique among eukaryotes in possessing a novel variant of H2B designated H2B.Z. The combination of PTMs and the use of histone variants is important for gene regulation inT. gondii,offering new targets for drug development. In this work,T. gondiiparasites were generated in which the 5 N-terminal acetylatable lysines in H2B.Z were mutated to either alanine (c-Myc-A) or arginine (c-Myc-R). c-Myc-A mutant only displayed a mild effect in its ability to kill mice. c-Myc-R mutant presented an impaired ability to grow and an increase in differentiation to latent bradyzoites. This mutant line was also more sensitive to DNA damage, displayed no virulence in mice, and provided protective immunity against future infection. While nucleosome composition was unaltered, key genes were abnormally expressed duringin vitrobradyzoite differentiation. Our results show that the N-terminal positive charge patch of H2B.Z is important for these procceses. Pull down assays with acetylated N-terminal H2B.Z peptide and unacetylated one retrieved common and differential interactors. Acetylated peptide pulled down proteins associated with chromosome maintenance/segregation and cell cycle, opening the question of a possible link between H2B.Z acetylation status and mitosis.