bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coexistence in diverse communities with higher-order interactions
Authors: Gibbs Theo , Levin Simon A. , Levine Jonathan M. 
Published: March 2022

AbstractA central assumption in most ecological models is that the interactions in a community operate only between pairs of species. However, the interaction between two species may be fundamentally changed by the presence of others. Although interactions among three or more species, called higher-order interactions, have the potential to modify our theoretical understanding of coexistence, ecologists lack clear expectations for how these interactions shape community structure. Here, we analytically predict and numerically confirm how the variability and strength of higher-order interactions affect species coexistence. We found that, as higher-order interaction strengths become more variable across species, fewer species coexist, echoing the behavior of pairwise models. If inter-specific higher-order interactions become too harmful relative to self-regulation, coexistence was destabilized, but coexistence was also lost when these interactions were too weak and mutualistic effects became prevalent. Last, we showed that more species rich communities structured by higher-order interactions lose species more readily than their species poor counterparts, generalizing classic results for community stability. Our work provides needed theoretical expectation for how higher-order interactions impact species coexistence in diverse communities.
Oxytocin via oxytocin receptor excites neurons in the endopiriform nucleus of juvenile mice
Authors: Biggs Lindsey M. , Hammock Elizabeth A.D. 
Published: March 2022

AbstractThe neuropeptide oxytocin (OXT) modulates social behaviors across species and may play a developmental role for these behaviors and their mediating neural pathways. Despite having high, stable levels of OXT receptor (OXTR) ligand binding from birth, endopiriform nucleus (EPN) remains understudied. EPN integrates olfactory and gustatory input and has bilateral connections with several limbic areas. Because the role of OXTR signaling in EPN is unknown, we sought to provide anatomical and electrophysiological information about OXTR signaling in mouse EPN neurons. Using in situ hybridization, we found that most EPN neurons co-express Oxtr mRNA and the marker for VGLUT1 and are thus glutamatergic cells. Based on high levels of OXTR ligand binding in EPN, we hypothesized that oxytocin application would modulate activity in these cells as measured by whole-cell patch-clamp electrophysiology. Bath application of OXT and an OXTR specific ligand (TGOT) increased the excitability of EPN neurons in wild-type, but not in OXTR-knockout tissue. These results show an effect of OXT on a presumably glutamatergic cell population within EPN. Given the robust, relatively stable OXTR expression in EPN throughout life, OXTR in this multi-sensory and limbic integration area may be important for modulating activity in response to an array of social or other salient stimuli throughout the lifespan and warrants further study.Significance statementThere is a high level of oxytocin receptor (OXTR) expression in the mouse endopiriform nucleus (EPN) throughout development, however little is known about the effect of oxytocin on these neurons. We show here that Oxtr mRNA co-expresses mainly with VGLUT1, a glutamatergic cell marker. Using OXTR-EGFP mice to identify EPN, we show that OXT has a mainly excitatory effect on EPN neurons. Thus, activity in EPN neurons may be modulated by OXT during exposure to salient or social stimuli throughout development and this could affect development of behavioral responses during social exposure.
Machine Learning–Informed Predictions of Nanoparticle Mobility and Fate in the Mucus Barrier
Authors: Kaler Logan , Joyner Katherine , Duncan Gregg A. 
Published: March 2022

ABSTRACTDiffusion and transport of nanomaterials through mucus, is of critical importance to many basic and applied areas of research such as drug delivery and infectious disease. However, it is often challenging to interpret the dynamics of nanoparticles within the mucus gel due to its inherently heterogeneous microstructure and biochemistry. In this study, we measured the diffusion of densely PEGylated nanoparticles (NP) in human airway mucusex vivousing multiple particle tracking and utilized machine learning to classify NP movement as either traditional Brownian motion (BM) or one of two different models of anomalous diffusion, fractional Brownian motion (FBM) and continuous time random walk (CTRW). Specifically, we employed a physics-based neural network model to predict the modes of diffusion experienced by individual NP in human airway mucus. We observed rapidly diffusing NP primarily exhibit BM whereas CTRW and FBM exhibited lower diffusion rates. Given the use of muco-inert nanoparticles, the observed transition from diffusive (BM) to sub-diffusive (CTRW/FBM) motion is likely a result of patient-to-patient variation in mucus network pore size. Using mathematic models that account for the mode of NP diffusion, we predicted the percentage of nanoparticles that would cross the mucus barrier over time in human airway mucus with varied total solids concentration. We also applied this approach to explore the transport modes and predicted fate of influenza A virus within human mucus. These results provide new tools to evaluate the extent of synthetic and viral nanoparticle penetration through mucus in the lung and other tissues.
Biological constraints on stereotaxic targeting of functionally-defined cortical areas
Authors: Narayanan Divya P , Tsukano Hiroaki , Kline Amber M , Onodera Koun , Kato Hiroyuki K 
Published: March 2022

SummaryUnderstanding computational principles in hierarchically organized sensory systems requires functional parcellation of brain structures and their precise targeting for manipulations. Although brain atlases are widely used to infer area locations in the mouse neocortex, it has been unclear whether stereotaxic coordinates based on standardized brain morphology accurately represent functional domains in individual animals. Here, we used intrinsic signal imaging to evaluate the accuracy of area delineation in the atlas by mapping functionally-identified auditory cortices onto bregma-based stereotaxic coordinates. We found that auditory cortices in the brain atlas correlated poorly with the true complexity of functional area boundaries. Inter-animal variability in functional area locations predicted surprisingly high error rates in stereotaxic targeting with atlas coordinates. This variability was not simply attributed to brain sizes or suture irregularities but instead reflected differences in cortical geography across animals. Our data thus indicate that functional mapping in individual animals is essential for dissecting cortical area-specific roles with high precision.
Ultrasensitive Dopamine Detection with Graphene Aptasensor Multitransistor Arrays
Authors: Abrantes Mafalda , Rodrigues Diana , Domingues Telma , Nemala Siva S. , Monteiro Patricia , Borme Jérôme , Alpuim Pedro , Jacinto Luis 
Published: March 2022

AbstractDopamine is a neurotransmitter with critical roles in the human brain and body, and abnormal dopamine levels underlie brain disorders such as Parkinson’s Disease, Alzheimer’s Disease, and substance addiction. Herein, we present a novel high-throughput biosensor based on graphene multitransistor arrays (gMTAs) functionalized with a selective aptamer for robust ultrasensitive dopamine detection. The miniaturized biosensor integrates multiple electrolyte-gated graphene field-effect transistors (EG-gFETs) in an array configuration, fabricated by high-yield reproducible and scalable methodologies optimized at the wafer level. With these gMTA aptasensors, we reliably detected ultra-low dopamine concentrations in physiological buffers, including undiluted phosphate-buffered saline (PBS), artificial cerebral spinal fluid (aCSF), and high ionic strength complex biological samples. We report a record limit-of-detection (LOD) of 1 aM (10−18) for dopamine in both PBS, and dopamine-depleted brain homogenate samples spiked with dopamine. The gMTAs also display wide sensing ranges across all media, up to 100 μM (10−8), with a 22 mV/decade peak sensitivity in aCSF. Furthermore, we show that the gMTAs can detect minimal changes in dopamine concentrations in small working volume biological CSF samples obtained from a mouse model of Parkinson’s Disease.
SARS-CoV-2 remodels the Golgi apparatus to facilitate viral assembly and secretion
Authors: Zhang Jianchao , Kennedy Andrew , de Melo Jorge Daniel Macedo , Xing Lijuan , Reid Whitney , Bui Sarah , Joppich Joseph , Rose Molly , Ercan Sevval , Tang Qiyi , Tai Andrew W. , Wang Yanzhuang 
Published: March 2022

AbstractThe COVID-19 pandemic is caused by SARS-CoV-2, an enveloped RNA virus. Despite extensive investigation, the molecular mechanisms for its assembly and secretion remain largely elusive. Here, we show that SARS-CoV-2 infection induces global alterations of the host endomembrane system, including dramatic Golgi fragmentation. SARS-CoV-2 virions are enriched in the fragmented Golgi. Disrupting Golgi function with small molecules strongly inhibits viral infection. Significantly, SARS-CoV-2 infection down-regulates GRASP55 but up-regulates TGN46 protein levels. Surprisingly, GRASP55 expression reduces both viral secretion and spike number on each virion, while GRASP55 depletion displays opposite effects. In contrast, TGN46 depletion only inhibits viral secretion without affecting spike incorporation into virions. TGN46 depletion and GRASP55 expression additively inhibit viral secretion, indicating that they act at different stages. Taken together, we show that SARS-CoV-2 alters Golgi structure and function to control viral assembly and secretion, highlighting the Golgi as a potential therapeutic target for blocking SARS-CoV-2 infection.
Identification and evolutionary analysis of a Triticeae tribe specific novel non-autonomous DNA transposon in DREB related Dehydration Responsive Factor1 gene
Authors: Thiyagarajan K , Latini A , Cantale C , Porceddu E , Galeffi P 
Published: March 2022

AbstractA non-autonomous DNA transposon was identified in the DRF1 gene, belonging to the DREB gene family, the presence of this element was initially assessed in the Triticum durum DRF1 gene and subsequently it was also identified in Aegilops speltoides and Triticum urartu DRF1 genes. The DRF1 gene consists of four exons and three introns, the transposon carrying core element is inserted between the first and the third introns. Our studies identified inverted repeats, target site duplications and the presence of many internal reverse and direct short tandem and long tandem repeats, that all represent signals of a transposable element. Based on transposon specific sequence and position of the terminal inverted repeats, a possible transposition mechanism was inferred. As the identified transposable element does not possess a sequence coding for a transposase enzyme, it represents a non-autonomous element. The transposon encompasses a core element with two small, transcribed regions (Exon 2 and Exon 3) that are combined by alternative splicing during gene expression and an intron (intron2). A possible role of this non-autonomous DNA transposon in the alternative splicing regulation was investigated by a genomics approach. Divergence time analysis supported the relatively recent evolution of this transposon in Triticeae comparing to other tribes and further there is no footprints or highly disrupted footprints sequence such as TIR, TSD in other earlier evolved Poaceae member species were observed, which revealed the novelty and well-preserved nature of these signals in Triticeae. While other monocots (apart from Poaceae) and dicots, including Arabidopsis thaliana, neither showed this transposon insertion and nor revealed the existence of alternative spliced gene transcripts. In Poaceae members the core element is well preserved with disturbed transposon and transposon signals, while the tribe Triticeae especially wheat, its progenitors have intact DRF1 transposon and its signals.
Cetacean “gas-bubble thromboembolic polycystic liver disease”: “Budd-Chiari like syndrome” in dolphins?
Authors: Fernandez Antonio , Jepson Paul D , Diaz-Delgado Josue , de Quiros Yara Bernaldo , Sierra Eva , Mompeo Blanca , Vela Ana Isabel , Di Guardo Giovanni , Suarez-Santana Cristian , de los Monteros Antonio Espinosa , Herraez Pedro , Andrada Marisa , Caballero Maria Jose , Rivero Miguel , Consoli Francesco , Castro Ayoze , Quesada Oscar , Arbelo Manuel 
Published: March 2022

AbstractNearly two decades ago, pathologic examination results suggested acoustic factors, such as mid-frequency active naval military sonar (MFAS) could be the cause of acute decompression-like sickness in stranded beaked whales. Acute systemic gas embolism in these beaked whales was published together with enigmatic cystic liver lesions (CLL), characterized by intrahepatic encapsulated gas-filled cysts, tentatively interpreted as “gas-bubble” lesions in various cetacean species. Here we provide a pathologic reinterpretation of CLL in cetaceans. From 1,200 cetaceans necropsied, CLL were only observed in striped dolphins (Stenella coeruleoalba), with a low prevalence (2%), and recapitulated pathologic features of Budd-Chiari syndrome in humans. Our results strongly suggest that CLL are the result of the combination of pre-existing or concomitant hepatic vascular disorder (e.g., severe hepatobiliary trematodiasis) superimposed and exacerbated by gas bubbles, and clearly differ from acute systemic gas embolism in stranded beaked whales linked to MFAS.
Bessel-droplet foci enable high-resolution and high-contrast volumetric imaging of synapses and circulation in the brainin vivo
Authors: Chen Wei , Zhang Qinrong , Natan Ryan , Fan Jianglan , Ji Na 
Published: March 2022

AbstractBessel beam has long been utilized in physics for its ability to maintain lateral confinement during propagation. When used for two-photon fluorescence microscopy, Bessel foci have enabled high-speed volumetric imaging of the brain. At high numeric aperture (NA), however, the substantial energy in the side rings of Bessel foci reduces image contrast. Therefore, a compromise between resolution and contrast has to be made, limiting Bessel foci in microscopy to low NA. Here, we describe a method of generating axially extended Bessel-droplet foci with much suppressed side rings. Shaping the excitation wavefront with novel phase patterns, we generated Bessel-droplet foci of variable NAs at high power throughput and scanned them interferometrically along the axial direction for continuous volume imaging. More resistant to optical aberrations than Bessel foci, Bessel-droplet foci enabled high-resolution and high-contrast volumetric imaging of synaptic anatomy and function as well as lymphatic circulation in the mouse brainin vivo.
Revealing cell populations catching the early stages of the human embryo development in naïve pluripotent stem cells
Authors: Moya-Jódar Marta , Ullate-Agote Asier , Barlabé Paula , Rodríguez-Madoz Juan Roberto , Abizanda Gloria , Barreda Carolina , Carvajal-Vergara Xonia , Vilas-Zornoza Amaia , Romero Juan Pablo , Garate Leire , Agirre Xabier , Coppiello Giulia , Prósper Felipe , Aranguren Xabier L. 
Published: March 2022

ABSTRACTNaïve human pluripotent stem cells (hPSCs) are defined as the in vitro counterpart of the human preimplantation embryo’s epiblast and are used as a model system to study developmental processes. In this study, we report the discovery and characterization of distinct cell populations coexisting with epiblast-like cells in 5iLAF naïve human induced PSCs (hiPSCs) cultures. Noteworthily these populations closely resemble different cell types of the human embryo at early developmental stages. While epiblast-like cells represented the main cell population, interestingly we detected a cell population with gene and transposable element expression profile closely resembling the totipotent 8-Cell (8C) stage human embryo, and three cell populations analogous to trophectoderm (TE) cells at different stages of their maturation process: transition, early and mature stage. Thus, 5iLAF naïve hiPSCs cultures provide an excellent opportunity to model the earliest events of human embryogenesis, from the 8C stage to the peri-implantation period.Graphical abstract
Downregulation of the secreted protein with an altered thrombospondin repeat (SPATR) impacts the infectivity of malaria sporozoites
Authors: Costa David Mendes , Sá Mónica , Teixeira Ana Rafaela , Pérez-Cabezas Begoña , Golba Sylvain , Sefiane-Djemaoune Hélèna , Formaglio Pauline , Franke-Fayard Blandine , Janse Chris J. , Amino Rogerio , Tavares Joana 
Published: March 2022

AbstractThe identification of surface proteins of the sporozoite stage of malaria parasites important for sporozoite infectivity could aid in the improvement of the efficacy of vaccines targeting pre-erythrocytic stages. Thus, we set out to disclose the role of the secreted protein with an altered thrombospondin repeat (SPATR), which is highly expressed in sporozoites. Previous studies showed an essential function in blood stages, while no role was detected in sporozoites despite high expression. To achieve downregulation of expression in sporozoites while maintaining blood stage expression, a promoter swap approach was used to generate a mutant where the Plasmodium berghei spatr gene was placed under transcriptional control of the hado gene promoter. Downregulation of expression in oocysts and sporozoites resulted in formation of sporozoites with impaired motility, strongly reduced capacity to invade salivary glands, and decreased infectivity to mice. In conclusion, we revealed a new role for SPATR in sporozoite infectivity, highlighting the importance to use complementary methods in studies on sporozoite biology.
Masculinizer-induced dosage compensation is achieved by transcriptional downregulation of both copies of Z-linked genes in the silkworm, Bombyx mori
Authors: Tomihara Kenta , Kawamoto Munetaka , Suzuki Yutaka , Katsuma Susumu , Kiuchi Takashi 
Published: March 2022

AbstractDosage compensation balances the expression of sex-chromosome-linked genes with autosome-linked genes in the heterogametic sex. The silkworm (Bombyx mori), a lepidopteran model insect, uses the female heterogametic WZ sex determination system. In B. mori, a Z-linked gene, Masculinizer (Masc), is the primary determinant of maleness and dosage compensation. However, it remains unknown whether one of the two Z chromosomes is inactivated or both Z chromosomes are suppressed in B. mori males. Hence, we performed transcriptome analysis using hybrids between two B. mori strains and analyzed the allele-specific expression (ASE) to solve the problem. The ASE analysis revealed that the genes located on the maternal and paternal Z chromosomes are transcriptionally upregulated in Masc knocked down males. Also, our results revealed that two Z chromosomes are transcriptionally downregulated in B. mori males as observed in Caenorhabditis elegans.
Paired single-cell host profiling with multiplex-tagged bacterial mutants reveals intracellular virulence-immune networks
Authors: Heyman Ori , Yehezkel Dror , Blumberger Neta , Rosenberg Gili , Mattioli Camilla Ciolli , Solomon Aryeh , Hoffman Dotan , Ben-Moshe Noa Bossel , Avraham Roi 
Published: March 2022

SummaryEncounters between host cells and intracellular bacterial pathogens lead to complex phenotypes that determine the outcome of infection. Single-cell RNA-sequencing (scRNA-seq) are increasingly used to study the host factors underlying diverse cellular phenotypes. But current approaches do not permit the simultaneous unbiased study of both host and bacterial factors during infection. Here, we developed scPAIR-seq, an approach to analyze both host and pathogen factors during infection by combining multiplex-tagged mutant bacterial library with scRNA-seq to identify mutant-specific changes in host transcriptomes. We applied scPAIR-seq to macrophages infected with a library of Salmonella Typhimurium secretion system effector mutants. We developed a pipeline to independently analyze redundancy between effectors and mutant-specific unique fingerprints, and mapped the global virulence network of each individual effector by its impact on host immune pathways. ScPAIR-seq is a powerful tool to untangle bacterial virulence strategies and their complex interplay with host defense strategies that drive infection outcome.
A comprehensive analysis of immune landscape of Indian triple negative breast cancer
Authors: Korlimarla Aruna , Hari PS , Prabhu Jyoti , Ragulan Chanthirika , Patil Yatish , Snijesh VP , Desai Krisha , Mathews Aju , Appachu Sandhya , Diwakar Ravi B. , Srinath BS , Cheang Maggie , Sadanandam Anguraj 
Published: March 2022

AbstractBackgroundTriple-negative breast cancer (TNBC) is a heterogeneous disease with a significant clinical challenge. TNBC alarmingly comprises 25-30% of breast cancers in India compared with only 10-15% in the West. However, immunotherapy was approved for high-risk early-stage TNBCs in the West. Hence, a long-standing question is whether Indian TNBCs immunologically and clinically resemble Western TNBCs such that they respond similarly to immunotherapies. Here we sought to elucidate the immune landscape of Indian TNBCs for the first time, compare them to Western disease and associate them with clinical parameters, cellular types/signaling, and immunotherapy response.MethodsWe profiled 730 immune genes in 88 retrospective Indian TNBC samples using NanoString platform, clustered them into subtypes using a machine-learning approach, and compared them with Western TNBCs (n=422; public datasets). Subtype-specific gene signatures were identified, followed by clinicopathological, immune cell type, and pathway (multiomics) analyses. We also assessed responses to (cross-cancer) immunotherapy. Tumor-infiltrating lymphocytes (TILs) and pan-macrophage marker were evaluated using hematoxilin-eosin staining and immunohistochemistry, respectively.ResultsWe identified three robust and similarly distributed TNBC immune transcriptome subtypes (Subtypes-1-3) in Indian women, and they are represented correspondingly in Western TNBCs and associated with well-known TNBC subtypes. Irrespective of the ethnicity, Subtype-1 harbored tumor microenvironmental and anti-tumor immune events associated with smaller tumors, younger age, and a better prognosis. Subtype-1 mainly represented basal-like/claudin-low breast cancer and immunomodulatory TNBC subtypes. Subtype-1 showed an increase in a cascade of events, including damage-associated molecular patterns, acute inflammation, Th1 responses, T-cell receptor-related and chemokine-specific signaling, antigen presentation, and viral-mimicry pathways. Subtype-1 was significantly (p<0.05) associated with pre-menopausal women, dense TILs and responses and/or improved prognosis to anti-PD-L1 and MAGEA3 immunotherapies. Subtype-2 was enriched for Th2/Th17 responses, CD4+ regulatory cells, basal-like/mesenchymal subtypes, and an intermediate prognosis. Subtype-3 patients expressed innate immune genes/proteins, including those representing macrophages and neutrophils, and had poor survival.ConclusionWe identified three immune-specific TNBC subtypes in Indian patients with differential clinical and immune behaviors, which largely overlapped with the Western TNBC cohorts. This study suggests cancer immunotherapy in TNBC may work similarly in both populations. Hence, this may expedite pharmaceutical adoption of immunotherapy to Indian TNBC patients.