bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmission of vibrations in buzz-pollinated plant species with disparate floral morphologies
Authors: Nevard Lucy , Russell Avery L. , Foord Karl , Vallejo-Marin Mario 
Published: April 2021

AbstractIn buzz-pollinated plants, bees apply vibrations produced by their thoracic muscles to the flower, causing pollen release from anthers, often through small apical pores. During floral buzzing, bees grasp one or more anthers with their mandibles, and vibrations are transmitted to the focal anther(s), adjacent anthers, and the whole flower. Because pollen release depends on the vibrations experienced by the anther, the transmission of vibrations through flowers with different morphologies may determine patterns of release, affecting both bee foraging and plant fitness. Anther morphology and intra-floral arrangement varies widely among buzz-pollinated plants. Here, we compare the transmission of vibrations among focal and non-focal anthers in four species with contrasting anther morphologies:Cyclamen persicum(Primulaceae),Exacum affine(Gentianaceae),Solanum dulcamaraandS. houstonii(Solanaceae). We used a mechanical transducer to apply bee-like artificial vibrations to focal anthers, and simultaneously measured the vibration frequency and displacement amplitude at the tips of focal and non-focal anthers using high-speed video analysis (6,000 frames per second). In flowers in which anthers are tightly held together (C. persicumandS. dulcamara), vibrations in focal and non-focal anthers are indistinguishable in both frequency and displacement amplitude. In contrast, flowers with loosely arranged anthers (E. affine) including those in which stamens are morphologically differentiated within the same flower (heterantherousS. houstonii), show the same frequency but higher displacement amplitude in non-focal anthers compared to focal anthers. Our results suggest that stamen arrangement affects vibration transmission with potential consequences for pollen release and bee behaviour.
Extracellular Hsp90α Detoxifies β-Amyloid Fibrils Through an NRF2 and Autophagy Dependent Pathway
Authors: Murshid Ayesha , Lang Benjamin J. , Borges Thiago J. , Okusha Yuka , Doshi Sachin P. , Yasmine Suraya , Clark-Matott Joanne , Choudhury Reeham , Ang Lay-Hong , Woodbury Maya , Ikezu Tsuneya , Calderwood Stuart K. 
Published: April 2021

AbstractWe have investigated the role ofextracellularHeatshockprotein90alpha(eHsp90α) in conferring protection of neuronal cells against fibrillary amyloid beta (f-Aβ1-42) toxicity mediated by microglial cells. Formation of f-Aβ1-42plaques leads to neurotoxic inflammation, a critical pathological feature of Alzheimer’s Disease. We observed increased uptake and clearance of internalized f-Aβ1-42by microglial cells treated with eHsp90α, an effect associated with activation of NRF2 (NF-E2-related factor 2) - mediated autophagy. eHsp90α thus mitigated the neuronal toxicity of f-Aβ1-42-activated microglia. In addition, eHsp90α facilitated f-Aβ1-42engulfment by microglial cellsin vitro. In summary, eHsp90α triggers NRF2-mediated autophagy in microglia and thus protects against the neurotoxic effects of f-Aβ1-42.
Whole Chloroplast Genomes reveals the uniqueness of Bolivian native cacao (Theobroma cacao) from the northern part of Bolivia
Authors: Gumiel M , Rollano-Peñaloza OM , Peralta-Rivero C , Tejeda L , Palma V , Cartagena P , Mollinedo P , Peñarrieta JM 
Published: April 2021

ABSTRACTWe report the complete chloroplast sequences of two varieties ofTheobroma cacaocollected in the Bolivian Amazonia using Next-Generation Sequencing. Comparisons made between these two chloroplast genomes and the Belizean reference plastid genome identified 19 and 22 nucleotide variants. The phylogenetic analysis reported three mainT. cacaoclades belonging to the Forastero, Criollo and Trinitario groups. The Bolivian Native Cacao varieties were located inside the Trinitario group forming their unique branch. The Bolivian Native Cacao branch reveals a possible new subpopulation different from the well-characterizedT. cacaosubpopulations. The phylogenetic trees showed that the relationships among theT. cacaovarieties were consistent with their geographical locations placing the Cacao Center of Origin in Western Amazon. The data presented here will contribute to the usage of ultrabarcoding to distinguish differentT. cacaovarieties and to identify native cacaos from introduced cacaos. Thus helping in the conservation of local native varieties ofT. cacao.
A competitive activity-based protein profiling platform yields cell wall synthesis inhibitors active against replicating and non-replicatingMycobacterium tuberculosis
Authors: Li Michael , Patel Hiren V. , Cognetta Armand B. , Smith Trever C. , Mallick Ivy , Cavalier Jean-François , Canaan Stephane , Aldridge Bree B. , Cravatt Benjamin F. , Seeliger Jessica C. 
Published: April 2021

ABSTRACTThe identification and validation of a small molecule’s targets is a major bottleneck in the discovery process for tuberculosis antibiotics. Activity-based protein profiling (ABPP) is an efficient tool for determining a small molecule’s targets within complex proteomes. However, how target inhibition relates to biological activity is often left unexplored. Here we studied the effects of 1,2,3-triazole ureas onMycobacterium tuberculosis(Mtb). After screening ~200 compounds, we focused on two inhibitors active against both exponentially replicating and hypoxia-induced drug-tolerantMtbthat form part of a four-compound structure-activity series. The compound with negligible activity revealed potential false positive targets not addressed in other ABPP studies. Biochemistry, computational docking, and morphological analysis confirmed that active compounds preferentially inhibit serine hydrolases with cell wall and lipid metabolism functions and that disruption of the cell wall underlies biological activity. Our findings showed that ABPP identifies the targets most likely relevant to a compound’s antibacterial activity.
TDP-43 regulates GAD1 mRNA splicing and GABA signaling in Drosophila brains
Authors: Romano Giulia , Holodkov Nikola , Klima Raffaella , Feiguin Fabian 
Published: April 2021

ABSTRACTAlterations in the function of the RNA-binding protein TDP-43 is largely associated with the pathogenesis of amyotrophic lateral sclerosis (ALS), a devastating disease of the human motor system that leads to motoneurons degeneration and reduced life expectancy by molecular mechanisms not well known. Regarding to that, we found that the expression levels of the glutamic acid decarboxylase enzyme (GAD1), responsible to convert glutamate to γ-aminobutyric acid (GABA), were downregulated in TBPH-null flies and motoneurons derived from ALS patients carrying mutations in TDP-43 suggesting that defects in the regulation of GAD1 may lead to neurodegeneration by affecting neurotransmitter balance. In this study, we observed that TBPH was required to regulate GAD1 pre-mRNA splicing and GABA levels in Drosophila brains. Interestingly, we discovered that pharmacological treatments aimed to modulate GABA neurotransmission were able to revert locomotion deficiencies in TBPH-minus flies revealing novel mechanisms and therapeutic strategies in ALS.
A gene regulatory network for neural induction
Authors: Trevers Katherine E. , Lu Hui-Chun , Yang Youwen , Thiery Alexandre , Strobl Anna C. , Pálinkášová Božena , de Oliveira Nidia M. M. , de Almeida Irene M. , Khan Mohsin A. F. , Moncaut Natalia , Luscombe Nicholas M. , Dale Leslie , Streit Andrea , Stern Claudio D. 
Published: April 2021

AbstractDuring early vertebrate development, signals from a special region of the embryo, the organizer, can re-direct the fate of non-neural ectoderm cells to form a complete, patterned nervous system. This is called neural induction and has generally been imagined as a single signalling event, causing a switch of fate. Here we undertake a comprehensive analysis, in very fine time-course, of the events following exposure of ectoderm to the organizer. Using transcriptomics and epigenomics we generate a Gene Regulatory Network comprising 175 transcriptional regulators and 5,614 predicted interactions between them, with fine temporal dynamics from initial exposure to the signals to expression of mature neural plate markers. Using in situ hybridization, single-cell RNA-sequencing and reporter assays we show that neural induction by a grafted organizer closely resembles normal neural plate development. The study is accompanied by a comprehensive resource including information about conservation of the predicted enhancers in different vertebrate systems.
Defective satellite DNA clustering into chromocenters underlies hybrid incompatibility inDrosophila
Authors: Jagannathan Madhav , Yamashita Yukiko M. 
Published: April 2021

AbstractAlthough rapid evolution of pericentromeric satellite DNA repeats is theorized to promote hybrid incompatibility (HI)(1–4), how divergent repeats affect hybrid cells remains poorly understood. Recently, we demonstrated that sequence-specific DNA-binding proteins cluster satellite DNA from multiple chromosomes into ‘chromocenters’, thereby bundling chromosomes to maintain the entire genome in a single nucleus(5, 6). Here we show that ineffective clustering of divergent satellite DNA in the cells ofDrosophilahybrids results in chromocenter disruption, associated micronuclei formation and tissue atrophy. We further demonstrate that previously identified HI factors trigger chromocenter disruption and micronuclei in hybrids, linking their function to a conserved cellular process. Together, we propose a unifying framework that explains how the widely observed satellite DNA divergence between closely related species can cause reproductive isolation.
MHC-matched allogeneic bone marrow transplants fail to eliminate SHIV-infected cells from ART-suppressed Mauritian cynomolgus macaques
Authors: Weinfurter Jason T. , D’souza Saritha S. , Matschke Lea M. , Bennett Sarah , Kelnhofer-Millevolte Laurel E. , Suknuntha Kran , Kumar Akhilesh , Coonen Jennifer , Capitini Christian M. , Hematti Peiman , Golos Thaddeus G. , Slukvin Igor I. , Reynolds Matthew R. 
Published: April 2021

AbstractBackgroundAllogeneic hematopoietic stem cell transplants (allo-HSCTs) dramatically reduce HIV reservoirs in antiretroviral therapy (ART) suppressed individuals. However, the mechanism(s) responsible for these post-transplant viral reservoir declines are not fully understood but may include pre-transplant conditioning regimens, ART-mediated protection of donor cells, and graft-versus-host (GvH) responses. Therefore, we modeled allo-HSCT in ART-suppressed simian-human immunodeficiency virus (SHIV)-infected Mauritian cynomolgus macaques (MCMs) to illuminate factors contributing to transplant-induced viral reservoir decay.ResultsWe infected four MCMs with CCR5-tropic SHIV162P3 and started ART 6-16 weeks post-infection (p.i.) to establish robust viral reservoirs. We maintained the MCMs on continuous ART during myeloablative conditioning with total body irradiation (TBI) and while transplanting allogeneic MHC-matched α/β T cell-depleted bone marrow cells. Post-transplant, we prophylactically treated the MCMs with cyclophosphamide and tacrolimus to prevent GvH disease (GvHD). The transplants produced ~85% whole blood donor chimerism without causing high-grade GvHD. Consequently, three MCMs had undetectable SHIV DNA in their peripheral blood mononuclear cells post-transplant. However, SHIV-harboring cells persisted in various tissues. We detected viral DNA in lymph node biopsies and terminal analyses of tissues between 38 and 62 days post-transplant. Further, we removed ART from one MCM at 63 days post-transplant, resulting in viral rebound within seven days and viral loads nearing 1×108SHIV RNA copies/ml of plasma after treatment interruption.ConclusionsOur results indicate that myeloablative conditioning and maintaining ART through the peri-transplant period alone are insufficient for eradicating latent viral reservoirs early after allo-HSCTs. Furthermore, our findings suggest that extended ART and GvH responses may be necessary to substantially deplete viral reservoirs after allo-HSCTs.
Stronger net selection on males across animals
Authors: Winkler Lennart , Moiron Maria , Morrow Edward H. , Janicke Tim 
Published: April 2021

AbstractSexual selection is considered the major driver for the evolution of manifold sex differences. However, the eco-evolutionary dynamics of sexual selection and their role for a population’s adaptive potential to respond to environmental change have only recently been explored. Theory predicts that sexual selection promotes adaptation at a low demographic cost only if net selection is stronger on males compared to females. We used a comparative approach to show that net selection is indeed stronger in males in species prone to intense sexual selection. Given that both sexes share the vast majority of their genes, our findings corroborate the notion that the genome is often confronted with a more stressful environment when expressed in males. Collectively, our study supports a long-standing key assumption required for sexual selection to bolster adaptation, and intense sexual selection may therefore enable some species to track environmental change more efficiently.One sentence summaryComparative study finds support for stronger net selection in males.
A crosstalk between E2F1 and GLP-1 signaling pathways modulates insulin secretion
Authors: Bourouh Cyril , Courty Emilie , Pasquetti Gianni , Gromada Xavier , Rabhi Nabil , Carney Charlène , Moreno Maeva , Boutry Raphaël , Rolland Laure , Caron Emilie , Benfodda Zohra , Meffre Patrick , Kerr-Conte Julie , Pattou François , Froguel Philippe , Bonnefond Amélie , Oger Frédérik , Annicotte Jean-Sébastien 
Published: April 2021

AbstractCompromised β-cell function contributes to type 2 diabetes (T2D) development. The glucagon like peptide 1 (Glp-1) has emerged as a hormone with broad pharmacological potential toward T2D treatment, notably by improving β-cell functions. Recent data have shown that the transcription factor E2f1, besides its role as a cell cycle regulator, is involved in glucose homeostasis by modulating β-cell mass, function and identity. Here, we demonstrate a crosstalk between the E2F1, phosphorylation of retinoblastoma protein (pRb) and Glp-1 signaling pathways. We found that β-cell specificE2f1deficient mice (E2f1β−/−) presented with impaired glucose homeostasis and decreased glucose stimulated-insulin secretion mediated by exendin 4 (i.e., GLP1R agonist), which were associated with decreased expression ofGlp1rencoding Glp-1 receptor (GLP1R) inE2f1β−/−pancreatic islets. Decreasing E2F1 transcriptional activity with an E2F inhibitor in islets from nondiabetic humans decreasedGLP1Rlevels and blunted the incretin effect of exendin 4 on insulin secretion. Conversely, overexpressingE2f1in pancreatic β cells increasedGlp1rexpression associated with enhanced insulin secretion mediated by GLP1R agonist. Interestingly, kinome analysis of mouse islets demonstrated that an acute treatment with exendin 4 increased pRb phosphorylation and subsequent E2f1 transcriptional activity. This study suggests a molecular crosstalk between the E2F1/pRb and GLP1R signaling pathways that modulates insulin secretion and glucose homeostasis.
A polysaccharide deacetylase enhances bacterial adhesion in high ionic strength environments
Authors: Chepkwony Nelson K. , Brun Yves V. 
Published: April 2021

SUMMARYThe adhesion of organisms to surfaces in aquatic environments provides a diversity of benefits such as better access to nutrients or protection from the elements or from predation. Differences in ionic strength, pH, temperature, shear forces, and other environmental factors impact adhesion and organisms have evolved various strategies to optimize their adhesins for their specific environmental conditions. We know essentially nothing about how bacteria evolved their adhesive mechanisms to attach efficiently in environments with different physico-chemical conditions. Many species of Alphaproteobacteria, including members of the orderCaulobacterales, use a polar adhesin, called holdfast, for surface attachment and subsequent biofilm formation in both freshwater and marine environments.Hirschia baltica,a marine member ofCaulobacterales,produces a holdfast adhesin that tolerates a drastically higher ionic strength than the holdfast produced by its freshwater relative,Caulobacter crescentus. In this work, we show that the holdfast polysaccharide deacetylase HfsH plays an important role in adherence in high ionic strength environments. We show that deletion ofhfsHinH. balticadisrupts holdfast binding properties and structure. Increasing expression of HfsH inC. crescentusimproved holdfast binding in high salinity, whereas lowering HfsH expression inH. balticareduced holdfast binding at high ionic strength. We conclude that HfsH plays a role in modulating holdfast binding at high ionic strength and hypothesize that this modulation occurs through varied deacetylation of holdfast polysaccharides.
Gasdermin D mediates inflammation-induced defects in reverse cholesterol transport and promotes atherosclerosis
Authors: Opoku Emmanuel , Alicia Traughber C. , Zhang David , Iacano Amanda J , Khan Mariam , Han Juying , Smith Jonathan D , Gulshan Kailash 
Published: April 2021

AbstractActivation of inflammasomes, such as Nlrp3 and Aim2, can exacerbate atherosclerosis in mice and humans. Gasdermin D (GsdmD) serves as a final executor of inflammasome activity, by generating membrane pores for the release of mature Interleukin-1beta (IL-1β). Inflammation dampens reverse cholesterol transport (RCT) and promotes atherogenesis, while anti-IL-1β antibodies were shown to reduce cardiovascular disease in humans. Though Nlrp3/AIM2 and IL-1β nexus is an emerging atherogenic pathway, the direct role of GsdmD in atherosclerosis is not yet fully clear. Here, we used in-vivo Nlrp3 inflammasome activation to show that the GsdmD-/-mice release ~80% less IL-1β vs WT mice. The GsdmD-/-macrophages were more resistant to Nlrp3 inflammasome mediated reduction in cholesterol efflux, showing ~26% decrease vs. ~60% reduction in WT macrophages. GsdmD expression in macrophages exacerbated foam cell formation in an IL-1β dependent fashion. The GsdmD-/-mice were resistant to Nlrp3 inflammasome mediated defect in RCT, with ~32% reduction in plasma RCT vs. ~ 57% reduction in WT mice, ~ 17% reduction in RCT to liver vs. 42% in WT mice, and ~ 37% decrease in RCT to feces vs. ~ 61% in WT mice. The LDLr anti-sense oligonucleotides (ASO) induced hyperlipidemic mouse model showed the role of GsdmD in promoting atherosclerosis. The GsdmD-/-mice exhibit ~42% decreased atherosclerotic lesion area in females and ~33% decreased lesion area in males vs. WT mice. The atherosclerotic plaque-bearing sections stained positive for the cleaved N-terminal fragment of GsdmD, indicating cleavage of GsdmD in atherosclerotic plaques. Our data show that GsdmD mediates inflammation-induced defects in RCT and promotes atherosclerosis.SummaryGsdmD mediates inflammation-induced defects in RCT and promotes atherosclerosis.
Causal roles of prefrontal cortex during spontaneous perceptual switching are determined by brain state dynamics
Authors: Watanabe Takamitsu 
Published: April 2021

AbstractThe prefrontal cortex (PFC) is thought to orchestrate cognitive dynamics. However, in tests of bistable visual perception, no direct evidence supporting such presumable causal roles of the PFC has been reported. Here, using a novel brain-state-dependent neural stimulation system, we found that three PFC regions—right frontal eye fields and anterior/posterior dorsolateral PFCs (a/pDLPFCs)—have causal effects on perceptual dynamics but the behavioural effects are detectable only when we modulated the PFC activity in brain-state-/state-history-dependent manners. Also, we revealed that the brain-dynamics-dependent behavioural causality is underpinned by transient changes in the brain state dynamics, and such neural changes are determined by structural transformations of hypothetical energy landscapes. Moreover, we identified different functions of the three PFC areas: in particular, we found that aDLPFC enhances the integration of the two PFC-active brain states, whereas pDLPFC promotes the diversity between them. This work resolves the controversy over the PFC roles in spontaneous perceptual switching and underlines brain state dynamics in fine investigations of brain-behaviour causality.Impact statementPrefrontal causal roles are changing during bistable visual perception, which was determined by large-scale brain state dynamics and attributable to hypothetical energy landscapes that underpin the brain state dynamics.
Florigen revisited: proteins of the FT/CETS/PEBP/PKIP/YbhB family may be the enzymes of small molecule metabolism
Authors: Tsoy Olga , Mushegian Arcady 
Published: April 2021

AbstractFlowering signals are sensed in plant leaves and transmitted to the shoot apical meristems, where the formation of flowers is initiated. Searches for a diffusible hormone-like signaling entity (“florigen”) went on for many decades, until in the 1990s a product of plant geneFTwas identified as the key component of florigen, based on genetic evidence and protein localization studies. Sequence homologs of FT protein are found throughout prokaryotes and eukaryotes; some eukaryotic family members appear to bind phospholipids or interact with the components of the signal transduction cascades. We studied molecular features of the FT homologs in prokaryotes and analyzed their genome context, to find tentative evidence connecting the bacterial family members with small molecule metabolism, often involving sugar- or ribonucleoside-containing substrates. Most FT homologs share a constellation of five charged residues, three of which, i.e., two histidines and an aspartic acid, circumfere the rim of a well-defined cavity on the protein surface. We argue that this conserved feature is more likely to be an enzymatic active center than a catalytically inactive ligand-binding site. We propose that most of FT-related proteins are enzymes operating on small diffusible molecules, which may constitute an overlooked essential ingredient of the florigen signal.
Axis formation in annual killifish: Nodal coordinates morphogenesis in absence of Huluwa prepatterning
Authors: Abitua Philip B. , Aksel Deniz C. , Schier Alexander F. 
Published: April 2021

AbstractAxis formation in fish and amphibians is initiated by a prepattern of maternal gene products in the blastula. The embryogenesis of annual killifish challenges prepatterning models because blastomeres disperse and then re-aggregate to form the germ layers and body axes. This dispersion-aggregation process prompts the question how axis determinants such as Huluwa and germ layer inducers such as Nodal function in annual killifish. Here we show inNothobranchius furzerithathuluwa, the factor thought to break symmetry by stabilizing β-catenin, is a non-functional pseudogene. Nuclear β-catenin is not selectively stabilized on one side of the blastula but accumulates in cells forming the incipient aggregate. Inhibition of Nodal signaling blocks aggregation and disrupts coordinated cell migration, establishing a novel role for this signaling pathway. These results reveal a surprising departure from classic mechanisms of axis formation: canonical Huluwa-mediated prepatterning is dispensable and Nodal coordinates morphogenesis.One Sentence SummaryAxis formation in annual killifish relies on Nodal to coordinate cell migration and is independent of Huluwa-mediated prepatterning.