bluuebunny/crossref_metadata_2025_split huggingface dataset:
How altricial birds respond to a heat challenge: organismal perspectives on coping with a future climate scenario
Authors: Woodruff Mary J. , Tsueda Susanna N. , Cutrell Tiernan S. , Guardado Ethan A. , Rusch Douglas B. , Buechlein Aaron , Rosvall Kimberly A. 
Published: January 2024

AbstractThe ability to cope with heatwaves is likely to influence species success amidst climate change. However, relatively little is known about heat-coping mechanisms in endotherms, which are increasingly pushed to their thermoregulatory limits. We experimentally elevated nest temperatures by 4.5°C for 4 hours, focused on 12-day-old tree swallows (Tachycineta bicolor).Nestlings exposed to sub-lethal heat moved towards cooler air at the nest box entrance, they panted more, and they weighed less than controls, suggesting panting-induced water loss. They also exhibited higher heat shock protein (HSP) gene expression in the blood, alongside widespread transcriptional differences related to antioxidant defenses, inflammation, and apoptosis. Nestlings exposed to milder heat were more likely to recruit into the breeding population, suggesting these coping mechanisms may be quite effective.We also tested hypotheses on the drivers of variation in HSP gene expression, which was especially marked after heat-exposure. Even siblings in the same nest differed in HSP gene expression by over 14-fold. Heat-induced HSP levels were unrelated to individual body mass, or among-nest differences in brood size, temperature, and behavioral thermoregulation. However, nest ID explained a significant amount of HSP variation, which was larger between nests than within nests, pointing to genetic or early developmental factorsThese results fill key knowledge gaps on thermoregulatory mechanisms in birds. We document ample individual variation upon which selection may act in the context of climate change and we underscore the need to understand intra-specific variation, an oft-ignored element that nevertheless shapes what is possible for future adaptation or acclimation to heat.
Targeted-Neuroinflammation Mitigation Using Inflammasome-Inhibiting Nanoligomers is Therapeutic in Experimental Autoimmune Encephalomyelitis (EAE) Mouse Model
Authors: Sharma Sadhana , Risen Sydney , Gilberto Vincenzo , Boland Sean , Chatterjee Anushree , Moreno Julie A. , Nagpal Prashant 
Published: January 2024

ABSTRACTMultiple Sclerosis (MS) is a debilitating autoimmune disease that impacts millions of patients worldwide, disproportionately impacting women (4:1), and often presenting at highly productive stages of life. This disease affects the spinal cord and brain, and is characterized by severe neuroinflammation, demyelination, and subsequent neuronal damage, resulting in symptoms like loss of mobility. While untargeted and pan-immunosuppressive therapies have proven to be disease-modifying and manage (or prolong the time between) symptoms in many patients, a significant fraction are unable to achieve remission. Recent work has suggested more targeted neuroinflammation mitigation through selective inflammasome-inhibition can offer relief to patients, while preserving key components of immune function. Here we show a screening of potential therapeutic targets using inflammasome-inhibiting Nanoligomers (NF-κB1, TNFR1, TNF-α, IL-6), that meet or far-exceed commercially available small-molecule counterparts like Ruxolitinib, MCC950, and Deucravacitinib. Using the human brain organoid model, top Nanoligomer combinations (NF-κB1+TNFR1: NI111, and NF-κB1+NLRP3: NI112) were shown to significantly reduce neuroinflammation, without any observable negative impact on organoid function. Further testing of these top Nanoligomer combinations in an aggressive Experimental Autoimmune Encephalomyelitis (EAE) mouse model for MS using intraperitoneal (IP) injections showed that NF-κB1and NLRP3 targeting Nanoligomer combination NI112 rescues mice without observable loss of mobility or disability, minimal inflammation in brain and spinal cord histology, and minimal to no immune cell infiltration of the spinal cord and no demyelination, similar to or at par with mice that received no EAE injections (negative control). Mice receiving NI111 (NF-κB1+TNFR1) also showed reduced neuroinflammation compared to saline (sham) treated EAE mice and at par/similar to other inflammasome-inhibiting small molecule treatments, although it was significantly higher than NI112 leading to subsequent worsening clinical outcomes. Furthermore, treatment with an oral formulation of NI112 at lower doses showed a significant reduction in EAE severity, albeit with higher variance owing to administration and formulation/fill-and-finish variability. Overall, these results point to the potential of further development and testing these inflammasome targeting Nanoliogmers as an effective neuroinflammation treatment for multiple neurodegenerative diseases, and potentially benefit several patients suffering from such debilitating autoimmune diseases like MS.TOC GRAPHIC
Male contributions to female-male mutualism overcome the twofold cost of sex
Authors: Yasui Yukio , Hasegawa Eisuke 
Published: January 2024

ABSTRACTThe increasing rate of anisogamy (fusion between eggs and sperm) against asexual thelytoky is necessarily halved under a 1:1 sex ratio because males lay no eggs. The present dominance of anisogamy despite this twofold cost of male production is the greatest enigma in evolutionary biology. Various benefits of sex are insufficient to overcome this cost. How can anisogamy be maintained? Here, we propose hypotheses that anisogamy evolved as a female-male mutualism in which females produce large eggs to ensure zygote development and males produce many sperm to ensure fertilisation. In the real world with finite resources, thelytoky cannot express its twofold increasing potential, and various male functions reduce the thelytoky’s performance. Thus, the twofold cost is an artefact of the infinite resource assumption. Simple mathematical models and simulations showed that when males and thelytokous females are equally competitive and acquire the same amount of resources but males can develop with fewer resources than females, anisogamy outcompetes thelytoky. When males need more growth costs than females, as in sexually selected species, the excess mating activity of “harmful” males reduces the fitness of thelytokous females. The significance of sexes, a question since Aristotle’s time, is explained by male contribution to sustaining mutualism.
Shrimp Hemocyanin elicits a potent humoral response in mammals and is favorable to hapten conjugation
Authors: Sun Huiwen , Wei Moris , Guo Amber , Zhang Ci , Wang Yuefeng , Huang Renhui , Li Xiaoxiao , Zhan Jeffrey , Wu Jonny , Jiang Bruce 
Published: January 2024

AbstractConjugation to a carrier protein is essential to give rise to the antigenicity of hapten, which is a small molecule and cannot induce an immune response by itself alone. Three carrier proteins e.g. KLH (Keyhole Limpet Hemocyanin), BSA (Bovine Serum Albumin), and OVA (Ovalbumin) were used mostly. KLH is advantageous to the others, majorly owing to its strong immunogenicity and limited usage in other biological assays. However, the solubility of KLH is not as well as the others, especially after hapten conjugation. Besides, the high market price of KLH results in high costs in vaccine and antibody development. Here, we extracted the shrimp hemocyanin (SHC) fromPenaeus vannamei (P. vannamei)with a production yield of > 1 g proteins (98 % pure) per 1 kg shrimp. Compared to KLH, the peptide-SHC conjugates exhibit higher solubility after hapten conjugation. Furthermore, compared with KLH, SHC induces comparable antibody production efficiency in mammals, with or without conjugation. Finally, rabbit polyclonal antibodies or mouse monoclonal antibodies were generated by immunizing SHC-peptide conjugates, and their applications in western blot, immunofluorescence and immunohistochemistry were confirmed. Therefore, we demonstrated that SHC may be used as a substitute for KLH in future antibody and vaccine development.
Identification of a distinct cluster of GDF15highmacrophages exhibiting anti-inflammatory activities
Authors: Dai Chaochao , Zhang Hongyu , Zheng Zhijian , Li Chun Guang , Ma Mingyuan , Gao Haiqing , Zhang Qunye , Cui Xiaopei , Jiang Fan 
Published: January 2024

AbstractMacrophage-mediated inflammatory response may have crucial roles in the pathogenesis of a variety of human diseases. Growth differentiation factor 15 (GDF15) is a cytokine of the transforming growth factor-β superfamily, with potential anti-inflammatory activities. Previous studies observed in human lungs some macrophages which expressed a high level of GDF15. In the present study, we employed multiple techniques, including immunofluorescence, flow cytometry, and single-cell RNA sequencing, in order to further clarify the identity of such GDF15highmacrophages. We demonstrated that macrophages derived from human peripheral blood mononuclear cells and rat bone marrow mononuclear cells byin vitrodifferentiation with granulocyte-macrophage colony stimulating factor contained a minor population (∼1%) of GDF15highcells. GDF15highmacrophages did not exhibit a typical M1 or M2 phenotype, but had a unique molecular signature as revealed by single-cell RNA sequencing. Functionally, GDF15highmacrophages were associated with reduced responsiveness to pro-inflammatory activation; furthermore, GDF15highmacrophages could inhibit the pro-inflammatory functions of other macrophages via a paracrine mechanism. We further confirmed that GDF15per sewas a key mediator of the anti-inflammatory effects of GDF15highmacrophage. Also, we provided direct evidence showing that GDF15highmacrophages were also present in other macrophage-residing human tissues in addition to the lungs. Our results suggest that the GDF15highmacrophage may represent a distinct cluster of macrophage cells with intrinsic anti-inflammatory functions. The (patho)physiological importance of these cellsin vivowarrants further investigation.
Imipridones inhibit tumor growth and improve survival in an orthotopic liver metastasis mouse model of human uveal melanoma
Authors: Chattopadhyay Chandrani , Roszik Jason , Bhattacharya Rajat , Alauddin Md , Mahmud Iqbal , Yadugiri Sirisha , Ali Mir Mustafa , Khan Fatima S. , Prabhu Varun Vijay , Lorenzi Phillip , Burton Elizabeth , Morey Rohini R. , Lazcano Rossana , Davies Michael A. , Patel Sapna P. , Grimm Elizabeth A. 
Published: January 2024

AbstractPurposeUveal melanoma (UM) is a highly aggressive disease with very few treatment options. We previously demonstrated that mUM is characterized by high oxidative phosphorylation (OXPHOS). Here we tested the anti-tumor, signaling and metabolic effects of imipridones, CLPP activators which reduce OXPHOS indirectly and have demonstrated safety in patients.Experimental DesignWe assessed CLPP expression in UM patient samples. We tested the effects of imipridones (ONC201, ONC212) on the growth, survival, signaling and metabolism of UM cell linesin vitro,and for therapeutic effectsin vivoin UM liver metastasis models.ResultsCLPP expression was confirmed in primary and mUM patient samples. ONC201/212 treatment of UM cell linesin vitrodecreased OXPHOS effectors, inhibited cell growth and migration, and induced apoptosis. ONC212 increased metabolic stress and apoptotic pathways, inhibited amino acid metabolism, and induced cell death-related lipids. ONC212 also decreased tumor burden and increased survivalin vivoin two UM liver metastasis models.ConclusionImipridones are a promising strategy for further testing and development in mUM.
A multi-scale feature fusion model based on biological knowledge graph and transformer-encoder for drug-drug interaction prediction
Authors: Wang Tao , Deng Qiang , Hu Jialu , Wang Yongtian , Peng Jiajie , Chen Jing , Shang Xuequn 
Published: January 2024

AbstractDrug-Drug Interaction (DDI) refers to the combined effects that occur when a patient takes multiple medications simultaneously or within the same period. This interaction can either enhance the therapeutic effects of the drugs or inhibit their efficacy, and in severe cases, it can even lead to adverse drug reactions (ADRs). Thus, it is crucial to identify potential DDIs, as this information is significant for both biological research and clinical medicine. However, most existing works only consider the information of individual drugs or focus on the local correlation between a few medical entities, thus overlooking the global performance of the entire human medical system and the potential synergistic effects of multi-scale information. Consequently, these limitations hinder the predictive ability of models. In this paper, we propose an innovative multi-scale feature fusion model called ALG-DDI, which can comprehensively incorporate attribute information, local biological information, and global semantic information. To achieve this, we first employ the Attribute Masking method to obtain the embedding vector of the molecular graph. Next, ALG-DDI leverages heterogeneous graphs to capture the local biological information between drugs and several highly related biological entities. The global semantic information is also learned from the medicine-oriented large knowledge graphs. Finally, we employ a transformer encoder to fuse the multi-scale drug representations and feed the resulting drug pair vector into a fully connected neural network for prediction. Experimental evaluations on datasets of varying sizes and different classification tasks demonstrate that ALG-DDI outperforms other state-of-the-art models.
Beyond microtubules: The cellular environment at the endoplasmic reticulum attracts proteins to the nucleus, enabling nuclear transport
Authors: Chae Seok Joo , Kim Dae Wook , Igoshin Oleg A. , Lee Seunggyu , Kim Jae Kyoung 
Published: January 2024

SummaryAll proteins are translated in the cytoplasm, yet many, including transcription factors, play vital roles in the nucleus. While previous research has concentrated on molecular motors for the transport of these proteins to the nucleus, recent observations reveal perinuclear accumulation even in the absence of an energy source, hinting at alternative mechanisms. Here, we propose that structural properties of the cellular environment, specifically the endoplasmic reticulum (ER), can promote molecular transport to the perinucleus without requiring additional energy expenditure. Specifically, physical interaction between proteins and the ER impedes their diffusion and leads to their accumulation near the nucleus. This result explains why larger proteins, more frequently interacting with the ER membrane, tend to accumulate at the perinucleus. Interestingly, such diffusion in a heterogeneous environment follows Chapman’s law rather than the popular Fick’s law. Our findings suggest a novel protein transport mechanism arising solely from characteristics of the intracellular environment.HighlightsThe interaction of proteins with ER slows down their diffusion at the perinucleus.This leads proteins to migrate toward the perinucleus without ATP consumption.Frequent ER interaction of larger proteins promotes perinuclear accumulation.Diffusion with the physical interaction can be described by Chapman’s law.Graphical abstract
Circatidal control of gene expression in the deep-sea hot vent shrimpRimicaris leurokolos
Authors: Zhang Hongyin , Yahagi Takuya , Miyamoto Norio , Chen Chong , Jiang Qingqiu , Qian Pei-Yuan , Sun Jin 
Published: January 2024

AbstractBiological clocks are a ubiquitous feature of all life, enabling the use of natural environmental cycles to track time. Although studies on circadian rhythms have contributed greatly to the knowledge of chronobiology, biological rhythms in dark biospheres such as the deep sea remain poorly understood. Here, based on a laboratory free-running experiment, we reveal potentially endogenous rhythms in gene expression of the deep-sea hydrothermal vent shrimpRimicaris leurokolos. Oscillations with ∼12-hour periods, likely reflecting tidal influence, greatly prevail over others in the temporal transcriptome, indicatingR. leurokoloslikely depends on a circatidal clock consisting of at least some components independent of the circadian clocks. The tidal transcripts exhibit an antiphased expression pattern divided into two internally synchronized clusters, correlated with wide-ranging biological processes that occur in the nucleus and cytoplasm, respectively. In addition, comparing the tidal transcripts with the ∼12-hour ultradian rhythms genes in fruit flies and mice shows large similarity, indicating the likely scenario of broad impact of the tide on the ∼12-hour oscillations across the metazoan. These findings not only provide new insights into the temporal adaptations in deep-sea organisms but also highlight deep-sea hydrothermal vent organisms as intriguing models for chronobiological, particularly 12-hour ultradian rhythms, studies.
Cannabinoid type-1 (CB1) receptors in glial cells promote neuromuscular junction repair following nerve injury
Authors: Piovesana Roberta , Charron Sophie , Arbour Danielle , Marsicano Giovanni , Bellocchio Luigi , Robitaille Richard 
Published: January 2024

AbstractCannabinoids are frequently used in the treatment of neuropathic pain related to nerve injury. However, despite evidence for their roles in the regulation of axonal guidance and synapse formation during development of the central nervous system (CNS), their possible involvement in response to peripheral nerve injury remains poorly defined and the knowledge of its role is mostly related to the peripheral sensory system.Following nerve injury, contemporary to axonal repair, massive morphological and functional changes reshape synaptic elements at neuromuscular junctions (NMJs) aiming to promote their reinnervation. This process is mediated in part by Perisynaptic Schwann cells (PSCs), glial cells at the NMJ essential for its maintenance and repair.Here we investigated the novel role of Cannabinoid type-1 receptor (CB1R) at NMJ, in particular on PSCs, during motor nerve recovery following nerve injury. Using morphological analysis, we studied the consequences of CB1R pharmacological and genetic blockade following denervation and reinnervation in adult NMJs. CB1R blockade caused an acceleration of the denervation process followed by a great delay in reinnervation as indicated by a significant percentage of denervated NMJs, accompanied by a decrease of mono- and poly-innervated NMJs. Remarkably, a similar phenomenon was observed when CB1R is selectively knocked-out in glia, indicating that the protective actions of these receptors are largely glia-dependent.These data highlight a novel role of the endocannabinoid system at NMJs, where the CB1Rs on PSCs can control NMJ denervation and reinnervation following nerve injury. A better understanding of the functional mechanisms underlying CB1R role in NMJ repair may contribute to finding a new pharmacological treatment having a dual role in improvements of motor recovery and in pain-related relief.
Complex interspecific interactions influence the interactions between pest control and pollination in coffee agroecosystems
Authors: Vaidya Chatura , Dominguez Martine Gabriel , Vandermeer John 
Published: January 2024

AbstractEcosystem services mediated by biodiversity are essential for the well-being of human beings. While there is ample research on individual ecosystem services (such as pollination, nutrient cycling), there is now growing recognition to examine the interactions between multiple ecosystem services and their contribution to productivity in order to manage agroecosystems sustainably. In this study, we examined the interactions between pollination and pest control in coffee agroecosystems in Chiapas, Mexico. We tested how management of shade trees, particularly of nitrogen-fixing shade trees, at the farm scale mediated the outcome of the interactions between two ES. We found that there was no trade-off between pest control and pollination services despite the deterrence of pollinators by the dominant and aggressive ant species,Azteca sericeasur, which also controls the coffee berry borer, a major pest ofCoffea arabica. We found additive effects of pest-control and pollination on early fruit set and fruit weight of coffee plants. Proximity to nitrogen-fixing shade trees had indirect effects on pest-control via the reduction ofAzteca sericeasuractivity on the coffee bushes. These findings highlight that ecosystem services are a result of complex interspecific interactions and that biodiversity-friendly management practices can promote favorable outcomes of these interactions on coffee yield.
Uncovering the genetic architecture and evolutionary roots of androgenetic alopecia in African men
Authors: Janivara Rohini , Hazra Ujani , Pfennig Aaron , Harlemon Maxine , Kim Michelle S. , Eaaswarkhanth Muthukrishnan , Chen Wenlong C. , Ogunbiyi Adebola , Kachambwa Paidamoyo , Petersen Lindsay N. , Jalloh Mohamed , Mensah James E. , Adjei Andrew A. , Adusei Ben , Joffe Maureen , Gueye Serigne M. , Aisuodionoe-Shadrach Oseremen I. , Fernandez Pedro W. , Rohan Thomas E. , Andrews Caroline , Rebbeck Timothy R. , Adebiyi Akindele O. , Agalliu Ilir , Lachance Joseph 
Published: January 2024

AbstractAndrogenetic alopecia is a highly heritable trait. However, much of our understanding about the genetics of male pattern baldness comes from individuals of European descent. Here, we examined a novel dataset comprising 2,136 men from Ghana, Nigeria, Senegal, and South Africa that were genotyped using a custom array. We first tested how genetic predictions of baldness generalize from Europe to Africa, finding that polygenic scores from European GWAS yielded AUC statistics that ranged from 0.513 to 0.546, indicating that genetic predictions of baldness in African populations performed notably worse than in European populations. Subsequently, we conducted the first African GWAS of androgenetic alopecia, focusing on self-reported baldness patterns at age 45. After correcting for present age, population structure, and study site, we identified 266 moderately significant associations, 51 of which were independent (p-value < 10-5, r2< 0.2). Most baldness associations were autosomal, and the X chromosomes does not appear to have a large impact on baldness in African men. Finally, we examined the evolutionary causes of continental differences in genetic architecture. Although Neanderthal alleles have previously been associated with skin and hair phenotypes, we did not find evidence that European-ascertained baldness hits were enriched for signatures of ancient introgression. Most loci that are associated with androgenetic alopecia are evolving neutrally. However, multiple baldness-associated SNPs near theEDA2RandARgenes have large allele frequency differences between continents. Collectively, our findings illustrate how evolutionary history contributes to the limited portability of genetic predictions across ancestries.