bluuebunny/crossref_metadata_2025_split huggingface dataset:
qMaLioffG: A single green fluorescent protein FLIM indicator enabling quantitative imaging of endogenous ATP
Authors: Arai Satoshi , Itoh Hideki , Vu Cong Quang , Nakayama Mizuho , Oshima Masanobu , Morita Atsuya , Okamoto Kazuko , Okuda Satoru , Teranishi Aki , Osawa Madori , Tamura Yoshiteru , Nonoyama Shigeaki , Takuma Megumi , Fujie Toshinori , Sarker Satya Ranjan , Sudhaharan Thankiah , Kiya Taketoshi , Lane E. Birgitte , Kitaguchi Tetsuya 
Published: August 2023

AbstractThe widespread use of fluorescence lifetime imaging microscopy (FLIM) for quantitative imaging is hindered by the limited availability of a FLIM-based genetically encoded indicator using a conventional 488 nm laser. Here, we present qMaLioffG, a single green fluorescent protein FLIM indicator showing a fluorescence lifetime change in ATP concentration within the physiological range. This allows quantitative imaging of endogenous ATP to investigate cellular energy status of different cell types.
Decoding the Influence of Central LEAP2 on Hedonic Food Intake and its association with Dopaminergic Reward Pathways
Authors: Tufvesson-Alm Maximilian , Zhang Qian , Aranäs Cajsa , Blid Sköldheden Sebastian , Edvardsson Christian E , Jerlhag Elisabet 
Published: August 2023

AbstractThe gut-brain peptide ghrelin and its receptor (GHSR) are established as a regulator of hunger and reward-processing. However, the recently recognized GHSR inverse agonist, liver-expressed antimicrobial peptide 2 (LEAP2), is less characterized. Given the role of GHSR in many central processes, and in particular reward, understanding the central effects of LEAP2 is of high interest to understand reward-related behaviors and disorders, including hedonic feeding in eating disorders. The present study aimed to elucidate LEAP2s central effect on reward-related behaviors through hedonic feeding and its mechanism. LEAP2 was administrated centrally in male mice and effectively reduced hedonic feeding but had no or little effect on homeostatic chow intake when a more palatable option was available. Strikingly, the effect on hedonic feeding was correlated to the preference of the palatable food option, where peanut butter showed the highest preference and the greatest reduction by LEAP2. Further, LEAP2 reduced the rewarding memory of high-preference foods, as well as attenuated the accumbal dopamine release associated with peanut butter exposure and eating. Interestingly, LEAP2 was widely expressed in the brain, and in particular in reward-related brain areas such as the laterodorsal tegmental area (LDTg). The expression in this area was also markedly altered when given free access to peanut butter. Accordingly, infusion of LEAP2 into the LDTg was sufficient to attenuate acute peanut butter eating. Taken together, the present results show that central LEAP2 has a profound effect on central dopaminergic reward signaling and affects several aspects of hedonic eating. The present study highlights LEAP2s effect on reward, which may have application not only for hedonic feeding, but for other reward-related psychiatric disorders as well.
An efficient and robust ABC approach to infer the rate and strength of adaptation
Authors: Murga-Moreno Jesús , Casillas Sònia , Barbadilla Antonio , Uricchio Lawrence , Enard David 
Published: August 2023

AbstractInferring the effects of positive selection on genomes remains a critical step in characterizing the ultimate and proximate causes of adaptation across species, and quantifying positive selection remains a challenge due to the confounding effects of many other evolutionary processes. Robust and efficient approaches for adaptation inference could help characterize the rate and strength of adaptation in non-model species for which demographic history, mutational processes, and recombination patterns are not currently well-described. Here, we introduce an efficient and user-friendly extension of the McDonald-Kreitman test (ABC-MK) for quantifying long-term protein adaptation in specific lineages of interest. We characterize the performance of our approach with forward simulations and find that it is robust to many demographic perturbations and positive selection configurations, demonstrating its suitability for applications to non-model genomes. We apply ABC-MK to the human proteome and a set of known Virus Interacting Proteins (VIPs) to test the long-term adaptation in genes interacting with viruses. We find substantially stronger signatures of positive selection on RNA-VIPs than DNA-VIPs, suggesting that RNA viruses may be an important driver of human adaptation over deep evolutionary time scales.
Metabolites with benzene ring from sugarcane leaf play important role in plant-Spodoptera frugiperdainteraction
Authors: Su Liangyinan , Hu Chunyu , Wang Chaoqi , Chen Baoshan , Zhao Yang 
Published: August 2023

AbstractSecondary metabolism plays important role in plant growth and development, however, the relationship between secondary metabolism and adaptive plant-insect communication is largely unknown. The present study used sugarcane line highly susceptible toSpodoptera frugiperdaand sister line with medium resistance to analyze the role of plant non-volatile organic compounds (NOCs) and volatile organic compounds (VOCs) in sugarcane-S. frugiperdainteraction. A total of 46 plant NOCs and 15 plant VOCs significantly different between resistant and susceptible lines and were continuously up-regulated and down-regulated at different time points before/afterS.frugiperdatreatment were screened. Phenolic acids containing benzene ring accounted for the largest proportion of differential NOCs. Levels of 66.7% of these phenolic acids were higher in susceptible line. Feeding supplemented with NOCs showed that phenoxyacetic acid (phenolic acid) and 4-methoxybenzaldehyde (aromatic phenolic acid) both increased the male-to-female ratio ofS. frugiperda. Aromatics containing benzene ring, accounted for the largest of differential VOCs in susceptible line. Two aromatics,p-cymene and benzene and 1-ethenyl-4-methoxy-, with higher level in susceptible line, were attractive toS. frugiperda. Terpenoids, aldehyde, and esters accounted for most of higher-in-resistant VOCs, with most tested to be repellent toS. frugiperda. Furthermore, transcriptome analysis ofS. frugiperdafeeding on susceptible and resistant lines combined with feeding assays revealed that tryptophan, as a precursor of aromatic compounds that also contains benzene ring, could promote the growth and development ofS. frugiperdain nutritional deficiency condition. These findings together suggested that benzene-ring containing compounds play a critical role in plant-Spodoptera frugiperdainteraction.
Social learning of a challenging two-step action sequence fulfils key criteria of cumulative culture in an insect
Authors: Bridges Alice D. , Royka Amanda , Wilson Tara , Chittka Lars 
Published: August 2023

SummaryCulture in non-human animals refers to behaviour that is socially learned and persists within a population over time. Human culture is notable in that it iscumulative: new innovations have built on previous ones over thousands of years. As a result, what is acquired via social learning often goes far beyond the capacity of any individual to independently discover it during their lifetime1–3. To date, no previous study has convincingly demonstrated this phenomenon in a non-human animal. Here, we show that bumblebees can learn from a trained demonstrator to open a novel, 3D-printed two-step puzzle box to obtain food rewards, even though they fail to do so independently. Experimenters were unable to train demonstrators to perform the unrewarded first step of the behaviour without providing a temporary reward linked to this action: the reward then being removed during later stages of training. However, a third of naïve observers learned to open the two-step box from these demonstrators, without ever having been rewarded after the first step. This suggested that social learning might permit the acquisition of behaviours too complex to “re-innovate” via individual learning. Furthermore, naïve bees failed to open the box despite extended exposure over the course of 12 days. The temporal and spatial distance of the unrewarded first step from the reward appeared to inhibit acquisition of two-step box-opening via individual associative learning, but this limitation was overcome by the presence of a trained conspecific. To our knowledge, these results make bumblebees the first animal to demonstrate the ability to socially learn a behaviour that is beyond their ability to innovate individually. This finding challenges the prevailing opinion of the field, which generally considers cumulative culture, which is built on this capacity, to be unique to humans.
Lignin, glutathione and kinases play important roles inPaspalum regnelliidefense against spittlebug (Mahanarva spectabilis) attack
Authors: Begnami Isabela dos Santos , Aono Alexandre Hild , Graciano Diego da Silva , Carmello-Guerreiro Sandra Maria , Ferreira Rebecca Caroline Ulbricht , Malagó Wilson , Gusmão Marcos Rafael , de Souza Anete Pereira , Vigna Bianca Baccili Zanotto 
Published: August 2023

SummarySpittlebugs cause large production losses that affect agribusiness worldwide. Understanding plant-herbivore interactions at molecular level may be the key to developing resistant cultivars.We assembled ade novotranscriptome for elucidate the roots response from twoPaspalum regnelliigenotypes (BGP 248 and 344) to spittlebug (Mahanarva spectabilis)nymph attack, integrating differential expression analysis and complex network modeling, supplemented by a resistance field experiment and root anatomical analysis.GO terms related to different stress responses were enriched in BGP 248, such as salicylic acid catabolic process, while some specific to spittlebugs like response to herbivores were enriched in BP 344. KEGG enriched pathways were related to structural differences between genotypes, for example, cutin, suberin and wax biosynthesis. BP 344 also presented pathways related to induced defense, such as glutathione metabolism. Metabolic networks highlighted kinases, and coexpression networks demonstrated a greater complexity in their response cascade, which includes lncRNAs.This study provides the first molecular insights into the defense mechanisms ofP. regnelliiagainstM. spectabilis.It was identified that the genotype with the highest nymph mortality (BGP 344) has constitutive barriers, such as lignin, which delay the attack. In addition to presenting a glutathione pathway enriched and greater presence of kinases.
Lymphatic vessel transit seeds precursors to cytotoxic resident memory T cells in skin draining lymph nodes
Authors: Heim Taylor A. , Schultz Austin C. , Delclaux Ines , Cristaldi Vanessa , Churchill Madeline J. , Lund Amanda W. 
Published: August 2023

AbstractResident memory T cells (TRM) provide rapid, localized protection in peripheral tissues to pathogens and cancer. While TRMare also found in lymph nodes (LN), how they develop during primary infection and their functional significance remains largely unknown. Here, we track the anatomical distribution of anti-viral CD8+T cells as they simultaneously seed skin and LN TRMusing a model of skin infection with restricted antigen distribution. We find exquisite localization of LN TRMto the draining LN of infected skin. LN TRMformation depends on lymphatic transport and specifically egress of effector CD8+T cells that appear poised for residence as early as 12 days post infection. Effector CD8+T cell transit through skin is necessary and sufficient to populate LN TRMin draining LNs, a process reinforced by antigen encounter in skin. Importantly, we demonstrate that LN TRMare sufficient to provide protection against pathogenic rechallenge. These data support a model whereby a subset of tissue infiltrating CD8+T cells egress during viral clearance, and establish regional protection in the draining lymphatic basin as a mechanism to prevent pathogen spread.One Sentence SummaryT cell egress out of virally infected skin via afferent lymphatic vessels seeds CD8+resident memory T cells in the draining lymph node.
Different Purkinje cell pathologies cause specific patterns of progressive ataxia in mice
Authors: Jaarsma Dick , Birkisdóttir Maria B. , van Vossen Randy , Oomen Demi W.G.D. , Akhiyat Oussama , Vermeij Wilbert P. , Koekkoek Sebastiaan K.E. , De Zeeuw Chris I. , Bosman Laurens W.J. 
Published: August 2023

BackgroundGait ataxia is one of the most common and impactful consequences of cerebellar dysfunction. Purkinje cells, the sole output neurons of the cerebellar cortex, are often involved in the underlying pathology, but their specific functions during locomotor control in health and disease remain obfuscated.ObjectivesWe aimed to describe the effect of gradual adult-onset Purkinje cell degeneration on gaiting patterns in mice and whether two different mechanisms that both lead to Purkinje cell degeneration caused different patterns in the development of gait ataxia.MethodsUsing the ErasmusLadder together with a newly developed limb detection algorithm and machine learning-based classification, we subjected mice to a physically challenging locomotor task with detailed analysis of single limb parameters, intralimb coordination and whole-body movement. We tested two Purkinje cell-specific mouse models, one involving stochastic cell death due to impaired DNA repair mechanisms (Pcp2-Ercc1-/-), the other carrying the mutation that causes spinocerebellar ataxia type 1 (Pcp2-ATXN1[82Q]).ResultsBoth mouse models showed increasingly stronger gaiting deficits, but the sequence with which gaiting parameters deteriorated depended on the specific mutation.ConclusionsOur longitudinal approach revealed that gradual loss of Purkinje cell function can lead to a complex pattern of loss of function over time, and this pattern depends on the specifics of the pathological mechanisms involved. We hypothesize that this variability will also be present in disease progression in patients, and our findings will facilitate the study of therapeutic interventions in mice, as very subtle changes in locomotor abilities can be quantified by our methods.
Zebrafishacta1bas a Candidate for Modeling Human Actin Cardiomyopathies
Authors: Prill Kendal , Ojehomon Matiyo , Sandhu Love , Young Sarah , Dawson John F. 
Published: August 2023

AbstractHeart failure is the leading cause of mortality worldwide, primarily associated with cardiovascular disease. Many heart muscle diseases are caused by mutations in genes that encode contractile proteins, including cardiac actin mutations. Zebrafish are an advantageous system for modelling cardiac diseases due to their ability to develop without a functional heart throughout embryonic development. However, genome duplication in the teleost lineage poses a unique challenge by increasing the number of genes involved in heart development. Four actin genes are expressed in the zebrafish heart:acta1b, actc2, and duplicates ofactc1aon chromosomes 19 and 20. In this study, we characterize the actin genes involved in early zebrafish heart development usingin situhybridization and CRISPR targeting to determine the most suitable gene for modelling actin changes observed in human patients with heart disease. Theactc1aandacta1bgenes are predominantly expressed during embryonic heart development, resulting in severe cardiac phenotypes when targeted with CRISPR. Considering the duplication of theactc1agene, we recommendacta1bas the best gene for targeted cardiac actin research.
Antibody effector functions are required for broad and potent protection of neonates from herpes simplex virus infection
Authors: Slein Matthew D. , Backes Iara M. , Garland Callaghan R. , Kelkar Natasha S. , Leib David A. , Ackerman Margaret E. 
Published: August 2023

SummaryThe failure of multiple herpes simplex virus (HSV) vaccine candidates that induce neutralizing antibody responses raises the hypothesis that other activities, such as Fc domain-dependent effector functions, may be critical for protection. While neonatal HSV (nHSV) infection result in mortality and lifelong neurological morbidity in humans, it is uncommon among neonates with a seropositive birthing parent, suggesting the potential efficacy of antibody-based therapeutics to protect neonates. We therefore investigated the mechanisms of monoclonal antibody (mAb)-mediated protection in a mouse model of nHSV infection. Both neutralization and effector functions contributed to robust protection against nHSV-1. In contrast, effector functions alone were sufficient to protect against nHSV-2, exposing a functional dichotomy between virus types that is consistent with vaccine trial results. Together, these results emphasize that effector functions are crucial for optimal mAb-mediated protection, informing effective Ab and vaccine design, and demonstrating the potential of polyfunctional Abs as potent therapeutics for nHSV infections.Graphical abstract.Mechanistic dissection of antibody-mediated protection from HSV.Monoclonal antibodies (mAbs) with varying neutralizing potencies and Fc modifications that impact effector function were evaluated in wildtype (WT) and FcγR-/- mice to define mechanisms of antibody-mediated protection from HSV infection. To model human vulnerability to HSV disease during the neonatal period, neonatal mice were challenged with HSV, treated with mAb, and then assessed for morbidity and mortality. We observed that polyfunctional mAbs provide broader and more potent protection than antibodies with either low neutralization or low effector function. Moreover, while sufficient for protection against HSV-1, neutralization activity alone was unable to protect from HSV-2 infection.
Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): An open access disease specific drug discovery portal
Authors: Priyadarsinee Lipsa , Jamir Esther , Nagamani Selvaraman , Mahanta Hridoy Jyoti , Kumar Nandan , John Lijo , Sarma Himakshi , Kumar Asheesh , Gaur Anamika Singh , Sahoo Rosaleen , Vaikundamani S. , Murugan N. Arul , Priyakumar U. Deva , Raghava G.P.S. , Bharatam Prasad V. , Parthasarathi Ramakrishnan , Subramanian V. , Sastry G. Madhavi , Sastry G. Narahari 
Published: August 2023

AbstractComputational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDSTB). As specific computational tools are often required for a given disease, developing a disease specific web portal is highly desirable. This paper emphasises on the development of the customised web portal for COVID-19 infection and is referred to as MPDSCOVID-19. Expectedly, the MPDS suites of programs have modules which are essentially independent of a given disease, whereas some modules are specific to a particular disease. In the MPDSCOVID-19portal, there are modules which are specific to COVID-19, and these are clubbed in SARS-COV-2 disease library. Further, the new additions and/or significant improvements were made to the disease independent modules, besides the addition of tools from galaxy toolshed. This manuscript provides a latest update on the disease independent modules of MPDS after almost 6 years, as well as provide the contemporary information and tool-shed necessary to engage in the drug discovery research of COVID-19. The disease independent modules include file format converter and descriptor calculation under the data processing module; QSAR, pharmacophore, scaffold analysis, active site analysis, docking, screening, drug repurposing tool, virtual screening, visualisation, sequence alignment, phylogenetic analysis under the data analysis module; and various machine learning packages, algorithms and in-house developed machine learning antiviral prediction model are available. The MPDS suite of programs are expected to bring a paradigm shift in computational drug discovery, especially in the academic community, guided through a transparent and open innovation approach. The MPDSCOVID-19can be accessed athttp://mpds.neist.res.in:8085.
Substrate-Specific Function of PNPLA3 Facilitates Hepatic VLDL-Triglyceride Secretion During Stimulated Lipogenesis
Authors: Johnson Scott , Bao Hanmei , McMahon Cailin , Chen Yongbin , Burr Stephanie , Anderson Aaron , Madeyski-Bengtson Katja , Lindén Daniel , Han Xianlin , Liu Jun 
Published: August 2023

AbstractThe I148M variant of PNPLA3 is strongly linked to hepatic steatosis. Evidence suggests a gain-of-function role for the I148M mutant as an ATGL inhibitor, leaving the physiological relevance of wild-type PNPLA3 undefined. Here we show that PNPLA3 selectively degrades triglycerides (TGs) enriched in polyunsaturated fatty acids (PUFAs) independently of ATGL in cultured cells and mice. Lipidomics and metabolite tracing analyses demonstrated that PNPLA3 mobilizes PUFAs from intracellular TGs for phospholipid desaturation, supporting hepatic secretion of TG-rich lipoproteins. Consequently, mice with liver-specific knockout or acute knockdown of PNPLA3 both exhibited aggravated liver steatosis and concomitant decreases in plasma VLDL-TG, phenotypes that manifest only under lipogenic conditions. I148M-knockin mice similarly displayed impaired hepatic TG secretion during lipogenic stimulation. Our results highlight a specific context whereby PNPLA3 facilitates the balance between hepatic TG storage and secretion and suggest the potential contributions of I148M variant loss-of-function to the development of hepatic steatosis in humans.Summary StatementWe define the physiological role of wild type PNPLA3 in maintaining hepatic VLDL-TG secretion.
Strong genetic differentiation but limited niche partitioning in a sympatric species pair separated by an allochronic reproductive barrier
Authors: Irvine Mitchell , Stewart Zachary , Kumaran Nagalingam , Manawaduge Chapa G. , Ryan James , Balagawi Solomon , Missenden Brendan , Starkie Melissa , Clarke Anthony R. , Hurwood David , Prentis Peter 
Published: August 2023

AbstractThe combination of differential adaptation to ecological niches and the development of reproductive barriers are considered helpful for maintaining co-existing species. In the absence of one of these elements, species boundaries are expected to breakdown. The tephritid fruit fly species pair,Bactrocera tryoniandB. neohumeralis, have significant overlap in geographic range and host use, with time of day of male mating the only known difference in their mating systems. Using a combination of ecological (seasonal abundance, host use and habitat use) and genomic data, we tested the differing roles of competition and assortative mating on the maintenance of the species boundaries in this species pair. Genome-wide SNP analyses found strong genetic differentiation between the species with no evidence for hybridization in the field. Most outlier SNPs were restricted to narrow regions towards the centromeres and telomeres of chromosomes and high nucleotide diversity rates were observed throughout the chromosomes of both species. Enrichment of annotation terms indicated an overabundance of genes with the ‘abnormal neuroanatomy’ term. Terms of interest associated with sleep and circadian rhythm, potentially important to the allochronic reproductive barrier, were non-enriched. Ecological data found limited evidence for ecological differentiation between the two species based on significant positive correlations between species numbers trapped at different times of the year, trapped in different habitats within a region, or when reared from fruit.Our study highlights the significance of assortative mating over ecological differentiation for sympatric maintenance of theB. tryoni/B. neohumeralissibling pair.