bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accurate energy barriers for catalytic reaction pathways: an automatic training protocol for machine learning force fields
Authors: Schaaf Lars L. , Fako Edvin , De Sandip , Schäfer Ansgar , Csányi Gábor 
Published: October 2023

AbstractWe introduce a training protocol for developing machine learning force fields (MLFFs), capable of accurately determining energy barriers in catalytic reaction pathways. The protocol is validated on the extensively explored hydrogenation of carbon dioxide to methanol over indium oxide. With the help of active learning, the final force field obtains energy barriers within 0.05 eV of Density Functional Theory. Thanks to the computational speedup, not only do we reduce the cost of routine in-silico catalytic tasks, but also find an alternative path for the previously established rate-limiting step, with a 40% reduction in activation energy. Furthermore, we illustrate the importance of finite temperature effects and compute free energy barriers. The transferability of the protocol is demonstrated on the experimentally relevant, yet unexplored, top-layer reduced indium oxide surface. The ability of MLFFs to enhance our understanding of extensively studied catalysts underscores the need for fast and accurate alternatives to direct ab-initio simulations.
Self-amplifying mRNA seasonal influenza vaccines elicit mouse neutralizing antibody and cell-mediated immunity and protect ferrets
Authors: Cheung Michael , Chang Cheng , Rathnasinghe Raveen , Rossignol Evan , Zhang Yunfei , Ferrari Annette , Patel Harsh , Huang Yanjun , Sanchez Guillen Michelle , Scalzo Tina , Lee Changkeun , Otten Gillis R. , Settembre Ethan C. , Music Nedzad , Palladino Giuseppe , Wen Yingxia 
Published: October 2023

AbstractCurrently licensed influenza vaccines focus immune responses on viral hemagglutinin (HA), while the other major surface glycoprotein neuraminidase (NA) is not tightly controlled in inactivated vaccine formulations despite evidence that anti-NA antibodies reduce clinical disease. We utilized a bicistronic self-amplifying mRNA (sa-mRNA) platform encoding both HA and NA from four seasonal influenza strains, creating a quadrivalent influenza vaccine. sa-mRNA vaccines encoding an NA component induced the production of NA-inhibiting antibodies and CD4+ T-cell responses in both monovalent and quadrivalent formulations. Including NA in the vaccine enabled cross-neutralization against antigenically drifted strains and provided greater protection than HA alone upon A(H3N2) challenge in ferrets. These results demonstrate that next-generation bicistronic sa-mRNA vaccines expressing HA and NA induce potent antibodies against both viral coat proteins, as well as vaccine-specific cell-mediated immunity. When formulated as a quadrivalent seasonal influenza vaccine, the sa-mRNA platform provides an opportunity to increase the breadth of protection through cross-neutralizing anti-NA antibodies.
Bridging two insect flight modes in evolution, physiology and robophysics
Authors: Gau Jeff , Lynch James , Aiello Brett , Wold Ethan , Gravish Nick , Sponberg Simon 
Published: October 2023

AbstractSince taking flight, insects have undergone repeated evolutionary transitions between two seemingly distinct flight modes1–3. Some insects neurally activate their muscles synchronously with each wingstroke. However, many insects have achieved wingbeat frequencies beyond the speed limit of typical neuromuscular systems by evolving flight muscles that are asynchronous with neural activation and activate in response to mechanical stretch2–8. These modes reflect the two fundamental ways of generating rhythmic movement: time-periodic forcing versus emergent oscillations from self-excitation8–10. How repeated evolutionary transitions have occurred and what governs the switching between these distinct modes remain unknown. Here we find that, despite widespread asynchronous actuation in insects across the phylogeny3,6, asynchrony probably evolved only once at the order level, with many reversions to the ancestral, synchronous mode. A synchronous moth species, evolved from an asynchronous ancestor, still preserves the stretch-activated muscle physiology. Numerical and robophysical analyses of a unified biophysical framework reveal that rather than a dichotomy, these two modes are two regimes of the same dynamics. Insects can transition between flight modes across a bridge in physiological parameter space. Finally, we integrate these two actuation modes into an insect-scale robot11–13that enables transitions between modes and unlocks a new self-excited wingstroke strategy for engineered flight. Together, this framework accounts for repeated transitions in insect flight evolution and shows how flight modes can flip with changes in physiological parameters.
A high throughput screen for pharmacological inhibitors of the carbohydrate response element
Authors: You Shaochen , Bollong Michael J. 
Published: October 2023

AbstractA central regulator of metabolism, transcription factor carbohydrate response element binding protein (ChREBP) senses and responds to dietary glucose levels by stimulating the transcription of glycolytic and lipogenic enzymes. Genetic depletion of ChREBP rescues β-cell dysfunction arising from high glucose levels, suggesting that inhibiting ChREBP might represent an attractive therapeutic approach to manage diabetes and other metabolic diseases. However, the molecular mechanisms governing ChREBP activation are poorly understood and chemical tools to probe the cellular activity of ChREBP are lacking. Here, we report a high-throughput pharmacological screen in INS-1E β-cells that identified novel inhibitors of ChREBP-driven transcription at carbohydrate response element sites, including three putative covalent inhibitors and two likely non-covalent chemical scaffolds. This work affords a pharmacological toolkit to help uncover the signaling logic controlling ChREBP activation and may ultimately reveal potential therapeutic approaches for treating metabolic disease.
Impact of decreased levels of total CO2 on in-hospital mortality in patients with COVID-19
Authors: Kim Yaerim , Kwon Soie , Kim Seong Geun , Lee Jeonghwan , Han Chung-hee , Yu Sungbong , Kim Byunggun , Paek Jin Hyuk , Park Woo Yeong , Jin Kyubok , Han Seungyeup , Kim Dong Ki , Lim Chun Soo , Kim Yon Su , Lee Jung Pyo 
Published: October 2023

AbstractDecreased total CO2 (tCO2) is significantly associated with all-cause mortality in critically ill patients. Because of a lack of data to evaluate the impact of tCO2 in patients with COVID-19, we assessed the impact of tCO2 on all-cause mortality in this study. We retrospectively reviewed the data of hospitalized patients with COVID-19 in two Korean referral hospitals between February 2020 and September 2021. The primary outcome was in-hospital mortality. We assessed the impact of tCO2 as a continuous variable on mortality using the Cox-proportional hazard model. In addition, we evaluated the relative factors associated with tCO2 ≤ 22 mmol/L using logistic regression analysis. In 4,423 patients included, the mean tCO2 was 24.8 ± 3.0 mmol/L, and 17.9% of patients with tCO2 ≤ 22 mmol/L. An increase in mmol/L of tCO2 decreased the risk of all-cause mortality by 4.8% after adjustment for age, sex, comorbidities, and laboratory values. Based on 22 mmol/L of tCO2, the risk of mortality was 1.7 times higher than that in patients with lower tCO2. This result was maintained in the analysis using a cutoff value of tCO2 24 mmol/L. Higher white blood cell count; lower hemoglobin, serum calcium, and eGFR; and higher uric acid, and aspartate aminotransferase were significantly associated with a tCO2 value ≤ 22 mmol/L. Decreased tCO2 significantly increased the risk of all-cause mortality in patients with COVID-19. Monitoring of tCO2 could be a good indicator to predict prognosis and it needs to be appropriately managed in patients with specific conditions.
Human scent as a first-line defense against disease
Authors: Gordon Amy R. , Lundström Johan N. , Kimball Bruce A. , Karshikoff Bianka , Sorjonen Kimmo , Axelsson John , Lekander Mats , Olsson Mats J. 
Published: October 2023

AbstractIndividuals may have a different body odor, when they are sick compared to healthy. In the non-human animal literature, olfactory cues have been shown to predict avoidance of sick individuals. We tested whether the mere experimental activation of the innate immune system in healthy human individuals can make an individuals’ body odor be perceived as more aversive (intense, unpleasant, and disgusting). Following an endotoxin injection (lipopolysaccharide; 0.6 ng/kg) that creates a transient systemic inflammation, individuals smelled more unpleasant compared to a placebo group (saline injection). Behavioral and chemical analyses of the body odor samples suggest that the volatile components of samples from “sick” individuals changed qualitatively rather than quantitatively. Our findings support the hypothesis that odor cues of inflammation in axillary sweat are detectable just a few hours after experimental activation of the innate immune system. As such, they may trigger behavioral avoidance, hence constituting a first line of defense against pathogens of infected conspecifics.
Behavioral responses of wild chimpanzees toward a juvenile that suddenly lost its animacy due to a fall accident
Authors: Shimada Masaki , Yano Wataru 
Published: October 2023

AbstractDetailed observations of animal reactions to a collapsed individual in wild are rare but essential to debates about the perception of death by nonhuman animals, including chimpanzees. A male juvenile chimpanzee named Volta, a member of the M group in the Mahale Mountains National Park, fell from a tall tree and was temporarily incapacitated, suffering a severe concussion and nasal bone fracture. However, Volta showed signs of gradual recovery. We compared the behavior of other chimpanzees towards Volta with the previous reports on the behavior towards collapsed or recently dead group members. We found that behaviors towards Volta were similar to those observed towards collapsed or dead members. These included other-regarding behaviors and aggressive behaviors, and notably, licking of Volta’s blood, which has not been previously reported. Adult males tended to be in close proximity to Volta for longer periods than adult females. The social situation with adult males including alpha male, surrounding Volta likely influenced the behavior of other individuals. Exploring the state of recovery of the injured individual, by closely approaching, directing various behaviors, and observing the reactions of the victim, and demonstrate tolerance and consideration towards the victim.
Following the footsteps of Burmeister's leaf frog (Phyllomedusa burmeisteri) in the Atlantic forest of Brazil
Authors: Pareja-Mejía Daniela , Benevides Júlia , Gomes Lidiane , Moreira Da Silva Neto Edvaldo , Queiroz Menezes Vinícius , Silva Roseno Rafaella , Sabino Martins Amanda , Solé Mirco 
Published: October 2023

AbstractAmphibians are organisms which mainly have a biphasic life cycle. When at the larval stage, their habitat is generally aquatic, and when adults, they become terrestrial. Pond-breeding amphibians are sensitive to some disturbances in their environment which lead to the decline of a population. The interactions between the species and their environment are performed through movement. Movement ecology combines and explains the movement data of organisms with biotic and abiotic factors and because of this, knowing the movement of these creatures is of great ecological importance. We used the spool-and-line methodology in individuals of the treefrog Phyllomedusa burmeisteri, at the Reserva Ecologica Michelin, located in the southern region of Bahia in Brazil to study their movement patterns in different environments inside and outside of the forest. We monitored 19 P. burmeisteri individuals that presented a mean total movement distance of 2160.76 cm (S.D. 1152.42). We found no significant difference in the trajectories of individuals in forested and open areas, as well as a positive relationship between the distances individuals moved and their weight only in forested areas. no relationship between distance and weight of these individuals. We observed that individuals followed non-linear paths and the number of steps from one place to another varied among individuals. Our movement ecology data allows us to answer questions about short-term movement patterns of Phyllomedusa burmeisteri. This is the first step to start understanding the spatial cognition of treefrogs from the Atlantic Forest and to fill gaps about life habits of these frogs. Information on the movement patterns of a species, as well as its home range can help to create conservation strategies, regarding the creation or delimitation of protected areas, for example.
Circulatory extracellular vesicle derived miR-195-5p promotes cellular apoptosis and suppresses cell proliferation in the buffalo endometrial primary cell culture
Authors: Pal Ankit , Karanwal Seema , Chera Jatinder Singh , Batra Vipul , Kumaresan Arumugam , Sarwalia Parul , Datta Tirtha K. , Kumar Rakesh 
Published: October 2023

AbstractIn pregnant animals, communication between the mother and conceptus occurs via extracellular vesicles (EVs) that carry several biomolecules such as nucleic acids (miRNAs, mRNAs), proteins, and lipids. At the time of implantation, the endometrium undergoes several morphological and physiological changes, such as angiogenesis, apoptosis, and cell proliferation regulation at the implantation site, to attain a receptive state. This study was conducted to detect pregnancy-specific miRNAs derived from extracellular vesicles in the systemic circulation of Bubalus bubalis (water buffalo) and to assess their functional significance in the modulation of endometrial primary cells. The extracellular vesicles were isolated from the blood plasma using a precipitation-based method and further characterized by various methods such as Differential light scattering, Nanoparticle tracking assay, Western blot, and transmission electron microscopy. The relative expression of the selected extracellular vesicles associated miRNAs (EV-miRNA) at different intervals (days 15, 19, 25, and 30) post artificial insemination (AI) was analyzed using RT-qPCR, and expression of miR-195-5p was found to be significantly higher (P < 0.01) in pregnant animals on day 19 post AI (implantation window) as compared to day 15 post AI. The elevated expression might indicate the involvement of this miRNA in the maternal-conceptus cross-talk occurring during the implantation period. The KEGG pathway enrichment and Gene Ontology analyses of the miR-195-5p target genes revealed that these were mostly involved in the PI3-Akt, MAPK, cell cycle, ubiquitin-mediated proteolysis, and mTOR signaling pathways, which are related to the regulation of cell proliferation. Transfecting the in vitro cultured cells with miR-195-5p mimic significantly suppressed (P < 0.05) the expression of its target genes such as YWHAQ, CDC27, AKT-3, FGF-7, MAPK8, SGK1, VEGFA, CACAND1, CUL2, MKNK1, and CACAN2D1. Furthermore, the downregulation of the miR-195-5p target genes was positively correlated with a significant increase in the apoptotic rate and a decrease in the proliferation. In conclusion, the current findings provide vital information on the presence of EV miR-195-5p in maternal circulation during the implantation window indicating its important role in the modulation of buffalo endometrium epithelial cells via promoting cell death. Altogether, the milieu of miR-195-5p may serve as a novel and potential molecular factor facilitating the implantation of the early embryo during the establishment of pregnancy in buffaloes. Thus, miR-195-5p may be identified as a unique circulatory EV biomarker related to establishing pregnancy in buffaloes as early as day 19 post-AI.
Pinostilbene inhibits full-length and splice variant of androgen receptor in prostate cancer
Authors: Shin Won Sik , Han Seung Hyun , Jo Kyung Won , Cho Yunje , Kim Kyong-Tai 
Published: October 2023

AbstractProstate cancer is the most prevalent cancer in men worldwide and is promoted by the sex hormone androgen. Expression of androgen from the testis can be significantly reduced through castration. However, as most prostate cancer patients acquire castration resistance, additional therapeutic solutions are necessary. Although anti-androgens, such as enzalutamide, have been used to treat castration-resistant prostate cancer (CRPC), enzalutamide-resistant CRPC (Enz-resistant CRPC) has emerged. Therefore, development of novel treatments for Enz-resistant CRPC is urgent. In this study, we found a novel anti-androgen called pinostilbene through screening with a GAL4-transactivation assay. We confirmed that pinostilbene directly binds to androgen receptor (AR) and inhibits its activation and translocalization. Pinostilbene treatment also reduced the protein level and downstream gene expression of AR. Furthermore, pinostilbene reduced the protein level of AR variant 7 in the Enz-resistant prostate cancer cell line 22Rv1 and inhibited cell viability and proliferation. Our results suggest that pinostilbene has the potential to treat Enz-resistant CRPC.
Superconductivity in a breathing kagome metals ROs2 (R = Sc, Y, Lu)
Authors: Górnicka Karolina , Winiarski Michał J. , Walicka Dorota I. , Klimczuk Tomasz 
Published: October 2023

AbstractWe have successfully synthesized three osmium-based hexagonal Laves compounds ROs2 (R = Sc, Y, Lu), and discussed their physical properties. LeBail refinement of pXRD data confirms that all compounds crystallize in the hexagonal centrosymmetric MgZn2-type structure (P63/mmc, No. 194). The refined lattice parameters are a = b = 5.1791(1) Å and c = 8.4841(2) Å for ScOs2, a = b = 5.2571(3) Å and c = 8.6613(2) Å for LuOs2 and a = b = 5.3067(6) Å and c = 8.7904(1) Å for YOs2. ROs2 Laves phases can be viewed as a stacking of kagome nets interleaved with triangular layers. Temperature-dependent magnetic susceptibility, resistivity and heat capacity measurements confirm bulk superconductivity at critical temperatures, Tc, of 5.36, 4.55, and 3.47 K for ScOs2, YOs2, and LuOs2, respectively. We have shown that all investigated Laves compounds are weakly-coupled type-II superconductors. DFT calculations revealed that the band structure of ROs2 is intricate due to multiple interacting d orbitals of Os and R. Nonetheless, the kagome-derived bands maintain their overall shape, and the Fermi level crosses a number of bands that originate from the kagome flat bands, broadened by interlayer interaction. As a result, ROs2 can be classified as (breathing) kagome metal superconductors.
Colonization routes uncovered in a widely introduced Mediterranean gecko, Tarentola mauritanica
Authors: Rato Catarina , Deso Gregory , Renet Julien , Delaugerre Michel Jean , Marques Valéria , Mochales-Riaño Gabriel 
Published: October 2023

AbstractIn this study, we aimed to understand the contemporary and ancient colonization routes of the Moorish gecko,Tarentola mauritanica, using simple sequence repeats. By analyzing the genetic diversity of populations in different regions, we found that Morocco is the genetic diversity hotspot for the species, followed by the Iberian Peninsula. However, historical gene flow estimates identified the Iberian Peninsula, not Morocco, as the primary contributor of colonizing individuals, along with continental Italy to a lesser extent. Currently, mainland Italy is the main source of introduced individuals, likely due to the plant nursery trade. The study suggests that human-facilitated introductions from various geographical origins, with numerous regions colonized through continental Italy during two distinct periods, are responsible for the recurrent entry of individuals belonging to the European lineage ofT. mauritanicainto the Mediterranean and Macaronesia. These findings can inform better monitoring surveys and conservation programs by identifying putative current colonization routes of alien species.
Planktonic ecological networks support quantification of changes in ecosystem health and functioning
Authors: Loschi Matteo , D’Alelio Domenico , Camatti Elisa , Bernardi Aubry Fabrizio , Beran Alfred , Libralato Simone 
Published: October 2023

AbstractPlankton communities are the foundation of marine food webs and have a large effect on the dynamics of entire ecosystems. Changes in physicochemical factors strongly influence planktonic organisms and their turnover rates, making their communities useful for monitoring ecosystem health. We studied and compared the planktonic food webs of Palude della Rosa (Venice Lagoon, Italy) in 2005 and 2007. The food webs were developed using a novel approach based on the Monte Carlo random sampling of parameters within specific and realistic ranges to derive 1000 food webs for July of each year. The consumption flows involving Strombididae, Evadne spp. and Podon spp. were identified as the most important in splitting food webs of the July of the two years. Although functional nodes (FNs) differed both in presence and abundance in July of the two years, the whole system indicators showed very similar results. Sediment resuspension acted as a source of stress for the Venice Lagoon, being the most used resource by consumers while inhibiting primary producers by increasing water turbidity. Primary production in the water column was mainly generated by benthic FNs. Although the system was near an equilibrium point, it tended to increase its resilience at the expense of efficiency due to stress. This study highlights the role of plankton communities, which can serve to assess ecosystem health.
Evaluation of potential reference genes in the biting midge Culicoides sonorensis for real-time quantitative PCR analyses
Authors: Osborne Cameron , Cooper Anastasia M. W. , Hall Brandon , Bird Edward , Nayduch Dana , Silver Kristopher 
Published: October 2023

AbstractStudies examining differentially expressed genes and gene silencing by RNA interference (RNAi) require a set of stably expressed reference genes for accurate normalization. The biting midge Culicoides sonorensis is an important vector of livestock pathogens and is often used as a model species for biting midge research. Here, we examine the stable expression of six candidate reference genes in C. sonorensis: actin, β-tubulin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), ribosomal protein subunit (RPS) 18, vacuolar ATPase subunit A (VhaA), and elongation factor 1-beta (EF1b). Gene expression was assessed under seven conditions, including cells treated with double-stranded RNA (dsRNA), 3rd and 4th instar larvae treated with dsRNA, six developmental stages, four adult female body parts or tissue groups, and females injected with bluetongue virus or vesicular stomatitis virus. Stable gene expression was assessed using RefFinder, NormFinder, geNorm, and BestKeeper. The ranked results for each analysis tool under each condition and a comprehensive ranking for each condition are presented. The data show that optimal reference genes vary between conditions and that just two reference genes were necessary for each condition. These findings provide reference genes for use under these conditions in future studies using real-time quantitative PCR to evaluate gene expression in C. sonorensis.