bluuebunny/crossref_metadata_2025 huggingface dataset:
Sea Surface Wind Structure in the Outer Region of Tropical Cyclones Observed by Wave Gliders
Authors: Tian Di , Zhang Han , Wang Shuai , Zhang Wenyan , Sun Xiujun , Zhou Ying , Zheng Gang , Jiang Han , Yang Shili , Zhou Feng
Published: January 2023

Understanding the sea surface wind structure during tropical cyclones (TCs) is the key for study of ocean response and parameterization of air‐sea surface in numerical simulation. However, field observations are scarce. In 2019, three wave gliders were deployed in the South China Sea and the adjacent Western Pacific region, which acquired sea surface wind structure of eight TCs. Analysis of the field data suggests that the wave glider‐observed surface winds are consistent with most analysis/reanalysis data (i.e., ERA5, Cross‐Calibrated Multi‐Platform, and National Centers for Environmental Prediction‐Global Data Assimilation System) and Soil Moisture Active Passive. Both wave glider observations and analysis/reanalysis data indicate that TC wind fields induce an obvious increase in speed toward the sea surface together with a sharp change in direction, showing an asymmetric wind structure which is sensitive to TC translation speed and intensity. Larger mean values of wind speed and inflow angle are located on the right side along TC tracks. The inflow angle shows a highly dynamic dependence on the radial distance from the TC center, the TC intensity, as well as the TC‐relative azimuth. Comparisons between field observations and theoretical models indicate that the most widely used, ideal TC wind profile models can largely represent the observed sea surface wind structure, but generally underestimate the wind speed due to lack of consideration of background wind. Moreover, simple ideal models (e.g., the modified Rankine vortex model) may outperform complex models when accurate information of TCs is limited. Wave glider observations have potential for better understanding of air‐sea exchanges and for improvements of the corresponding parameterization schemes.
Modeling Land‐Atmosphere Coupling at Cloud‐Resolving Scale Within the Multiple Atmosphere Multiple Land (MAML) Framework in SP‐E3SM
Authors: Lin Guangxing , Leung L. Ruby , Lee Jungmin , Harrop Bryce E. , Baker Ian T. , Branson Mark D. , Denning A. Scott , Jones Christopher R. , Ovchinnikov Mikhail , Randall David A. , Yang Zhao
Published: January 2023

Representing subgrid variabilities of land surface processes and their upscaled effects is crucial for global climate modeling. Here, we implement a multiple atmosphere multiple land (MAML) framework in the superparamaterized version of E3SM (SP‐E3SM) to explicitly simulate the subgrid variabilities of land states and fluxes at cloud‐resolving scale and their interactions with atmosphere. Comparing to the standard SP‐E3SM in which all the atmospheric columns of the cloud resolving model embedded within the global atmospheric model grid interact with the same land surface (i.e., multiple atmosphere single land (MASL)), the impact of MAML on the strength of land‐atmosphere coupling is limited, partly because the current implementation mainly facilitates one‐way coupling between the cloud‐resolving model and the land surface model. Despite such limitation, MAML increases the surface latent heat flux at the expense of sensible heat flux, and increases precipitation in India, Amazon, and Central Africa, reducing the model dry bias compared to the standard SP‐E3SM. By employing a normalized gross moist stability (NGMS) diagnostic framework, we find that the increase in precipitation minus evaporation (P‐E) is primarily driven by the change in large‐scale moisture convergence, particularly by the increase of water vapor in the lower atmosphere, while the local effect of total surface energy flux plays a minor role in the P‐E change. More specifically, MAML changes the surface energy partitioning (evaporative fraction), increases the atmosphere water vapor, and further increases P‐E by decreasing the NGMS. Finally, future development in the MAML framework is discussed.
Cenozoic Exhumation and Deformation of the Intermontane Pastos Chicos Basin in the Southern Central Andes: Implications for the Tectonic Evolution of the Andean Plateau (Puna) and the Eastern Cordillera Between 23° and 24°S, NW Argentina
Authors: Pingel Heiko , Deeken Anke , Coutand Isabelle , Alonso Ricardo N. , Riller Ulrich , Sobel Edward R. , Cottle John M. , Strecker Manfred R.
Published: January 2023

The Andean Plateau of north‐western Argentina (Puna) at a mean elevation of ca. 4.2 km constitutes the southern continuation of the Altiplano; it is a compressional basin‐and‐range province comprising fault‐bounded, high‐elevation mountain ranges and largely internally drained basins with often thick sedimentary and volcaniclastic fill. Growing sedimentological and structural evidence supports the notion that the north‐western Argentine Andes between 22° and 26°S developed from an initial extensive broken‐foreland system that extended across the present‐day eastern Andean flank during the early to middle Eocene. However, compelling evidence of the tectonic history of this region is still missing. Here, we present new apatite fission track and zircon (U–Th)/He thermochronological data and U–Pb zircon ages from intercalated volcanic ash deposits from the Pastos Chicos Basin (23.5°S, 66.5°W) to constrain basin formation and the timing of major crustal deformation in the northern Puna. Inverse thermal modeling of the thermochronological data provides further temporal constraints on the late Cenozoic cooling history of the crust in this region and, by inference, on the timing of upper‐crustal shortening, range uplift, and basin formation in the northern sector of the present‐day Puna Plateau. Specifically, we argue for plateau‐wide distributed deformation in the Eocene between 23° and 24°S, followed by spatially disparate and diachronous deformation (Oligocene to Pliocene).
BET inhibitors rescue anti-PD1 resistance by enhancing TCF7 accessibility in leukemia-derived terminally exhausted CD8+ T cells
Authors: Romine Kyle A. , MacPherson Kevin , Cho Hyun-jun , Kosaka Yoko , Flynn Patrick A. , Byrd Kaelan H. , Coy Jesse L. , Newman Matthew T. , Pandita Ravina , Loo Christopher P. , Scott Jaime , Adey Andrew C. , Lind Evan F.
Published: January 2023

Many acute myeloid leukemia (AML) patients exhibit hallmarks of immune exhaustion, such as increased myeloid-derived suppressor cells, suppressive regulatory T cells and dysfunctional T cells. Similarly, we have identified the same immune-related features, including exhausted CD8+ T cells (TEx) in a mouse model of AML. Here we show that inhibitors that target bromodomain and extra-terminal domain (BET) proteins affect tumor-intrinsic factors but also rescue T cell exhaustion and ICB resistance. Ex vivo treatment of cells from AML mice and AML patients with BET inhibitors (BETi) reversed CD8+ T cell exhaustion by restoring proliferative capacity and expansion of the more functional precursor-exhausted T cells. This reversal was enhanced by combined BETi and anti-PD1 treatment. BETi synergized with anti-PD1 in vivo, resulting in the reduction of circulating leukemia cells, enrichment of CD8+ T cells in the bone marrow, and increase in expression of Tcf7, Slamf6, and Cxcr5 in CD8+ T cells. Finally, we profiled the epigenomes of in vivo JQ1-treated AML-derived CD8+ T cells by single-cell ATAC-seq and found that JQ1 increases Tcf7 accessibility specifically in Tex cells, suggesting that BETi likely acts mechanistically by relieving repression of progenitor programs in Tex CD8+ T cells and maintaining a pool of anti-PD1 responsive CD8+ T cells.
The complex clinical response to selective serotonin reuptake inhibitors in depression: a network perspective
Authors: Boschloo Lynn , Hieronymus Fredrik , Lisinski Alexander , Cuijpers Pim , Eriksson Elias
Published: January 2023

The clinical response to selective serotonin reuptake inhibitors (SSRIs) in depression takes weeks to be fully developed and is still not entirely understood. This study aimed to determine the direct and indirect effects of SSRIs relative to a placebo control condition on clinical symptoms of depression. We included data of 8262 adult patients with major depression participating in 28 industry-sponsored US Food and Drug Administration (FDA) registered trials on the efficacy of SSRIs. Clinical symptoms of depression were assessed by the 17 separate items of the Hamilton Depression Rating Scale (HDRS) after 1, 2, 3, 4 and 6 weeks of treatment. Network estimation techniques showed that SSRIs had quick and strong direct effects on the two affective symptoms, i.e., depressed mood and psychic anxiety; direct effects on other symptoms were weak or absent. Substantial indirect effects were found for all four cognitive symptoms, which showed larger reductions in the SSRI condition but mainly in patients reporting larger reductions in depressed mood. Smaller indirect effects were found for two arousal/somatic symptoms via the direct effect on psychic anxiety. Both direct and indirect effects on sleep problems and most arousal/somatic symptoms were weak or absent. In conclusion, our study revealed that SSRIs primarily caused reductions in affective symptoms, which were related to reductions in mainly cognitive symptoms and some specific arousal/somatic symptoms. The results can contribute to disclosing the mechanisms of action of SSRIs, and has the potential to facilitate early detection of responders and non-responders in clinical practice.
Fecal microbiota transplantation improves VPA-induced ASD mice by modulating the serotonergic and glutamatergic synapse signaling pathways
Authors: Wang Jifeng , Cao Yuan , Hou Weiliang , Bi Dexi , Yin Fang , Gao Yaohui , Huang Dengfeng , Li Yingying , Cao Zhan , Yan Yinmei , Zhao Jianhua , Kong Dewu , Lv Xiaoqiong , Huang Linsheng , Zhong Hui , Wu Chunyan , Chen Qiyi , Yang Rong , Wei Qing , Qin Huanlong
Published: January 2023

Autism spectrum disorder (ASD) is a complex behavioral disorder diagnosed by social interaction difficulties, restricted verbal communication, and repetitive behaviors. Fecal microbiota transplantation (FMT) is a safe and efficient strategy to adjust gut microbiota dysbiosis and improve ASD-related behavioral symptoms, but its regulatory mechanism is unknown. The impact of the microbiota and its functions on ASD development is urgently being investigated to develop new therapeutic strategies for ASD. We reconstituted the gut microbiota of a valproic acid (VPA)-induced autism mouse model through FMT and found that ASD is in part driven by specific gut dysbiosis and metabolite changes that are involved in the signaling of serotonergic synapse and glutamatergic synapse pathways, which might be associated with behavioral changes. Further analysis of the microbiota showed a profound decrease in the genera Bacteroides and Odoribacter, both of which likely contributed to the regulation of serotonergic and glutamatergic synapse metabolism in mice. The engraftment of Turicibacter and Alistipes was also positively correlated with the improvement in behavior after FMT. Our results suggested that successful transfer of the gut microbiota from healthy donors to ASD mice was sufficient to improve ASD-related behaviors. Modulation of gut dysbiosis by FMT could be an effective approach to improve ASD-related behaviors in patients.
DNA damage triggers squamous metaplasia in human lung and mammary cells via mitotic checkpoints
Authors: Juan Lucía San , Freije Ana , Sanz-Gómez Natalia , Jiménez-Matías Beatriz , Pleguezuelos-Manzano Cayetano , Sanz J. Ramón , de Diego Ernesto , Naranjo Sara , Clevers Hans , Gandarillas Alberto
Published: January 2023

Epithelial transdifferentiation is frequent in tissue hyperplasia and contributes to disease in various degrees. Squamous metaplasia (SQM) precedes epidermoid lung cancer, an aggressive and frequent malignancy, but it is rare in the epithelium of the mammary gland. The mechanisms leading to SQM in the lung have been very poorly investigated. We have studied this issue on human freshly isolated cells and organoids. Here we show that human lung or mammary cells strikingly undergo SQM with polyploidisation when they are exposed to genotoxic or mitotic drugs, such as Doxorubicin or the cigarette carcinogen DMBA, Nocodazole, Taxol or inhibitors of Aurora-B kinase or Polo-like kinase. To note, the epidermoid response was attenuated when DNA repair was enhanced by Enoxacin or when mitotic checkpoints where abrogated by inhibition of Chk1 and Chk2. The results show that DNA damage has the potential to drive SQM via mitotic checkpoints, thus providing novel molecular candidate targets to tackle lung SCC. Our findings might also explain why SCC is frequent in the lung, but not in the mammary gland and why chemotherapy often causes complicating skin toxicity.
Resveratrol protects osteocytes against oxidative stress in ovariectomized rats through AMPK/JNK1-dependent pathway leading to promotion of autophagy and inhibition of apoptosis
Authors: Wei Liwei , Chai Shuang , Yue Chen , Zhang Hong , Li Jitian , Qin Na
Published: January 2023

A large number of studies in recent years indicate that osteocytes are the orchestrators of bone remodeling by regulating both osteoblast and osteoclast activities. Oxidative stress-induced osteocyte apoptosis plays critical roles in the pathological processes of postmenopausal osteoporosis. Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis. However, whether resveratrol regulates osteocyte apoptosis via autophagy remains largely unknown. The effects of resveratrol on regulating osteocyte apoptosis and autophagy were analyzed both in vivo and in vitro. In vitro, cultured MLO-Y4 cells were exposed to H2O2 with or without resveratrol. In vivo, an ovariectomy-induced osteoporosis model was constructed in rats with or without daily intraperitoneal injection of 10 mg/kg body weight resveratrol. It was found that resveratrol attenuated H2O2-induced apoptosis through activating autophagy in cultured MLO-Y4 cells, which was mediated by the dissociation of Beclin-1/Bcl-2 complex in AMPK/JNK1-dependent pathway, ultimately regulating osteocytes function. Furthermore, it was shown that resveratrol treatment reduced osteocytes oxidative stress, inhibited osteocytes apoptosis and promoted autophagy in ovariectomized rats. Our study suggests that resveratrol protects against oxidative stress by restoring osteocytes autophagy and alleviating apoptosis via AMPK/JNK1 activation, therefore dissociating Bcl-2 from Beclin-1.
Polycomb deficiency drives a FOXP2-high aggressive state targetable by epigenetic inhibitors
Authors: Chen Fan , Byrd Aria L. , Liu Jinpeng , Flight Robert M. , DuCote Tanner J. , Naughton Kassandra J. , Song Xiulong , Edgin Abigail R. , Lukyanchuk Alexsandr , Dixon Danielle T. , Gosser Christian M. , Esoe Dave-Preston , Jayswal Rani D. , Orkin Stuart H. , Moseley Hunter N. B. , Wang Chi , Brainson Christine Fillmore
Published: January 2023

Inhibitors of the Polycomb Repressive Complex 2 (PRC2) histone methyltransferase EZH2 are approved for certain cancers, but realizing their wider utility relies upon understanding PRC2 biology in each cancer system. Using a genetic model to delete Ezh2 in KRAS-driven lung adenocarcinomas, we observed that Ezh2 haplo-insufficient tumors were less lethal and lower grade than Ezh2 fully-insufficient tumors, which were poorly differentiated and metastatic. Using three-dimensional cultures and in vivo experiments, we determined that EZH2-deficient tumors were vulnerable to H3K27 demethylase or BET inhibitors. PRC2 loss/inhibition led to de-repression of FOXP2, a transcription factor that promotes migration and stemness, and FOXP2 could be suppressed by BET inhibition. Poorly differentiated human lung cancers were enriched for an H3K27me3-low state, representing a subtype that may benefit from BET inhibition as a single therapy or combined with additional EZH2 inhibition. These data highlight diverse roles of PRC2 in KRAS-driven lung adenocarcinomas, and demonstrate the utility of three-dimensional cultures for exploring epigenetic drug sensitivities for cancer.
Selective CO2 electrolysis to CO using isolated antimony alloyed copper
Authors: Li Jiawei , Zeng Hongliang , Dong Xue , Ding Yimin , Hu Sunpei , Zhang Runhao , Dai Yizhou , Cui Peixin , Xiao Zhou , Zhao Donghao , Zhou Liujiang , Zheng Tingting , Xiao Jianping , Zeng Jie , Xia Chuan
Published: January 2023

Renewable electricity-powered CO evolution from CO2emissions is a promising first step in the sustainable production of commodity chemicals, but performing electrochemical CO2reduction economically at scale is challenging since only noble metals, for example, gold and silver, have shown high performance for CO2-to-CO. Cu is a potential catalyst to achieve CO2reduction to CO at the industrial scale, but the C-C coupling process on Cu significantly depletes CO* intermediates, thus limiting the CO evolution rate and producing many hydrocarbon and oxygenate mixtures. Herein, we tune the CO selectivity of Cu by alloying a second metal Sb into Cu, and report an antimony-copper single-atom alloy catalyst (Sb1Cu) of isolated Sb-Cu interfaces that catalyzes the efficient conversion of CO2-to-CO with a Faradaic efficiency over 95%. The partial current density reaches 452 mA cm−2with approximately 91% CO Faradaic efficiency, and negligible C2+products are observed. In situ spectroscopic measurements and theoretical simulations reason that the atomic Sb-Cu interface in Cu promotes CO2adsorption/activation and weakens the binding strength of CO*, which ends up with enhanced CO selectivity and production rates.
Sensory nerve niche regulates mesenchymal stem cell homeostasis via FGF/mTOR/autophagy axis
Authors: Pei Fei , Ma Li , Jing Junjun , Feng Jifan , Yuan Yuan , Guo Tingwei , Han Xia , Ho Thach-Vu , Lei Jie , He Jinzhi , Zhang Mingyi , Chen Jian-Fu , Chai Yang
Published: January 2023

Mesenchymal stem cells (MSCs) reside in microenvironments, referred to as niches, which provide structural support and molecular signals. Sensory nerves are niche components in the homeostasis of tissues such as skin, bone marrow and hematopoietic system. However, how the sensory nerve affects the behavior of MSCs remains largely unknown. Here we show that the sensory nerve is vital for mesenchymal tissue homeostasis and maintenance of MSCs in the continuously growing adult mouse incisor. Loss of sensory innervation leads to mesenchymal disorder and a decrease in MSCs. Mechanistically, FGF1 from the sensory nerve directly acts on MSCs by binding to FGFR1 and activates the mTOR/autophagy axis to sustain MSCs. Modulation of mTOR/autophagy restores the MSCs and rescues the mesenchymal tissue disorder of Fgfr1 mutant mice. Collectively, our study provides insights into the role of sensory nerves in the regulation of MSC homeostasis and the mechanism governing it.
The rocky road to organics needs drying
Authors: Andreani Muriel , Montagnac Gilles , Fellah Clémentine , Hao Jihua , Vandier Flore , Daniel Isabelle , Pisapia Céline , Galipaud Jules , Lilley Marvin D. , Früh Green Gretchen L. , Borensztajn Stéphane , Ménez Bénédicte
Published: January 2023

How simple abiotic organic compounds evolve toward more complex molecules of potentially prebiotic importance remains a missing key to establish where life possibly emerged. The limited variety of abiotic organics, their low concentrations and the possible pathways identified so far in hydrothermal fluids have long hampered a unifying theory of a hydrothermal origin for the emergence of life on Earth. Here we present an alternative road to abiotic organic synthesis and diversification in hydrothermal environments, which involves magmatic degassing and water-consuming mineral reactions occurring in mineral microcavities. This combination gathers key gases (N2, H2, CH4, CH3SH) and various polyaromatic materials associated with nanodiamonds and mineral products of olivine hydration (serpentinization). This endogenous assemblage results from re-speciation and drying of cooling C–O–S–H–N fluids entrapped below 600 °C–2 kbars in rocks forming the present-day oceanic lithosphere. Serpentinization dries out the system toward macromolecular carbon condensation, while olivine pods keep ingredients trapped until they are remobilized for further reactions at shallower levels. Results greatly extend our understanding of the forms of abiotic organic carbon available in hydrothermal environments and open new pathways for organic synthesis encompassing the role of minerals and drying. Such processes are expected in other planetary bodies wherever olivine-rich magmatic systems get cooled down and hydrated.
A generative deep learning framework for inverse design of compositionally complex bulk metallic glasses
Authors: Zhou Ziqing , Shang Yinghui , Liu Xiaodi , Yang Yong
Published: January 2023

The design of bulk metallic glasses (BMGs) via machine learning (ML) has been a topic of active research recently. However, the prior ML models were mostly built upon supervised learning algorithms with human inputs to navigate the high dimensional compositional space, which becomes inefficient with the increasing compositional complexity in BMGs. Here, we develop a generative deep-learning framework to directly generate compositionally complex BMGs, such as high entropy BMGs. Our framework is built on the unsupervised Generative Adversarial Network (GAN) algorithm for data generation and the supervised Boosted Trees algorithm for data evaluation. We studied systematically the confounding effect of various data descriptors and the literature data on the effectiveness of our framework both numerically and experimentally. Most importantly, we demonstrate that our generative deep learning framework is capable of producing composition-property mappings, therefore paving the way for the inverse design of BMGs.
Correspondence analysis for dimension reduction, batch integration, and visualization of single-cell RNA-seq data
Authors: Hsu Lauren L. , Culhane Aedín C.
Published: January 2023

Effective dimension reduction is essential for single cell RNA-seq (scRNAseq) analysis. Principal component analysis (PCA) is widely used, but requires continuous, normally-distributed data; therefore, it is often coupled with log-transformation in scRNAseq applications, which can distort the data and obscure meaningful variation. We describe correspondence analysis (CA), a count-based alternative to PCA. CA is based on decomposition of a chi-squared residual matrix, avoiding distortive log-transformation. To address overdispersion and high sparsity in scRNAseq data, we propose five adaptations of CA, which are fast, scalable, and outperform standard CA and glmPCA, to compute cell embeddings with more performant or comparable clustering accuracy in 8 out of 9 datasets. In particular, we find that CA with Freeman–Tukey residuals performs especially well across diverse datasets. Other advantages of the CA framework include visualization of associations between genes and cell populations in a “CA biplot,” and extension to multi-table analysis; we introducecorralmfor integrative multi-table dimension reduction of scRNAseq data. We implement CA for scRNAseq data incorral, an R/Bioconductor package which interfaces directly with single cell classes in Bioconductor. Switching from PCA to CA is achieved through a simple pipeline substitution and improves dimension reduction of scRNAseq datasets.
SLC11A2: a promising biomarker and therapeutic target in ovarian cancer
Authors: Tian Liming , Li Xuemei , Lai Huiling , Sun Tingting , Li Xiaohui , Wu Linxiang , Wu Chuling , Yao Shuzhong , Ren Yufeng , He Shasha , Yang Guofen
Published: January 2023

Ovarian cancer has the highest mortality rate among gynecologic tumors, with a 5-year survival rate of less than 25%. There is an urgent need for early diagnosis and new drugs to reduce the disease burden of ovarian cancer. The aim of this study was to investigate the effectiveness of SLC11A2 as a therapeutic target and marker for ovarian cancer. Expression data of SLC11A2 were obtained from public databases. Then, the biological functions of SLC11A2 were validated in four ovarian cancer cell lines. Finally, we collected ovarian cancer clinical tissues, serum, and plasma exosomes and used immunohistochemistry, Elisa, and liquid chromatography-mass spectrometry (LC–MS) to validate the test efficacy of SLC11A2. The results showed that ovarian cancers with high SLC11A2 mRNA expression had shorter 5-year PFS and MST. Knockdown of SLC11A2 reduced ovarian cancer migration and increased cisplatin-induced apoptosis. Serum SLC11A2 may help improve the detection rate of ovarian cancer.
Evaluation of emphysema on thoracic low-dose CTs through attention-based multiple instance deep learning
Authors: Fuhrman Jordan , Yip Rowena , Zhu Yeqing , Jirapatnakul Artit C. , Li Feng , Henschke Claudia I. , Yankelevitz David F. , Giger Maryellen L.
Published: January 2023

In addition to lung cancer, other thoracic abnormalities, such as emphysema, can be visualized within low-dose CT scans that were initially obtained in cancer screening programs, and thus, opportunistic evaluation of these diseases may be highly valuable. However, manual assessment for each scan is tedious and often subjective, thus we have developed an automatic, rapid computer-aided diagnosis system for emphysema using attention-based multiple instance deep learning and 865 LDCTs. In the task of determining if a CT scan presented with emphysema or not, our novel Transfer AMIL approach yielded an area under the ROC curve of 0.94 ± 0.04, which was a statistically significant improvement compared to other methods evaluated in our study following the Delong Test with correction for multiple comparisons. Further, from our novel attention weight curves, we found that the upper lung demonstrated a stronger influence in all scan classes, indicating that the model prioritized upper lobe information. Overall, our novel Transfer AMIL method yielded high performance and provided interpretable information by identifying slices that were most influential to the classification decision, thus demonstrating strong potential for clinical implementation.
Deterministic and probabilistic regularities underlying risky choices are acquired in a changing decision context
Authors: Kóbor Andrea , Tóth-Fáber Eszter , Kardos Zsófia , Takács Ádám , Éltető Noémi , Janacsek Karolina , Csépe Valéria , Nemeth Dezso
Published: January 2023

Predictions supporting risky decisions could become unreliable when outcome probabilities temporarily change, making adaptation more challenging. Therefore, this study investigated whether sensitivity to the temporal structure in outcome probabilities can develop and remain persistent in a changing decision environment. In a variant of the Balloon Analogue Risk Task with 90 balloons, outcomes (rewards or balloon bursts) were predictable in the task’s first and final 30 balloons and unpredictable in the middle 30 balloons. The temporal regularity underlying the predictable outcomes differed across three experimental conditions. In the deterministic condition, a repeating three-element sequence dictated the maximum number of pumps before a balloon burst. In the probabilistic condition, a single probabilistic regularity ensured that burst probability increased as a function of pumps. In the hybrid condition, a repeating sequence of three different probabilistic regularities increased burst probabilities. In every condition, the regularity was absent in the middle 30 balloons. Participants were not informed about the presence or absence of the regularity. Sensitivity to both the deterministic and hybrid regularities emerged and influenced risk taking. Unpredictable outcomes of the middle phase did not deteriorate this sensitivity. In conclusion, humans can adapt their risky choices in a changing decision environment by exploiting the statistical structure that controls how the environment changes.
Visuospatial information foraging describes search behavior in learning latent environmental features
Authors: Barack David L. , Bakkour Akram , Shohamy Daphna , Salzman C. Daniel
Published: January 2023

In the real world, making sequences of decisions to achieve goals often depends upon the ability to learn aspects of the environment that are not directly perceptible. Learning these so-called latent features requires seeking information about them. Prior efforts to study latent feature learning often used single decisions, used few features, and failed to distinguish between reward-seeking and information-seeking. To overcome this, we designed a task in which humans and monkeys made a series of choices to search for shapes hidden on a grid. On our task, the effects of reward and information outcomes from uncovering parts of shapes could be disentangled. Members of both species adeptly learned the shapes and preferred to select tiles expected to be informative earlier in trials than previously rewarding ones, searching a part of the grid until their outcomes dropped below the average information outcome—a pattern consistent with foraging behavior. In addition, how quickly humans learned the shapes was predicted by how well their choice sequences matched the foraging pattern, revealing an unexpected connection between foraging and learning. This adaptive search for information may underlie the ability in humans and monkeys to learn latent features to support goal-directed behavior in the long run.
Synthetic two-species allodiploid and three-species allotetraploid Saccharomyces hybrids with euploid (complete) parental subgenomes
Authors: Antunovics Zsuzsa , Szabo Adrienn , Heistinger Lina , Mattanovich Diethard , Sipiczki Matthias
Published: January 2023

Combination of the genomes of Saccharomyces species has great potential for the construction of new industrial strains as well as for the study of the process of speciation. However, these species are reproductively isolated by a double sterility barrier. The first barrier is mainly due to the failure of the chromosomes to pair in allodiploid meiosis. The second barrier ensures that the hybrid remains sterile even after genome duplication, an event that can restore fertility in plant interspecies hybrids. The latter is attributable to the autodiploidisation of the allotetraploid meiosis that results in sterile allodiploid spores (return to the first barrier). Occasionally, mating-competent alloaneuploid spores arise by malsegregation of MAT-carrying chromosomes. These can mate with cells of a third species resulting in aneuploid zygotes having at least one incomplete subgenome. Here we report on the construction of euploid three-species hybrids by making use of “rare mating” between a sterile S. kudriavzevii x S. uvarum allodiploid hybrid and a diploid S. cerevisiae strain. The hybrids have allotetraploid 2nScnSk nSu genomes consisting of complete sets of parental chromosomes. This is the first report on the production of euploid three-species Saccharomyces hybrids by natural mating, without genetic manipulation. The hybrids provide possibilities for studying the interactions of three allospecific genomes and their orthologous genes present in the same cell.
Codon modification of Tuba1a alters mRNA levels and causes a severe neurodevelopmental phenotype in mice
Authors: Leca Ines , Phillips Alexander William , Ushakova Lyubov , Cushion Thomas David , Keays David Anthony
Published: January 2023

The tubulinopathies are an umbrella of rare diseases that result from mutations in tubulin genes and are frequently characterised by severe brain malformations. The characteristics of a given disease reflect the expression pattern of the transcript, the function of a given tubulin gene, and the role microtubules play in a particular cell type. Mouse models have proved to be valuable tools that have provided insight into the molecular and cellular mechanisms that underlie the disease state. In this manuscript we compare two Tuba1a mouse models, both of which express wild-type TUBA1A protein but employ different codon usage. We show that modification of the Tuba1a mRNA sequence results in homozygous lethality and a severe neurodevelopmental phenotype. This is associated with a decrease in the number of post-mitotic neurons, PAX6 positive progenitors, and an increase in the number of apoptotic cells. We attribute this to a decrease in the stability of the modified Tuba1a transcript, and the absence of compensation by the other neurogenic tubulins. Our findings highlight the importance of maintaining the wild-type coding sequence when engineering mouse lines and the impact of synonymous genetic variation.
Analyses of binding partners and functional domains for the developmentally essential protein Hmx3a/HMX3
Authors: Haws William , England Samantha , Grieb Ginny , Susana Gabriela , Hernandez Sophie , Mirer Hunter , Lewis Katharine
Published: January 2023

HMX3 is a homeodomain protein with essential roles in CNS and ear development. Homeodomains are DNA-binding domains and hence homeodomain-containing proteins are usually assumed to be transcription factors. However, intriguingly, our recent data suggest that zebrafish Hmx3a may not require its homeodomain to function, raising the important question of what molecular interactions mediate its effects. To investigate this, we performed a yeast two-hybrid screen and identified 539 potential binding partners of mouse HMX3. Using co-immunoprecipitation, we tested whether a prioritized subset of these interactions are conserved in zebrafish and found that Tle3b, Azin1b, Prmt2, Hmgb1a, and Hmgn3 bind Hmx3a. Next, we tested whether these proteins bind the products of four distinct hmx3a mutant alleles that all lack the homeodomain. Embryos homozygous for two of these alleles develop abnormally and die, whereas zebrafish homozygous for the other two alleles are viable. We found that all four mutations abrogate binding to Prmt2 and Tle3b, whereas Azin1b binding was preserved in all cases. Interestingly, Hmgb1a and Hmgn3 had more affinity for products of the viable mutant alleles. These data shed light on how HMX3/Hmx3a might function at a molecular level and identify new targets for future study in these vital developmental processes.
Clonal population expansion of Staphylococcus aureus occurs due to escape from a finite number of intraphagocyte niches
Authors: Pidwill Grace R. , Pyrah Josie F. , Sutton Joshua A. F. , Best Alex , Renshaw Stephen A. , Foster Simon J.
Published: January 2023

Staphylococcus aureus is a human commensal and also an opportunist pathogen causing life threatening infections. During S. aureus disease, the abscesses that characterise infection can be clonal, whereby a large bacterial population is founded by a single or few organisms. Our previous work has shown that macrophages are responsible for restricting bacterial growth such that a population bottleneck occurs and clonality can emerge. A subset of phagocytes fail to control S. aureus resulting in bacterial division, escape and founding of microabscesses that can seed other host niches. Here we investigate the basis for clonal microabscess formation, using in vitro and in silico models of S. aureus macrophage infection. Macrophages that fail to control S. aureus are characterised by formation of intracellular bacterial masses, followed by cell lysis. High-resolution microscopy reveals that most macrophages had internalised only a single S. aureus, providing a conceptual framework for clonal microabscess generation, which was supported by a stochastic individual-based, mathematical model. Once a threshold of masses was reached, increasing the number of infecting bacteria did not result in greater mass numbers, despite enhanced phagocytosis. This suggests a finite number of permissive, phagocyte niches determined by macrophage associated factors. Increased understanding of the parameters of infection dynamics provides avenues for development of rational control measures.
Synapsid tracks with skin impressions illuminate the terrestrial tetrapod diversity in the earliest Permian of equatorial Pangea
Authors: Calábková Gabriela , Březina Jakub , Nosek Vojtěch , Madzia Daniel
Published: January 2023

Lower Permian deposits of the Boskovice Basin in the Czech Republic have long been renowned for extraordinarily abundant specimens of discosauriscid seymouriamorphs, some of which showing exceptional preservation, including widespread soft tissues. The only other tetrapods from the strata are represented by rare temnospondyls. However, recent fieldwork in the Asselian (lowermost Permian) of the Boskovice Basin has yielded a diverse assemblage of tetrapod tracks, illuminating a hidden terrestrial tetrapod diversity. Here, we describe well-preserved isolated tracks, manus-pes couples, and a slab with trackways composed of approximately 20 tracks in at least four different directions belonging to early-diverging, or ‘pelycosaur-grade’, synapsids. The material originates from three localities situated within the Letovice and Padochov formations and is assignable to the ichnotaxon Dimetropus. The best-preserved specimen further shows rare skin impressions, which have not been observed from the hands or feet of early-diverging mammal-line amniotes before. The new material adds to the scarce record of synapsids from the Carboniferous/Permian transitional interval of equatorial Pangea. At the same time, it highlights the significance of the ichnological record of the Boskovice Basin which has long been neglected despite offering evidence for the presence of diverse faunal components that have not been reported from these basinal deposits before.
Novel methods for coupled prediction of extreme wind speeds and wave heights
Authors: Gaidai Oleg , Xing Yihan , Xu Xiaosen
Published: January 2023

Two novel methods are being outlined that, when combined, can be used for spatiotemporal analysis of wind speeds and wave heights, thus contributing to global climate studies. First, the authors provide a unique reliability approach that is especially suited for multi-dimensional structural and environmental dynamic system responses that have been numerically simulated or observed over a substantial time range, yielding representative ergodic time series. Next, this work introduces a novel deconvolution extrapolation technique applicable to a wide range of environmental and engineering applications. Classical reliability approaches cannot cope with dynamic systems with high dimensionality and responses with complicated cross-correlation. The combined study of wind speed and wave height is notoriously difficult, since they comprise a very complex, multi-dimensional, non-linear environmental system. Additionally, global warming is a significant element influencing ocean waves throughout the years. Furthermore, the environmental system reliability method is crucial for structures working in any particular region of interest and facing actual and often harsh weather conditions. This research demonstrates the effectiveness of our approach by applying it to the concurrent prediction of wind speeds and wave heights from NOAA buoys in the North Pacific. This study aims to evaluate the state-of-the-art approach that extracts essential information about the extreme responses from observed time histories.
Soil organic carbon, total nitrogen stocks and CO2 emissions in top- and subsoils with contrasting management regimes in semi-arid environments
Authors: Okolo Chukwuebuka C. , Gebresamuel Girmay , Zenebe Amanuel , Haile Mitiku , Orji Jephter E. , Okebalama Chinyere B. , Eze Chinedu E. , Eze Emmanuel , Eze Peter N.
Published: January 2023

This study aims to investigate soil organic carbon (SOC) and total nitrogen (TN) contents and stocks, CO2emissions and selected soil properties in croplands, grazing lands, exclosures and forest lands of semi-arid Ethiopia. Sampling was done at 0–30, 30–60 and 60–90 cm soil depths and concentration and stocks of SOC, TN and selected soil properties were determined using standard routine laboratory procedures. There were variations in distribution of SOC and TN stock over 90 cm depth across land use types and locations, decreasing from topsoils to subsoil, with average values ranging from 48.68 Mg C ha−1and 4.80 Mg N ha−1in Hugumburda cropland to 303.53 Mg C ha−1and 24.99 Mg N ha−1in Desa’a forest respectively. Forest sequestered significant higher SOC and TN stock, decreasing with depth, compared with other land use types. In Desa'a and Hugumburda, the conversion of forest to cropland resulted in a total loss of SOC stock of 9.04 Mg C ha−1and 2.05 Mg C ha−1, respectively, and an increase in CO2emission of 33.16 Mg C ha−1and 7.52 Mg C ha−1 yr−1, respectively. The establishment of 10 years (Geregera) and 6 years (Haikihelet) exclosures on degraded grazing land increased SOC stock by 13% and 37% respectively.
Resilience of soybean cultivars to drought stress during flowering and early-seed setting stages
Authors: Poudel Sadikshya , Vennam Ranadheer Reddy , Shrestha Amrit , Reddy K. Raja , Wijewardane Nuwan K. , Reddy Krishna N. , Bheemanahalli Raju
Published: January 2023

Drought stress during the reproductive stage and declining soybean yield potential raise concerns about yield loss and economic return. In this study, ten cultivars were characterized for 20 traits to identify reproductive stage (R1–R6) drought-tolerant soybean. Drought stress resulted in a marked reduction (17%) in pollen germination. The reduced stomatal conductance coupled with high canopy temperature resulted in reduced seed number (45%) and seed weight (35%). Drought stress followed by rehydration increased the hundred seed weight at the compensation of seed number. Further, soybean oil decreased, protein increased, and cultivars responded differently under drought compared to control. In general, cultivars with high tolerance scores for yield displayed lower tolerance scores for quality content and vice versa. Among ten cultivars, LS5009XS and G4620RX showed maximum stress tolerance scores for seed number and seed weight. The observed variability in leaf reflectance properties and their relationship with physiological or yield components suggested that leaf-level sensing information can be used for differentiating drought-sensitive soybean cultivars from tolerant ones. The study led to the identification of drought-resilient cultivars/promising traits which can be exploited in breeding to develop multi-stress tolerant cultivars.
Determinants of early neonatal mortality (hospital based retrospective cohort study in Somali region of Ethiopia)
Authors: Ahmed Ahmed Tahir , Farah Abdifatah Elmi , Ali Hussein Nooh , Ibrahim Muse Obsiye
Published: January 2023

Early neonatal mortality occurs when a newborn dies within the first seven days of life. Despite interventions, neonatal mortality remains public health problem over time in Ethiopia (33 per 1000 live births). Determinants varies on level of neonatal mortality. The study's goal was to determine magnitude of early newborn death, as well as its determinants and causes in Newborn Intensive Care Unit of Referral hospital in Ethiopia's Somali region. Health facility based retrospective study review was conducted between May 2019 to May 2021 in Shiek Hassan Yabare Referral Hospital of Jigjiga University of Ethiopia. All neonates admitted at neonatal intensive care unit (NICU) with complete data and get registered using the new NICU registration book from May 2019 to May 2021 were included. Kobo toolkit was used for data collection and analyzed in SPSS 20. The magnitude of early neonatal mortality rate was defined as death between 0 and 7 days. Logistic regression model was used to estimate maternal and neonatal characteristics as a determinant variables on neonatal mortality. The statistical significance was considered at P-value < 0.05. The magnitude of early neonatal mortality rate of Ethiopia’s Somali region is estimated to be 130 per 1000 live births—that is say 130 newborn couldn’t celebrate their seventh day in every 1000 live births. Hypothermia, prematurity, maternal death at birth and shorter length of stay in NICU were increasing the chance of neonatal mortality at early stage while neonatal resuscitation had shown protective effect against neonatal mortality. Similarly birth asphyxia, preterm, sepsis, and congenital abnormalities were major causes of admission and death in the NICU. The magnitude of early neonatal mortality is considerable and most of the determinants are preventable. Enhancing quality of intra-partum and NICU care including infection prevention, managing hypothermia and neonatal resuscitation as per the national standard within the first golden hour is key.
Reprogramming of fibroblast cells to totipotent state by DNA demethylation
Authors: Ghazimoradi Mohammad H. , Hasegawa Kouichi , Zolghadr Ehsan , Montazeri Samaneh , Farivar Shirin
Published: January 2023

Many attempts have been made to induce high-quality embryonic stem cells such as pluripotent stem cells and totipotent stem cells, but challenges remain to be overcome such as appropriate methods and sources. Demethylation of the genome after fertilization is an important step to initiate zygote gene activation, which can lead to the development of new embryos. Here, we tried to induce totipotent stem cells by mimicking DNA demethylation patterns of the embryo. Our data showed, after induction of DNA demethylation via chemicals or knockdown of Dnmts, cells positive for Nanog, and Cdx2 emerged. These cells could differentiate into the pluripotent and trophoblast lineage cells in-vitro. After transferring these cells to the uterus, they can implant and form embryo-like structures. Our study showed the importance of DNA demethylation roles in totipotent stem cell induction and a new and easy way to induce this cell type.
Variability of trunk muscle synergies underlying the multidirectional movements and stability trunk motor tasks in healthy individuals
Authors: Saito Hiroki , Yokoyama Hikaru , Sasaki Atsushi , Matsushita Kazuya , Nakazawa Kimitaka
Published: January 2023

Muscle synergy analysis is useful for investigating trunk coordination patterns based on the assumption that the central nervous system reduces the dimensionality of muscle activation to simplify movement. This study aimed to quantify the variability in trunk muscle synergy during various trunk motor tasks in healthy participants to provide reference data for evaluating trunk control strategies in patients and athletes. Sixteen healthy individuals performed 11 trunk movement and stability tasks with electromyography (EMG) recording of their spinal and abdominal muscles (6 bilaterally). Non-negative matrix factorization applied to the concatenated EMG of all tasks identified the five trunk muscle synergies (W) with their corresponding temporal patterns (C). The medians of within-cluster similarity defined by scalar products in W and rmax coefficient using the cross-correlation function in C were 0.73–0.86 and 0.64–0.75, respectively, while the inter-session similarities were 0.81–0.96 and 0.74–0.84, respectively. However, the lowest and highest values of both similarity indices were broad, reflecting the musculoskeletal system’s redundancy within and between participants. Furthermore, the significant differences in the degree of variability between the trunk synergies may represent the different neural features of synergy organization and strategies to overcome the various mechanical demands of a motor task.