Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural genomic variation and migratory behavior in a wild songbird

Structural variants (SVs) are a major source of genetic variation, but accurate descriptions in natural populations and connections with phenotypic traits remain scarce. We integrated advances in genomic sequencing and animal tracking to begin filling this knowledge gap in the Eurasian blackcap. Specifically, we (i) characterized the genome-wide distribution, frequency and overall fitness effects of SVs using haplotype-resolved assemblies for 79 birds, and (ii) used these SVs to study the genetics of seasonal migration. We detected >15K SVs. Many SVs overlapped repetitive regions and exhibited evidence of purifying selection suggesting they have overall deleterious effects on fitness. We used estimates of genomic differentiation to identify SVs exhibiting evidence of selection in blackcaps with different migratory strategies. Insertions and deletions dominated these SVs and were associated with genes that are either directly (e.g., regulatory motifs that maintain circadian rhythms) or indirectly (e.g., through immune response) related to migration. We also broke migration down into individual traits (direction, distance and timing) using existing tracking data and tested if genetic variation at the SVs we identified could account for phenotypic variation at these traits. This was only the case for one trait – direction – and one specific SV (a deletion on chromosome 27) accounted for much of this variation. Our results highlight the evolutionary importance of SVs in natural populations and provide insight into the genetic basis of seasonal migration.
Modeling TEC Maps Over China Using Particle Swarm Optimization Neural Networks and Long‐Term Ground‐Based GPS, COSMIC, and Fengyun Data

This paper presents a new model for ionospheric total electron content (TEC) over China. The new model is developed using a hybrid method composed of the particle swarm optimization (PSO) and artificial neural network and long‐term observations from 257 ground‐based global navigation satellite systems (GNSS) stations and space‐borne GNSS radio occultation systems (COSMIC and Fengyun) during the 14‐year period of 2008–2021. The PSO algorithm is used to optimize the traditional back‐propagation neural network (BP‐NN) model by reducing the effects of the local minimum problem. The new model is validated using out‐of‐sample data, and its results are compared to the BP‐NN, IRI‐2016 model, and global ionospheric maps provided by the International GNSS Service. Results show that TEC predicted from the new model agrees better with the reference TEC than the BP‐NN and IRI‐2016 models. The improvements made by the new model over the BP‐NN and IRI‐2016 models in the equinox, summer, and winter seasons of the solar maximum year (2015) are 4%–20%/20%–36%, 9%–21%/26%–42%, and 6%–22%/21%–43%, respectively, and their corresponding results in the solar minimum year (2019) are 12%–24%/41%–59%, 9%–24%/28%–56%, and 10%–26%/53%–72%. Furthermore, the new model well captures the diurnal evolution, seasonal variation, and variations in the ionospheric TEC under different solar activity levels. It also well captures the mid‐latitude summer nighttime anomaly over China, and the diurnal anomaly is more pronounced in the solar minimum year (2019) than in the solar maximum year (2015) in terms of the nighttime‐to‐noontime ratio and the range of months it lasts in a year.
Potential application of Kanade–Lucas–Tomasi tracker on satellite images for automatic change detection

Abstract. Monitoring agricultural areas is still a very challenging task. Various models and methodologies have been developed for monitoring the agricultural areas with satellite images, but their practical applicability is limited due to the complexity in processing and dependence on a priori information. Therefore, in this paper, an attempt has been made to investigate the utility of the Kanade–Lucas–Tomasi (KLT) tracker, which is generally useful for tracking objects in video images, for monitoring agricultural areas. The KLT tracker was proposed to deal with the problem of image registration, but the use of the KLT tracker in satellite images for land cover monitoring is rarely reported. Advanced Land Observing Satellite Phased Array type L-band Synthetic Aperture Radar (ALOS PALSAR) data has been used to identify and track the agricultural areas. The tracked pixels were compared with the agriculture pixels obtained from a decision tree algorithm and both results are closely matched. An image differencing change detection technique has been applied after KLT tracker implementation to observe the “change” and “no change” pixels in agricultural areas. It is observed that two kinds of changes are being detected. The areas where agriculture was not there earlier, but now is present, the changes are called positive changes. In the areas where agriculture was present earlier, but now is not present, those changes are referred to as negative changes. Unchanged areas retrieved from both the images are labeled as “no change” pixels. The novelty of the proposed algorithm is that it uses a simplified version of the KLT tracker to efficiently select and track the agriculture features on the basis of their spatial information and does not require a priori information every time.
Vitamin D deficiency linked to abnormal bone and lipid metabolism predicts high-risk multiple myeloma with poorer prognosis

Purpose Vitamin D deficiency is frequent in patients with multiple myeloma (MM), however, its prognostic relevance in MM was rather inconclusive. We first investigated the association of vitamin D deficiency with abnormal bone and lipid metabolism in newly diagnosed multiple myeloma (NDMM), and next assessed the impact of serum ratio of vitamin D to carboxy-terminal telopeptide of type I collagen (β-CTX) on progression-free survival (PFS) and overall free survival (OS) in patients with NDMM. Methods The data of 431 consecutive patients with NDMM at Beijing Jishuitan Hospital from September 2013 to December 2022 were collected and retrospectively reviewed through our electronic medical record system. The measurement of 25-hydroxyvitamin D in the blood is an indicator of an individual’s overall vitamin D status. Results The serum levels of vitamin D were negatively correlated with β-CTX in NDMM patients. Of note, positive correlation between vitamin D and cholesterol levels in the serum was found in this study. The cohort (n = 431) was divided into two groups based on the serum ratio of vitamin D to β-CTX. Compared to the group with a higher vitamin D to β-CTX ratio, the group with a lower vitamin D to β-CTX ratio (n = 257, 60%) exhibited hypocholesterolemia, inferior PFS and OS, along with increased cases of ISS stage-III and R-ISS stage-III, a higher number of plasma cells in the bone marrow, and elevated serum calcium levels. Consistent with this, multivariate analysis confirmed that the vitamin D to β-CTX ratio was an independent unfavorable indicator for survival in NDMM patients. Conclusion Our data demonstrated the ratio of vitamin D to β-CTX in the serum is a unique biomarker for NDMM patients to identify the high-risk cases with poor prognosis, which is superior to vitamin D itself for predicting PFS and OS in NDMM. Also, it is worth mentioning that our data on the connection between vitamin D deficiency and hypocholesterolemia might help clarify novel mechanistic aspects of myeloma development.
Hippocampal area CA2: interneuron disfunction during pathological states

Hippocampal area CA2 plays a critical role in social recognition memory and has unique cellular and molecular properties that distinguish it from areas CA1 and CA3. In addition to having a particularly high density of interneurons, the inhibitory transmission in this region displays two distinct forms of long-term synaptic plasticity. Early studies on human hippocampal tissue have reported unique alteration in area CA2 with several pathologies and psychiatric disorders. In this review, we present recent studies revealing changes in inhibitory transmission and plasticity of area CA2 in mouse models of multiple sclerosis, autism spectrum disorder, Alzheimer’s disease, schizophrenia and the 22q11.2 deletion syndrome and propose how these changes could underly deficits in social cognition observed during these pathologies.
High density lipoprotein-associated proteins in non-obese women with and without polycystic ovary syndrome

Introduction Dyslipidemia frequently occurs in women with polycystic ovary syndrome (PCOS), but it is unclear whether dyslipidemia is due to obesity and insulin resistance (IR) or is inherent to PCOS. To address this, proteomic analysis of proteins important in lipid metabolism, particularly for high-density lipoprotein cholesterol (HDL-C), was performed in non-obese, non-insulin resistant PCOS women compared to matched controls. Methods Weight and aged-matched non-obese subjects with PCOS (n=24) and without IR were compared with control women (n=24). 19 proteins were measured by Somalogic proteomic analysis: alpha-1-antichymotrypsin, alpha-1-antitrypsin, apolipoproteins A-1, B, D, E, E2, E3, E4, L1, M, clusterin, complement C3, hemopexin, heparin cofactor-II (HCFII), kininogen-1, serum amyloid A-1, amyloid beta A-4 and paraoxonase-1. Results Women with PCOS had a higher free androgen index (FAI) (p<0.001) and anti-Mullerian hormone (AMH) (p<0.001), but IR and C-reactive protein (CRP), a marker of inflammation, did not differ from controls (p>0.05). The triglyceride:HDL-cholesterol ratio was elevated (p=0.03) in PCOS. Alpha-1-antitrypsin levels were lower (p<0.05) and complement C3 levels were higher (p=0.001) in PCOS. C3 correlated with body mass index (BMI) (r=0.59, p=0.001), IR (r=0.63, p=0.0005) and CRP (r=0.42, p=0.04) in women with PCOS, though no correlations of these parameters with alpha-1-antitrypsin were found. Total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol and levels of the other 17 lipoprotein metabolism-associated proteins did not differ between the two groups (p>0.05). However, in PCOS, alpha-1-antichymotrypsin correlated negatively with BMI (r=-0.40, p<0.04) and HOMA-IR (r=-0.42, p<0.03), apoM correlated positively with CRP (r=0.36, p<0.04) and HCFII correlated negatively with BMI (r=-0.34, p<0.04). Conclusion In PCOS subjects, when obesity, IR and inflammation confounders were absent, alpha-1-antitrypsin was lower and complement C3 was higher than in non-PCOS women, suggesting increased cardiovascular risk; however, subsequent obesity related IR/inflammation likely stimulates other HDL-associated protein abnormalities, thus increasing cardiovascular risk further.
Mesoscale phenomena and their contribution to the global response: a focus on the magnetotail transition region and magnetosphere-ionosphere coupling

An important question that is being increasingly studied across subdisciplines of Heliophysics is “how do mesoscale phenomena contribute to the global response of the system? ” This review paper focuses on this question within two specific but interlinked regions in Near-Earth space: the magnetotail’s transition region to the inner magnetosphere and the ionosphere. There is a concerted effort within the Geospace Environment Modeling (GEM) community to understand the degree to which mesoscale transport in the magnetotail contributes to the global dynamics of magnetic flux transport and dipolarization, particle transport and injections contributing to the storm-time ring current development, and the substorm current wedge. Because the magnetosphere-ionosphere is a tightly coupled system, it is also important to understand how mesoscale transport in the magnetotail impacts auroral precipitation and the global ionospheric system response. Groups within the Coupling, Energetics and Dynamics of Atmospheric Regions Program (CEDAR) community have also been studying how the ionosphere-thermosphere responds to these mesoscale drivers. These specific open questions are part of a larger need to better characterize and quantify mesoscale “messengers” or “conduits” of information—magnetic flux, particle flux, current, and energy—which are key to understanding the global system. After reviewing recent progress and open questions, we suggest datasets that, if developed in the future, will help answer these questions.
CD38: an ecto-enzyme with functional diversity in T cells

CD38, a nicotinamide adenine dinucleotide (NAD)+ glycohydrolase, is considered an activation marker of T lymphocytes in humans that is highly expressed during certain chronic viral infections. T cells constitute a heterogeneous population; however, the expression and function of CD38 has been poorly defined in distinct T cell compartments. We investigated the expression and function of CD38 in naïve and effector T cell subsets in the peripheral blood mononuclear cells (PBMCs) from healthy donors and people with HIV (PWH) using flow cytometry. Further, we examined the impact of CD38 expression on intracellular NAD+ levels, mitochondrial function, and intracellular cytokine production in response to virus-specific peptide stimulation (HIV Group specific antigen; Gag). Naïve T cells from healthy donors showed remarkably higher levels of CD38 expression than those of effector cells with concomitant reduced intracellular NAD+ levels, decreased mitochondrial membrane potential and lower metabolic activity. Blockade of CD38 by a small molecule inhibitor, 78c, increased metabolic function, mitochondrial mass and mitochondrial membrane potential in the naïve T lymphocytes. PWH exhibited similar frequencies of CD38+ cells in the T cell subsets. However, CD38 expression increased on Gag-specific IFN-γ and TNF-α producing cell compartments among effector T cells. 78c treatment resulted in reduced cytokine production, indicating its distinct expression and functional profile in different T cell subsets. In summary, in naïve cells high CD38 expression reflects lower metabolic activity, while in effector cells it preferentially contributes to immunopathogenesis by increasing inflammatory cytokine production. Thus, CD38 may be considered as a therapeutic target in chronic viral infections to reduce ongoing immune activation.
Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats

Background: The Department of Health and Human Services reports that prescription pain reliever (e.g., oxycodone) misuse was initiated by 4,400 Americans each day in 2019. Amid the opioid crisis, effective strategies to prevent and treat prescription opioid use disorder (OUD) are pressing. In preclinical models, the orexin system is recruited by drugs of abuse, and blockade of orexin receptors (OX receptors) prevents drug-seeking behavior. The present study sought to determine whether repurposing suvorexant (SUV), a dual OX receptor antagonist marketed for the treatment of insomnia, can treat two features of prescription OUD: exaggerated consumption and relapse. Methods: Male and female Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i. v., 8 h/day) in the presence of a contextual/discriminative stimulus (SD) and the ability of SUV (0–20 mg/kg, p. o.) to decrease oxycodone self-administration was tested. After self-administration testing, the rats underwent extinction training, after which we tested the ability of SUV (0 and 20 mg/kg, p. o.) to prevent reinstatement of oxycodone seeking elicited by the SD. Results: The rats acquired oxycodone self-administration and intake was correlated with the signs of physical opioid withdrawal. Additionally, females self-administered approximately twice as much oxycodone as males. Although SUV had no overall effect on oxycodone self-administration, scrutiny of the 8-h time-course revealed that 20 mg/kg SUV decreased oxycodone self-administration during the first hour in males and females. The oxycodone SD elicited strong reinstatement of oxycodone-seeking behavior that was significantly more robust in females. Suvorexant blocked oxycodone seeking in males and reduced it in females. Conclusions: These results support the targeting of OX receptors for the treatment for prescription OUD and repurposing SUV as pharmacotherapy for OUD.
Pathogen genomics and phage-based solutions for accurately identifying and controlling Salmonella pathogens

Salmonella is a food-borne pathogen often linked to poultry sources, causing gastrointestinal infections in humans, with the numbers of multidrug resistant (MDR) isolates increasing globally. To gain insight into the genomic diversity of common serovars and their potential contribution to disease, we characterized antimicrobial resistance genes, and virulence factors encoded in 88 UK and 55 Thai isolates from poultry; the presence of virulence genes was detected through an extensive virulence determinants database compiled in this study. Long-read sequencing of three MDR isolates, each from a different serovar, was used to explore the links between virulence and resistance. To augment current control methods, we determined the sensitivity of isolates to 22 previously characterized Salmonella bacteriophages. Of the 17 serovars included, Salmonella Typhimurium and its monophasic variants were the most common, followed by S. Enteritidis, S. Mbandaka, and S. Virchow. Phylogenetic analysis of Typhumurium and monophasic variants showed poultry isolates were generally distinct from pigs. Resistance to sulfamethoxazole and ciprofloxacin was highest in isolates from the UK and Thailand, respectively, with 14–15% of all isolates being MDR. We noted that >90% of MDR isolates were likely to carry virulence genes as diverse as the srjF, lpfD, fhuA, and stc operons. Long-read sequencing revealed the presence of global epidemic MDR clones in our dataset, indicating they are possibly widespread in poultry. The clones included MDR ST198 S. Kentucky, harboring a Salmonella Genomic Island-1 (SGI)-K, European ST34 S. 1,4,[5],12:i:-, harboring SGI-4 and mercury-resistance genes, and a S. 1,4,12:i:- isolate from the Spanish clone harboring an MDR-plasmid. Testing of all isolates against a panel of bacteriophages showed variable sensitivity to phages, with STW-77 found to be the most effective. STW-77 lysed 37.76% of the isolates, including serovars important for human clinical infections: S. Enteritidis (80.95%), S. Typhimurium (66.67%), S. 1,4,[5],12:i:- (83.3%), and S. 1,4,12: i:- (71.43%). Therefore, our study revealed that combining genomics and phage sensitivity assays is promising for accurately identifying and providing biocontrols for Salmonella to prevent its dissemination in poultry flocks and through the food chain to cause infections in humans.
Regulation of semen quality by fatty acids in diets, extender, and semen

Fatty acids (FAs) are classified into different types according to the degree of hydrocarbon chain saturation, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), omega-3 polyunsaturated fatty acids (omega-3 PUFAs) and omega-6 polyunsaturated fatty acids (omega-6 PUFAs), which play an important role in maintaining semen quality. This review focuses on the regulation of FAs in semen, diet and extender on semen quality, and expounds its effects on sperm motility, plasma membrane integrity, DNA integrity, hormone content, and antioxidant capacity. It can be concluded that there are species differences in the FAs profile and requirements in sperm, and their ability to regulate semen quality is also affected by the addition methods or dosages. Future research directions should focus on analyzing the FAs profiles of different species or different periods of the same species and exploring suitable addition methods, doses and mechanism of regulating semen quality.
Klf4 protects thymus integrity during late pregnancy

Pregnancy causes abrupt thymic atrophy. This atrophy is characterized by a severe decrease in the number of all thymocyte subsets and qualitative (but not quantitative) changes in thymic epithelial cells (TECs). Pregnancy-related thymic involution is triggered by progesterone-induced functional changes affecting mainly cortical TECs (cTECs). Remarkably, this severe involution is rapidly corrected following parturition. We postulated that understanding the mechanisms of pregnancy-related thymic changes could provide novel insights into signaling pathways regulating TEC function. When we analyzed genes whose expression in TECs was modified during late pregnancy, we found a strong enrichment in genes bearing KLF4 transcription factor binding motifs. We, therefore, engineered a Psmb11-iCre : Klf4lox/lox mouse model to study the impact of TEC-specific Klf4 deletion in steady-state conditions and during late pregnancy. Under steady-state conditions, Klf4 deletion had a minimal effect on TEC subsets and did not affect thymic architecture. However, pregnancy-induced thymic involution was much more pronounced in pregnant females lacking Klf4 expression in TECs. These mice displayed a substantial ablation of TECs with a more pronounced loss of thymocytes. Transcriptomic and phenotypic analyses of Klf4 -/- TECs revealed that Klf4 maintains cTEC numbers by supporting cell survival and preventing epithelial-to-mesenchymal plasticity during late pregnancy. We conclude that Klf4 is essential for preserving TEC’s integrity and mitigating thymic involution during late pregnancy.
The potential of the gut microbiome for identifying Alzheimer’s disease diagnostic biomarkers and future therapies

Being isolated from the peripheral system by the blood–brain barrier, the brain has long been considered a completely impervious tissue. However, recent findings show that the gut microbiome (GM) influences gastrointestinal and brain disorders such as Alzheimer’s disease (AD). Despite several hypotheses, such as neuroinflammation, tau hyperphosphorylation, amyloid plaques, neurofibrillary tangles, and oxidative stress, being proposed to explain the origin and progression of AD, the pathogenesis remains incompletely understood. Epigenetic, molecular, and pathological studies suggest that GM influences AD development and have endeavored to find predictive, sensitive, non-invasive, and accurate biomarkers for early disease diagnosis and monitoring of progression. Given the growing interest in the involvement of GM in AD, current research endeavors to identify prospective gut biomarkers for both preclinical and clinical diagnoses, as well as targeted therapy techniques. Here, we discuss the most recent findings on gut changes in AD, microbiome-based biomarkers, prospective clinical diagnostic uses, and targeted therapy approaches. Furthermore, we addressed herbal components, which could provide a new venue for AD diagnostic and therapy research.