Miracle-dz/UniFAR-FTUs huggingface dataset:
Higher Intercellular Variation in Genome-Wide Recombination Rate in Female Mice

Meiotic recombination affects fertility, shuffles genomes, and modulates the effectiveness of natural selection. Despite conservation of the recombination pathway, the rate of recombination varies among individuals and along chromosomes. Recombination rate also differs among cells from the same organism, but this form of variation has received less attention. To identify patterns that characterize intercellular variation in the genome-wide recombination rate, we counted foci of the MLH1 recombination-associated protein in oocytes and spermatocytes from a panel of wild-derived inbred strains of house mice. Females show higher intercellular variation in MLH1 focus count than males from the same inbred strains. This pattern is consistent across strains from multiple subspecies, including 2 strains in which the average MLH1 focus count is higher in males. The sex difference in genome-wide recombination rate we report suggests that selection targeting recombination rate will be more efficient in males than in females.
Running away or running to? Do prey make decisions solely based on the landscape of fear or do they also include stimuli from a landscape of safety?

Predator prey interactions are a key part of ecosystem function, and non-consumptive effects fall under the landscape of fear theory. Under the landscape of fear, the antipredator responses of prey are based on the spatial and temporal distribution of predatory cues in the environment. However, the aversive stimuli (fear) are not the only stimuli prey can utilize when making behavioral decisions. Prey might also be using attractive stimuli that represent safety to guide decision making. Using a novel, orthogonal design, we were able to spatially separate aversive and attractive stimuli to determine if prey are utilizing safety cues to navigate their environment. Crayfish Faxonius rusticus were placed in the center of a behavioral arena. Aversive stimuli of either predatory bass Micropterus salmoides cues or conspecific alarm cues increased along the x-axis of the behavioral arena. Safety cues (shelters) increased along the y-axis by decreasing the number of shelter openings in this direction. Crayfish were allowed two phases to explore the arena: one without the fearful stimuli and one with the stimuli. Linear mixed models were conducted to determine if movement behaviors and habitat utilization were affected by the phase of the trial and the type of aversive stimuli. Crayfish responded more strongly to alarm cues than fear cues, with only alarm cues significantly impacting habitat utilization. When responding to alarm cues, crayfish used safety cues as well as fear cues to relocate themselves within the arena. Based on these results, we argue that crayfish are utilizing a landscape of safety in conjunction with a landscape of fear when navigating their environment.
Extracellular matrix remodeling is associated with the survival of cardiomyocytes in the subendocardial region of the ischemic myocardium

A significant amount of cardiomyocytes in subendocardial region survive from ischemic insults. In order to understand the mechanism by which these cardiomyocytes survive, the present study was undertaken to examine changes in these surviving cardiomyocytes and their extracellular matrix. Male C57BL/6 mice aged 8–12 weeks old were subjected to a permanent left anterior descending coronary artery ligation to induce ischemic injury. The hearts were collected at 1, 4, 7, or 28 days after the surgery and examined by histology. At day 1 after left anterior descending ligation, there was a significant loss of cardiomyocytes through apoptosis, but a proportion of cardiomyocytes were surviving in the subendocardial region. The surviving cardiomyocytes were gradually changed from rod-shaped to round-shaped, and appeared disconnected. Connexin 43, an important gap junction protein, was significantly decreased, and collagen I and III deposition was significantly increased in the extracellular matrix. Furthermore, lysyl oxidase, a copper-dependent amine oxidase catalyzing the cross-linking of collagens, was significantly increased in the extracellular matrix, paralleled with the surviving cardiomyocytes. Inhibition of lysyl oxidase activity reduced the number of surviving cardiomyocytes. Thus, the extracellular matrix remodeling is correlated with the deformation of cardiomyocytes, and the electrical disconnection between the surviving cardiomyocytes due to connexin 43 depletion and the increase in lysyl oxidase would help these deformed cardiomyocytes survive under ischemic conditions.
Comparative Stress Response of Black and Gold Howler Monkey (Alouatta caraya) in Urban and Rural Environments of Northern Argentina

The expansion of human populations associated with urbanization results in extensive modification of natural habitats. While many species cannot persist in these highly modified environments, some species adopt new strategies, which contribute to their survival. Several primate species have persisted in altered habitats, including members of the genus Alouatta. To improve our understanding of this interplay, we compared glucocorticoid (GCC) levels in male and female black and gold howler monkeys (Alouatta caraya) in urban and rural areas in northeastern Argentina. Fecal samples (n = 60) were collected from adults and hormone extracts were analyzed by enzyme immunoassays (EIA). Monkeys living in urban areas (females: 109.15 ± 18.83; males: 106.15 ± 10.48) had lower GCClevels than monkeys living in rural areas (females: 152.01 ± 19.50; males:139,82 ± 10.85). Interestingly, males living in urban areas had lower GCC levels compared to those living in rural areas, whereas no differences were observed in GCC levels between females living in urban and rural areas. While these results suggest that urban areas may provide a release from intergroup competition for male howler monkeys, future work is needed to better understand the dynamics of this association to best inform management and conservation of this vulnerable species.
Characterization of aquaporin1b (AQP1b) mRNA in mud loach (Misgurnus mizolepis) in response to heavy metal and immunostimulant stimuli

Aquaporins (AQPs) facilitate the transport of water or other small solutes into cells in the presence of osmotic gradients. However, the current understanding of piscine AQP gene with cellular stress responses has been still limitedly exemplified. In present study, we characterized the mud loach AQP1b gene at the nucleotide and amino acid levels. We identified three AQP 1b transcript variants (mmAQP1b_tv1, mmAQP1b_tv2, and mmAQP1b_tv3). Then, we examined the AQP1b promoter region and observed several transcription factor binding sites (TFBS) for nuclear factor of activated T-cells (NFAT), SRY-box, c-AMP responsive element binding protein (CREB), GATA binding factor, and hepatic nuclear factor-1. Interestingly, mmAQP1b transcription was differentially modulated by heavy metal or immunostimulant challenge. Further studies to deepen the knowledge of fish AQP-mediated adaptation response potentially relevant to molecular pathogenesis are warranted. Summary statement We identified mud loach AQP1b transcript variants and consensus sequences involved in stress or innate immunity in promotor region. AQP1b transcription was differentially modulated by heavy metal or immunostimulant challenge.
Host- and age-dependent transcriptional changes in Mycobacterium tuberculosis cell envelope biosynthesis genes after exposure to human alveolar lining fluid

Tuberculosis (TB) infection, caused by the airborne pathogen Mycobacterium tuberculosis (M.tb), resulted in almost 1.4 million deaths in 2019 and the number of deaths is predicted to increase by 20% over the next 5 years due to the COVID-19 pandemic. Upon reaching the alveolar space, M.tb comes in close contact with the lung mucosa before and after its encounter with host alveolar compartment cells. Our previous studies show that homeostatic innate soluble components of the alveolar lining fluid (ALF) can quickly alter the cell envelope surface of M.tb upon contact, defining subsequent M.tb-host cell interactions and infection outcomes in vitro and in vivo. We also demonstrated that ALF from 60+ year old elders (E-ALF) vs. healthy 18- to 45-year-old adults (A-ALF) is dysfunctional with loss of homeostatic capacity and impaired innate soluble responses linked to high local oxidative stress. In this study, a targeted transcriptional assay demonstrates that M.tb exposure to human ALF alters the expression of its cell envelope genes. Specifically, our results indicate that A-ALF-exposed M.tb upregulates cell envelope genes associated with lipid, carbohydrate, and amino acid metabolism, as well as genes associated with redox homeostasis and transcriptional regulators. Conversely, M.tb exposure to E-ALF shows lesser transcriptional response, with most of the M.tb genes unchanged or downregulated. Overall, this study indicates that M.tb responds and adapts to the lung alveolar environment upon contact, and that the host ALF status determined by factors such as age might play an important role in determining infection outcome.
Synthesis and Anti‐Proliferation Activity Evaluation of Novel 2‐Chloroquinazoline as Potential EGFR‐TK Inhibitors

A novel series of 2‐chloroquinazoline derivatives had been synthesized and their anti‐proliferation activities against the four EGFR high‐expressing cells A549, NCI‐H1975, AGS and HepG2 cell lines were evaluated. The preliminary SAR study of the scaffold of new compounds showed that the compounds with a chlorine substituent on R3 had a better anti‐proliferation activity than those substituted by hydrogen atom or vinyl group. Among them, 2‐chloro‐N‐[2‐chloro‐4‐(3‐chloro‐4‐fluoroanilino)quinazolin‐6‐yl]acetamide (10b) had the best activity, and the corresponding IC50 were 3.68, 10.06, 1.73 and 2.04 μM, respectively. And compound 10b had better or equivalent activity against four cell lines than Gefitinib. The activity of the compound 10b on the EGFR enzyme was subsequently tested. The Wound Healing of A549, AGS and HepG2 cells by this compound showed that the compound can inhibit the migration of cancer cells. Finally, the action channel of the compound 10b was supported by western blotting experiments. It provides useful information for the design of EGFR‐TK inhibitors.
Benefits of Using Activity Recommender Technology for Self-management of Depressive Symptoms

Behavioral Activation (BA)therapy has shown to be effective in treating depression. Recommending healthy activities is a core principle in Behavioral Activation (BA), which is typically done by the therapist. However, most BA smartphone applications do not recommend specific activities. This article reports quantitative results from an 8-week feasibility study of a previously presented smartphone-based BA recommender system. The system supports the planning and enacting of pleasurable activities and promotes activation of diverse activity types. Enrollment included 43 clinically depressed patients who installed the system on their phone and initiated activity scheduling. Twenty-nine patients used the system daily for more than a week.These patients presented a significant reduction in depressive symptoms during the study period. They displayed a more personalized usage approach and created recurring health goals comprising of their own customized activities. Furthermore, they took inspiration within various types of activities, thereby displaying more activity diversity. This study suggests that enacting a diverse mixture of activities that promote good sleep, personal hygiene, exercise, social contact, and leisure time can be essential in managing depressive symptoms. A smartphone-based activity recommender system can help patients achieve this.
Preliminary Wildfire Detection Using State-of-the-art PTZ (Pan, Tilt, Zoom) Camera Technology and Convolutional Neural Networks

Wildfires are uncontrolled fires in the environment that can be caused by humans or nature. In 2020 alone, wildfires in California have burned 4.2 million acres, damaged 10,500 buildings or structures, and killed more than 31 people, exacerbated by climate change and a rise in average global temperatures. This also means there has been an increase in the costs of extinguishing these treacherous wildfires. The objective of the research is to detect forest fires in their earlier stages to prevent them from spreading, prevent them from causing damage to a variety of things, and most importantly, reduce or eliminate the chances of someone dying from a wildfire. A fire detection system should be efficient and accurate with respect to extinguishing wildfires in their earlier stages to prevent the spread of them along with their consequences. Computer Vision is potentially a more reliable, fast, and widespread method we need. The current research in the field of preliminary fire detection has several problems related to unrepresentative data being used to train models and their existing varied amounts of label imbalance in the classes of their dataset. We propose a more representative and evenly distributed data through better settings, lighting, atmospheres, etc., and class distribution in the entire dataset. After thoroughly examining the results of this research, it can be inferred that they supported the datasets strengths by being a viable resource when tested in the real world on unfamiliar data. This is evident since as the model trains on the dataset, it is able to generalize on it, hence confirming this is a viable Machine Learning setting that has practical impact.
MARCH8 Restricts Influenza A Virus Infectivity but Does Not Downregulate Viral Glycoprotein Expression at the Surface of Infected Cells

The antiviral activity of MARCH8 has been associated with the downregulation of envelope glycoproteins from a range of different viruses, resulting in reduced incorporation into nascent virions. Here, we show that MARCH8 restricts IAV at a late stage in virus replication, but this was not associated with reduced expression of IAV envelope glycoproteins on the surfaces of infected cells, pointing to a distinct mechanism of antiviral activity. ABSTRACT Membrane-associated RING-CH8 (MARCH8) impairs the cell surface expression of envelope glycoproteins from different viruses, reducing their incorporation into virions. Using stable cell lines with inducible MARCH8 expression, we show that MARCH8 did not alter susceptibility to influenza A virus (IAV) infection, but virions released from infected cells were markedly less infectious. Knockdown of endogenous MARCH8 confirmed its effect on IAV infectivity. The expression of MARCH8 impaired the infectivity of both H3N2 and H1N1 strains and was dependent on its E3 ligase activity. Although virions released in the presence of MARCH8 expressed smaller amounts of viral hemagglutinin (HA) and neuraminidase (NA) proteins, there was no impact on levels of the viral HA, NA, or matrix 2 (M2) proteins detected on the surface of infected cells. Moreover, mutation of lysine residues in the cytoplasmic tails of HA, NA, and/or M2, or in the viral M1 protein, did not abrogate MARCH8-mediated restriction. While MARCH1 and -8 target similar immunological ligands and both restrict HIV-1, only MARCH8 inhibited IAV infectivity. Deletion of the N-terminal cytoplasmic (N-CT) domain of MARCH8 confirmed it to be a critical determinant of IAV inhibition. Of interest, deletion of the MARCH1 N-CT or its replacement with the MARCH8 N-CT resulted in acquisition of IAV restriction. Together, these data demonstrate that MARCH8 restricts a late stage in IAV replication by a mechanism distinct to its reported activity against other viruses. Moreover, we show that the N-CT of MARCH8 is essential for anti-IAV activity, whereas the MARCH1 N-CT inhibits its ability to restrict IAV. IMPORTANCE The antiviral activity of MARCH8 has been associated with the downregulation of envelope glycoproteins from a range of different viruses, resulting in reduced incorporation into nascent virions. Here, we show that MARCH8 restricts IAV at a late stage in virus replication, but this was not associated with reduced expression of IAV envelope glycoproteins on the surface of infected cells, pointing to a distinct mechanism of antiviral activity. Our studies also demonstrate the differential ability of MARCH1 and -8 to restrict IAV infectivity, highlighting the critical role of the N-CT domain of each protein in modulating IAV restriction. Overall, these studies provide novel insights regarding the mechanisms by which MARCH proteins contribute to cell-intrinsic immunity against IAV.
An Integrated Analysis of C5AR2 Related to Malignant Properties and Immune Infiltration of Breast Cancer

Background C5AR2 (GPR77, C5L2) is the second receptor for C5a that is a potent protein generated by complement activation. C5AR2 can mediate its own signaling events and exert significant immunomodulatory effects through those events. However, research of C5AR2 in cancer is limited, and its function remains unclear in breast cancer. Methods The expression of C5AR2 and its correlations with prognosis, immune infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI) in more than thirty types of cancers were described through GTEx, TCGA, PrognoScan, TIMER2.0, CCLE, HPA, and TISIDB database. C5AR2 showed strong relationships to those immune marker sets in breast cancer. Otherwise, CCK8 assay and Transwell assay were conducted to illustrate the role of C5AR2 in migration, invasion, and proliferation of breast cancer cells. Results Generally, C5AR2 expression differed across most cancerous and noncancerous tissues, and high C5AR2 expression significantly related to poor prognosis in BRCA, GBM, KICH, LAML, LGG, LIHC, PAAD, and STAD. Moreover, C5AR2 expression levels were dramatically correlated with recognized immune infiltration, especially the polarization of macrophages in breast cancer. Gene set enrichment analysis confirmed that C5AR2 participates in regulating multiple signaling pathways involved in tumorigenesis as well as tumor immunity. C5AR2 overexpression facilitated the functions such as migration, invasion, and proliferation in breast cancer cells, which is consistent with bioinformatics analysis. Conclusions C5AR2 is involved in immune infiltration and malignant characteristics of breast cancer, which may be a prospective biomarker for breast cancer.
Decrease in Serum Urate Level Is Associated With Loss of Visceral Fat in Male Gout Patients

Objective To clarify the relationship between serum urate (SU) decrease and visceral fat area (VFA) reduction in patients with gout. Methods We retrospectively analyzed 237 male gout patients who had two sets of body composition and metabolic measurements within 6 months. Subjects included had all been treated with urate-lowering therapy (ULT) (febuxostat 20–80 mg/day or benzbromarone 25–50 mg/day, validated by the medical record). All patients were from the specialty gout clinic of The Affiliated Hospital of Qingdao University. The multiple linear regression model evaluated the relationship between change in SU [ΔSU, (baseline SU) – (final visit SU)] and change in VFA [ΔVFA, (baseline VFA) – (final visit VFA)]. Results ULT resulted in a mean (standard deviation) decrease in SU level (464.22 ± 110.21 μmol/L at baseline, 360.93 ± 91.66 μmol/L at the final visit, p <0.001) accompanied by a decrease in median (interquartile range) VFA [97.30 (81.15–118.55) at baseline, 90.90 (75.85–110.05) at the final visit, p < 0.001]. By multiple regression model, ΔSU was identified to be a significant determinant variable of decrease in VFA (beta, 0.302; p = 0.001). Conclusions The decrease in SU level is positively associated with reduced VFA. This finding provides a rationale for clinical trials to affirm whether ULT promotes loss of visceral fat in patients with gout.
Therapeutic Effects of Berberine Hydrochloride on Stress-Induced Diarrhea-Predominant Irritable Bowel Syndrome Rats by Inhibiting Neurotransmission in Colonic Smooth Muscle

The etiology of diarrhea-predominant irritable bowel syndrome (IBS-D) is complicated and closely related to neurotransmission in the gastrointestinal (GI) tract. Developing new strategies for treating this disease is a major challenge for IBS-D research. Berberine hydrochloride (BBH), the derivative of berberine, is a herbal constituent used to treat IBS. Previous studies have shown that BBH has potential anti-inflammatory, antibacterial, analgesic, and antidiarrheal effects and a wide range of biological activities, especially in regulating the release of some neurotransmitters. A modified IBS-D rat model induced by chronic restraint stress was used in all experiments to study the effects of BBH on the GI tract. This study measured the abdominal withdrawal reflex (AWR) response to graded colorectal distention (CRD; 20, 40, 60, and 80 mmHg) and observed the fecal areas of stress-induced IBS-D model. Experiments were conducted using organ bath techniques, which were performed in vitro using strips of colonic longitudinal smooth muscle. Inhibitory and excitatory neurotransmitter agents were added to each organ bath to observe contractile responses on the strips and the treatment effect exerted by BBH. The IBS-D rat model was successfully induced by chronic restraint stress, which resulted in an increased defecation frequency and visceral hypersensitivity similar to that of humans. BBH could reduce 4-h fecal areas and AWR response to CRD in IBS-D. The stress-induced IBS-D model showed upregulated colonic mRNA expression levels of 5-hydroxytryptamine-3A receptor and downregulated expression levels of neuronal nitric oxide synthase. Meanwhile, BBH could reverse this outcome. The responses of substances that regulate the contraction induced by related neurotransmission in the longitudinal smooth muscle of IBS-D colon (including the agonist of acetylcholine, carbachol; NOS inhibitor, L-NAME; and P2Y1 receptor antagonist, MRS2500) can be inhibited by BBH. In summary, BBH promotes defecation frequency and visceral hypersensitivity in IBS-D and exerts inhibitory effects on contractile responses in colonic longitudinal smooth muscle. Thus, BBH may represent a new therapeutic approach for treating IBS-D.
To Do or Not to Do… Primary Health Care Professionals Experiences With Mothers With Children Born of Sexual Violence

Mothers and their children born of sexual violence are at heightened risk for developing an insecure attachment relationship. These mothers and their children often enter care late or not at all, as they are not identified by health care professionals. In this qualitative study, semi structured interviews were conducted with sixteen professionals in primary care for pregnant women and/or young mothers with the aim to identify the status quo in knowledge and skills, challenges, and opportunities. Participants included among others professionals working at Youth Services, psychologists, and clinical nurse specialists. Through a thematic analysis, five themes were identified: the knowledge of the professional, discussing the sexual violence, suitable interventions, points of attention during care, and recommendations. Analysis revealed that three groups of professionals can be distinguished, based on their level of awareness of this target group and their available knowledge and skills. To improve primary care for mothers with children born of sexual violence an increase in awareness, knowledge, and skills is a necessary prerequisite. Scientifically based best practices are therefore necessary for health care professionals to provide adequate care for mothers with children born of sexual violence.