Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome-wide analysis reveals signatures of complex introgressive gene flow in macaques (genus Macaca)

The genus Macaca serves as an ideal research model for speciation and introgressive gene flow due to its short period of diversification (about five million years ago) and rapid radiation of constituent species. To understand evolutionary gene flow in macaques, we sequenced four whole genomes (two M. arctoides and two M. thibetana) and combined them with publicly available macaque genome data for genome-wide analyses. We analyzed 14 individuals from nine Macaca species covering all Asian macaque species groups and detected extensive gene flow signals, with the strongest signals between the fascicularis and silenus species groups. Notably, we detected bidirectional gene flow between M. fascicularis and M. nemestrina. The estimated proportion of the genome inherited via gene flow between the two species was 6.19%. However, the introgression signals found among studied island species, such as Sulawesi macaques and M. fuscata, and other species were largely attributed to the genomic similarity of closely related species or ancestral introgression. Furthermore, gene flow signals varied in individuals of the same species (M. arctoides, M. fascicularis, M. mulatta, M. nemestrina and M. thibetana), suggesting very recent gene flow after the populations split. Pairwise sequentially Markovian coalescence (PSMC) analysis showed all macaques experienced a bottleneck five million years ago, after which different species exhibited different fluctuations in demographic history trajectories, implying they have experienced complicated environmental variation and climate change. These results should help improve our understanding of the complicated evolutionary history of macaques, particularly introgressive gene flow.
Anomalous functional connectivity within the default-mode network in treatment-naive patients possessing first-episode major depressive disorder

Abstract Background and Objective: Previous studies have shown that the default-mode network (DMN) has a substantial role in patients with major depressive disorder (MDD). However, there is a shortage of information regarding variations in the functional connectivity (FC) of the DMN of treatment-naive patients with first-episode MDD. The present study aims to explore the FC of the DMN in such patients. Methods: The study population consisted of 33 patients and 35 controls, paired regarding age, gender, education level, and health condition. Depression severity was assessed through the Hamilton Depression Scale (HAM-D), and subjects underwent evaluation during the resting-state through functional magnetic resonance imaging (rs-fMRI). To assess the result, we used FC and ICA. We used Spearman's correlation test to detect potential correlations between anomalous FC and severity of HAM-D scores. Results: We have found a decreased FC in the left medial orbitofrontal gyrus (MOFG) and right marginal gyrus (SMG) in depressive patients compared to controls. There was a negative correlation between abnormal FC in the right SMG and HAM-D scores. We have not found any increase in FC of the DMN in treatment-naive, first-episode of MDD patients. Conclusions: Our study provided evidence of a negative correlation between abnormal FC in the DMN and severity of depression symptoms measured by HAM-D in treatment-naive MDD patients. This finding could shed some light on the relevance of DMN for understanding the pathophysiology of cognitive impairment in MDD.
Spatial and Temporal Genetic Diversity and Population Structure of Hemileia vastatrix from Peruvian Coffee Plantations

Population genetic studies of Hemileia vastatrix have been conducted in order to describe the evolutionary dynamics of the pathogen and the disease epidemiology as consequence of changes in disease management and host distribution occurred in Peru after the 2013 epidemic. These analyses were performed by sequencing the internal transcribed spacers of the nuclear ribosomal DNA (rDNA-ITS) of H. vastatrix collected from two coffee growing areas in 2014 and 2018. H. vastatrix population showed high haplotype diversity (Hd = 0.9373 ± 0.0115) with a low nucleotide diversity (π = 0.00322 ± 0.00018). Likewise, AMOVA indicated that fungus population has behaved as a large population without structuring by geographical origin and sampling years (FST = 0.00180, P = 0.20053 and FST = 0.00241, P = 0.19693, respectively). Additionally, the haplotype network based on intraspecific phylogenetic analysis of H. vastatrix using Peruvian and NCBI sequences revealed that Peruvian ancestral haplotypes, which were maintained in time and space, would correspond to the reported sequences of the races II and XXII. This result suggests that no substantial changes have occurred through time in Peruvian Hemileia vastatrix population.
Treatment experience in a HIV-infected patient with Vogt–Koyanagi–Harada disease – a case report

Vogt–Koyanagi–Harada (VKH) disease is a multisystem autoimmune inflammatory disorder encompassing ophthalmic, auditory, dermatologic, and neurologic manifestations. 1–3 Previous studies had shown that HIV patients had an increased risk of some autoimmune diseases including Sjögren syndrome, psoriasis, systemic lupus erythematosus (SLE), autoimmune hemolytic anemia, and uveitis. 4 To the best of our knowledge, there have been limited reports of VKH disease in patients with HIV infection. 5 Herein, we report a case of bilateral VKH in an HIV-infected patient and discuss the clinical course and treatment.
USP11 degrades KLF4 via its deubiquitinase activity in liver diseases

Krüppel‐like factor 4 (KLF4) is a zinc‐finger containing DNA‐binding transcription factor involved in tumorigenesis and acts as a tumour suppressor or an oncogene depending on the tissue. In hepatocellular carcinoma (HCC), KLF4 has been considered as a tumour suppressor, although the mechanism underlying its action remains largely unknown. In this study, we identified the ubiquitin‐specific peptidase USP11 as a KLF4‐interacting deubiquitinating enzyme using a proteomic approach. USP11 destabilizes KLF4 through the removal of K63‐dependent polyubiquitination, thereby inhibiting KLF4 expression. We also provide mechanistic insights into KLF4 degradation and show that USP11 depletion inhibits growth and chemoresistance of HCC cells by enhancing KLF4 stability. Importantly, lipid content was reduced and genes involved in fatty acid metabolism were down‐regulated in an in vitro steatosis conditions upon USP11 knockout. Finally, elevated USP11 and reduced KLF4 levels were detected both in a hepatic steatosis in vitro model and in public clinical data of non‐alcoholic fatty liver disease and HCC patients. Collectively, these findings suggest that USP11, as KLF4‐binding partner, is an important mediator of hepatic tumorigenesis that functions via degradation of KLF4 and is a potential treatment target for liver diseases.
Tele-forensic interviewing can be a reasonable alternative to face-to-face interviewing of child witnesses.

OBJECTIVE Tele-forensic interviews have the potential to aid investigations when children live far from interviewers, there is a risk of disease transmission, or when expertise is not locally available. However, it is unknown whether tele-forensic interviewing is an effective alternative to face-to-face interviewing, particularly for children most prone to suggestibility and lapses of attention. HYPOTHESES Previous studies suggested that school-age children would provide similar amounts of information across interview modes but provided no basis for predicting how misinformation impacts accuracy across modes or how 4- and 5-year-olds would react to tele-forensic interviewing. METHOD Children (4-8 years, N = 261, Mage = 6.42 years, 48% female) interacted with male assistants who violated a no-touching rule, parents read children a book containing misinformation about that event, and female assistants conducted interviews (usually 2 weeks after the event) face-to-face or via a video conference application. RESULTS The children were more talkative during a practice narrative phase when interviewed face-to-face rather than on screen (incidence rate ratio [IRR] = 1.26, 95% CI [1.06, 1.51]), and 4-, 5-, and 6-year-olds said more in response to open-ended prompts when interviewed face-to-face (IRR = 1.50, 95% CI [1.08, 2.09]). Children younger than 7 years also disclosed the face touch and noncompleted handshake in response to earlier and less directive prompts when interviewed face-to-face, rs(53) = . 28, p = . 037, and rs(48) = . 33, p = . 021, respectively. Children 8 years and older, however, disclosed the face touch more readily when they spoke on screen, rs(28) = -. 38, p = . 036, and older 7-year-olds and 8-year-olds disclosed the noncompleted handshake more readily on screen, rs(30) = -. 36, p = . 042. Across interview modes, children reported comparable numbers of touch events, however, and were equally accurate on challenging source-monitoring and detail questions. CONCLUSIONS Tele-forensic interviewing can be a reasonable alternative to face-to-face interviewing. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Associations and interaction effects of maternal smoking and genetic polymorphisms of cytochrome P450 genes with risk of congenital heart disease in offspring

Supplemental Digital Content is available in the text Abstract To assess associations and interactions of maternal smoking and cytochrome P450 (CYP450) genetic variants with the developments of congenital heart disease (CHD) and specific subtypes. A case–control study of 654 cases and 666 controls was conducted from November 2017 to March 2020. The exposures of interest were maternal active and passive smoking before/in the early pregnancy and CYP450 genetic polymorphisms. Data were analyzed using the Chi-square test and logistic regression analysis. After adjusting for the potential confounding factors, our study showed maternal active (ORadj = 2.34, 95%CI: 1.19–4.60) or passive (ORadj = 1.76, 95%CI: 1.34–2.31) smoking before pregnancy, passive smoking in the early pregnancy (ORadj = 3.05, 95%CI: 2.26–4.12), as well as polymorphisms of CYP450 at rs1065852 (G/A vs G/G: ORadj = 1.46, 95%CI: 1.07–1.99; A/A vs G/G: ORadj = 1.63, 95%CI: 1.15–2.33) and rs16947 (A/A vs G/G: ORadj = 3.61, 95%CI: 2.09–6.23), were significantly associated with risk of total CHD in offspring. Similar results were also found for some subtypes of CHD. Additionally, significant interactions between maternal smoking and CYP450 genes on the risk of CHD were observed. Maternal smoking and CYP450 genetic variants were associated with increased risk of CHD and specific subtypes in offspring. And the effects of CYP450 genes on CHD may be modified by maternal smoking.
Regulation of microglia population dynamics throughout development, health, and disease

The dynamic expansions and contractions of the microglia population in the central nervous system (CNS) to achieve homeostasis are likely vital for their function. Microglia respond to injury or disease but also help guide neurodevelopment, modulate neural circuitry throughout life, and direct regeneration. Throughout these processes, microglia density changes, as does the volume of area that each microglia surveys. Given that microglia are responsible for sensing subtle alterations to their environment, a change in their density could affect their capacity to mobilize rapidly. In this review, we attempt to synthesize the current literature on the ligands and conditions that promote microglial proliferation across development, adulthood, and neurodegenerative conditions. Microglia display an impressive proliferative capacity during development and in neurodegenerative diseases that is almost completely absent at homeostasis. However, the appropriate function of microglia in each state is critically dependent on density fluctuations that are primarily induced by proliferation. Proliferation is a natural microglial response to insult and often serves neuroprotective functions. In contrast, inappropriate microglial proliferation, whether too much or too little, often precipitates undesirable consequences for nervous system health. Thus, fluctuations in the microglia population are tightly regulated to ensure these immune cells can execute their diverse functions.
A case report on severe nivolumab-induced adverse events similar to primary sclerosing cholangitis refractory to immunosuppressive therapy

Abstract Introduction: Immune checkpoint inhibitors (ICIs), particularly anti-PD-1 antibody, have dramatically changed cancer treatment; however, fatal immune-related adverse events (irAEs) can develop. Here, we describe a severe case of sclerosing cholangitis-like irAE. We report the use of 3 immunosuppressive agents that resulted in the death of the patient due to treatment inefficacy. According to a postmarketing study of nivolumab, the frequency of ICI-related sclerosing cholangitis is 0.27% and that of ICI-related cholangitis is 0.20%. There have been 4 case reports of sclerosing cholangitis-like irAE, with imaging findings, including typical intrahepatic bile duct beaded constriction in primary sclerosing cholangitis. Treatment starts with prednisolone and is combined with an immunosuppressant in refractory cases. There are no reports of severe cases that ultimately led to death. Patients concerns: The patient is a 64-year-old male with Stage IV squamous cell lung carcinoma; he was hospitalized with abdominal pain and elevation of aspartate transaminase and alanine transaminase, approximately 4 months after ICI administration was suspended. This occurred because the patient treated with nivolumab as the second-line chemotherapy and developed type 1 diabetes mellitus after 11 courses. Diagnosis: A grade 3 increase in bilirubin was observed and he was diagnosed with sclerosing cholangitis, based on magnetic resonance cholangiopancreatography imaging and pathological findings of the liver and bile duct. Interventions: Prednisolone, mycophenolate mofetil, and tacrolimus combination therapy was administered. Outcomes: The treatment was difficult and failed. He died from liver failure 8 months after diagnosis. In this case, hepatitis and cholangitis, mainly alanine transaminase-dominant liver disorder, developed in the early stages of irAEs. Although he showed some improvement after prednisolone administration, bilirubin levels began rising again, and sclerosing cholangitis did not improve even with the use of 3 immunosuppressive agents recommended by the ESMO Clinical Practice Guidelines for immune-related hepatotoxicity management. Although the antitumor effect showed a complete response, liver failure led to death. Conclusion: This is the first case report on the ineffectiveness of triple immunosuppressant combination therapy recommended by the guidelines for immune-related hepatotoxicity. It is necessary to develop more appropriate treatment for severe sclerosing cholangitis-like irAE based on the robust evidence.
Olive Leaf Powder Modulate Insulin Production and Circulating Adipokines in Streptozotocin Induced Diabetic Rats

Abstract Olives (Olea europaea) have natural phytochemical compounds that are of great importance for their potential beneficially health effects. This study aimed to evaluate the effects of olive leaf powder (OLP) on insulin production and circulating adipokines in streptozotocin-induced diabetic rats. Forty Wistar-albino male rats, weighing 200–225 g were divided into four groups (n = 10); group I: Normal healthy rats received balanced diet; group II: Diabetic control rats receiving balanced diet; group III: Diabetic rats receiving balanced diet + standard antidiabetic drugs (metformin, 600 mg/bw) and group four: Diabetic rats received diet supplemented with 2.0% OLP. The experiment was conducted for four weeks. Our results showed that the consumption of 2.0% OLP decreased serum glucose, triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels, whereas serum high density lipoprotein (HDL) level was increased. OLP supplementation also inhibited the atherogenic index [AI; log (TG/HDL-C) and atherogenic coefficient (AC)] levels relative to those of the untreated diabetic group. Moreover, OLP increased serum adiponectin concentration, and decreased serum leptin concentration. Liver and kidney functions were also attenuated by OLP. This finding also implies that OLP can play an important role in the treatment and delay of diabetic complications.
Attentional Modulation of Hierarchical Speech Representations in a Multi-Talker Environment

Humans are remarkably adept in listening to a desired speaker in a crowded environment, while filtering out non-target speakers in the background. Attention is key to solving this difficult cocktail-party task, yet a detailed characterization of attentional effects on speech representations is lacking. It remains unclear across what levels of speech features and how much attentional modulation occurs in each brain area during the cocktail-party task. To address these questions, we recorded whole-brain BOLD responses while subjects either passively listened to single-speaker stories, or selectively attended to a male or a female speaker in temporally-overlaid stories in separate experiments. Spectral, articulatory, and semantic models of the natural stories were constructed. Intrinsic selectivity profiles were identified via voxelwise models fit to passive listening responses. Attentional modulations were then quantified based on model predictions for attended and unattended stories in the cocktail-party task. We find that attention causes broad modulations at multiple levels of speech representations while growing stronger towards later stages of processing, and that unattended speech is represented up to the semantic level in parabelt auditory cortex. These results provide insights on attentional mechanisms that underlie the ability to selectively listen to a desired speaker in noisy multi-speaker environments.
Chaperone-assisted soluble expression and characterization of chitinase chiZJ408 in Escherichia coli BL21 and the chitin degradation by recombinant enzyme

Abstract The chaperone-assisted soluble expression and characterization of high molecular weight chitinase chiZJ408 in Escherichia coli BL21 were investigated. Chitin degradation products by chitinase chiZJ408 were analyzed. The results indicated that the introduction of the chaperone GroELS promoted the correct folding of chitinase chiZJ408 and increased its soluble expression by 14.9% (p < 0.05) in E. coli BL21. The optimal pH and temperature of chitinase chiZJ408 were respectively 6.0 and 50 °C. Chitinase chiZJ408 was stable at pHs of 4.0 ∼ 7.0 and at below 40 °C. Mg2+and Ca2+ had a significant impact on improving the activity of chitinase chiZJ408. Chitinase chiZJ408 was demonstrated to be exochitinase that cleaved the β-1,4-glycosidic bond of the chitin chain to generate only N,N’-diacetylchitobiose. This study broadens our understanding of chitinase and provides a basis for solving the problem of inclusion body formed by long fragment gene expression in E. coli.
The pivotal roles of the host immune response in the fine-tuning the infection and the development of the vaccines for SARS-CoV-2

ABSTRACT SARS-CoV2 infection induces various degrees of infections ranging from asymptomatic to severe cases and death. Virus/host interplay contributes substantially to these outcomes. This highlights the potential roles of the host immune system in fighting virus infections. SARS-CoV-2. We highlighted the potential roles of host immune response in the modulation of the outcomes of SARS-CoV infections. The newly emerged SARS-CoV-2 mutants complicated the control and mitigation strategies measures. We are highlighting the current progress of some already deployed vaccines worldwide as well as those still in the pipelines. Recent studies from the large ongoing global vaccination campaign are showing promising results in reducing the hospitality rates as well as the number of severe SARS-CoV-2 infected patients. Careful monitoring of the genetic changes of the virus should be practiced. This is to prepare some highly sensitive diagnostic assays as well as to prepare some homologous vaccines matching the circulating strains in the future.
RUNNING HEAD: PROTECTION FROM UNCERTAINTY Protection from uncertainty in the exploration/exploitation trade-off

The exploration/exploitation trade-off (EE trade-off) describes how, when faced with several competing alternatives, decision-makers must often choose between a known good alternative (exploitation) and one or more unknown but potentially more rewarding alternatives (exploration). Prevailing theory on how humans perform the EE trade-off states that uncertainty is a major motivator for exploration: the more uncertain the environment, the more exploration that will occur. The current paper examines whether exploratory behaviour in both choice and attention may be impacted differently depending on whether uncertainty is onset suddenly (unexpected uncertainty), or more slowly (expected uncertainty). It is shown that when uncertainty was expected, participants tended to explore less with their choices, but not their attention, than when it was unexpected. Crucially, the impact of this "protection from uncertainty" on exploration only occurred when participants had an opportunity to learn the structure of the task prior to experiencing uncertainty. This suggests that the interaction between uncertainty and exploration is more nuanced than simply more uncertainty leading to more exploration, and that attention and choice behaviour may index separate aspects of the EE trade-off.
Emotional Arousal and Valence Jointly Modulate the Auditory Response: A 40-Hz ASSR Study

Emotion is defined as a response to external stimuli and internal mental representations. It has been characterized as a multidimensional concept, primarily comprising two dimensions: valence and arousal. Existing studies have demonstrated that emotional experience exerts a powerful impact on auditory processing in terms of valence. However, it has also been shown that while negative emotion can improve auditory perception in healthy subjects, patients with depression show deficits in auditory perception. We thus speculated that both arousal and valence jointly modulate auditory perception. To examine the emotion-driven effects on the auditory response, we induced positive, negative, and neutral emotional states in healthy subjects and collected auditory steady-state response (ASSR) evoked by a 40-Hz chirp sound. We calculated peak-to-peak amplitude (PPA) and event-related spectral perturbation (ERSP) of evoked ASSRs and observed that the positive emotions significantly enhanced brain responses to auditory stimuli (p < 0.001), but that ASSRs in a negative state were not significantly enhanced compared with the neutral state. Subsequently, regression analysis showed a significant positive multiple linear relationship between the PPA and ratings of two emotional dimensions, indicating that arousal and valence jointly regulated the auditory cortex’s synchronous oscillation, rather than the valence in isolation, offering the potential to clarify the conflicting results surrounding the role of negative emotions in auditory responses. Because depression is generally characterized by low arousal and low valence in actual life, whereas the negative emotion evoked under laboratory conditions is always with low valence but high arousal.