Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomic characterization of the normal human medial meniscus body using data‐independent acquisition mass spectrometry

Recent research suggests an important role of the meniscus in the development of knee osteoarthritis. We, therefore, aimed to analyze the proteome of the normal human meniscus body, and specifically to gain new knowledge on global protein expression in the different radial zones. Medial menisci were retrieved from the right knees of 10 human cadaveric donors, from which we cut a 2 mm radial slice from the mid‐portion of the meniscal body. This slice was further divided into three zones: inner, middle, and peripheral. Proteins were extracted and prepared for mass spectrometric analysis using data‐independent acquisition. We performed subsequent data searches using Spectronaut Pulsar and used fixed‐effect linear regression models for statistical analysis. We identified 638 proteins and after statistical analysis, we observed the greatest number of differentially expressed proteins between the inner and peripheral zones (163 proteins) and the peripheral and middle zones (136 proteins), with myocilin being the protein with the largest fold‐change in both comparisons. Chondroadherin was one of eight proteins that differed between the inner and middle zones. Functional enrichment analyses showed that the peripheral one‐third of the medial meniscus body differed substantially from the two more centrally located zones, which were more similar to each other. This is probably related to the higher content of cells and vascularization in the peripheral zone, whereas the middle and inner zones of the meniscal body appear to be more similar to hyaline cartilage, with high levels of extracellular matrix proteins such as aggrecan and collagen type II.
Goldfish adipocytes are pancreatic beta cell‐like, glucose‐responsive insulin‐producing cells

Glucose homeostasis plays a key role in maintaining stable physiological conditions, and its dysfunction causes severe chronic health issues including diabetes. In this study, we have characterized goldfish adipocytes as cells with properties similar to that of pancreatic β‐cells: they express considerable high levels of preproinsulin mRNAs, possess the necessary machinery for processing preproinsulin (prohormone convertases 1 and 2, carboxypeptidase E and trypsin) and responding to extracellular glucose (glucokinase and the glucose transporters 1, 2, and 4), produce insulin in a glucose‐responsive manner and express key transcription factors typically involved in pancreas development (Pdx1, Neurogenin3, Nkx2.2, Pax6, and FOXO1A). These findings reinforce the feature of fish adipocytes as alternate sources of active insulin, holding the promise that they could eventually be developed as transplantable sources of this vital hormone.
Outbreaks of Bemisia tabaci Mediterranean species in vegetable crops in São Paulo and Paraná States, Brazil

Abstract The whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is one of the most important agricultural pests and virus vectors worldwide. Bemisia tabaci is considered a complex of cryptic species with at least 44 species. Among them, the species Middle East-Asia Minor 1 (MEAM1, formerly B biotype) and Mediterranean (MED, formerly Q biotype) are the most important, and they have attained global status. In Brazil, MEAM1 was first reported in the 1990s and is currently the predominant species in the country, meanwhile, MED was recently reported in the South and Southeast regions and was found to be mainly associated with ornamental plants. Currently, an increasing problem in the management of whitefly infestations in greenhouses associated with bell pepper was observed in São Paulo State, Brazil. The whiteflies were collected and identified based on a microsatellite locus (primer pair BEM23F and BEM23R) and the mitochondrial cytochrome oxidase I gene followed by restriction fragment length polymorphism analysis and sequencing. We observed that MED was the predominant species collected on bell pepper, but it was also found on tomato, cucumber, eggplant, and weeds grown in greenhouses. In open field, we found MED on tomatoes, bell peppers, and eggplants. In addition, MED was identified in Goiás State in association with ornamental plants. The begomovirus Tomato severe rugose virus and the crinivirus Tomato chlorosis virus was detected on bell pepper and tomato, respectively. Only MED specimens were found associated with the virus-infected plants. Moreover, we also investigated the endosymbionts present in the MED whiteflies. The collected populations of B. tabaci MED harbored a diversity of secondary endosymbionts, with Hamiltonella (H) found predominantly in 89 specimens of the 129 tested. These results represent a new concern for Brazilian agriculture, especially for the management of the newly introduced whitefly MED species, which must be implemented to limit the spreading and establishment of this pest in different crops in this country.
Correlates of resilience after childhood sexual abuse among men who have sex with men

ABSTRACT Men who have sex with men (MSM) are at high risk for physical and mental health conditions and are often discussed in the health literature as “at risk” versus “at promise”. However, there is an ongoing need to examine factors that place MSM “at promise” for optimal well-being. This manuscript examines correlates of resilience, the ability to “bounce back” and function adaptively after adversities, among MSM. One hundred and five MSM with a history of childhood sexual abuse, who were enrolled in a randomized control trial were recruited for a supplemental study assessing resilience and other psychosocial factors. Participants completed measures assessing resilient trait and coping (i.e. “I am able to adapt” and “I tend to bounce back”), symptoms of trauma, trauma-related thoughts, and distress tolerance (ability to regulate unpleasant feelings). Findings from multivariable linear regressions controlling for covariates (age, education, race/ethnicity, and income) indicated that higher resilience was associated with (a) lower trauma scores on reexperiencing severity (b = −1.41, SE = .53, p = .01) and avoidance severity (b = −1.61, SE= .67, p = .02), (b) lower post-traumatic cognitions (b = −11.39, SE = 5.08, p = .03) especially negative cognitions about the self (b = −.44, SE = .16, p = .007), and (c) higher distress tolerance (b = .26, SE = .10, p = .01). Our preliminary findings suggest that resilient coping/traits are important to research after childhood sexual abuse among MSM, potentially assess in clinical settings, and address in interventions.
Biomass allocation and productivity–richness relationship across four grassland types at the Qinghai Plateau

Abstract Aboveground biomass (AGB) and belowground biomass (BGB) allocation and productivity–richness relationship are controversial. Here, we assessed AGB and BGB allocation and the productivity–richness relationship at community level across four grassland types based on the biomass data collected from 80 sites across the Qinghai Plateau during 2011–2012. The reduced major axis regression and general linear models were used and showed that (a) the median values of AGB were significantly higher in alpine meadow than in other three grassland types; the ratio of root to shoot (R/S) was significantly higher in desert grassland (36.06) than intemperate grassland (16.60), alpine meadow (13.35), and meadow steppe (19.46). The temperate grassland had deeper root distribution than the other three grasslands, with about 91.45% roots distributed in the top 30 cm soil layer. (b) The slopes between log AGB and log BGB in the temperate grassland and meadow steppe were 1.09 and 1, respectively, whereas that in the desert grassland was 1.12, which was significantly different from the isometric allocation relationship. A competitive relationship between AGB and BGB was observed in the alpine meadow with a slope of −1.83, indicating a trade‐off between AGB and BGB in the alpine meadow. (c) A positive productivity–richness relationship existed across the four grassland types, suggesting that the positive productivity–richness relationship might not be affected by the environmental factors at the plant location. Our results provide a new insight for biomass allocation and biodiversity–ecosystem functioning research.
Outcomes of induction antibody therapies in the nonbroadly sensitized adult deceased donor kidney transplant recipients: a retrospective cohort registry analysis

The outcomes of lymphocyte‐depleting antibody induction therapy (LDAIT), [thymoglobulin (ATG) or alemtuzumab (ALM)] versus interleukin‐2 receptor antagonist (IL‐2RA) in the nonbroadly‐sensitized [pretransplant calculated panel reactive antibody (cPRA), <80%] adult deceased donor kidney transplant recipients (adult‐DDKTRs) are understudied. In this registry, study of 55 593 adult‐DD‐KTRs, outcomes of LDAIT [(ATG, N = 32 985) and (ALM, N = 9429)], and IL‐2RA (N = 13 179) in <10% and 10–79% cPRA groups was analyzed. Adjusted odds ratio (aOR) of one‐year biopsy‐proven acute rejection (BPAR) was lower; while, aOR of 1‐year composite of re‐hospitalization, graft loss, or death was higher with LDAIT than IL2‐RA in both cPRA groups. Adjusted odds ratio (aOR) of delayed graft function was higher with LDAIT than IL‐2RA in the <10% cPRA group. Adjusted hazard ratio (aHR) of 5‐year death‐censored graft loss (DCGL) in both <80% cPRA groups seemed higher with ALM than other inductions [(<10% cPRA: ALM versus IL2RA, aHR = 1.11, 95% CI = 1.00–1.23 and ATG versus ALM: aHR = 0.84, 95% CI = 0.77–0.91; 10–79% cPRA: ALM versus IL2RA, aHR = 1.29, 95% CI = 1.02–1.64; and ATG versus ALM, aHR = 0.83, 95% CI = 0.70–0.98)]. Five‐year aHR of death did not differ among induction therapies in both cPRA groups. In nonbroadly sensitized adult‐DDKTRs, LDAIT is more protective against 1‐year BPAR (not 5‐year mortality) than IL‐2RA; the trend of a higher 5‐year DCGL risk with ALM than ATG or IL‐2RA needs further investigation.
Ultrahigh Responsivity Photodetectors of 2D Covalent Organic Frameworks Integrated on Graphene

2D materials exhibit superior properties in electronic and optoelectronic fields. The wide demand for high‐performance optoelectronic devices promotes the exploration of diversified 2D materials. Recently, 2D covalent organic frameworks (COFs) have emerged as next‐generation layered materials with predesigned π‐electronic skeletons and highly ordered topological structures, which are promising for tailoring their optoelectronic properties. However, COFs are usually produced as solid powders due to anisotropic growth, making them unreliable to integrate into devices. Here, by selecting tetraphenylethylene monomers with photoelectric activity, elaborately designed photosensitive 2D‐COFs with highly ordered donor‐acceptor topologies are in situ synthesized on graphene, ultimately forming COF‐graphene heterostructures. Ultrasensitive photodetectors are successfully fabricated with the COFETBC–TAPT‐graphene heterostructure and exhibited an excellent overall performance with a photoresponsivity of ≈3.2 × 107 A W−1 at 473 nm and a time response of ≈1.14 ms. Moreover, due to the high surface area and the polarity selectivity of COFs, the photosensing properties of the photodetectors can be reversibly regulated by specific target molecules. The research provides new strategies for building advanced functional devices with programmable material structures and diversified regulation methods, paving the way for a generation of high‐performance applications in optoelectronics and many other fields.
Age-Related Differences in Intentional Forgetting of Prospective Memory

This study investigated age-related differences in intentional forgetting (IF) of prospective memory (memory for actions to be performed in the future) in young (19–30 years) and late-midlife adults (LMA; 57–75 years). Prospective memory (PM) performance was examined by using the Virtual Week (VW) Task. An IF procedure was embedded into the VW task and the participants were instructed to forget some of the PM tasks that they were to remember and execute later on a virtual day. The study compared performances of the young and the LMA participants in the context of event- or time-based regular and irregular tasks. The results confirmed previous findings in showing that LMA participants exhibited worse PM than younger participants in lab-based tasks. In addition, although PM and IF performances separately have been shown to be affected by cognitive aging, larger age-related differences were not found in PM performance under IF conditions.
Kinetic and thermodynamic study of beta-Boswellic acid interaction with Tau protein investigated by surface plasmon resonance and molecular modeling methods

Introduction: Beta-Boswellic acid (BBA) is a pentacyclic terpene which has been obtained from frankincense and its beneficial effects on neurodegenerative disorders such as Alzheimer’s disease (AD) have been addressed. Methods: In the present study, thermodynamic and kinetic aspects of BBA interaction with Tau protein as one of the important proteins involved in AD in the absence and presence of glucose has been investigated using surface plasmon resonance (SPR) method. Tau protein was immobilized onto the carboxy methyl dextran chip and its binding interactions with BBA were studied at physiological pH at various temperatures. Glucose interference with these interactions was also investigated. Results: Results showed that BBA forms a stable complex with Tau (KD=8.45×10-7 M) at 298 K. Molecular modeling analysis showed a hydrophobic interaction between BBA and HVPGGG segment of R2 and R4 repeated domains of Tau. Conclusion: The binding affinity increased by temperature enhancement, while it decreased significantly in the presence of glucose. Both association and dissociation of the BBA-Tau complex were accompanied with an entropic activation barrier; however, positive enthalpy and entropy changes revealed that hydrophobic bonding is the main force involved in the interaction.
The Repressor Function of the Chlamydia Late Regulator EUO Is Enhanced by the Plasmid-Encoded Protein Pgp4

Chlamydia trachomatis is an important human pathogen that causes more than 150 million active cases of genital and eye infection in the world. This obligate intracellular bacterium produces infectious progeny within an infected human cell through the expression of late chlamydial genes. We showed that the ability of a key chlamydial transcription factor, EUO, to repress late genes was enhanced by a plasmid-encoded protein, Pgp4. In addition, studies with Chlamydia Pgp4-deficient strains provide evidence that Pgp4 delays late gene expression in infected cells. Thus, Pgp4 is a novel regulator of late gene expression in Chlamydia through its ability to enhance the repressor function of EUO. ABSTRACT A critical step in intracellular Chlamydia infection is the production of infectious progeny through the expression of late genes. This differentiation step involves conversion from a reticulate body (RB), which is the replicating form of the bacterium, into an elementary body (EB), which is the developmental form that spreads the infection to a new host cell. EUO is an important chlamydial transcription factor that controls the expression of late genes, but the mechanisms that regulate EUO are not known. We report that a plasmid-encoded protein, Pgp4, enhanced the repressor activity of EUO. Pgp4 did not function as a transcription factor because it did not bind or directly modulate transcription of its target promoters. Instead, Pgp4 increased the ability of EUO to bind and repress EUO-regulated promoters in vitro and physically interacted with EUO in pulldown assays with recombinant proteins. We detected earlier onset of EUO-dependent late gene expression by immunofluorescence microscopy in Pgp4-deficient C. trachomatis and C. muridarum strains. In addition, the absence of Pgp4 led to earlier onset of RB-to-EB conversion in C. muridarum. These data support a role for Pgp4 as a negative regulator of chlamydial transcription that delays late gene expression. Our studies revealed that Pgp4 also has an EUO-independent function as a positive regulator of chlamydial transcription. IMPORTANCE Chlamydia trachomatis is an important human pathogen that causes more than 150 million active cases of genital and eye infection in the world. This obligate intracellular bacterium produces infectious progeny within an infected human cell through the expression of late chlamydial genes. We showed that the ability of a key chlamydial transcription factor, EUO, to repress late genes was enhanced by a plasmid-encoded protein, Pgp4. In addition, studies with Chlamydia Pgp4-deficient strains provide evidence that Pgp4 delays late gene expression in infected cells. Thus, Pgp4 is a novel regulator of late gene expression in Chlamydia through its ability to enhance the repressor function of EUO.
Impact of Genetic and Nongenetic Factors on Body Mass Index and Waist-Hip Ratio Change in HIV-Infected Individuals Initiating Antiretroviral Therapy

Abstract Objective There is limited data on abdominal obesity and the influence of genetics on weight change after antiretroviral therapy (ART) initiation. We assessed body mass index (BMI) and waist hip ration (WHR) change over time in the Swiss HIV Cohort study (SHCS). Methods Mixed-effects models characterizing BMI and WHR change over time in 1090 SHCS participants initiating ART between 2005 and 2015 were developed and used to quantify the influence of demographics, clinical factors, and genetic background. Results Individuals with CD4 nadir <100 cells/µL gained 6.4 times more BMI than individuals with ≥200, and 2.8 times more WHR than individuals with ≥100 (P < .001) during the first 1.5 and 2.5 years after ART initiation, respectively. The risk of being overweight or obese after 1.5 years increased with CD4 nadir <100 cells/µL compared to 100–199 (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.63–2.74) and ≥200 (OR, 1.69; 95% CI, 1.26–2.32), persisting after 10 years of ART. The risk of abdominal obesity after 2.5 years increased with CD4 nadir <100 compared to ≥100 (OR, 1.35; 95% CI, 1.17–1.54 [in men]; OR, 1.36; 95% CI, 1.18–1.57 [in women]), persisting after 10 years of ART. No significant differences were found across antiretroviral drug classes or genetic scores. Conclusions The risk of general and abdominal obesity increased with CD4 nadir <100 cells/µL. Based on our results, including the genetic background would not improve obesity predictions in HIV-infected individuals.
A novel quantification of information for longitudinal data analyzed by mixed‐effects modeling

Nonlinear mixed‐effects (NLME) modeling is one of the most powerful tools for analyzing longitudinal data especially under the sparse sampling design. The determinant of the Fisher information matrix is a commonly used global metric of the information that can be provided by the data under a given model. However, in clinical studies, it is also important to measure how much information the data provide for a certain parameter of interest under the assumed model, for example, the clearance in population pharmacokinetic models. This paper proposes a new, easy‐to‐interpret information metric, the “relative information” (RI), which is designed for specific parameters of a model and takes a value between 0% and 100%. We establish the relationship between interindividual variability for a specific parameter and the variance of the associated parameter estimator, demonstrating that, under a “perfect” experiment (eg, infinite samples or/and minimum experimental error), the RI and the variance of the model parameter estimator converge, respectively, to 100% and the ratio of the interindividual variability for that parameter and the number of subjects. Extensive simulation experiments and analyses of three real datasets show that our proposed RI metric can accurately characterize the information for parameters of interest for NLME models. The new information metric can be readily used to facilitate study designs and model diagnosis.
Assessment of the nucleotide modifications in the high-resolution cryo-electron microscopy structure of the Escherichia coli 50S subunit

Abstract Post-transcriptional ribosomal RNA (rRNA) modifications are present in all organisms, but their exact functional roles and positions are yet to be fully characterized. Modified nucleotides have been implicated in the stabilization of RNA structure and regulation of ribosome biogenesis and protein synthesis. In some instances, rRNA modifications can confer antibiotic resistance. High-resolution ribosome structures are thus necessary for precise determination of modified nucleotides’ positions, a task that has previously been accomplished by X-ray crystallography. Here, we present a cryo-electron microscopy (cryo-EM) structure of the Escherichia coli 50S subunit at an average resolution of 2.2 Å as an additional approach for mapping modification sites. Our structure confirms known modifications present in 23S rRNA and additionally allows for localization of Mg2+ ions and their coordinated water molecules. Using our cryo-EM structure as a testbed, we developed a program for assessment of cryo-EM map quality. This program can be easily used on any RNA-containing cryo-EM structure, and an associated Coot plugin allows for visualization of validated modifications, making it highly accessible.
Repeat expansion and methylation-sensitive triplet-primed polymerase chain reaction for fragile X mental retardation 1 gene screening in institutionalised intellectually disabled individuals.

INTRODUCTION Fragile X syndrome (FXS) is the most prevalent X-linked intellectual disability (ID) and a leading genetic cause of autism, characterised by cognitive and behavioural impairments. The hyperexpansion of a CGG repeat in the fragile X mental retardation 1 (FMR1) gene leads to abnormal hypermethylation, resulting in the lack or absence of its protein. Tools for establishing the diagnosis of FXS have been extensively developed, including assays based on triplet-primed polymerase chain reaction (TP-PCR) for detection and quantification of the CGG trinucleotide repeat expansion, as well as determination of the methylation status of the alleles. This study aimed to utilise a simple, quick and affordable method for high sensitivity and specificity screening and diagnosis of FXS in institutionalised individuals with ID. METHODS A total of 109 institutionalised individuals at the Center for Social Rehabilitation of Intellectual Disability Kartini, Temanggung, Central Java, Indonesia, were screened in a three-step process using FastFrax™ Identification, Sizing and Methylation Status Kits. RESULTS Two samples that were classified as indeterminate with respect to the 41-repeat control at the identification step were subsequently determined to be non-expanded by both sizing and methylation status analyses. Two samples classified as expanded at the identification step were determined to carry full mutation expansions > 200 repeats that were fully methylated using sizing and methylation status analyses, respectively, yielding a disease prevalence of 1.83%. CONCLUSION Repeat expansion and methylation-specific TP-PCR is practical, effective and inexpensive for the diagnosis of FXS, especially in high-risk populations of individuals with ID of undetermined aetiology.