Miracle-dz/UniFAR-FTUs huggingface dataset:
A Simple Method for Discovering Druggable, Specific Glycosaminoglycan-Protein Systems. Elucidation of Key Principles from Heparin/Heparan Sulfate-Binding Proteins

Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG–protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity. GBSs are better identified by considering the potential at neutral hydrogen bond donors such as asparagine or glutamine sidechains. Our studies also reveal that an unusual constellation of ionic and non-ionic residues in the binding site leads to specificity. Nature engineers the local environment of Asn45 of antithrombin, Gln255 of 3-O-sulfotransferase 3, Gln163 and Asn167 of 3-O-sulfotransferase 1 and Asn27 of basic fibroblast growth factor in the respective GBSs to induce specificity. Such residues are distinct from other uncharged residues on the same protein structure in possessing a significantly higher electrostatic potential, resultant from the local topology. In contrast, uncharged residues on nonspecific GBSs such as thrombin and serum albumin possess a diffuse spread of electrostatic potential. Our findings also contradict the paradigm that GAG-binding sites are simply a collection of contiguous Arg/Lys residues. Our work demonstrates the basis for discovering specifically interacting and druggable GAG-protein systems based on the structure of protein alone, without requiring access to any structure-function relationship data.
High-Resolution Transcriptome Analysis with Long-Read RNA Sequencing

RNA sequencing (RNA-seq) enables characterization and quantification of individual transcriptomes as well as detection of patterns of allelic expression and alternative splicing. Current RNA-seq protocols depend on high-throughput short-read sequencing of cDNA. However, as ongoing advances are rapidly yielding increasing read lengths, a technical hurdle remains in identifying the degree to which differences in read length influence various transcriptome analyses. In this study, we generated two paired-end RNA-seq datasets of differing read lengths (2×75 bp and 2×262 bp) for lymphoblastoid cell line GM12878 and compared the effect of read length on transcriptome analyses, including read-mapping performance, gene and transcript quantification, and detection of allele-specific expression (ASE) and allele-specific alternative splicing (ASAS) patterns. Our results indicate that, while the current long-read protocol is considerably more expensive than short-read sequencing, there are important benefits that can only be achieved with longer read length, including lower mapping bias and reduced ambiguity in assigning reads to genomic elements, such as mRNA transcript. We show that these benefits ultimately lead to improved detection of cis-acting regulatory and splicing variation effects within individuals.
Threat Intensity Widens Fear Generalization Gradients

Research in nonhuman animals reveals threat-sensitive generalization of defensive behavior that favors widespread generalization when threat intensity is high and limited generalization (i.e., specificity) when threat intensity is low. Here, we used Pavlovian fear conditioning to systematically investigate whether threat intensity widens behavioral generalization gradients to stimuli that decreasingly resemble a learned threat cue. Using a between-subjects design, volunteers underwent fear conditioning with a tone paired with either a high-intensity or low-intensity aversive stimulus prior to a test of fear generalization to novel tones. Results showed no effect of threat intensity on initial acquisition of conditioned fear. However, volunteers who underwent fear conditioning with a high-intensity aversive stimulus exhibited widespread generalization of autonomic arousal (skin conductance responses) as compared to volunteers who received a low-intensity aversive stimulus. These results show a transition from normal (selective) to overgeneralized fear as threat intensity increases, and have implications for understanding overgeneralization characteristic of trauma- and stress-related disorders.
Rare copy number alterations and copy‐neutral loss of heterozygosity revealed in ameloblastomas by high‐density whole‐genome microarray analysis

BACKGROUND Ameloblastoma (unicystic, UA, or multicystic, MA) is a rare tumor associated with bone destruction and facial deformity. Its malignant counterpart is the ameloblastic carcinoma (AC). The BRAFV600E mutation is highly prevalent in all these tumors subtypes and cannot account for their different clinical behaviors. METHODS We assessed copy number alterations (CNAs) and copy-neutral loss of heterozygosity (cnLOH) in UA (n = 2), MA (n = 3), and AC (n = 1) using the CytoScan HD Array (Affymetrix) and the BRAFV600E status. RT-qPCR was applied in four selected genes (B4GALT1, BAG1, PKD1L2, and PPP2R5A) covered by rare alterations, also including three MA and four normal oral tissues. RESULTS Fifty-seven CNAs and cnLOH were observed in the ameloblastomas and six CNAs in the AC. Seven of the CNAs were rare (six in UA and one in MA), four of them encompassing genes (gains of 7q11.21, 1q32.3, and 9p21.1 and loss of 16q23.2). We found positive correlation between rare CNA gene dosage and the expression of B4GALT1, BAG1, PKD1L2, and PPP2R5A. The AC and 1 UA were BRAF wild-type; however, this UA showed rare genomic alterations encompassing genes associated with RAF/MAPK activation. CONCLUSION Ameloblastomas show rare CNAs and cnLOH, presenting a specific genomic profile with no overlapping of the rare alterations among UA, MA, and AC. These genomic changes might play a role in tumor evolution and in BRAFV600E-negative tumors.
Study of fiber packing density of lyocell ring‐spun yarns

The study of yarn structure and related yarn properties has been the subject of much research. However, the study of the fiber packing density, which has practical significance for a number of yarns and their characteristics, has been limited to circular yarns because of the disordered yarn structure. In this paper, the fiber packing density of lyocell ring‐spun yarns is determined with the image analysis method. This method does not have any limitation with regard to the fiber cross‐sectional shape. The effect of yarn count, twist factor, spindle speed, traveler weight and front roller diameter on the fiber packing density in the yarn cross‐section is analyzed. The results of this paper and the data published in other scientific works are in good agreement.
Research on image reconstruction based and pixel unmixing based sub-pixel mapping methods

The sub-pixel mapping technique, which can provide a fine-resolution map of class labels, has attracted more and more attention in recent years. Generally speaking, there are two kinds of methods used to realize the sub-pixel labeling. The first kind are image reconstruction based methods, which first improve the spatial resolution of an image by the super-resolution technique, and then perform a hard classification on the super-resolved image. The second kind are pixel unmixing based methods, where the sub-pixel mapping is implemented based on the results of image unmixing. In this paper, we present a sparse representation method and a back-propagation (BP) neural network method for image reconstruction based and pixel unmixing based mapping, respectively. The advantages and disadvantages of both kinds of methods are analyzed and discussed.
Acupuncture ‘dose’ (Number of Treatments) and Insurance Benefits in the Usa

Background An adequate treatment dose, including a sufficient number of acupuncture treatments, is important for the clinical effectiveness of acupuncture treatment for common conditions. Objective To examine the characteristics of US adults who used a full course of acupuncture (≥6 treatments), a short course (1–5 treatments) or no acupuncture, including use of insurance benefits for acupuncture among users. Methods We used population-based survey data from the 2012 National Health Interview Survey (NHIS), the most current nationally representative data including use of acupuncture. We described subgroups of acupuncture users and used logistic regression to estimate the odds of past year acupuncture use versus non-use and completion of a full treatment course versus a short course. Covariates included demographic factors and health status. Analyses used strata, weights and clustering to account for the complex sample design. Results Among acupuncture users, 38% completed a full course. Acupuncture use was low (1.5%), but odds were higher among women and those with greater education and less poverty. Those who used acupuncture insurance benefits and who had greater education were more likely to receive a full treatment course. Insurance benefits attenuated disparities in use by sex and race/ethnicity. Conclusion Nationally, most people who use acupuncture do not receive a full treatment course. Considering evidence of effectiveness, low risk and relatively low cost of delivery, acupuncture could play a larger role in non-pharmaceutical treatment of common conditions such as pain. Policymakers should consider that, without insurance benefits for acupuncture, people are less likely to complete a full treatment course, which may contribute to disparities in use and health outcomes.
GLINT: a user‐friendly toolset for the analysis of high‐throughput DNA‐methylation array data

Summary: GLINT is a user‐friendly command‐line toolset for fast analysis of genome‐wide DNA methylation data generated using the Illumina human methylation arrays. GLINT, which does not require any programming proficiency, allows an easy execution of Epigenome‐Wide Association Study analysis pipeline under different models while accounting for known confounders in methylation data. Availability and Implementation: GLINT is a command‐line software, freely available at https://github.com/cozygene/glint/releases. It requires Python 2.7 and several freely available Python packages. Further information and documentation as well as a quick start tutorial are available at http://glint‐epigenetics.readthedocs. io. Contact: elior.rahmani@gmail.com or ehalperin@cs.ucla. edu
General laws of multiple fracture at static, cyclic and dynamic loading

Multiple fracture patterns of specimens from low and medium carbon steel tested in conditions of static, dynamic and cyclic loading were studied. Cumulative distributions of microcracks by length under static and cyclic loading, distributions of the number of fragments by their mass under dynamic loading and amplitude distributions of acoustic emission signals were plotted. The parameters of these distributions at different stages of loading were estimated. It was studied the influence of specimen thickness, the distance to the fracture surface, the grain size and the failure mechanism on these parameters. The general laws characterizing multiple fractures at different loading conditions were found. They include, in particular, a change in function describing the distributions and a reduction of the exponents of these functions before fracture. The physical meaning of the estimated distribution parameters, the possibility of their use for the fracture prediction and material selection are discussed.
Rhinovirus-16 Induced Release of IP-10 and IL-8 Is Augmented by Th2 Cytokines in a Pediatric Bronchial Epithelial Cell Model

Background In response to viral infection, bronchial epithelial cells increase inflammatory cytokine release to activate the immune response and curtail viral replication. In atopic asthma, enhanced expression of Th2 cytokines is observed and we postulated that Th2 cytokines may augment the effects of rhinovirus-induced inflammation. Methods Primary bronchial epithelial cell cultures from pediatric subjects were treated with Th2 cytokines for 24 h before infection with RV16. Release of IL-8, IP-10 and GM-CSF was measured by ELISA. Infection was quantified using RTqPCR and TCID50. Phosphatidyl inositol 3-kinase (PI3K) and P38 mitogen activated protein kinase (MAPK) inhibitors and dexamethasone were used to investigate differences in signaling pathways. Results The presence of Th2 cytokines did not affect RV replication or viral titre, yet there was a synergistic increase in IP-10 release from virally infected cells in the presence of Th2 cytokines. Release of IL-8 and GM-CSF was also augmented. IP-10 release was blocked by a PI3K inhibitor and IL-8 by dexamethasone. Conclusion Th2 cytokines increase release of inflammatory cytokines in the presence of rhinovirus infection. This increase is independent of effects of virus replication. Inhibition of the PI3K pathway inhibits IP-10 expression.
Childhood exposure to emotional abuse and later life stress among Kenyan women: a mediation analysis of cross-sectional data

ABSTRACT Background and objective: We explore whether perceived stress among Kenyan mothers is predicted by childhood exposure to emotional abuse – both witnessed among parents and experienced directly. Further, we explore whether this association is mediated by social support, family functioning and polygynous marriage. Design: We used cross-sectional data from a systematic random sample (n = 1974) of mothers in semi-rural Kenya. Methods: Data were collected using validated scales and trained interviewers. Analyses were conducted using bootstrapped structural equation models and fixed-effects linear regression models, controlling for age and household wealth. Results: Reported experience of emotional abuse – both directly experienced and observed among household adults – was high in the present population (72.5% and 69%, respectively). Perceived stress among women was significantly higher if they were exposed to more emotional abuse during childhood (p < .001). Lower social support, worse family functioning and higher rates of polygynous marriage mediated pathways between emotional abuse exposure during childhood and adult perceived stress. Conclusion: Future research should investigate whether social integration, identity formation and self-esteem underlie observed dynamics in sub-Saharan Africa. Efforts to promote social integration and support should target children currently experiencing emotional abuse, and may include child-targeted high quality television programing and adult-targeted media and celebrity campaigns.
Guard Cell Chloroplasts Are Essential for Blue Light-Dependent Stomatal Opening in Arabidopsis

Blue light (BL) induces stomatal opening through the activation of H+-ATPases with subsequent ion accumulation in guard cells. In most plant species, red light (RL) enhances BL-dependent stomatal opening. This RL effect is attributable to the chloroplasts of guard cell, the only cells in the epidermis possessing this organelle. To clarify the role of chloroplasts in stomatal regulation, we investigated the effects of RL on BL-dependent stomatal opening in isolated epidermis, guard cell protoplasts, and intact leaves of Arabidopsis thaliana. In isolated epidermal tissues and intact leaves, weak BL superimposed on RL enhanced stomatal opening while BL alone was less effective. In guard cell protoplasts, RL enhanced BL-dependent H+-pumping and DCMU, a photosynthetic electron transport inhibitor, eliminated this effect. RL enhanced phosphorylation levels of the H+-ATPase in response to BL, but this RL effect was not suppressed by DCMU. Furthermore, DCMU inhibited both RL-induced and BL-dependent stomatal opening in intact leaves. The photosynthetic rate in leaves correlated positively with BL-dependent stomatal opening in the presence of DCMU. We conclude that guard cell chloroplasts provide ATP and/or reducing equivalents that fuel BL-dependent stomatal opening, and that they indirectly monitor photosynthetic CO2 fixation in mesophyll chloroplasts by absorbing PAR in the epidermis.
Molecular Epidemiology of Nontuberculous Mycobacteria Isolates from Clinical and Environmental Sources of a Metropolitan City

Introduction While NTM infection is mainly acquired from environmental exposure, monitoring of environmental niches for NTM is not a routine practice. This study aimed to find the prevalence of environmental NTM in soil and water in four highly populated suburbs of Tehran, Iran. Material and Methods A total of 4014 samples from soil and water resources were collected and studied. Sediments of each treated sample were cultured in Lowenstein-Jensen medium and observed twice per week for growth rate, colony morphology, and pigmentation. Colonies were studied with phenotypic tests. Molecular analysis was performed on single colonies derived from subculture of original isolates. Environmental samples were compared with 34 NTM isolates from patients who were residents of the study locations. Results Out of 4014 samples, mycobacteria were isolated from 862 (21.4%) specimens; 536 (62.1%) belonged to slow growing mycobacteria (SGM) and 326 (37.8%) were rapid growing mycobacteria (RGM). The five most frequent NTM were M. farcinogens (105/862; 12.1%), M. fortuitum (72/862; 8.3%), M. senegalense (58/862; 6.7%), M. kansasii (54/862; 6.2%), and M. simiae (46/862; 5.3%). In total, 62.5% (539/862) of mycobacterial positive samples were isolated from water and only 37.4% (323/862) of them were isolated from soil samples (P<0.05). Out of 5314 positive clinical samples for mycobacteria, 175 (3.2%) isolates were NTM. The trend of NTM isolates increased from 1.2% (13 out of 1078) in 2004 to 3.8% (39 out of 1005) in 2014 (P = 0.0001). The major clinical isolates were M. simiae (51; 29.1%), M. kansasii (26; 14.8%), M. chelonae (28; 16%), and M. fortuitum (13; 7.4%). Conclusions Comparing the distribution pattern of environmental NTM isolates with clinical isolates suggests a possible transmission link, but this does not apply to all environmental NTM species. Our study confirms an increasing trend of NTM isolation from clinical samples that needs further investigation.
Associations of ABCB1 3435C>T and IL-10-1082G>A Polymorphisms With Long-Term Sirolimus Dose Requirements in Renal Transplant Patients

Backgrounds. Sirolimus (SRL) absorption and metabolism are affected by p-glycoprotein-mediated transport and CYP3A enzyme activity, which are further under the influences of cytokine concentrations. This retrospective study determined the associations of adenosine triphosphate-binding cassette, subfamily B, member 1 (ABCB1) 1236C>T, 2677 G>T/A, and 3435C>T, cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) −392A>G, cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5) 6986A>G and 14690G>A, interleukin (IL)-10 −1082G>A, and tumor necrosis factor (TNF) −308G>A polymorphisms with SRL dose-adjusted, weight-normalized trough concentrations (C/D) at 7 days, and at 1, 3, 6, and 12 months after initiation of SRL. Methods. Genotypes for 86 renal transplant patients who received SRL-based maintenance immunosuppressive therapy were determined using polymerase chain reaction followed by chip-based mass spectrometry. The changes of log-transformed C/D over the days posttransplantation were analyzed using a linear mixed-effects model, with adjustments for body mass index and weight-normalized doses of tacrolimus, prednisone, clotrimazole, and statins. Results. ABCB1 3435C>T and IL-10 −1082G>A were significantly associated with log C/D (P=0.0016 and 0.0394, respectively). Mean SRL C/D was 48% higher in patients with ABCB1 3435CT/TT genotype than those with 3435CC genotype, and was 24% higher in IL-10 −1082GG compared with −1082AG/AA. Conclusions. ABCB1 3435C>T and IL-10 −1082G>A were significantly associated with long-term SRL dose requirements. Genetics can play a significant role in SRL dosing and may be useful in therapeutic monitoring of SRL in renal transplantation. Future replication studies are needed to confirm these associations.
Probing astrocytes with carbon nanotubes and assessing their effects on astrocytic structural and functional properties

Single-walled carbon nanotubes, chemically-functionalized with polyethylene glycol (SWCNT-PEG) have been shown to modulate the morphology and proliferation characteristics of astrocytes in culture, when applied to the cells as colloidal solutes or as films upon which the cells can attach and grow. These changes were associated with a change in the immunoreactivity of the astrocyte-specific protein, glial fibrillary acidic protein (GFAP); the solutes and films caused an increase and a decrease in GFAP levels, respectively. To assess if these morpho-functional changes induced by the SWCNT-PEG modalities are dependent on GFAP or if the changes in GFAP levels are independent events, I used astrocytes isolated from GFAP knockout mice and found that selected changes induced by the SWCNT-PEG modalities are mediated by GFAP, namely the changes in perimeter, shape and cell death for colloidal solutes and the rate of proliferation for films. Since the loss GFAP has been shown to hamper the trafficking of glutamate transporters to the surface of astrocytes, which plays a vital role in the uptake of extracellular glutamate and maintaining homeostasis in the brain and spinal cord, in a
Identification of Genes Associated with Reproduction in the Mud Crab (Scylla olivacea) and Their Differential Expression following Serotonin Stimulation

The central nervous system (CNS) is often intimately involved in reproduction control and is therefore a target organ for transcriptomic investigations to identify reproduction-associated genes. In this study, 454 transcriptome sequencing was performed on pooled brain and ventral nerve cord of the female mud crab (Scylla olivacea) following serotonin injection (5 µg/g BW). A total of 197,468 sequence reads was obtained with an average length of 828 bp. Approximately 38.7% of 2,183 isotigs matched with significant similarity (E value < 1e−4) to sequences within the Genbank non-redundant (nr) database, with most significant matches being to crustacean and insect sequences. Approximately 32 putative neuropeptide genes were identified from nonmatching blast sequences. In addition, we identified full-length transcripts for crustacean reproductive-related genes, namely farnesoic acid o-methyltransferase (FAMeT), estrogen sulfotransferase (ESULT) and prostaglandin F synthase (PGFS). Following serotonin injection, which would normally initiate reproductive processes, we found up-regulation of FAMeT, ESULT and PGFS expression in the female CNS and ovary. Our data here provides an invaluable new resource for understanding the molecular role of the CNS on reproduction in S. olivacea.
Issues with data and analyses: Errors, underlying themes, and potential solutions

Some aspects of science, taken at the broadest level, are universal in empirical research. These include collecting, analyzing, and reporting data. In each of these aspects, errors can and do occur. In this work, we first discuss the importance of focusing on statistical and data errors to continually improve the practice of science. We then describe underlying themes of the types of errors and postulate contributing factors. To do so, we describe a case series of relatively severe data and statistical errors coupled with surveys of some types of errors to better characterize the magnitude, frequency, and trends. Having examined these errors, we then discuss the consequences of specific errors or classes of errors. Finally, given the extracted themes, we discuss methodological, cultural, and system-level approaches to reducing the frequency of commonly observed errors. These approaches will plausibly contribute to the self-critical, self-correcting, ever-evolving practice of science, and ultimately to furthering knowledge.