Miracle-dz/UniFAR-FTUs huggingface dataset:
Modified sites and functional consequences of 4-oxo-2-nonenal adducts in HDL that are elevated in familial hypercholesterolemia

The lipid aldehyde 4-oxo-2-nonenal (ONE) is a highly reactive protein crosslinker derived from peroxidation of n-6 polyunsaturated fatty acids and generated together with 4-hydroxynonenal (HNE). Lipid peroxidation product-mediated crosslinking of proteins in high-density lipoprotein (HDL) causes HDL dysfunction and contributes to atherogenesis. Although HNE is relatively well-studied, the role of ONE in atherosclerosis and in modifying HDL is unknown. Here, we found that individuals with familial hypercholesterolemia (FH) had significantly higher ONE-ketoamide (lysine) adducts in HDL (54.6 ± 33.8 pmol/mg) than healthy controls (15.3 ± 5.6 pmol/mg). ONE crosslinked apolipoprotein A-I (apoA-I) on HDL at a concentration of > 3 mol ONE per 10 mol apoA-I (0.3 eq), which was 100-fold lower than HNE, but comparable to the potent protein crosslinker isolevuglandin. ONE-modified HDL partially inhibited HDL's ability to protect against lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) gene expression in murine macrophages. At 3 eq, ONE dramatically decreased apoA-I exchange from HDL, from ∼46.5 to ∼18.4% (p < 0.001). Surprisingly, ONE modification of HDL or apoA-I did not alter macrophage cholesterol efflux capacity. LC-MS/MS analysis revealed that Lys-12, Lys-23, Lys-96, and Lys-226 in apoA-I are modified by ONE ketoamide adducts. Compared with other dicarbonyl scavengers, pentylpyridoxamine (PPM) most efficaciously blocked ONE-induced protein crosslinking in HDL and also prevented HDL dysfunction in an in vitro model of inflammation. Our findings show that ONE-HDL adducts cause HDL dysfunction and are elevated in individuals with FH who have severe hypercholesterolemia.
Synergistic action of the transcription factors Krüppel homolog 1 and Hairy in juvenile hormone/Methoprene-tolerant-mediated gene-repression in the mosquito Aedes aegypti

Arthropod-specific juvenile hormones control numerous essential functions in development and reproduction. In the dengue-fever mosquito Aedes aegypti, in addition to its role in immature stages, juvenile hormone III (JH) governs post-eclosion (PE) development in adult females, a phase required for competence acquisition for blood feeding and subsequent egg maturation. During PE, JH through its receptor Methoprene-tolerant (Met) regulate the expression of many genes, causing either activation or repression. Met-mediated gene repression is indirect, requiring involvement of intermediate repressors. Hairy, which functions downstream of Met in the JH gene-repression hierarchy, is one such factor. Krüppel-homolog 1, a zinc-finger transcriptional factor, is directly regulated by Met and has been implicated in both activation and repression of JH-regulated genes. However, the interaction between Hairy and Kr-h1 in the JH-repression hierarchy is not well understood. Our RNAseq-based transcriptomic analysis of the Kr-h1-depleted mosquito fat body revealed that 92% of Kr-h1 repressed genes are also repressed by Met, supporting the existence of a hierarchy between Met and Kr-h1 as previously demonstrated in various insects. Notably, 130 genes are co-repressed by both Kr-h1 and Hairy, indicating regulatory complexity of the JH-mediated PE gene repression. A mosquito Kr-h1 binding site in genes co-regulated by this factor and Hairy was identified computationally. Moreover, this was validated using electrophoretic mobility shift assays. A complete phenocopy of the effect of Met RNAi depletion on target genes could only be observed after Kr-h1 and Hairy double RNAi knockdown, suggesting a synergistic action between these two factors in target gene repression. This was confirmed using a cell-culture-based luciferase reporter assay. Taken together, our results indicate that Hairy and Kr-h1 not only function as intermediate downstream factors, but also act together in a synergistic fashion in the JH/Met gene repression hierarchy.
Possible roles of local oviductal estradiol-17β in luteal formation phase on the function of bovine oviductal epithelium

Oviducts play an important role in the reproductive process, such as in gamete transport, fertilization, and early embryonic development. However, the regulation of oviductal function during luteal formation phase (3−5 days post-ovulation), which is a crucial phase for early embryonic development, remains poorly understood. This study investigated the roles of oviductal estradiol-17β (E2) and progesterone (P4) concentrations on bovine oviductal functions in the luteal formation phase using RT-qPCR for some genes of oviductal epithelial cells. Bovine oviducts ipsilateral to the corpus luteum (CL) in the luteal formation phase were collected from a slaughterhouse. The concentration of oviductal E2 was positively correlated with the mRNA expressions of nuclear P4 receptor (PGR) and protein disulfide isomerase family A member 4 (PDIA4), which is related to protein secretion, in the ampulla and with estrogen receptor α (ESR1) mRNA expression in the isthmus. In contrast, the concentration of oviductal P4 was not correlated with oviductal mRNA expressions in either regions. Furthermore, for the candidate factor related to the oviductal E2 concentration, the CL parameters (CL size and tissue P4 concentration), first-wave dominant follicle (W1DF) parameters (follicle size and intrafollicular E2 concentration), and W1DF location (ipsilateral or contralateral to CL) did not influence the oviductal E2 concentration. In conclusion, our results suggest that the local oviductal E2 is a potential oviductal function regulator during the luteal formation phase.
Developing and Testing the Detén El Zika Campaign in Puerto Rico

Responding to an emerging health threat often requires rapid deployment of behavior change communication. Health communication best practices include developing and testing draft messages and materials to ensure that they resonate with and inspire priority groups to act. However, when faced with an emergency health threat, the timeline for these activities can be compressed from months to weeks. This article discusses the rapid development and implementation of a Zika virus prevention campaign for pregnant women in Puerto Rico. The goal of the campaign was to increase knowledge among and motivate pregnant women, their partners and family members, and the community to follow Zika virus prevention recommendations. The steps in campaign development include environmental scanning, concept development and testing, and message testing to ensure development of campaign materials that resonated with and were well-received by key audience groups. The materials adhere to principles of behavior change communication, and offer our insights for development of future campaigns when under time constraints.
NutriGenomeDB: a nutrigenomics exploratory and analytical platform

Habitual consumption of certain foods has shown beneficial and protective effects against multiple chronic diseases. However, it is not clear by which molecular mechanisms they may exert their beneficial effects. Multiple -omic experiments available in public databases have generated gene expression data following the treatment of human cells with different food nutrients and bioactive compounds. Exploration of such data in an integrative manner offers excellent possibilities for gaining insights into the molecular effects of food compounds and bioactive molecules at the cellular level. Here we present NutriGenomeDB, a web-based application that hosts manually curated gene sets defined from gene expression signatures, after differential expression analysis of nutrigenomics experiments performed on human cells available in the Gene Expression Omnibus (GEO) repository. Through its web interface, users can explore gene expression data with interactive visualizations. In addition, external gene signatures can be connected with nutrigenomics gene sets using a gene pattern-matching algorithm. We further demonstrate how the application can capture the primary molecular mechanisms of a drug used to treat hypertension and thus connect its mode of action with hosted food compounds.
Suicide Prevention in Social Work Education: How Prepared Are Social Work Students?

The prevalence of suicide suggests social workers will encounter clients at risk for suicide, but research shows social workers receive little to no training on suicide and suicide prevention and feel unprepared to work effectively with clients at risk. Baseline results from a randomized intervention study of the Question, Persuade, and Refer suicide prevention gatekeeper training with 73 advanced master’s of social work student interns show suicide knowledge was average, attitudes about suicide prevention were generally neutral, and use of suicide prevention practice skills was low. These results indicate an opportunity for enhancing student outcomes through training and inform social work education regarding necessary preparation for student interns and new graduates to identify and respond effectively to client suicide risk.
Controlled local delivery of RNA : regulating tissue morphogenesis

RNA interference (RNAi) is a powerful technology that provides a means to alter the expression of a specific protein based on a targeted RNA sequence. This is done by taking advantage of existing cellular machinery present within all eukaryotic cells which use short double-stranded RNA sequences as guides for RNA induced silencing. The potential for RNAi in medicine is enormous, providing a new approach to treat the complex biological dysregulation underlying many diseases. This promise of a new branch of therapeutics however has been mired with difficulties. RNA is quickly degraded by nucleases that are prevalent in the blood and throughout the body, it is highly immunogenic, and systemic delivery is complicated by high clearance rates. As such, developing formulations for the effective delivery of short RNAs presents significant hurdles. Local delivery can limit numerous unwanted systemic side effects of therapies and it maintains the highest therapeutic index possible in a targeted area before clearance. As such, the local delivery of siRNA may hold just as much potential as systemic delivery with significantly reduced complications. Layer-by-layer (LbL) assembly is a robust method that has been successfully demonstrated for the localized and sustained delivery of many biologic therapeutics and biomolecules. Developing an LbL film capable of delivering siRNA locally would offer a powerful new approach to the treatment of local disorders. This approach could be combined with existing medical devices to improve patient outcomes by directly addressing pathologic
IPD-IMGT/HLA Database

Abstract The IPD-IMGT/HLA Database, http://www.ebi. ac.uk/ipd/imgt/hla/, currently contains over 25 000 allele sequence for 45 genes, which are located within the Major Histocompatibility Complex (MHC) of the human genome. This region is the most polymorphic region of the human genome, and the levels of polymorphism seen exceed most other genes. Some of the genes have several thousand variants and are now termed hyperpolymorphic, rather than just simply polymorphic. The IPD-IMGT/HLA Database has provided a stable, highly accessible, user-friendly repository for this information, providing the scientific and medical community access to the many variant sequences of this gene system, that are critical for the successful outcome of transplantation. The number of currently known variants, and dramatic increase in the number of new variants being identified has necessitated a dedicated resource with custom tools for curation and publication. The challenge for the database is to continue to provide a highly curated database of sequence variants, while supporting the increased number of submissions and complexity of sequences. In order to do this, traditional methods of accessing and presenting data will be challenged, and new methods will need to be utilized to keep pace with new discoveries.
National Aboriginal Community Controlled Health Organisation (NACCHO) submission to the Senate Inquiry-Community Affairs References Committee: Inquiry into the effectiveness of the special arrangements for the supply of Pharmaceutical Benefits Scheme (PBS) medicines to Remote Area Aboriginal Health 

[Extract]1.0 Introduction Special arrangements exist for the supply of pharmaceutical benefits to clients of eligible Remote Area Aboriginal Health Services (RAAHS), primarily due to Aboriginal peoples and Torres Strait Islanders having by far the worst health outcomes and the clearest inequity in health care provision of any identifiable group in the Australian population. These special arrangements for access to Pharmaceutical Benefits Scheme (PBS) medicines ג€“ based on Section 100 of the National Health Act (1953) ג€“ aim to alleviate these disadvantages, and assist in 'Closing the Gap' (CTG) between Aboriginal and other Australians.
Diversity and Horizontal Transfer of Antarctic Pseudomonas spp. Plasmids

Pseudomonas spp. are widely distributed in various environments around the world. They are also common in the Antarctic regions. To date, almost 200 plasmids of Pseudomonas spp. have been sequenced, but only 12 of them were isolated from psychrotolerant strains. In this study, 15 novel plasmids of cold-active Pseudomonas spp. originating from the King George Island (Antarctica) were characterized using a combined, structural and functional approach, including thorough genomic analyses, functional analyses of selected genetic modules, and identification of active transposable elements localized within the plasmids and comparative genomics. The analyses performed in this study increased the understanding of the horizontal transfer of plasmids found within Pseudomonas populations inhabiting Antarctic soils. It was shown that the majority of the studied plasmids are narrow-host-range replicons, whose transfer across taxonomic boundaries may be limited. Moreover, structural and functional analyses enabled identification and characterization of various accessory genetic modules, including genes encoding major pilin protein (PilA), that enhance biofilm formation, as well as active transposable elements. Furthermore, comparative genomic analyses revealed that the studied plasmids of Antarctic Pseudomonas spp. are unique, as they are highly dissimilar to the other known plasmids of Pseudomonas spp.
Audiogenic Seizures in the Fmr1 Knock-Out Mouse Are Induced by Fmr1 Deletion in Subcortical, VGlut2-Expressing Excitatory Neurons and Require Deletion in the Inferior Colliculus

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading monogenetic cause of autism. One symptom of FXS and autism is sensory hypersensitivity (also called sensory over-responsivity). Perhaps related to this, the audiogenic seizure (AGS) is arguably the most robust behavioral phenotype in the FXS mouse model—the Fmr1 knock-out (KO) mouse. Therefore, the AGS may be considered a mouse model of sensory hypersensitivity. Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and the leading monogenetic cause of autism. One symptom of FXS and autism is sensory hypersensitivity (also called sensory over-responsivity). Perhaps related to this, the audiogenic seizure (AGS) is arguably the most robust behavioral phenotype in the FXS mouse model—the Fmr1 knock-out (KO) mouse. Therefore, the AGS may be considered a mouse model of sensory hypersensitivity. Hyperactive circuits are hypothesized to underlie dysfunction in a number of brain regions in patients with FXS and Fmr1 KO mice, and the AGS may be a result of this. But the specific cell types and brain regions underlying AGSs in the Fmr1 KO are unknown. We used conditional deletion or expression of Fmr1 in different cell populations to determine whether Fmr1 deletion in those cells was sufficient or necessary, respectively, for the AGS phenotype in males. Our data indicate that Fmr1 deletion in glutamatergic neurons that express vesicular glutamate transporter 2 (VGlut2) and are located in subcortical brain regions is sufficient and necessary to cause AGSs. Furthermore, the deletion of Fmr1 in glutamatergic neurons of the inferior colliculus is necessary for AGSs. When we demonstrate necessity, we show that Fmr1 expression in either the larger population of VGlut2-expressing glutamatergic neurons or the smaller population of inferior collicular glutamatergic neurons—in an otherwise Fmr1 KO mouse—eliminates AGSs. Therefore, targeting these neuronal populations in FXS and autism may be part of a therapeutic strategy to alleviate sensory hypersensitivity. SIGNIFICANCE STATEMENT Sensory hypersensitivity in fragile X syndrome (FXS) and autism patients significantly interferes with quality of life. Audiogenic seizures (AGSs) are arguably the most robust behavioral phenotype in the FXS mouse model—the Fmr1 knockout—and may be considered a model of sensory hypersensitivity in FXS. We provide the clearest and most precise genetic evidence to date for the cell types and brain regions involved in causing AGSs in the Fmr1 knockout and, more broadly, for any mouse mutant. The expression of Fmr1 in these same cell types in an otherwise Fmr1 knockout eliminates AGSs indicating possible cellular targets for alleviating sensory hypersensitivity in FXS and other forms of autism.
MiR‐34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2

In various kinds of carcinomas, the special AT‐rich sequence‐binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR‐34a downstream is the intended endeavor of this study. In te OSCCs the miR‐34a expression was determined by quantitative real‐time polymerase chain reaction (q‐PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q‐PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR‐34a on the initiation of OSCC were conducted. As a direct target of the miR‐34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR‐34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR‐34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR‐34a was confirmed by the cotransfection of miR‐34a mimics specifically the decrease in the expression of luciferase of SATB2–3′UTR‐wt reporter. As a whole, our study confirmed the inhibition of miR‐34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.
Meta-analytic structural equation modeling with moderating effects on SEM parameters.

Meta-analytic structural equation modeling (MASEM) is an increasingly popular meta-analytic technique that combines the strengths of meta-analysis and structural equation modeling. MASEM facilitates the evaluation of complete theoretical models (e.g., path models or factor analytic models), accounts for sampling covariance between effect sizes, and provides measures of overall fit of the hypothesized model on meta-analytic data. We propose a novel MASEM method, one-stage MASEM, which is better suitable to explain study-level heterogeneity than existing methods. One-stage MASEM allows researchers to incorporate continuous or categorical moderators into the MASEM, in which any parameter in the structural equation model (e.g., path coefficients and factor loadings) can be modeled by the moderator variable, while the method does not require complete data for the primary studies included in the meta-analysis. We illustrate the new method on two real data sets, evaluate its empirical performance via a computer simulation study, and provide user-friendly R-functions and annotated syntax to assist researchers in applying one-stage MASEM. We close the article by presenting several future research directions. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Cooperation and spatial self-organization determine rate and efficiency of particulate organic matter degradation in marine bacteria

Significance Microorganisms can cooperate by secreting public goods that benefit local neighbors; however, the conditions that favor cooperative growth in the environment, and the way in which this growth alters microbes’ contribution to ecosystem functions, remain unexplored. Here, we show that cooperation mediates the degradation of polysaccharide particles recalcitrant to hydrolysis in aquatic environments. Combining experiments and models, we define the physiological and environmental parameters that mediate the transition from cooperation to competition. Cooperation emerges through the self-organization of cells into ∼10- to 20-µm clusters that enable uptake of diffusible hydrolysis products. When cooperation is required, the degradation of recalcitrant biopolymers can only take place when degraders exceed a critical cell concentration, underscoring the importance of microbial interactions for ecosystem function. The recycling of particulate organic matter (POM) by microbes is a key part of the global carbon cycle. This process is mediated by the extracellular hydrolysis of polysaccharides, which can trigger social behaviors in bacteria resulting from the production of public goods. Despite the potential importance of public good-mediated interactions, their relevance in the environment remains unclear. In this study, we developed a computational and experimental model system to address this challenge and studied how the POM depolymerization rate and its uptake efficiency (2 main ecosystem function parameters) depended on social interactions and spatial self-organization on particle surfaces. We found an emergent trade-off between rate and efficiency resulting from the competition between oligosaccharide diffusion and cellular uptake, with low rate and high efficiency being achieved through cell-to-cell cooperation between degraders. Bacteria cooperated by aggregating in cell clusters of ∼10 to 20 µm, in which cells were able to share public goods. This phenomenon, which was independent of any explicit group-level regulation, led to the emergence of critical cell concentrations below which degradation did not occur, despite all resources being available in excess. In contrast, when particles were labile and turnover rates were high, aggregation promoted competition and decreased the efficiency of carbon use. Our study shows how social interactions and cell aggregation determine the rate and efficiency of particulate carbon turnover in environmentally relevant scenarios.