Miracle-dz/UniFAR-FTUs huggingface dataset:
Prenatal diagnosis of glutaric acidemia type 2 with the use of exome sequencing - an up-to-date review and new case report.

INTRODUCTION Inborn errors of metabolism (IEM) also called metabolic diseases constitute a large and heterogenous group of disorders characterized by a failure of essential cellular functions. Antenatal manifestation of IEM is absent or nonspecific, which makes prenatal diagnosis challenging. Glutaric acidemia type 2 (GA2) is a rare metabolic disease clinically manifested in three different ways: neonatal-onset with congenital anomalies, neonatal-onset without congenital anomalies and late-onset. Neonatal forms are usually lethal. Congenital anomalies present on prenatal ultrasound as large, hyperechoic or cystic kidneys with reduced amniotic fluid volume. MATERIAL AND METHODS We present a systematic literature review describing prenatal diagnosis of GA2 and a new prenatal case. RESULTS Ten prenatally diagnosed cases of GA2 have been published to date, mainly based on biochemical methods. New case of GA2 was diagnosed using exome sequencing method. DISCUSSION All prenatal cases from literature review had positive history of GA2 running in the family. In our study trio exome sequencing was performed in case of fetal hyperechoic kidneys without a history of GA2. Consequently, we were able to identify two novel pathogenic variants of the ETFDH gene and to indicate their parental origin. SUMMARY Exome sequencing approach used in case of fetal hyperechoic kidneys allows to identify pathogenic variants without earlier knowledge of the precise genetic background of the disease. Hyperechoic, enlarged kidneys could be one of the clinical features of metabolic diseases. After exclusion of chromosomal abnormalities, urinary tract obstruction and intrauterine infections, glutaric acidemia type 2 and number of monogenic disorders should be consider.
Effects of Hexane on Protein Profile, Solubility and Foaming Properties of Defatted Proteins Extracted from Tenebrio molitor Larvae

Inclusion of edible insects in human diets is increasingly promoted as a sustainable source of proteins with high nutritional value. While consumer acceptability remains the main challenge to their integration into Western food culture, the use of edible insects as meal and protein concentrate could decrease neophobia. The defatting of edible insects, mostly done with hexane, is the first step in producing protein ingredients. However, its impact on protein profiles and techno-functionality is still unclear. Consequently, this study compares the protein profiles of hexane-defatted and non-hexane-defatted yellow mealworm (Tenebrio molitor) meals and protein extracts, and evaluates the impact of hexane on protein solubility and foaming properties. Results showed that profiles for major proteins were similar between hexane-defatted and non-defatted samples, however some specific content differences (e.g., hexamerin 2) were observed and characterized using proteomic tools. Protein solubility was markedly lower for T. molitor meals compared to protein extracts. A large increase in the foaming capacity was observed for defatted fractions, whereas foam stability decreased similarly in all fractions. Consequently, although the hexane-defatting step was largely studied to produce edible insect protein ingredients, it is necessary to precisely understand its impact on their techno-functional properties for the development of food formulations.
Development and evaluation of a high performance T1‐weighted brain template for use in studies on older adults

Τhe accuracy of template‐based neuroimaging investigations depends on the template's image quality and representativeness of the individuals under study. Yet a thorough, quantitative investigation of how available standardized and study‐specific T1‐weighted templates perform in studies on older adults has not been conducted. The purpose of this work was to construct a high‐quality standardized T1‐weighted template specifically designed for the older adult brain, and systematically compare the new template to several other standardized and study‐specific templates in terms of image quality, performance in spatial normalization of older adult data and detection of small inter‐group morphometric differences, and representativeness of the older adult brain. The new template was constructed with state‐of‐the‐art spatial normalization of high‐quality data from 222 older adults. It was shown that the new template (a) exhibited high image sharpness, (b) provided higher inter‐subject spatial normalization accuracy and (c) allowed detection of smaller inter‐group morphometric differences compared to other standardized templates, (d) had similar performance to that of study‐specific templates constructed with the same methodology, and (e) was highly representative of the older adult brain.
Novel trichloroindolizine derivatives via intramolecular acylation of a bis(chloroacyl)bipyridine

3,3′-Bis(alkyloxycarbonyl)-2,2′-bipyridines are produced from the reaction of alcohols with 3,3′-bis(chlorocarbonyl)-2,2′-bipyridine which is generated from the corresponding dicarboxylic acid and thionyl chloride. When the dicarboxylic acid is reacted with a SOCl2–Cl2 mixture, significant amounts of trichloroindolizines are produced. This reaction is likely to take place via initial intramolecular N-chloroacylation of bipyridine 3.
Influence of N-glycosylation on Expression and Function of Pseudorabies Virus Glycoprotein gB

Envelope glycoprotein (g)B is conserved throughout the Herpesviridae and mediates fusion of the viral envelope with cellular membranes for infectious entry and spread. Like all viral envelope fusion proteins, gB is modified by asparagine (N)-linked glycosylation. Glycans can contribute to protein function, intracellular transport, trafficking, structure and immune evasion. gB of the alphaherpesvirus pseudorabies virus (PrV) contains six consensus sites for N-linked glycosylation, but their functional relevance is unknown. Here, we investigated the occupancy and functional relevance of N-glycosylation sites in PrV gB. To this end, all predicted N-glycosylation sites were inactivated either singly or in combination by the introduction of conservative mutations (N➔Q). The resulting proteins were tested for expression, fusion activity in cell–cell fusion assays and complementation of a gB-deficient PrV mutant. Our results indicate that all six sites are indeed modified. However, while glycosylation at most sites was dispensable for gB expression and fusogenicity, inactivation of N154 and N700 affected gB processing by furin cleavage and surface localization. Although all single mutants were functional in cell–cell fusion and viral entry, simultaneous inactivation of all six N-glycosylation sites severely impaired fusion activity and viral entry, suggesting a critical role of N-glycans for maintaining gB structure and function.
Differentially Expressed Genes and Their Clinical Significance in Ischaemic Stroke: An In-Silico Study

Background Ischaemic stroke (IS), a multifactorial neurological disorder, is mediated by interplay between genes and the environment and, thus, blood-based IS biomarkers are of significant clinical value. Therefore, this study aimed to find global differentially expressed genes (DEGs) in-silico, to identify key enriched genes via gene set enrichment analysis (GSEA) and to determine the clinical significance of these genes in IS. Methods Microarray expression dataset GSE22255 was retrieved from the Gene Expression Omnibus (GEO) database. It includes messenger ribonucleic acid (mRNA) expression data for the peripheral blood mononuclear cells of 20 controls and 20 IS patients. The bioconductor-package ‘affy’ was used to calculate expression and a pairwise t-test was applied to screen DEGs (P < 0.01). Further, GSEA was used to determine the enrichment of DEGs specific to gene ontology (GO) annotations. Results GSEA analysis revealed 21 genes to be significantly plausible gene markers, enriched in multiple pathways among all the DEGs (n = 881). Ten gene sets were found to be core enriched in specific GO annotations. JunD, NCX3 and fibroblast growth factor receptor 4 (FGFR4) were under-represented and glycoprotein M6-B (GPM6B) was persistently over-represented. Conclusion The identified genes are either associated with the pathophysiology of IS or they affect post-IS neuronal regeneration, thereby influencing clinical outcome. These genes should, therefore, be evaluated for their utility as suitable markers for predicting IS in clinical scenarios.
An immunohistochemical study of lymphatic elements in the human brain

Significance The connection between brain and peripheral lymphatics has been studied for 250 y, mainly in animals. Specific markers for lymphatic endothelial cells (LECs) were discovered about a decade ago. We stained postmortem human brains with LYVE1 and PDPN to identify LECs. Marker-positive cells were found in membranes covering the brain, walls of vessels, and perivascular spaces, and among nerve fibers. These spaces also seem to contain T cells and are connected to peripheral lymphatics through passageways in the nasal cavity, optic nerve, and base of the skull. Our findings show a path that brain waste products take when they leave the central nervous system, paths that may be bidirectional. Almost 150 papers about brain lymphatics have been published in the last 150 years. Recently, the information in these papers has been synthesized into a picture of central nervous system (CNS) “glymphatics,” but the fine structure of lymphatic elements in the human brain based on imaging specific markers of lymphatic endothelium has not been described. We used LYVE1 and PDPN antibodies to visualize lymphatic marker-positive cells (LMPCs) in postmortem human brain samples, meninges, cavernous sinus (cavum trigeminale), and cranial nerves and bolstered our findings with a VEGFR3 antibody. LMPCs were present in the perivascular space, the walls of small and large arteries and veins, the media of large vessels along smooth muscle cell membranes, and the vascular adventitia. Lymphatic marker staining was detected in the pia mater, in the arachnoid, in venous sinuses, and among the layers of the dura mater. There were many LMPCs in the perineurium and endoneurium of cranial nerves. Soluble waste may move from the brain parenchyma via perivascular and paravascular routes to the closest subarachnoid space and then travel along the dura mater and/or cranial nerves. Particulate waste products travel along the laminae of the dura mater toward the jugular fossa, lamina cribrosa, and perineurium of the cranial nerves to enter the cervical lymphatics. CD3-positive T cells appear to be in close proximity to LMPCs in perivascular/perineural spaces throughout the brain. Both immunostaining and qPCR confirmed the presence of adhesion molecules in the CNS known to be involved in T cell migration.
Determination of uptake kinetics (sampling rates) by lipid-containing semipermeable membrane devices (SPMDs) for polycyclic aromatic hydrocarbons (PAHs) in water

The use of lipid-containing semipermeable membrane devices (SPMDs) is becoming commonplace, but very little sampling rate data are available for the estimation of ambient contaminant concentrations from analyte levels in exposed SPMDs. We determined the aqueous sampling rates (Rss; expressed as effective volumes of water extracted daily) of the standard (commercially available design) 1-g triolein SPMD for 15 of the priority pollutant (PP) polycyclic aromatic hydrocarbons (PAHs) at multiple temperatures and concentrations. Under the experimental conditions of this study, recovery-corrected Rs values for PP PAHs ranged from ≈1.0 to 8.0 L/d. These values would be expected to be influenced by significant changes (relative to this study) in water temperature, degree of biofouling, and current velocity-turbulence. Included in this paper is a discussion of the effects of temperature and octanol−water partition coefficient (Kow); the impacts of biofouling and hydrodynamics are reported separately. Overall, SPMDs.
Early Life Exposure to Aflatoxin B1 in Rats: Alterations in Lipids, Hormones, and DNA Methylation among the Offspring

Aflatoxins are toxic compounds produced by molds of the Aspergillus species that contaminate food primarily in tropical countries. The most toxic aflatoxin, aflatoxin B1 (AFB1), is a major cause of hepatocellular carcinoma (HCC) in these countries. In sub-Saharan Africa, aflatoxin contamination is common, and perinatal AFB1 exposure has been linked to the early onset of HCC. Epigenetic programming, including changes to DNA methylation, is one mechanism by which early life exposures can lead to adult disease. This study aims to elucidate whether perinatal AFB1 exposure alters markers of offspring health including weight, lipid, and hormone profiles as well as epigenetic regulation that may later influence cancer risk. Pregnant rats were exposed to two doses of AFB1 (low 0.5 and high 5 mg/kg) before conception, throughout pregnancy, and while weaning and compared to an unexposed group. Offspring from each group were followed to 3 weeks or 3 months of age, and their blood and liver samples were collected. Body weights and lipids were assessed at 3 weeks and 3 months while reproductive, gonadotropic, and thyroid hormones were assessed at 3 months. Prenatal AFB1 (high dose) exposure resulted in significant 16.3%, 31.6%, and 7.5% decreases in weight of the offspring at birth, 3 weeks, and 3 months, respectively. Both doses of exposure altered lipid and hormone profiles. Pyrosequencing was used to quantify percent DNA methylation at tumor suppressor gene Tp53 and growth-regulator H19 in DNA from liver and blood. Results were compared between the control and AFB1 exposure groups in 3-week liver samples and 3-week and 3-month blood samples. Relative to controls, Tp53 DNA methylation in both low- and high-dose exposed rats was significantly decreased in liver samples and increased in the blood (p < 0.05 in linear mixed models). H19 methylation was higher in the liver from low- and high-exposed rats and decreased in 3-month blood samples from the high exposure group (p < 0.05). Further research is warranted to determine whether such hormone, lipid, and epigenetic alterations from AFB1 exposure early in life play a role in the development of early-onset HCC.
Molecular Properties of Bare and Microhydrated Vitamin B5–Calcium Complexes

Pantothenic acid, also called vitamin B5, is an essential nutrient involved in several metabolic pathways. It shows a characteristic preference for interacting with Ca(II) ions, which are abundant in the extracellular media and act as secondary mediators in the activation of numerous biological functions. The bare deprotonated form of pantothenic acid, [panto-H]−, its complex with Ca(II) ion, [Ca(panto-H)]+, and singly charged micro-hydrated calcium pantothenate [Ca(panto-H)(H2O)]+ adduct have been obtained in the gas phase by electrospray ionization and assayed by mass spectrometry and IR multiple photon dissociation spectroscopy in the fingerprint spectral range. Quantum chemical calculations at the B3LYP(-D3) and MP2 levels of theory were performed to simulate geometries, thermochemical data, and linear absorption spectra of low-lying isomers, allowing us to assign the experimental absorptions to particular structural motifs. Pantothenate was found to exist in the gas phase as a single isomeric form showing deprotonation on the carboxylic moiety. On the contrary, free and monohydrated calcium complexes of deprotonated pantothenic acid both present at least two isomers participating in the gas-phase population, sharing the deprotonation of pantothenate on the carboxylic group and either a fourfold or fivefold coordination with calcium, thus justifying the strong affinity of pantothenate for the metal.
Efficient Photocatalytic Overall Water Splitting Induced by the Giant Internal Electric Field of a g‐C3N4/rGO/PDIP Z‐Scheme Heterojunction

A graphitic carbon nitride/rGO/perylene diimide polymer (g‐C3N4/rGO/PDIP) Z‐scheme heterojunction is successfully constructed to realize high‐flux charge transfer and efficient photocatalytic overall water splitting. A giant internal electric field in the Z‐scheme junction is built, enabling the charge separation efficiency to be enhanced dramatically by 8.5 times. Thus, g‐C3N4/rGO/PDIP presents an efficient and stable photocatalytic overall water splitting activity with H2 and O2 evolution rate of 15.80 and 7.80 µmol h−1, respectively, ≈12.1 times higher than g‐C3N4 nanosheets. Meanwhile, a notable quantum efficiency of 4.94% at 420 nm and solar‐to‐hydrogen energy‐conversion efficiency of 0.30% are achieved, prominently surpassing many reported g‐C3N4‐based photocatalysts. Briefly, this work throws light on enhancing the internal electric field by interface control to dramatically improve the photocatalytic performance.
In vitro assessment of tick-borne encephalitis vaccine: Suitable human cell platforms and potential biomarkers.

Tick-borne encephalitis (TBE) virus causes a severe disease that can lead to permanent neurological complications. The whole inactivated TBE vaccine is highly effective, as proven by high seroconversion rates and near eradication of the disease in countries where vaccination programs have been implemented. TBE vaccine potency testing currently requires the use of in vivo methods that present issues of reproducibility as well as animal discomfort. As an alternative, public and private entities are currently exploring a batch-to-batch consistency approach which would demonstrate conformity of a newly produced vaccine batch with a batch with proven in vivo efficacy with respect to a range of in vitro measurable quality parameters. For the identification of a suitable cellular platform to be used in a panel of in vitro batch-to-batch assessments for the TBE vaccine, we exposed human cell-based systems, both of primary origin and cell line-derived, to vaccine formulations of high and low quality. Following stimulation, cell responses were evaluated by assessing the expression of selected genes by qPCR. Our findings show that the expression of interferon-stimulated genes differed after treatment with non-adjuvanted vaccine batches of different quality in peripheral blood mononuclear cells (PBMCs) and in monocyte-derived dendritic cells, but not in monocyte-free PBMC suspensions nor in cell line-derived immune cells. These results indicate suitable platforms and potential biomarkers for a cell-based assay that, together with other immunochemical analyses, could serve for batch-to-batch assessment of the TBE vaccine, reducing (and eventually replacing) in vivo methods for potency testing.
Mapping climate discourse to climate opinion: An approach for augmenting surveys with social media to enhance understandings of climate opinion in the United States

Surveys are commonly used to quantify public opinions of climate change and to inform sustainability policies. However, conducting large-scale population-based surveys is often a difficult task due to time and resource constraints. This paper outlines a machine learning framework—grounded in statistical learning theory and natural language processing—to augment climate change opinion surveys with social media data. The proposed framework maps social media discourse to climate opinion surveys, allowing for discerning the regionally distinct topics and themes that contribute to climate opinions. The analysis reveals significant regional variation in the emergent social media topics associated with climate opinions. Furthermore, significant correlation is identified between social media discourse and climate attitude. However, the dependencies between topic discussion and climate opinion are not always intuitive and often require augmenting the analysis with a topic’s most frequent n-grams and most representative tweets to effectively interpret the relationship. Finally, the paper concludes with a discussion of how these results can be used in the policy framing process to quickly and effectively understand constituents’ opinions on critical issues.
Preparation and Characterization of Ultrathin Films Layer-by-Layer Self-Assembled from Graphite Oxide Nanoplatelets and Polymers

Graphite, oxidized by HNO3 and NaClO3 to 25% (GO-25), 42% (GO-42), and 33% (GO-33), has been dispersed to partially exfoliated nanoplatelets and, along with poly(diallyldimethylammonium chloride) (PDDA) and poly(ethylene oxide) (PEO), layer-by-layer self-assembled to ultrathin S−(PDDA/GO)10, S−PDDA/(GO/PEO)10, and S−(PDDA/GO/PEO)10 films (where S is the indium tin oxide- or chromium/gold-coated glass or quartz substrate and GO refers to platelets of oxidized graphite). The GO powders have been characterized by X-ray diffraction prior and by transmission electron microscopy after their dispersions. Thicknesses of each of the successively adsorbed layers were comparatively determined by absorption spectrophotometry, surface plasmon resonance spectroscopy, quartz crystal microbalance, and scanning force microscopy. Good agreements were obtained by these three different techniques.
Catalytic Conversion of Glucose into Levulinic Acid Using 2-Phenyl-2-Imidazoline Based Ionic Liquid Catalyst

Levulinic acid (LA) is an industrially important product that can be catalytically valorized into important value-added chemicals. In this study, hydrothermal conversion of glucose into levulinic acid was attempted using Brønsted acidic ionic liquid catalyst synthesized using 2-phenyl-2-imidazoline, and 2-phenyl-2-imidazoline-based ionic liquid catalyst used in this study was synthesized in the laboratory using different anions (NO3, H2PO4, and Cl) and characterized using 1H NMR, TGA, and FT-IR spectroscopic techniques. The activity trend of the Brønsted acidic ionic liquid catalysts synthesized in the laboratory was found in the following order: [C4SO3HPhim][Cl] > [C4SO3HPhim][NO3] > [C4SO3HPhim][H2PO4]. A maximum 63% yield of the levulinic acid was obtained with 98% glucose conversion at 180 °C and 3 h reaction time using [C4SO3HPhim][Cl] ionic liquid catalyst. The effect of different reaction conditions such as reaction time, temperature, ionic liquid catalyst structures, catalyst amount, and solvents on the LA yield were investigated. Reusability of [C4SO3HPhim][Cl] catalyst up to four cycles was observed. This study demonstrates the potential of the 2-phenyl-2-imidazoline-based ionic liquid for the conversion of glucose into the important platform chemical levulinic acid.
Gentiana asclepiadea L. from Two High Mountainous Habitats: Inter- and Intrapopulation Variability Based on Species’ Phytochemistry

Natural populations of Gentiana asclepiadea L. , located at two mountainous sites, were HPLC-analyzed regarding the contents of six representative secondary metabolites. The contents of swertiamarin (SWM), gentiopicrin (GP), sweroside (SWZ), mangiferin (MGF), isoorientin (ISOOR), and isovitexin (ISOV) were determined in six populations (three per study site), and separately for aboveground and belowground plant parts. PCA showed a clear separation of four groups according to the contents of the analyzed secondary metabolites. Out of six analyzed compounds, five were present in all samples and only one (SWZ) was found in Golija populations (belowground parts) but not in Vlasina populations, and its presence can be indicative of the geolocation of populations. Clear separation of groups was mostly affected by the different contents of chemical compounds in plant parts (aboveground versus belowground) and by the differences related to population origin (higher content of SWM and GP in belowground parts of individuals from Vlasina populations and higher content of MGF and ISOOR of individuals from Golija populations). The results of this study contribute to the spatiochemical profiling of G. asclepiadea populations and a better understanding of inter- and intrapopulation variability of pharmacologically important compounds.