Miracle-dz/UniFAR-FTUs huggingface dataset:
New genetic data reveals a new species of Zospeum in Bosnia (Gastropoda, Ellobioidea, Carychiinae)

Abstract Recent integrative investigations of the terrestrial ellobiid genus, Zospeum, have revealed significant findings concerning its Alpine-Dinaric evolution and taxonomy. Due to the expected discrepancy between the useful, but limited, 1970s’ classification system based on shell data and the results of recent genetic analyses in the latest investigation, a revision of the entire radiation was undertaken, and a new classification system was devised by the present authors in an earlier paper. Concurrent to this work, molecular sequences from two Austrian caves were published independently of our revision by another research group. By incorporating these genetic data within our phylogenetic framework here, we show that the Austrian individuals are genetically most similar to Zospeumamoenum and consequently, classify them within that species. We additionally reveal two new genetic lineages from the largely under-sampled southern extension of Zospeum’s known distributional range. The first lineage, deriving from the region of Dubrovnik, Croatia, is a potential candidate for genetically clarifying Zospeumtroglobalcanicum. The second lineage derives from the municipality of Tomislavgrad, Bosnia-Herzegovina and is herein, described a new species: Zospeumsimplex Inäbnit, Jochum & Neubert, sp. nov.
Microbial risk reduction of withholding periods during public open space irrigation with recycled water

Treated effluent is increasingly being used to irrigate municipal green spaces such as sporting ovals, but the potential risks to human health from faecal-oral pathogens present in the effluent have remained largely unreported. This is the first reported study where a quantitative microbial risk assessment (QMRA) was performed to evaluate the effect of varying withholding periods in terms of pathogen inactivation credits to risks to human health from sporting ovals irrigated with secondary treated effluent. The calculations on pathogen removal rates in this study suggest that a mean 0.7 log removal for bacteria and 0.4 log for viral pathogens could be achieved over a 4 hour period.
Moving motives: How past and present strategy influence the market

We investigate the market’s reactions to serial acquirers that switch strategy. We collect data on 204 serial acquirers in four high tech industries, and use March’s explore-exploit framework, to classify these firms’ 1,415 acquisitions. We then distinguish, for example, exploration-based acquisitions, conducted after a series of exploitation-based acquisitions. Our results suggest that the market takes a portfolio perspective when reacting to an acquisition. In support of the ambidexterity literature, we show that the market responds positively to a switch from one type of strategy to another. Zooming in on the direction of the shift, we find that the market responds more positively to a switch towards exploration after exploitation, compared with the alternative. In so doing, we contribute to the literature on acquisition motives, by showing that prior announcements matter in explaining market reactions, and we contribute to the literature on ambidexterity, by showing that the market favours firms that oscillate between exploration and exploitation.
A review on bovine hydroxyapatite; extraction and characterization

High rate of bone grafting surgeries emphasizes the need for optimal bone substitutes. Biomaterials mimicking the interconnected porous structure of the original bone with osteoconductive and osteoinductive capabilities have long been considered. Hydroxyapatite (HA), as the main inorganic part of natural bone, has exhibited excellent regenerative properties in bone tissue engineering. This manuscript reviews the HA extraction methods from bovine bone, as one of the principal biosources. Essential points in the extraction process have also been highlighted. Characterization of the produced HA through gold standard methods such as XRD, FTIR, electron microscopies (SEM and TEM), mechanical/thermodynamic tests, and bioactivity analysis has been explained in detail. Finally, future perspectives for development of HA constructs are mentioned.
Effects of Satisfaction and Trust on Long-Term Orientation in Small Apparel Retailer–Supplier Relationships

The goal of this research was to examine how economic and social satisfactions influence trust-credibility and trust-benevolence and ultimately, long-term orientation in the context of the small apparel retailer-supplier relationship. Moreover, this study investigated the moderating influences of power in the relationships between trust-credibility, trust-benevolence, and long-term orientation. Findings indicated that economic and social satisfactions had a positive influence on both trust-credibility and trust-benevolence. Furthermore, the results showed positive influences of trust-credibility and trust-benevolence on long-term orientation. The balance of power between retailers and suppliers had a moderating influence on the relationship between trust-credibility and long-term orientation, but not on trust-benevolence and long-term orientation. The results of the research contribute to a more in-depth understanding of the small apparel retailer-supplier relationship, which is currently extremely limited.
Interactions between the foreign body reaction and Staphylococcus aureus biomaterial-associated infection. Winning strategies in the derby on biomaterial implant surfaces

Abstract Biomaterial-associated infections (BAIs) are an increasing problem where antibiotic therapies are often ineffective. The design of novel strategies to prevent or combat infection requires a better understanding of how an implanted foreign body prevents the immune system from eradicating surface-colonizing pathogens. The objective of this review is to chart factors resulting in sub-optimal clearance of Staphylococcus aureus bacteria involved in BAIs. To this end, we first describe three categories of bacterial mechanisms to counter the host immune system around foreign bodies: direct interaction with host cells, modulation of intercellular communication, and evasion of the immune system. These mechanisms take place in a time frame that differentiates sterile foreign body reactions, BAIs, and soft tissue infections. In addition, we identify experimental interventions in S. aureus BAI that may impact infectious mechanisms. Most experimental treatments modulate the host response to infection or alter the course of BAI through implant surface modulation. In conclusion, the first week after implantation and infection is crucial for the establishment of an S. aureus biofilm that resists the local immune reaction and antibiotic treatment. Although established and chronic S. aureus BAI is still treatable and manageable, the focus of interventions should lie on this first period.
Protein Profiling of RGS6, a Pleiotropic Gene Implicated in Numerous Neuropsychiatric Disorders, Reveals Multi-Isoformic Expression and a Novel Brain-Specific Isoform

Abstract A metanalysis identified regulator of G-protein signaling 6 (RGS6) as one of 23 loci with pleiotropic effects on four or more human psychiatric disorders. This finding is significant as it confirms/extends the findings of numerous other studies implicating RGS6 in CNS function and pathology. RGS6 is a highly conserved member of the RGS protein family whose cellular roles are likely affected by mRNA splicing and alternative domain inclusion/exclusion. Indeed, we previously identified multiple RGS6 splice variants predicted to produce 36 distinct protein isoforms containing either long (RGS6L) or short (RGS6S) N-terminal domains, an incomplete or intact GGL domain, and nine alternative C termini. Unfortunately, sequence similarities between the isoforms have made it difficult to confirm their individual existence and/or to determine their unique functions. Here, we developed three RGS6-specific antibodies that recognize all RGS6 protein isoforms (RGS6-fl), the N-terminus of RGS6L isoforms (RGS6-L), and an 18-amino acid alternate C-terminal sequence (RGS6-18). Using these antibodies, we demonstrate that RGS6L(+GGL) isoforms, predominating in both mouse (both sexes) CNS and peripheral tissues, are most highly expressed in the CNS. We further identify three novel RGS6 protein bands that are larger (61, 65, and 69-kDa) than the ubiquitously expressed 53- to 57-kDa RGS6L(+GGL) proteins. Importantly, we show that the 69-kDa protein is a brain-specific dephospho form of the 65-kDa band, the first identified phosphorylated RGS6 isoform. Together, these data begin to define the functional significance behind the complexity of RGS6 gene processing and further clarifies RGS6’s physiological roles by resolving tissue-specific RGS6 protein expression.
Risk factors that predict major amputations and amputation time intervals for hospitalised diabetic patients with foot complications

Diabetes‐related lower extremity amputations are an enormous burden on global health care and social resources because of the rapid worldwide growth of the diabetic population. This research aimed to determine risk factors that predict major amputation and analyse the time interval from first hospitalisation to amputation by using standard management protocols and Kaplan–Meier survival curves. Data from 246 patients with diabetes mellitus and diabetic foot ulcers from the Division of Plastic and Reconstructive Surgery of the Department of Surgery at XXX Hospital between January 2016 and May 2020 were analysed. Univariate and multivariate analyses of 44 potential risk factors, including invasive ulcer depth and C‐reactive protein levels, showed statistically significant differences for those at increased risk for major amputation. The median time from hospitalisation to lower extremity amputation was approximately 35 days. Most patients with abnormal C‐reactive protein levels and approximately 70% of patients with ulcers invading the bone were at risk for lower extremity amputations within 35 days. Therefore, invasive ulcer depth and C‐reactive protein levels are significant risk factors. Other potential risk factors for major amputation and the time intervals from first hospitalisation to amputation should be analysed to establish further prediction strategies.
Further supporting SMARCC2‐related neurodevelopmental disorder through exome analysis and reanalysis in two patients

BAFopathies are a heterogenous group of neurodevelopmental disorders caused by mutations in genes encoding subunits of the BAF complex, and they exhibit a broad clinical phenotypic spectrum. Pathogenic heterozygous variants in SMARCC2 have been implicated in Coffin–Siris syndrome 8 (MIM 618362) with variable neurodevelopmental presentations. We report here two relatively severely affected patients with two different SMARCC2 variants: one has de novo pathogenic variant, c. 1824_1826del, p.(Leu609del), in a suspected hotspot region through reanalysis of previously negative clinical exome data, and the other has a likely pathogenic loss‐of‐function variant, c. 1094_1097delAGAA, p.(Lys365Thrfs*12) through exome analysis in an adopted subject. Regardless of variant type, both patients have severe developmental delays, severe speech delay, short stature, hypotonia, seizures, and craniofacial dysmorphisms, blurring previously speculated genotype–phenotype correlation on missense and loss‐of‐function variants. This report extends our understanding of the genotypic and phenotypic spectrums of the SMARCC2‐related neurodevelopmental disorder.
Integrated analysis of the functions and prognostic values of RNA-binding proteins in neuroblastoma

Background Neuroblastoma (NB) is the most common solid tumor in children. NB treatment has made significant progress; however, given the high degree of heterogeneity, basic research findings and their clinical application to NB still face challenges. Herein, we identify novel prognostic models for NB. Methods We obtained RNA expression data of NB and normal nervous tissue from TARGET and GTEx databases and determined the differential expression patterns of RNA binding protein (RBP) genes between normal and cancerous tissues. Lasso regression and Cox regression analyses identified the five most important differentially expressed genes and were used to construct a new prognostic model. The function and prognostic value of these RBPs were systematically studied and the predictive accuracy verified in an independent dataset. Results In total, 348 differentially expressed RBPs were identified. Of these, 166 were up-regulated and 182 down-regulated RBPs. Two hubs RBPs (CPEB3 and CTU1) were identified as prognostic-related genes and were chosen to build the prognostic risk score models. Multivariate Cox analysis was performed on genes from univariate Cox regression and Lasso regression analysis using proportional hazards regression model. A five gene prognostic model: Risk score = (-0.60901*expCPEB3)+(0.851637*expCTU1) was built. Based on this model, the overall survival of patients in the high-risk subgroup was lower (P = 2.152e-04). The area under the curve (AUC) of the receiver-operator characteristic curve of the prognostic model was 0.720 in the TARGET cohort. There were significant differences in the survival rate of patients in the high and low-risk subgroups in the validation data set GSE85047 (P = 0.1237e-08), with the AUC 0.730. The risk model was also regarded as an independent predictor of prognosis (HR = 1.535, 95% CI = 1.368–1.722, P = 2.69E-13). Conclusions This study identified a potential risk model for prognosis in NB using Cox regression analysis. RNA binding proteins (CPEB3 and CTU1) can be used as molecular markers of NB.
A Microfluidic Platform for Multi-Antigen Immunofluorescence Assays

Traditional cell-based assays such as cell immunoassay that utilizes plastic (chamber slides, dishes, microtiter plates), Magnetic bead, enzyme-linked immunsorbent assays (ELISA) [1], FACS cell sorting is labor intensive, time consuming, and requires a large numbers of cells or reagents. In this report, a microfluidic device integrated with cell culture, washing, fixation, and antigen-antibody reaction is presented for high-throughput immunoassay. Using this microfluidic device, each assay can be performed on a small number of cells and nanolitre or picolitre of reagents, this is particularly beneficial for rare or expensive cell types such as stem cells, or flow sorted cell populations. The capability of the microfluidic device was demonstrated for seeding human umbilical cord blood mesenchymal stem cells (UC-MSCs) in chambers and detecting the expression of surface markers (CD34, CD44, CD45, CD73, CD105, HLA-DR) by immunofluorescence assay.
Spectroscopic profiling, DFT computations, molecular docking and molecular dynamic simulation of biologically active 5-isoquinolinesulfonic acid

Abstract The title compound 5-isoquinolinesulfonic acid (5IQSA) is characterized using the FT-IR, FT-Raman, NMR and UV-Vis spectra. The optimized molecular geometry, vibrational assignments, infrared intensities and Raman scattering are precisely calculated using Density Functional Theory (DFT) with the B3LYP/6-311++G(d,p) basis set. The 1H and 13C NMR chemical shifts are computed and compared with the experimental data. The TD-DFT/M062X/6-311++G(d,p) method is used to compute UV-Vis for different solvents, and the results are compared to UV-Vis spectra obtained experimentally. The HOMO-LUMO band gap energy is calculated for various solvents and compared to the band gap of UV-Vis spectra. Molecular dynamics simulations are used to investigate the biomolecular stability. Non-Linear Optical (NLO) behaviour has been illustrated using hyperpolarizability calculations. Topological studies such as Reduced Gradient Density (RDG), Electron Localization Function (ELF) and Localized Orbital Locator (LOL) are performed. The Molecular Electrostatic Potential (MEP), Natural Bond Orbital (NBO) analysis, Fukui functions and thermodynamic properties were analysed. To explore the biological behaviour of the examined compound, molecular docking was performed to evaluate the hydrogen bond distance and binding energies with (2XA4) kinase inhibitor protein. Communicated by Ramaswamy H. Sarma
Quantitative susceptibility mapping as a measure of cerebral oxygenation in neonatal piglets

Prominence of cerebral veins using susceptibility weighted magnetic resonance imaging (SWI) has been used as a qualitative indicator of cerebral venous oxygenation (CvO2). Quantitative susceptibility mapping (QSM) adds more precision to the assessment of CvO2, but has not been applied to neonatal hypoxic ischemic injury (HII). We proposed to study QSM measures of venous susceptibility and their correlation with direct measures of brain oxygenation and cerebral blood flow (CBF) in the neonatal piglet. The association of QSM intravascular cerebral venous susceptibility, with brain tissue O2 tension, CBF, cortical tissue oxyhemoglobin saturation, and the partial pressure of oxygen in arterial blood measurement during various oxygenation states was determined by linear regression. Compared to normoxia, venous susceptibility in the straight sinus increased 56.8 ± 25.4% during hypoxia, while decreasing during hyperoxia (23.5 ± 32.9%) and hypercapnia (23.3 ± 73.1%), which was highly correlated to all other measures of oxygenation (p < 0.0001) but did not correlate to CBF (p = 0.82). These findings demonstrate a strong relationship between venous susceptibility and brain tissue O2 tension. Our results suggest that QSM-derived venous susceptibility is sensitive to cerebral oxygenation status across various oxygenation states.
Vascular Endothelial (VE)-Cadherin-mediated Adherens Junctions involvement in cardiovascular progenitor cell specification.

Vascular Endothelial cadherin, a type II classical cadherin, is the major cadherin molecule participating in homotypic cell-cell adhesion structures between endothelial cells. It associates with cytoplasmic and membrane cytoskeletal elements to form endothelial adherens junctions (AJs), pivotal in regulating endothelial barrier function in the adult. VE-cadherin-mediated AJs are also involved in signaling via direct or indirect associations with receptors. The generation of mutant animals, especially mice and zebrafish, revealed many details about the role of VE-cadherin-mediated AJs in cardiovascular development. In general, VE-cadherin knockout (KO) in mice is embryonic lethal due to severe cardiovascular defects and major signaling pathways as well as vascular formation cues were discovered in developing endothelium. However, there is little information regarding AJs formation and their components in cardiovascular progenitors. We have characterized in detail the activation pattern of mouse VE-cadherin promoter (Pvec) in a mouse embryonic stem cells (ESCs) differentiation system in vitro. Surprisingly, we found that it is activated transiently in cardiac progenitors that belong to the second heart field. Based on Pvec activation we isolated this population in vitro and found that it can self-renew by induction of the Wnt/β-catenin pathway. Next, we successfully established cell culture conditions that allowed self-renewal of this population that consists of endothelial and cardiac progenitors. Transplantation in rat hearts showed that they can survive and differentiate to cardiomyocytes and endothelial cells. Although further characterization is needed, these cells can be used in cell-based therapies as well as in drug screening.
Association Between Time Spent Outdoors and Risk of Multiple Sclerosis

Background and Objectives This study aims to determine the contributions of sun exposure and ultraviolet radiation (UVR) exposure to risk of pediatric-onset multiple sclerosis (MS). Methods Children with MS and controls recruited from multiple centers in the United States were matched on sex and age. Multivariable conditional logistic regression was used to investigate the association of time spent outdoors daily in summer, use of sun protection, and ambient summer UVR dose in the year before birth and the year before diagnosis with MS risk, with adjustment for sex, age, race, birth season, child's skin color, mother's education, tobacco smoke exposure, being overweight, and Epstein-Barr virus infection. Results Three hundred thirty-two children with MS (median disease duration 7.3 months) and 534 controls were included after matching on sex and age. In a fully adjusted model, compared to spending <30 minutes outdoors daily during the most recent summer, greater time spent outdoors was associated with a marked reduction in the odds of developing MS, with evidence of dose-response (30 minutes–1 hour: adjusted odds ratio [AOR] 0.48, 95% confidence interval [CI] 0.23–0.99, p = 0.05; 1–2 hours: AOR 0.19, 95% CI 0.09–0.40, p < 0.001). Higher summer ambient UVR dose was also protective for MS (AOR 0.76 per 1 kJ/m2, 95% CI 0.62–0.94, p = 0.01). Discussion If this is a causal association, spending more time in the sun during summer may be strongly protective against developing pediatric MS, as well as residing in a sunnier location.
Mechanistic Basis for Understanding the Dual Activities of the Bifunctional Azotobacter vinelandii Mannuronan C-5-Epimerase and Alginate Lyase AlgE7

Postharvest valorization and upgrading of algal constituents are promising strategies in the development of a sustainable bioeconomy based on algal biomass. In this respect, alginate epimerases and lyases are valuable enzymes for tailoring the functional properties of alginate, a polysaccharide extracted from brown seaweed with numerous applications in food, medicine, and material industries. ABSTRACT The structure and functional properties of alginates are dictated by the monomer composition and molecular weight distribution. Mannuronan C-5-epimerases determine the monomer composition by catalyzing the epimerization of β-d-mannuronic acid (M) residues into α-l-guluronic acid (G) residues. The molecular weight is affected by alginate lyases, which catalyze a β-elimination mechanism that cleaves alginate chains. The reaction mechanisms for the epimerization and lyase reactions are similar, and some enzymes can perform both reactions. These dualistic enzymes share high sequence identity with mannuronan C-5-epimerases without lyase activity. The mechanism behind their activity and the amino acid residues responsible for it are still unknown. We investigate mechanistic determinants involved in the bifunctional epimerase and lyase activity of AlgE7 from Azotobacter vinelandii. Based on sequence analyses, a range of AlgE7 variants were constructed and subjected to activity assays and product characterization by nuclear magnetic resonance (NMR) spectroscopy. Our results show that calcium promotes lyase activity, whereas NaCl reduces the lyase activity of AlgE7. By using defined polymannuronan (polyM) and polyalternating alginate (polyMG) substrates, the preferred cleavage sites of AlgE7 were found to be M|XM and G|XM, where X can be either M or G. From the study of AlgE7 mutants, R148 was identified as an important residue for the lyase activity, and the point mutant R148G resulted in an enzyme with only epimerase activity. Based on the results obtained in the present study, we suggest a unified catalytic reaction mechanism for both epimerase and lyase activities where H154 functions as the catalytic base and Y149 functions as the catalytic acid. IMPORTANCE Postharvest valorization and upgrading of algal constituents are promising strategies in the development of a sustainable bioeconomy based on algal biomass. In this respect, alginate epimerases and lyases are valuable enzymes for tailoring the functional properties of alginate, a polysaccharide extracted from brown seaweed with numerous applications in food, medicine, and material industries. By providing a better understanding of the catalytic mechanism and of how the two enzyme actions can be altered by changes in reaction conditions, this study opens further applications of bacterial epimerases and lyases in the enzymatic tailoring of alginate polymers.