Miracle-dz/UniFAR-FTUs huggingface dataset:
Sulfated Alginate Hydrogels Prolong the Therapeutic Potential of MSC Spheroids by Sequestering the Secretome

Cell‐based approaches to tissue repair suffer from rapid cell death upon implantation, limiting the window for therapeutic intervention. Despite robust lineage‐specific differentiation potential in vitro, the function of transplanted mesenchymal stromal cells (MSCs) in vivo is largely attributed to their potent secretome comprising a variety of growth factors (GFs). Furthermore, GF secretion is markedly increased when MSCs are formed into spheroids. Native GFs are sequestered within the extracellular matrix (ECM) via sulfated glycosaminoglycans, increasing the potency of GF signaling compared to their unbound form. To address the critical need to prolong the efficacy of transplanted cells, alginate hydrogels are modified with sulfate groups to sequester endogenous heparin‐binding GFs secreted by MSC spheroids. The influence of crosslinking method and alginate modification is assessed on mechanical properties, degradation rate, and degree of sulfate modification. Sulfated alginate hydrogels sequester a mixture of MSC‐secreted endogenous biomolecules, thereby prolonging the therapeutic effect of MSC spheroids for tissue regeneration. GFs are sequestered for longer durations within sulfated hydrogels and retain their bioactivity to regulate endothelial cell tubulogenesis and myoblast infiltration. This platform has the potential to prolong the therapeutic benefit of the MSC secretome and serve as a valuable tool for investigating GF sequestration.
Familial severe myoclonic epilepsy of infancy: truncation of Nav1.1 and genetic heterogeneity.

BACKGROUND Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome has been long suspected of having a genetic origin. Recently, mutations in SCN1A and GABRG2 have been described in SMEI patients. The sporadic nature of the SMEI syndrome and the occurrence of SCN1A and GABRG2 mutations in a mild familial phenotype, termed generalized epilepsy with febrile seizure plus complicates genotype-phenotype correlations. In order to further investigate the role of SCN1A and GABRG2 in the pathogenesis of SMEI we have screened for mutations three families with at least two members affected by Dravet syndrome. METHODS Clinical criteria followed the international classification of epileptic syndromes. Mutational screening of SCN1A and GABRG2 genes was performed by denaturing high performance liquid chromatography (DHPLC) and direct sequencing of DNA fragments showing a variant chromatogram. RESULTS Thirty-eight fragments spanning 26 exons of SCN1A and nine exons of GABRG2 were analysed in three probands. Five variant chromatograms were identified; four corresponded to known polymorphisms, one to a novel dinucleotide insertion on exon 26 of SCN1A. The mutation leads to a frameshift and a premature stop codon at amino acid 1 779 of the protein. The mutation was present in the affected sibling and was inherited from the mother who had experienced a single febrile seizure in childhood. CONCLUSIONS Among three families analysed, a single family was mutant for SCN1A. Our study suggests that the syndrome is genetically heterogeneous. The variable expressivity we observed for the c5240insAA mutation suggests that other factors are needed for the development of the full SMEI phenotype.
The Israeli work permit scheme and the West Bank economy

The integration of the Israeli and Palestinian labor markets has for a long time attracted attention due the political-military conflict between the two regions and due to mobility restrictions. In the 1980s, access to Israeli labor markets accounted for a significant share of the total Palestinian employment. However, following the first and the second Palestinian uprisings, mobility restrictions and closures have been put in place and enforced. Depending on the intensity of the political tension, restrictions are either set at a high or at a low level. Taking advantage of this unique context, this study for the first time explores the implications for the West Bank economy consequent upon increases and decreases in access to the Israeli labour market. The study uses a SAM developed for the West Bank for the year 2011 with detailed representation of the labor market. Workers are categorized based on their demographic characteristics, their current workplace and eligibility to work permit in Israel. The behavioral relationships in a variant of STAGE suite of CGE models are extended to conform to the unique feature of the labor market between West Bank and Israel. The results demonstrate that while increases in the number of work permits increases welfare in the West Bank, it also distorts the operation of the West Bank labour market and economy. On the other hand, while decreases in the number of work permits reduces welfare, the limited opportunities in the West Bank restrict the ability of the West Bank economy to absorb the labour no longer employed in Israel. Keywords: labour markets, Conflict, Work permits, CGE, Palestine
Biogenesis of Nonspecific Lipid Transfer Protein and Sterol Carrier Protein x

Nonspecific lipid transfer protein (nsLTP; also called sterol carrier protein 2) with a molecular mass of 13 kDa is synthesized as a larger 15-kDa precursor (pre-nsLTP) with an N-terminal 20-amino acid extension presequence, as well as with the peroxisome targeting signal type 1 (PTS1), Ala-Lys-Leu, at the C terminus. The precursor pre-nsLTP is processed to mature nsLTP by proteolytic removal of the presequence, most likely after being imported into peroxisomes. Sterol carrier protein x (SCPx), a 59-kDa branched-chain fatty acid thiolase of peroxisomes, contains the entire pre-nsLTP moiety at the C-terminal part and is converted to the 46-kDa form and nsLTP after the transport to peroxisomes. We investigated which of these two potential topogenic sequences functions in biogenesis of nsLTP and SCPx. Morphological and biochemical analyses, making use of Chinese hamster ovary cell pex mutants such as the PTS1 receptor-impaired pex5 and PTS2 import-defectivepex7, as well as green fluorescent protein chimeras, revealed that both pre-nsLTP and SCPx are imported into peroxisomes by the Pex5p-mediated PTS1 pathway. Nearly half of the pre-nsLTP remains in the cytosol, as assessed by subcellular fractionation of the wild-type Chinese hamster ovary cells. In an in vitrobinding assay, only mature nsLTP, but not pre-nsLTP, from the cell lysates interacted with the Pex5p. It is likely, therefore, that modulation of the C-terminal PTS1 by the presequence gives rise to cytoplasmic localization of pre-nsLTP.
O-Antigen-Negative Salmonella enterica Serovar Typhimurium Is Attenuated in Intestinal Colonization but Elicits Colitis in Streptomycin-Treated Mice

ABSTRACT Lipopolysaccharide (LPS) is a major constituent of the outer membrane and an important virulence factor of Salmonella enterica subspecies 1 serovar Typhimurium (serovar Typhimurium). To evaluate the role of LPS in eliciting intestinal inflammation in streptomycin-treated mice, we constructed an O-antigen-deficient serovar Typhimurium strain through deletion of the wbaP gene. The resulting strain was highly susceptible to human complement activity and the antimicrobial peptide mimic polymyxin B. Furthermore, it showed a severe defect in motility and an attenuated phenotype in a competitive mouse infection experiment, where the ΔwbaP strain (SKI12) was directly compared to wild-type Salmonella. Nevertheless, the ΔwbaP strain (SKI12) efficiently invaded HeLa cells in vitro and elicited acute intestinal inflammation in streptomycin-pretreated mice. Our experiments prove that the presence of complete LPS is not essential for in vitro invasion or for triggering acute colitis.
Toward Value Co-Creation: Increasing Women’s Presence in Management Positions through Competition against a Set Target

Despite empirical evidence that women’s presence in management positions is a source of value co-creation for firms, these positions are still male-dominated. Some evidence from experimental economics suggests that one reason for this imbalance is that women shy away from competition. However, most of these studies have focused on competition systems that pit individuals against each other. We present an economic laboratory experiment that compares competition against others with competition against a set target. The crucial difference is that whereas the former involves competing against opponents, the latter does not. Our results show that significantly more women are willing to compete against a set target than against others. Furthermore, there is no reduction in men’s participation and no general efficiency reduction. Our findings suggest that firms that aim at value co-creation and sustainability through a gender-neutral promotion mechanism should introduce competition against a set target and reduce competition against others. This paper contributes to dispelling stereotypes about women’s reluctance to compete.
Jump Landing Strategies in Male and Female College Athletes and the Implications of Such Strategies for Anterior Cruciate Ligament Injury

Background: Female athletes are more likely than male athletes to injure the anterior cruciate ligament. Causes of this increased injury incidence in female athletes remain unclear, despite numerous investigations. Hypothesis: Female athletes will exhibit lower hamstring muscle activation and smaller knee flexion angles than male athletes during jump landings, especially when the knee muscles are fatigued. Study Design: Controlled laboratory study. Methods: Eight female and six male varsity college basketball athletes with no history of knee ligament injury performed jump landings on the dominant leg from a maximum height jump and from 25.4 cm and 50.8 cm high platforms under nonfatigued and fatigued conditions. Knee joint angle and surface electromyographic signals from the quadriceps, hamstring, and gastrocnemius muscles were recorded. Results: Women landed with greater knee flexion angles and greater knee flexion accelerations than men. Knee muscle activation patterns were generally similar in men and women. Conclusion: As compared with male college basketball players, female college basketball players did not exhibit altered knee muscle coordination characteristics that would predispose them to anterior cruciate ligament injury when landing from jumps. This conclusion is made within the parameters of this study and based on the observation that hamstring muscle activation was similar for both groups. The greater knee flexion we observed in the female subjects would be expected to decrease their risk of injury. Clinical Relevance: Factors other than those evaluated in this study need to be considered when attempting to determine the reasons underlying the increased incidence of anterior cruciate ligament injuries consistently observed in elite female athletes.
Power m-mode transcranial Doppler for diagnosis of patent foramen ovale and assessing transcatheter closure.

BACKGROUND AND PURPOSE Transcatheter closure of patent foramen ovale (PFO) can benefit from a less invasive diagnostic method than transesophageal echocardiography (TEE). Thirty-three gate power m-mode transcranial Doppler (pmTCD) was evaluated for its accuracy in diagnosis of PFO and utility in evaluating residual intracardiac right-to-left shunt (RLS) following transcatheter closure. METHODS The sensitivity of pmTCD and single-gate TCD (sgTCD) to detect contrast bubble emboli through RLS was compared during transcatheter PFO closure. During 100 preclosure diagnostic evaluations and in 81 postclosure assessments, embolic tracks on pmTCD were counted following intravenous contrast injections and were graded using a 6-level logarithmic scale. The accuracy of TEE and pmTCD was separately compared to PFO anatomical findings during transcatheter closures. RESULTS There were significantly more microemboli detectable on pmTCD (322 +/- 166; 95% confidence interval [CI], 388-257) than on sgTCD (186 +/- 109; 95% CI, 229-143; P < .001). McNemar change tests suggest that the diagnostic capabilities of pmTCD and TEE for detecting PFO are comparable and correspond to the anatomical findings determined during cardiac catheterization (P = .69 and .45, respectively). During 6-month postclosure evaluation (mean = 185 days), 66% of the patients demonstrated successful closure without significant RLS (ie, grades 0, I, or II), and 34% were found to have incomplete closure with significant RLS (ie, grades III, IV, or V). CONCLUSIONS pmTCD provides greater sensitivity to contrast bubble emboli than does sgTCD. Among candidates for transcatheter closure, pmTCD provides an improved noninvasive method for diagnosing PFO and evaluating transcatheter closure.
The epidemic of aging in renal replacement therapy: an update on elderly patients and their outcomes.

BACKGROUND In the past 2 decades, a rapid growth has occurred in the number of patients over 65 years of age accepted for renal replacement therapy (RRT) with an increasing need for dialysis resources as a consequence. The aim of this study is to describe the trends in incidence, treatment and outcome of RRT of these elderly patients included in the new ERA-EDTA Registry database. METHODS Data from 6 national renal registries have been included for the period 1985 - 1999, comprising data of 18,920 elderly patients starting RRT. We used Cox-proportional hazards regression to predict patient and technique survival. RESULTS The incidence and prevalence of RRT showed a 4- to 5-fold increase over the period, resulting in 48% of the new patients being older than 65 years in 1999. However, the rates varied considerably between countries. The 2-year patient survival was 51% in dialysis patients. Mortality due to social causes increased with age. Multivariate analysis showed no change with time in patient survival on dialysis, but the risk of death following a first renal allograft between 1995 and 1999 was reduced by 31%, compared with the 1985 - 1989 time period (RR 0.69; 95% CI: 0.54 - 0.90). The relative risk of peritoneal dialysis technique failure was more than doubled in the 1995 - 1999 cohort compared to the 1985 - 1989 cohort (RR 2.38; 95% CI: 1.89 - 3.01), with the highest technique failure rate in the first 2 years of the 1995 - 1999 cohort. CONCLUSIONS The number of elderly patients receiving RRT is rising rapidly. Patient survival on dialysis has been stable over the last 15 years, whereas transplant outcome has improved. The increased peritoneal dialysis technique failure and the high mortality due to social causes in the elderly age groups require further investigation. The challenge of the years ahead is to provide this life-prolonging therapy to all patients who need it in such a way that it improves quality of life and at a cost that a society can afford.
Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates

Aim: Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short‐term growth and urinary and plasma amino acids levels. Methods: Infants with a birthweight 1750 g and gestational age 34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid‐arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. Results: Twenty‐one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4±3.4 vs 20.5±3.3 g/kg/d; p=0.045) and lower mean change in Z‐scores for weight (−0.18±0.16 vs 0.00±0.09; p=0.009) and for head circumference (−0.06±0.13 vs 0.06±0.13; p=0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B.
Genetic Exchange Within and Between Assemblages of Giardia duodenalis

ABSTRACT. Meiotic sex evolved early in the history of eukaryotes. Giardia duodenalis (syn. Giardia lamblia, Giardia intestinalis), a parasitic protist belonging to an early diverging lineage of eukaryotes, shows no cytological or physiological evidence of meiotic or sexual processes. Recent molecular analyses challenge the idea that G. duodenalis is a strictly clonal organism by providing evidence of recombination between homologous chromosomes within one subgroup (Assemblage A) of this species as well as genetic transfer from one subgroup to another (Assemblage A–B). Because recombination is not well documented and because it is not known whether the observed inter‐assemblage transfer represents true reciprocal genetic exchange or a non‐sexual process, we analyzed genic sequences from all major subgroups (Assemblages A–G) of this species. For all assemblages, we detected molecular signatures consistent with meiotic sex or genetic exchange, including low levels of heterozygosity, as indicated by allelic sequence divergence within isolates, and intra‐ and inter‐assemblage recombination. The identification of recombination between assemblages suggests a shared gene pool and calls into question whether it is appropriate to divide the genetically distinct assemblages of G. duodenalis into a species complex.
Invasive pneumococcal disease and hemolytic uremic syndrome.

OBJECTIVE Severe pneumococcal infections have been associated with hemolytic uremic syndrome (HUS), usually with a poor clinical outcome when compared with Escherichia coli O157 gastroenteritis-associated (D+) HUS. We examined our experience with 12 cases of Streptococcus pneumoniae-associated HUS (SP-HUS) and compare it with a cohort of diarrhea-associated HUS (D+ HUS). METHODS A retrospective case survey compared 2 unrelated groups of HUS patients. Demographic factors, clinical indices of disease severity, and outcome were used to compare the 2 groups of HUS patients. RESULTS Twelve children with SP-HUS were studied. Pneumococcal pneumonia with empyema was the most common precipitating illness (67%), pneumococcal meningitis was present in 17% of children, pneumonia with bacteremia in 8%, and both pneumonia and meningitis in 8%. SP-HUS patients were younger than D+ HUS patients (22.1 vs 49 months) and had more severe renal and hematologic disease than D+ HUS patients. Compared with D+ HUS patients, SP-HUS patients were more likely to require dialysis (75% vs 59%) and had a longer duration of hospitalization (33.2 vs 16.1 days) and duration of thrombocytopenia (11.6 vs 6.8 days). SP-HUS patients were also more likely to require platelet transfusions (83% vs 47%) and needed more platelet (4.7 vs 0.5) and packed red blood cell transfusions (7.8 vs 2.0). The 2 groups did not differ significantly in the incidence of extrarenal HUS complications. There were no deaths in either group. Seven patients have been seen for long-term follow-up; 2 developed end-stage renal disease, and 5 have normal renal function. CONCLUSIONS HUS is a rare but severe complication of invasive pneumococcal infection. Although disseminated intravascular coagulation can also occur in these children, the treatment and follow-up may be different in the 2 conditions. Children with pneumococcal disease and severe hematologic or renal abnormalities should be investigated for evidence of HUS.
Sustaining a Study Abroad Program at Scale: What Motivates Faculty Members to Engage in Such Programs?

David Knight is Assistant Professor and Assistant Department Head for Graduate Programs in the Department of Engineering Education at Virginia Tech. He is also Director of International Engagement in Engineering Education and affiliate faculty with the Higher Education Program at Virginia Tech. His research tends to be at the macro-scale, focused on a systems-level perspective of how engineering education can become more effective, efficient, and inclusive.
The C-Ala Domain Brings Together Editing and Aminoacylation Functions on One tRNA

Transfer RNA Fix Accurate protein synthesis requires that transfer RNAs (tRNAs) must be acylated with the correct amino acid. Mistranslation of serine or glycine for alanine apparently presents a particular challenge and is corrected by an editing domain of alanyl-tRNA synthetases (AlaRSs). Guo et al. (p. 744) now show that aside from the aminoacylation and editing domains, a third domain, C-Ala, plays a key role in AlaRS function. It forms a nucleic acid–binding motif that promotes binding of both aminoacylation and editing domains to tRNAAla. The coupling of these two functions was likely important in the evolution of AlaRSs. Many alanyl–transfer RNA synthetases contain a domain that promotes aminoacylation and editing of transfer RNA. Protein synthesis involves the accurate attachment of amino acids to their matching transfer RNA (tRNA) molecules. Mistranslating the amino acids serine or glycine for alanine is prevented by the function of independent but collaborative aminoacylation and editing domains of alanyl-tRNA synthetases (AlaRSs). We show that the C-Ala domain plays a key role in AlaRS function. The C-Ala domain is universally tethered to the editing domain both in AlaRS and in many homologous free-standing editing proteins. Crystal structure and functional analyses showed that C-Ala forms an ancient single-stranded nucleic acid binding motif that promotes cooperative binding of both aminoacylation and editing domains to tRNAAla. In addition, C-Ala may have played an essential role in the evolution of AlaRSs by coupling aminoacylation to editing to prevent mistranslation.
“They give us hope”: HIV-positive caregivers' perspectives on the role of social support for health

A number of studies indicate that social support is associated with better health outcomes among HIV-positive caregivers of children, suggesting its potential importance for interventions aimed at safeguarding the well-being of this population. However, there is very little published literature assessing the support–health relationship or evaluating applied social support interventions with HIV-positive populations in HIV-endemic contexts of the developing world. The global literature on social support and health suggests that, in order to refine theory and improve interventions, greater attention should be paid to specific dimensions of support, such as types and sources, as well as the processes through which support may be affecting health outcomes. This article presents and discusses data from in-depth interviews with 12 HIV-positive primary caregivers of children living in an HIV-endemic, low-resourced, urban South African community. The primary aim of this qualitative work was to provide further insight into survey findings of a positive relationship between social support and self-reported general health and functioning, by exploring caregivers' personal experiences of being supported within their community, and their perceptions on how this “informal” support may be influencing their health. Our qualitative data highlight the importance of instrumental and emotional support for this population, the relevance of support provider characteristics and some of the processes or pathways that are likely explaining the support–health link. These processes include psychological factors such as mastery and hope, coping strategies and positive health behaviours. We provide recommendations for future research to further this work, and discuss implications for health interventions.