Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutations in Cog7 affect Golgi structure, meiotic cytokinesis and sperm development during Drosophila spermatogenesis

Summary The conserved oligomeric Golgi (COG) complex plays essential roles in Golgi function, vesicle trafficking and glycosylation. Deletions in the human COG7 gene are associated with a rare multisystemic congenital disorder of glycosylation that causes mortality within the first year of life. In this paper, we characterise the Drosophila orthologue of COG7 (Cog7). Loss-of-function Cog7 mutants are viable but male sterile. The Cog7 gene product is enriched in the Golgi stacks and in Golgi-derived structures throughout spermatogenesis. Mutations in the Cog7 gene disrupt Golgi architecture and reduce the number of Golgi stacks in primary spermatocytes. During spermiogenesis, loss of the Cog7 protein impairs the assembly of the Golgi-derived acroblast in spermatids and affects axoneme architecture. Similar to the Cog5 homologue, four way stop (Fws), Cog7 enables furrow ingression during cytokinesis. We show that the recruitment of the small GTPase Rab11 and the phosphatidylinositol transfer protein Giotto (Gio) to the cleavage site requires a functioning wild-type Cog7 gene. In addition, Gio coimmunoprecipitates with Cog7 and with Rab11 in the testes. Our results altogether implicate Cog7 as an upstream component in a gio-Rab11 pathway controlling membrane addition during cytokinesis.
Mediterranean Founder Mutation Database (MFMD): Taking Advantage from Founder Mutations in Genetics Diagnosis, Genetic Diversity and Migration History of the Mediterranean Population

The Mediterranean basin has been the theater of migration crossroads followed by settlement of several societies and cultures in prehistoric and historical times, with important consequences on genetic and genomic determinisms. Here, we present the Mediterranean Founder Mutation Database (MFMD), established to offer web‐based access to founder mutation information in the Mediterranean population. Mutation data were collected from the literature and other online resources and systematically reviewed and assembled into this database. The information provided for each founder mutation includes DNA change, amino‐acid change, mutation type and mutation effect, as well as mutation frequency and coalescence time when available. Currently, the database contains 383 founder mutations found in 210 genes related to 219 diseases. We believe that MFMD will help scientists and physicians to design more rapid and less expensive genetic diagnostic tests. Moreover, the coalescence time of founder mutations gives an overview about the migration history of the Mediterranean population. MFMD can be publicly accessed from http://mfmd.pasteur. ma.
A Comparison of Device Measures of Dorsal First Ray Mobility

Background: Devices built by Glasoe and Klaue have been used in several studies to measure first ray mobility. Both devices measure sagittal motion of the first ray in a dorsal direction. The primary difference in the devices is the method of the load imposed. This study investigates whether first ray mobility measured with the Glasoe device is similar to the amount of mobility measured with the Klaue device. Methods: Using the devices described by Glasoe and Klaue, dorsal first ray mobility was measured in 39 patients who had foot and ankle problems. Paired t-tests were computed to assess for differences between device measures of dorsal mobility. Intraclass correlation coefficient (ICC) and absolute difference values were computed to further assess the agreement in measures. Results: Dorsal mobility measured with the Glasoe device averaged 4.9 mm (1.8 to 9.3 mm). Dorsal mobility measured with the Klaue device averaged 5.2 mm (2.5 to 8.5 mm). Paired t-tests (p = 0.12) revealed no significant difference in measures. An ICC of 0.70 and a mean absolute difference of 0.9 mm (SD 0.8) were found between the two clinical measures further suggesting agreement. Conclusion: Results indicated that the two devices possess similar diagnostic accuracy in the measurement of dorsal first ray mobility.
Lower airway obstruction is associated with increased morbidity in children with sickle cell disease

The association between pulmonary function and morbidity in children with sickle cell disease (SCD) has not been previously evaluated. Our objective was to study the relationship between abnormalities in pulmonary function and morbidity as represented by the rate of hospitalizations for pain or acute chest syndrome (ACS) in children with SCD.
The effect of a new sewage treatment plant on faecal indicator numbers, campylobacters and bathing water compliance in Morecambe Bay

Until recently, sewage from Morecambe was macerated, but otherwise untreated, and discharged at high water via a short outfall pipe into Morecambe Bay adjacent to a recognized bathing water. In March 1997, a new biological sewage treatment plant came on‐line and the effluent was discharged via a longer outfall pipe into the Bay south of Heysham. The effect of the new sewage treatment on the quality of the bathing waters was monitored by testing sea water collected from the three EU designated bathing waters on Morecambe Bay: Morecambe North, Morecambe South and Heysham. After sewage treatment came on‐line, the numbers of faecal coliforms and faecal streptococci were lower at Morecambe North and Morecambe South but higher at Heysham. Although the changes in numbers were not always statistically significant, they were sufficient to affect compliance with the EU Bathing Water Directive Imperative (mandatory) standards. Compliance improved markedly at Morecambe North and South but declined at Heysham, the closest bathing site to the new outfall. Numbers of thermophilic campylobacters were similar in both years, which is suggestive of their sources being different from those of the indicator bacteria. Campylobacter lari and urease‐positive thermophilic campylobacters (UPTC) were the only species of Campylobacter isolated from Morecambe's bathing waters. Very low numbers of Salmonella were found, with Salm. arizonae the only species isolated.
Heat-Labile- and Heat-Stable-Toxoid Fusions (LTR192G-STaP13F) of Human Enterotoxigenic Escherichia coli Elicit Neutralizing Antitoxin Antibodies

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal disease in humans and animals. Adhesins and enterotoxins, including heat-labile (LT) and heat-stable (STa) toxins, are the key virulence factors. Antigenic adhesin and LT antigens have been used in developing vaccines against ETEC diarrhea. However, STa has not been included because of its poor immunogenicity and potent toxicity. Our recent study showed that porcine-type STa toxoids became immunogenic and elicited neutralizing anti-STa antibodies after being genetically fused to a full-length porcine-type LT toxoid, LTR192G (W. Zhang et al., Infect. Immun. 78:316-325, 2010). In this study, we mutated human-type LT and STa genes, which are highly homologous to porcine-type toxin genes, for a full-length LT toxoid (LTR192G) and a full-length STa toxoid (STaP13F) and genetically fused them to produce LT192-STa13 toxoid fusions. Mice immunized with LT192-STa13 fusion antigens developed anti-LT and anti-STa IgG (in serum and feces) and IgA antibodies (in feces). Moreover, secretory IgA antibodies from immunized mice were shown to neutralize STa and cholera toxins in T-84 cells. In addition, we fused the STa13 toxoid at the N terminus and C terminus, between the A1 and A2 peptides, and between the A and B subunits of LT192 to obtain different fusions in order to explore strategies for enhancing STa immunogenicity. This study demonstrated that human-type LT192-STa13 fusions induce neutralizing antitoxin antibodies and provided important information for developing toxoid vaccines against human ETEC diarrhea.
Acidovorax, a new genus for Pseudomonas facilis, Pseudomonas delafieldii, E. Falsen (EF) group 13, EF group 16, and several clinical isolates, with the species Acidovorax facilis comb. nov., Acidovorax delafieldii comb. nov., and Acidovorax temperans sp. nov.

Pseudomonas facilis and Pseudomonas delafieldii are inappropriately assigned to the genus Pseudomonas. They belong to the acidovorans rRNA complex in rRNA superfamily III (i.e., the beta subclass of the Proteobacteria). The taxonomic relationships of both of these species, two groups of clinical isolates (E. Falsen [EF] group 13 and EF group 16), and several unidentified or presently misnamed strains were examined by using DNA:rRNA hybridization, numerical analyses of biochemical and auxanographic features and of fatty acid patterns, polyacrylamide gel electrophoresis of cellular proteins, and DNA:DNA hybridization. These organisms form a separate group within the acidovorans rRNA complex, and we propose to transfer them to a new genus, Acidovorax. We describe the following three species in this genus: the type species, Acidovorax facilis (formerly Pseudomonas facilis), with type strain LMG 2193 (= CCUG 2113 = ATCC 11228); Acidovorax delafieldii (for the former Pseudomonas delafieldii and most of the EF group 13 strains), with type strain LMG 5943 (= CCUG 1779 = ATCC 17505); and Acidovorax temperans (for several former Pseudomonas and Alcaligenes strains and most of the EF group 16 strains), with type strain CCUG 11779 (= LMG 7169).
Periodontal therapy and low birth weight: preliminary results from an alternative methodologic strategy.

BACKGROUND The purpose of this study is to present the use of a non-randomized experimental design with multiple controls, with emphasis on a historical control group, as an alternative methodologic resource for studies on the association between periodontal disease and prematurity/low birth weight. METHODS The sample consisted of 234 pregnant women: 54 in the Test Group (treatment of periodontal disease); 68 in Control Group I (without periodontal disease); and 112 in Control Group II (historical control group, with untreated periodontal disease). The diagnosis of periodontal disease was established by means of a complete clinical examination, using measurements of probing depth, gingival recession, clinical attachment loss, and bleeding index. The women in the Test Group were treated for periodontitis and followed-up with periodontal support therapy throughout their pregnancies. After delivery, they were reevaluated regarding their periodontal condition, and information on the newborn's birth weight was obtained. This was also done for Control Groups I and II. Descriptive analyses on the study variables were performed using the χ(2) and Fisher exact tests. Association measurements (relative risk) were obtained using a significance level of 5%. RESULTS The frequency of low birth weight among the Test Group was similar to Control Group I and lower than Control Group II. CONCLUSION The results suggest that successful periodontal therapy in pregnant women suffering from periodontitis is a protective factor promoting the birth of children with normal weight.
α‐Adrenergic stimulation of cytosolic Ca2+ oscillations and exocytosis in identified rat corticotrophs

1 The patch clamp technique was used in conjunction with a fluorescent Ca2+ indicator (indo‐1, or indo‐1FF) to measure simultaneously cytosolic Ca2+ concentration ([Ca2+]i), ionic current and changes in membrane capacitance in single rat corticotrophs identified with the reverse haemolytic plaque assay. 2 Application of the adrenocorticotropin (ACTH) secretagogue noradrenaline (NA; norepinephrine), triggered [Ca2+]i oscillation in corticotrophs via α‐adrenergic receptors and the guanosine trisphosphate (GTP) binding protein‐coupled phosphoinositide pathway. 3 Simultaneous measurement of [Ca2+]i and capacitance shows that exocytosis was triggered during the first cycle of NA‐induced [Ca2+]i oscillation and the mean increase in cell membrane surface area was 1.4 ± 0.3 % (n= 6). 4 When Ca2+ was directly released from the inositol 1,4,5 trisphosphate (IP3)‐sensitive store via flash photolysis of caged IP3, the mean increase in cell surface area was 1.5 ± 0.5 % (n= 6). Thus, NA‐stimulated ACTH secretion in rat corticotrophs is closely coupled to intracellular Ca2+ release. 5 Large and rapid elevation of [Ca2+]i (>15 μm) via flash photolysis of caged Ca2+ triggered two phases of exocytosis: a rapid exocytic burst that was complete in ∼100 ms and a slow burst that continued for many seconds. 6 The rapid exocytic burst reflected the exhaustion of a pool of readily releasable granules and, on average, increased the cell surface by 2.8 ± 0.1 % (n= 14). 7 We suggest that the relatively weak exocytic response in corticotrophs during intracellular Ca2+ release may be partially attributed to a smaller pool of readily releasable granules.
The Cardiovascular Toxicity of Selective and Nonselective Cyclooxygenase Inhibitors: Comparisons, Contrasts, and Aspirin Confounding

The premature suspension of the Alzheimer Disease Anti‐inflammatory Prevention (ADAPT) and the Adenoma Prevention with Celecoxib (APC) trials prompted intense review of the cardiovascular safety profile of selective and nonselective cyclooxygenase (COX) inhibitors. This article reviews the current state of selective COX‐2 inhibitors, discusses the mechanistic evidence underlying the cardiovascular risk associated with selective COX‐2 inhibition, outlines the pharmacodynamics of aspirin effects on platelets and the interference of propionic acid derivatives (ibuprofen and naproxen) with these effects, and poses that aspirin confounding may have led to the erroneous conclusion of naproxen‐associated adverse cardiovascular outcomes in the ADAPT trial. Finally, recommendations regarding selective COX‐2 inhibitors and appropriate timing of aspirin coadministration with traditional NSAIDs are proposed in relevance to patient safety and future trial design.
The Actresses' Franchise League Prepares For War: Feminist Theatre in Camouflage

In the third week of December 1908, a group of 300–400 prominent actors, actresses, and dramatists gathered at the Criterion Theatre in London to celebrate the formation of the Actresses' Franchise League. The inaugurating resolution, passed with one dissent, read: “That this meeting of actresses calls upon the Government immediately to extend the franchise to women, that women claim the franchise as a necessary protection for the workers under modern industrial conditions, and maintain that by their labour they have earned the right to this defence” (Votes for Women 24 Dec. 1908, p. 211). The resolution's emphasis upon labour as the enabling criterion qualifying women for the franchise reflects the roots of the British suffrage movement in the working class industrial north, where, as David Rosen notes, the Independent Labour Party had supported early suffragists (57).
What Differentiates Employees' Job Performance Under Stressful Situations: The Role of General Self-Efficacy

ABSTRACT The aim of this research is to verify the two-dimensional challenge–hindrance stressor framework in the Chinese context, and investigate the moderating effect of general self-efficacy in the stress process. Data were collected from 164 Chinese employee–supervisor dyads. The results demonstrated that challenge stressors were positively related to job performance while hindrance stressors were negatively related to job performance. Furthermore, general self-efficacy strengthened the positive relationship between challenge stressors and job performance, whereas the attenuating effect of general self-efficacy on the negative relationship between hindrance stressors and job performance was nonsignificant. These findings qualify the two-dimensional challenge–hindrance stressor framework, and support the notion that employees with high self-efficacy benefit more from the positive effect of challenge stressors in the workplace. By investigating the role of an individual difference variable in the challenge–hindrance stressor framework, this research provides a more accurate picture of the nature of job stress, and enhances our understanding of the job stressor–job performance relationship.
Which members of a community need antibiotics to control trachoma? Conjunctival Chlamydia trachomatis infection load in Gambian villages.

PURPOSE Trachoma is the leading cause of infectious blindness worldwide. Control strategies target antibiotic therapy to individuals likely to be infected with Chlamydia trachomatis on the basis of clinical signs. However, many studies have found chlamydial infection in the absence of clinical disease. It has been unclear whether such individuals represent a significant reservoir of infection. In the current study, a quantitative polymerase chain reaction (PCR) assay was used to investigate the distribution and determinants of chlamydial infection load in an endemic community, and the findings were used to evaluate the potential effectiveness of different control strategies. METHODS Members of a trachoma-endemic community (n = 1319) in a rural area of The Gambia were examined for signs of disease, and tarsal conjunctival swab samples were collected. C. trachomatis was initially detected by qualitative PCR. The load of infection was then estimated by real-time quantitative PCR. RESULTS Chlamydial infection was detected in 7.2% of the population. The distribution of infection load was skewed, with a few individuals having high loads. Only 24% of infected individuals had signs of active trachoma. Infection loads were higher in those with clinically active disease and were highest among those with severe inflammatory trachoma. High infection loads were associated with having no accessible latrine and living with a person with active disease. CONCLUSIONS In this low-prevalence setting, infected individuals without signs of active trachoma constitute a significant reservoir of infection. Treatment of a defined unit of people who live with someone with clinically active trachoma would effectively target antibiotic treatment to infected people without signs of disease.
Uptake of Long-Circulating Immunoliposomes, Directed Against Colon Adenocarcinoma Cells, by Liver Metastases of Colon Cancer

Abstract Radiolabeled ([3H]cholesteryloleyl ether) immunoliposomes directed against rat colon adenocarcinoma CC531 cells were prepared by random coupling of a tumor cell-specific antibody, CC52, via a thio–ether bond. In vitro binding experiments demonstrated a saturable and specific interaction of CC52-immunoliposomes, which could be inhibited by free non-coupled CC52 but not by irrelevant antibodies. The in vivo targeting potential of CC52-immunoliposomes, which were pegylated to achieve prolonged circulation times, was tested in an established rat liver CC531 metastasis model. Twenty-four hours after injection of the liposomes, 25% of the CC52-immunoliposomes were still present in the blood, which was comparable with the control liposomes (either with or without antibody). Liposomes were mainly taken up from the blood by the liver and the spleen, although hepatic uptake of the immunoliposomes was higher and splenic uptake was lower as compared to liposomes without antibody. Within the metastatic tumor nodules in the liver, uptake of both the CC52-immunoliposomes and non-specific immunoliposomes was significantly higher than that of control liposomes without antibody. Visualization of fluorescently or gold labeled CC52-immunoliposomes revealed that, although targeting to liver metastases was achieved, the immunoliposomes were mostly not associated with tumor cells but rather localized in tumor associated cells, probably macrophages.
HIF-1-Dependent IL-6 Activation in Articular Chondrocytes Initiating Synovitis in Femoral Head Ischemic Osteonecrosis.

BACKGROUND Ischemic osteonecrosis of the femoral head in children is associated with chronic hip synovitis and increased levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in the synovial fluid due to unknown mechanisms. The purpose of this study was to investigate hypoxia-inducible factor-1 (HIF-1) activation as a molecular mechanism linking the induction of ischemic osteonecrosis to IL-6 production and the initiation of hip synovitis. METHODS Ischemic osteonecrosis was surgically induced in the right femoral head of 6 piglets. A histologic score, synovial fluid volume, and IL-6 level were used to assess hip synovitis. IL-6 immunostaining of articular cartilage and synovial tissue was performed as well. To study the role of HIF-1 in IL-6 activation, in vitro experiments using an HIF-1α activator (deferoxamine) and inhibitor (HIF-1 small interfering-RNA [siRNA]) were carried out. Synovial cell responses to hypoxic chondrocyte-conditioned media with and without an IL-6 receptor blocker (tocilizumab) were assessed on the basis of IL-1β and tumor necrosis factor-alpha (TNF-α) gene expressions and with a synovial cell-proliferation assay. RESULTS Induction of ischemic osteonecrosis produced hip synovitis and increased IL-6 levels in the synovial fluid. Immunostaining and protein analysis demonstrated articular chondrocytes as a source of increased IL-6 production. When articular chondrocytes were cultured under hypoxic conditions, significantly increased HIF-1α and IL-6 expressions were observed. Under hypoxic culture conditions, IL-6 gene expression was significantly increased by HIF-1α activation using deferoxamine and inhibited by HIF-1α inhibition using HIF-1 siRNA. Synovial cells exposed to hypoxic chondrocyte-conditioned medium showed significant increases in IL-1β and TNF-α gene expressions and cell proliferation, which were inhibited by the IL-6 receptor blocker tocilizumab. CONCLUSIONS Induction of ischemic osteonecrosis results in IL-6 production in the articular cartilage through an HIF-1-dependent pathway. IL-6 produced by hypoxic articular chondrocytes stimulates inflammatory cytokine responses in synovial cells, which were significantly decreased by tocilizumab. CLINICAL RELEVANCE This study provides new insight into the inherent relationship between the induction of ischemia and the initiation of hip synovitis following ischemic osteonecrosis and suggests a potential therapeutic target in the treatment of the synovitis.
Distributions of post-proline cleaving enzyme-, converting enzyme-, trypsin- and chymotrypsin-like activities in various nephron segments and in brush-border membranes isolated from rat kidney.

Distributions of post-proline cleaving enzyme-, converting enzyme-, chymotrypsin- and trypsin-like activities, were investigated in nephron segments and in brush-border membrane fraction isolated from rat kidney. These activities were found to be higher in the proximal tubule than in other segments, and were hardly detectable in the cortical collecting tubule. In the proximal tubule, trypsin-like activity showed the highest value in the pars convoluta, while the other peptidases showed their highest activities in the pars recta. Post-proline cleaving enzyme- and trypsin-like activities were also high in the glomerulus. In addition, post-proline cleaving enzymeand converting enzyme-like activities were found in the brush-border membrane, while chymotrypsin- and trypsin-like activities were found in the cell component (s) other than the brush-border membrane. From these distributions of the peptidases, it is speculated that peptides are degraded both in the glomerulus and in the proximal tubule, and that in the proximal tubule the peptides are degraded both in the brush-border membrane and in other cell component (s).