Miracle-dz/UniFAR-FTUs huggingface dataset:
SoxR‐dependent response to oxidative stress and virulence of Erwinia chrysanthemi: the key role of SufC, an orphan ABC ATPase

Erwinia chrysanthemi causes soft‐rot disease in a great variety of plants. In addition to the depolymerizing activity of plant cell wall‐degrading enzymes, iron acquisition and resistance to oxidative stress contribute greatly to the virulence of this pathogen. Here, we studied the pin10 locus originally thought to encode new virulence factors. The sequence analysis revealed six open reading frames that were homologous to the Escherichia coli sufA, sufB, sufC, sufD, sufS and sufE genes. Sequence similarity searching predicted that (i) SufA, SufB, SufD, SufS and SufE proteins are involved in iron metabolism and possibly in Fe–S cluster assembly; and (ii) SufC is an ATPase of an ABC transporter. The reverse transcription–polymerase chain reaction procedure showed that the sufABCDSE genes constitute an operon. Expression of a sufB::uidA fusion was found to be induced in iron‐deficient growth conditions and to be repressed by the iron‐sensing Fur repressor. Each of the six suf genes was inactivated by the insertion of a cassette generating a non‐polar mutation. The intracellular iron level in the sufA, sufB, sufC, sufS and sufE mutants was higher than in the wild type, as assessed by increased sensitivity to the iron‐activated antibiotic streptonigrin. In addition, inactivation of sufC and sufD led to increased sensitivity to paraquat. Virulence tests showed that sufA and sufC mutants exhibited reduced ability to cause maceration of chicory leaves, whereas a functional sufC gene was necessary for the bacteria to cause systemic invasion of Saintpaulia ionantha. The E. coli sufC homologue was inactivated by reverse genetic. This mutation was found to modify the soxR‐dependent induction of soxS gene expression. We discuss the possibility that SufC is a versatile ATPase that can associate either with the other Suf proteins to form a Fe–S cluster‐assembling machinery or with membrane proteins encoded elsewhere in the chromosome to form an Fe–S ABC exporter. Overall, these results stress the importance of the connection between iron metabolism and oxidative stress during the early steps of infection by E. chrysanthemi.
Implementation of an innovative grant programme to build partnerships between researchers, decision-makers and practitioners: The experience of the Quebec Social Research Council

Objectives This paper examines a grant programme developed by the Quebec Social Research Council in the 1990s to encourage the building of research partnerships between researchers, decision-makers and practitioners. In particular, it studies the perceptions of key participants concerning the reasons behind the programme's successful implementation and growth. Methods In addition to secondary data about institutional involvement in the programme, 10 researchers and administrators were consulted as key informants. The method of concept mapping was used in order to draw out a consensus on the different factors associated with the successful implementation of the programme. Results The participants identified 10 main factors that help explain the programme's successful implementation. These factors were then grouped into a model containing four dimensions: the leadership and coherence shown in the programmeme's implementation; the presence of a favourable political and social conjuncture; the programme's responsiveness to the needs of health and social services institutions; and the programme's responsiveness to the needs of the university milieu. Conclusions Although this model remains specific to the prevailing situation in Quebec at the time of its application, it may help stimulate reflection and contribute to an understanding of how research policies can encourage partnerships between researchers, practitioners and decision-makers.
Congenital generalized lipodystrophy: identification of novel variants and expansion of clinical spectrum

Congenital generalized lipodystrophy (CGL) is an autosomal recessive disorder with two major subtypes. Variants in AGPAT2 result in CGL type 1 with milder manifestations, whereas BSCL2 variants cause CGL type 2 with more severe features. Muscle hypertrophy caused by lack of adipose tissue is present early in life in CGL patients. Our aim was to investigate 10 CGL patients from 7 different countries and report genotype–phenotype relationships. Genetic analysis identified disease‐causing variants in AGPAT2 (five patients) and in BSCL2 (five patients), including three novel variants; c.134C>A (p.Ser45*), c.216C>G (p.Tyr72*) in AGPAT2 and c.458C>A (p.Ser153*) in BSCL2. We also report possible novel clinical features such as anemia, breast enlargement, steatorrhea, intraventricular hemorrhage and nephrolithiasis in CGL patients. Generalized lipodystrophy and muscular hypertrophy were the only features in all of our patients. Hepatomegaly was the second common feature. Some manifestations were exclusively noticed in our CGL2 patients; hypertrichosis, high‐pitched voice and umbilical hernia. Bone cysts and history of seizures were noticed only in CGL1 patients. The findings of this study expand our knowledge of genotype–phenotype correlations in CGL patients. These results have important clinical applications in diagnosis and management of the CGL patients as well as in genetic counseling in families at‐risk.
Attenuation correction of SPECT images based on separately performed CT

Summary Aim: A new software approach uses separately acquired CT images for attenuation correction after retrospective fusion with the SPECT data. This study evaluates the effect of this CT-based attenuation correction on indium- 111-pentetreotide-SPECT images. Methods: Indium- 111-pentetreotide-SPECT imaging using a dual-head gamma camera e.cam (Siemens Medical Solutions, Erlangen, Germany) as well as separate spiral computed tomography (CT) was performed in 13 patients. After fusion of SPECT and CT data, the bilinear attenuation coefficients were calculated for each pixel in the CT image volume using their Hounsfield unit values and attenuation- corrected images were reconstructed iteratively (OSEM 2D). Regions of interest (ROIs) were drawn on 24 suspicious foci and background, and target to background ratios were calculated for corrected (TBAC) and uncorrected (TBNAC) images. The shortest distance from the centre of the lesion to the surface of the body (DS) was measured on the corresponding CT slice. Furthermore, ROIs were drawn over the rim and the centre of the liver. Ratios of hepatic count rates for corrected (LRAC) and uncorrected (LRNAC) images were also compared. Results: In lesions located more centrally, TBAC was up to 52% higher, whereas in peripherally located lesions, TBAC was up to 63% lower than TBNAC. The TBAC/TBNAC quotient was linearly correlated with DS. In the liver, attenuation correction resulted in a 35% increase of LRAC compared with LRNAC. Conclusions: Attenuation correction of SPECT images performed by separately acquired CT data is quick and simple. It improves the contrast between target and background for lesions located more centrally in the body and improves homogeneity of the visualisation of tracer uptake in the liver.
Activating mutations in the calcium‐sensing receptor: genetic and clinical spectrum in 25 patients with autosomal dominant hypocalcaemia – a German survey

Objective Autosomal dominant hypocalcaemia or hypoparathyroidism is caused by activating mutations of the calcium‐sensing receptor (CaSR). Treatment with calcium and vitamin D often worsens hypercalciuria and nephrocalcinosis, and renal impairment can result. Our aim was to describe the phenotypic variance of this rare disorder in a large series and to evaluate the outcome after long‐term treatment.
Ethnically mismatched cord blood transplants in African Americans: the Saint Louis Cord Blood Bank experience.

BACKGROUND For ethnic minority patients where a suitably matched BM or peripheral blood donor is frequently unavailable, cord blood offers an opportunity for hematopoietic stem cell transplantation. Focused recruitment of ethnic minorities for cord blood donation has been proposed as the preferred strategy to improve access for minority recipients to cord blood for transplantation. The aim of this study was to evaluate cord blood characteristics for Caucasian and African American donors and the success of ethnically mismatched UC blood transplantation in African American recipients. METHODS Retrospective data analysis was performed comparing the characteristics of 556 cord blood units from African American and Caucasian donors. The outcomes of 18 African American ethnically mismatched transplant recipients were compared with a paired sample of 18 ethnically matched Caucasian recipients. RESULTS The fraction of collected units meeting acceptability criteria from African Americans was significantly lower compared with Caucasians (P = <0.0001). Additionally, African Americans had a significantly lower post-processing total nucleated cell count (TNC) compared with Caucasians (P=0.007) but there were no other significant differences in conventionally measured product characteristics. In the transplant analysis, there was no difference in overall survival at 1 year (P=0.85) or time to neutrophil engraftment (P=0.92) between the two patient populations. DISCUSSION At comparable levels of TNC dose and HLA matching, the use of ethnically mismatched UC blood units as a source for allogeneic unrelated transplant can result in successful transplant outcomes for African American patients.
Parental reactions to information about increased genetic risk of type 1 diabetes mellitus in infants.

OBJECTIVE To assess the anxiety, emotions, thoughts, and coping behaviors of parents 1 week after they receive the results of screening of their infant's genetic risk of type 1 diabetes mellitus. DESIGN Survey. SETTING The population-based Type 1 Diabetes Prediction and Prevention project conducted in Turku. PARTICIPANTS Parents of 443 consecutive high-risk infants and 506 next-born low-risk infants. INTERVENTIONS An infant's genetic risk of type 1 diabetes mellitus was measured from cord blood. High-risk information was delivered by telephone and low-risk information by mail 4 weeks later. MAIN OUTCOME MEASURES Anxiety measured using the state anxiety scale of the State-Trait Anxiety Inventory, and feelings, thoughts, and coping behaviors extracted from the questionnaire. RESULTS One week after obtaining the results, 67% of mothers and 63% of fathers of high-risk children and 58% of mothers and 54% of fathers of low-risk children had returned the questionnaire. Anxiety levels of parents of high-risk infants were similar to those of parents of low-risk infants (P = .86). More than 90% of the parents thought that it was good to know about the risk. Fifty-five percent of mothers and 37% of fathers of high-risk infants expressed modest worry. Increased anxiety was connected with other stressful life events, catastrophizing thoughts of diabetes mellitus risk, and emotion-focused or avoiding coping attitudes. CONCLUSIONS Learning about their infant's genetic diabetes mellitus risk induces only mild anxiety in most parents. Identifying the few parents with stronger anxiety helps focus intensified counseling.
Conventional and advanced implant treatment in the type II diabetic patient: surgical protocol and long-term clinical results.

PURPOSE To investigate the effect of type-2 diabetes on implant survival and complication rate. MATERIALS AND METHODS Prospective study enrolling type-2 diabetic patients suffering from edentulism, having a mean perioperative HbA1c level of 7.2%, and compliant with a maintenance program. All the patients underwent dental and periodontal examinations and had laboratory testing for HbA1c, fasting plasma glucose, blood lipids, and microalbuminuria. Nondiabetic patients matched for implant treatment indication served as controls. The influence of clinical diabetes-related factors and periodontal parameters (Plaque Index, bleeding on probing, probing depth) on implant survival were assessed via univariate then multivariate methods. RESULTS Forty-five diabetic patients, followed for 1 to 12 years, mean age 64.7 years, received 255 implants: 143 following a classical protocol and 112 in cases of sinus floor elevation, immediate loading, and guided bone regeneration. Forty-five nondiabetic control patients received 244 implants: 142 following a classical protocol and 102 in cases of advanced surgery. Implant survival following conventional or advanced implant therapy was not statistically different between the well-controlled (HbA1c < 7%, P = .33) and the fairly well-controlled group (HbA1c 7% to 9%, P = .37). The overall survival rate for the diabetic group was 97.2% (control 98.8%) and was not significantly different for age, gender, diabetes duration, smoking, or type of hypoglycemic therapy. The mean peri-implant bone loss was 0.41 +/- 0.58 mm (control, 0.49 +/- 0.64 mm). PI and BOP fairly correlated with postoperative complications. HbA1c was the only multivariate independent factor affecting the complication rate (P = .04). No statistically significant difference was found for patients (P = .81) or for implants (P = .66) for the advanced surgery cases or the conventional approach in diabetic patients compared to nondiabetic patients.
Synaptotagmin–Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation

Synaptotagmin I (Syt I), the putative Ca2+ sensor in regulated exocytosis, has two Ca2+‐binding modules, the C2A and C2B domains, and a number of putative effectors to which Syt I binds in a Ca2+‐dependent fashion. The role of Ca2+ binding to these domains remains unclear, as efforts to address questions about Ca2+‐triggered effector interactions have led to conflicting results. We have studied the effects of Ca2+ on fusion pores using amperometry to follow the exocytosis of single vesicles in real time and analyse the kinetics of fusion pore transitions. Elevating [Ca2+] in permeabilized cells reduced the fusion pore lifetime, indicating an action of Ca2+ during the actual fusion process. Analysing the Ca2+ dependence of the fusion pore lifetime, together with the frequency of pore openings and the proportion of openings that close without dilating (kiss‐and‐run events) enabled us to resolve exocytosis into a sequence of kinetic steps representing functional transitions in the fusion pore. Fusion pore opening and dilation were both accelerated by Ca2+, indicating separate Ca2+ control over each of these steps. Ca2+ ligand mutations in either the C2A or C2B domains of Syt I reduced fusion pore opening, but had opposite actions on the rate of fusion pore closure. These studies resolve two separate and distinct Ca2+‐triggered steps during regulated exocytosis. The C2A and C2B domains of Syt I have different actions during these steps, and these actions may be linked to their distinctive effector interactions.
Effect of human saliva on the fluoride sensitivity of glucose uptake by Streptococcus mutans

The fluoride (F) sensitivity of glucose uptake by whole cell suspensions of streptococcus mutans in the presence and absence of human whole salivary supernatant was studied. It was observed that dithiothreitol (DTT) and other thiols markedly reduced the F sensitivity of cells when saliva (50%, vol/vol) was present during glucose uptake. In the absence of saliva, cells were sensitive to 2 to 2.5 mM F regardless of the presence of thiols. Supplementation of cells in phosphate or tris(hydroxymethyl)aminomethane-hydrochloride buffers with physiological concentrations of calcium or phosphate had no effect on the F sensitivity of the organism. Experiments with permeabilized cells suggested that thiols themselves had no direct effect on the F sensitivity of enolase (a principal F target). Cells pretreated with DDT subsequently exhibited decreased F sensitivity when examined in the presence of saliva but not in the absence of saliva. Cells pretreated with whole salivary supernatant were found to be subsequently less sensitive to F in the absence of saliva during glucose uptake. Furthermore, in cases where cells were pretreated with saliva, subsequent additions of DDT were unnecessary to obtain maximal reduction in the F sensitivity of glucose uptake. It was concluded that the saliva-dependent reduction in F sensitivity of glucose uptake was not due to sequestration of available F by salivary constituents. The data suggest that a salivary component(s) interacts directly with the microorganism in some manner which results in reduced F sensitivity of the process under study. Possible mechanisms of saliva action are discussed.
Integrating sense of place within new housing developments: a community-based participatory research approach

This chapter looks at a Canadian project which critically explores the potential of an action-oriented, community-based participatory research (CBPR) approach to reveal ways in which communities can be resilient to the opportunities and challenges of ageing-in-place. As part of the ‘Place-making with Seniors’ housing redevelopment project, a CBPR approach was applied in order to understand the sense of place of older adults through multiple vantage points. This resulted in a number of positive outcomes that revealed how community resilience and empowerment, articulated through participants' voices within the action research project, transformed the redevelopment in ways that were beneficial for older adults. As such, and in recognition of community requirements and aspirations, a number of changes were implemented so as to create a better living environment for older tenants.
Inositol 1,4,5‐Trisphosphate Receptor/Ca2+ Channel Modulatory Role of Chromogranins A and B

Abstract: The secretory granules function as the major IP3‐sensitive intracellular Ca2+ store of secretory cells. Recently it was found that the secretory granules contain three isoforms of inositol 1,4,5‐trisphosphate receptor (IP3R)/Ca2+ channels and high‐capacity, low‐affinity Ca2+ storage proteins chromogranins A (CgA) and B (CgB). The IP3R/Ca2+ channel was shown to directly interact with CgA and CgB at the intragranular pH 5.5, and this coupling led to modulation of the IP3R/Ca2+ channel activity by the coupled chromogranins. These results provide the molecular structural basis of the IP3‐mediated Ca2+ release mechanism of secretory granules.
Galanin Contributes to the Excess Colonic Fluid Secretion Observed in Dextran Sulfate Sodium Murine Colitis

Galanin is present in enteric nerves lining the gastrointestinal (GI) tract where it is normally involved in regulating intestinal motility by binding to the galanin-1 receptor (Gal1R) subtype expressed by smooth muscle cells. In contrast, although epithelial cells lining the colon do not normally express Gal1R, this protein is upregulated by the inflammation-associated transcription factor NF-κB. We previously showed that the murine colitis induced by dextran sulfate sodium (DSS) was associated with increased Gal1R expression as well as by increased colonic fluid secretion. Although Gal1R up-regulation by colonic epithelial cells results in increased intestinal Cl− secretion, the relative contributions of galanin to this excess colonic fluid secretion could not be determined. We therefore created a mouse genetically incapable of synthesizing Gal1R (GAL1R−/− mice). We herein demonstrate that both wild-type and GAL1R−/− mice developed identical histologic lesions in response to DSS. This was characterized by a marked inflammatory infiltrate, activation of NF-κB in both enterocytes and enteric nerves, and a threefold increase in neuronal galanin. Colonic fluid secretion, while increased, was approximately half that in GAL1R−/− mice as compared with their wild-type littermates. Overall, then, these findings strongly suggest that approximately half of the increase in colonic fluid secretion in DSS colitis is due to up-regulation of the Gal1R.
Effects of health-care services and commodities cost on the patients at the primary health facilities in Zaria Metropolis, North Western Nigeria

Introduction: The payment for health-care services is a major problem for many poor patients in developing nations. The aim of the study was to examine the cost of services and commodities and how these affect the patients who utilizes the primary health-care centers in Zaria, North western Nigeria. Methodology: A descriptive cross-sectional survey of six primary health-care facilities in Zaria metropolis, namely Baban dodo, Tudun Wada, Magajiya PHCs from Zaria local government areas (LGA) and Samaru, Kwata, and Dogarawa PHCs from Sabon Gari LGA, was carried out. Result: The mean age of the respondents was 28.87± 8.63 years, most of them were married (53.3%), Hausa (63.3%), and Muslims (85.7%); also, they were unemployed housewives with daily stipends from their husbands less than 1 dollar/day. The major method for payment for health-care services was out of pocket (98.3%). More than one-third of the clients were not aware of the National Health Insurance Scheme (NHIS) (39%). There was a significant inverse relationship between the monthly income of the clients and the experience of financial stress and a positive association between patients' monthly income and awareness of the NHIS (P < 0.05). Conclusion: The respondents were paying user fees for essential health-care services at the primary health-care centers and this was not convenient for them. Recommendation: There is a need for the LGA health department to intensify the supervision of the activities at the PHCs. Standardization of prices of services and commodities and the implementation of the National Health Act may alleviate the burdens of the poor community members who access PHCs in Nigeria.
The use of inositol(s) isomers in the management of polycystic ovary syndrome: a comprehensive review

Abstract The aim of this review is to present the current data about the role of inositols in the management of polycystic ovary syndrome (PCOS) women and in the prevention and treatment of gestational diabetes mellitus (GDM). We analyzed the available literature with key words PCOS, Myo-inositol, D-chiro-inositol, assisted reproductive technologies and GDM. The most recent literature would suggest that Myo-inositol, D-chiro-inositol and their combination in physiological ratio 40:1 could represent an important therapeutic strategy for the improvement of metabolic, hormonal and reproductive aspects of PCOS. In assisted reproductive technologies, however, myo-inositol and the combined treatment, despite D-chiro-inositol monotherapy, are able to improve clinical outcomes. Myo-inositol monotherapy results more effective in preventing and treating GDM even if a larger cohort of studies is needed to better clarify these results.