B cell depletion in diffuse progressive systemic sclerosis: safety,skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial

Introduction  

An over-expression of CD19 has been shown in B cells of systemic sclerosis (SSc) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model. The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry.     

Gene Variation, Population Differentiation, and Sociogenetic Structure of Nests of Partamona seridoensis (Hymenoptera: Apidae, Meliponini)

Gene variation and the differentiation of two populations of Partamona seridoensis (Hymenoptera: Apidae: Meliponini) from the Caatinga biome, a semiarid ecosystem unique to Brazil, were estimated through allozymic and microsatellite analyses. These populations exhibited similar low degrees of enzyme gene variation. Observed genotype frequencies at the allozyme and microsatellite loci were in accordance with Hardy-Weinberg equilibrium in the two populations. Both markers demonstrated that the two populations are not genetically homogeneous and must be considered distinct populations. The occurrence of private alleles at the allozyme and microsatellite loci corroborates this differentiation, sustaining the hypothesis of a low level of interpopulation gene flow. The phenotypic segregations clearly demonstrated that the progeny inside each nest were the result of mating between the queen of the colony and only one male.     

Purification and biochemical characterization of a native invertase from the hydrogen-producing Thermotoga neapolitana (DSM 4359)

This is the first report describing the purification and enzymatic properties of a native invertase (β-D-fructosidase) in Thermotogales. The invertase of the hydrogen-producing thermophilic bacterium Thermotoga neapolitana DSM 4359 (hereby named Tni) was a monomer of about 47 kDa having an amino acid sequence quite different from other invertases studied up to now. Its properties and substrates specificity let us classify this protein as a solute-binding protein with invertase activity. Tni was specific for the fructose moiety and the enzyme released fructose from sucrose and raffinose and the fructose polymer inulin was hydrolyzed in an endo-type fashion. Tni had an optimum temperature of 85°C at pH 6.0. At temperatures of 80–85°C, the enzyme retained at least 50% of its initial activity during a 6 h preincubation period. Tni had a K _m and k _cat /K _m values (at 85°C and pH 6.0) of about 14 mM and 5.2 × 10⁸ M⁻¹ s⁻¹, respectively. Dedicated to the memory of Prof. R. A. Nicolaus, founder of the Institute (1968).     

The Drosophila dopamine 2-like receptor D2R (Dop2R) is required in the blood brain barrier for male courtship

The blood brain barrier (BBB) has the essential function to protect the brain from potentially hazardous molecules while also enabling controlled selective uptake. How these processes and signaling inside BBB cells control neuronal function is an intense area of interest. Signaling in the adult Drosophila BBB is required for normal male courtship behavior and relies on male-specific molecules in the BBB. Here we show that the dopamine receptor D2R is expressed in the BBB and is required in mature males for normal mating behavior. Conditional adult male knockdown of D2R in BBB cells causes courtship defects. The courtship defects observed in genetic D2R mutants can be rescued by expression of normal D2R specifically in the BBB of adult males. Drosophila BBB cells are glial cells. Our findings thus identify a specific glial function for the DR2 receptor and dopamine signaling in the regulation of a complex behavior.     

Tissue-specific organic acid metabolism in reproductive and non-reproductive parts of the fig fruit is partially induced by pollination

Organic acids are important components of overall fruit quality through flavor, taste, nutritional and medicinal values. Pollinated fig (Ficus carica L.) fruit quality is enhanced by increased acidity. We quantified the major organic acids and characterized the expression pattern of organic acid metabolic pathway-related genes in the reproductive part – inflorescence and non-reproductive part – receptacle of parthenocarpic and pollinated fig fruit during ripening. Essentially, pollinated fruit contains seeds in the inflorescence, as opposed to no seeds in the parthenocarpic inflorescence. The major organic acids – citrate and malate – were found in relatively high quantities in the inflorescence compared to the receptacle of both parthenocarpic and pollinated fig fruit. Notably, pollination increased citric acid content significantly in both inflorescence and receptacle. Genes related to the phosphoenolpyruvate carboxylase (PEPC) cycle, tricarboxylic acid cycle, citrate catabolism and glyoxylate cycle were identified in fig fruit. Expression levels of most of these genes were higher in inflorescences than in receptacles. In particular, FcPEPC and FcFUM (encoding fumarase) had significantly higher expression in the inflorescence of pollinated fruit. Most importantly, expression of the glyoxylate cycle genes FcMLS and FcICL (encoding malate synthase and isocitrate lyase, respectively) was induced to strikingly high levels in the inflorescence by pollination, and their expression level was highly positively correlated with the contents of all organic acids. Therefore, the glyoxylate cycle may be responsible for altering the accumulation of organic acids to upgrade the fruit taste during ripening, especially in the pollinated, seeded inflorescence.     

Screening for Drug and Alcohol Use Disorders and Their Association with HIV-Related Sexual Risk Behaviors among Men Who Have Sex with Men in Peru

Background

Peru''s HIV epidemic is concentrated among men who have sex with men (MSM). The contribution of alcohol use disorders (AUDs) to known high-risk behaviors associated with HIV transmission in this context has not been well characterized.

Methods

Between June and October 2011, 5,148 sexually active MSM were recruited using convenience sampling in five cities to participate in a cross-sectional bio-behavioral survey. Five high-risk sexual criteria previously associated with incident HIV infection in this setting were selected a priori as the dependent outcomes. Screening for AUDs used the validated Alcohol Use Disorders Identification Test (AUDIT) and AUDS were stratified by severity. Unadjusted and adjusted odds ratios (AOR) were computed to establish the independent correlates of the five dependent outcomes.

Results

The majority (62.8%) of participants met screening criteria for having an AUD, which were independently correlated with each of the following high-risk sexual risk behaviors in the previous 6 months: 1) >5 sexual partners [AOR = 1.76; (1.54–2.02)]; 2) sex with an HIV-infected partner [AOR = 1.29; (1.03–1.62)]; 3) having a sexually transmitted infection [AOR = 1.38; (1.13–1.68)]; 4) being a sex worker [AOR = 1.61; (1.40–1.87)]; and 5) unprotected sex during last encounter [AOR = 1.22; (1.09–1.38)]. Recent drug use was also correlated with having >5 sexual partners [AOR = 1.42 (1.19–1.71)], sex work [AOR = 1.97 (1.63–2.39)] and unprotected sex during last encounter [AOR = 1.31 (1.11–1.54)]. For each dependent variable, the association with AUDs significantly increased with increasing AUD severity.

Conclusions

AUDs are highly prevalent among MSM in Peru and are associated with increased HIV risk-taking behaviors that are associated with HIV transmission. Strategies that target problematic drinking such as medication-assisted therapy, behavioral counseling and structural interventions could potentially reduce risky behaviors and ultimately reduce HIV transmission among MSM in Peru.     

The actin-binding ERM protein Moesin binds to and stabilizes microtubules at the cell cortex

Ezrin, Radixin, and Moesin (ERM) proteins play important roles in many cellular processes including cell division. Recent studies have highlighted the implications of their metastatic potential in cancers. ERM’s role in these processes is largely attributed to their ability to link actin filaments to the plasma membrane. In this paper, we show that the ERM protein Moesin directly binds to microtubules in vitro and stabilizes microtubules at the cell cortex in vivo. We identified two evolutionarily conserved residues in the FERM (4.1 protein and ERM) domains of ERMs that mediated the association with microtubules. This ERM–microtubule interaction was required for regulating spindle organization in metaphase and cell shape transformation after anaphase onset but was dispensable for bridging actin filaments to the metaphase cortex. These findings provide a molecular framework for understanding the complex functional interplay between the microtubule and actin cytoskeletons mediated by ERM proteins in mitosis and have broad implications in both physiological and pathological processes that require ERMs.     

Microsporum canis Infection in Three Familial Cases with Tinea Capitis and Tinea Corporis

We report a familial infection caused by Microsporum canis. The first two patients were a 30-year-old female and her son, a 5-year-old boy, who came in contact with a pet dog at a farm house. The boy then suffered from hair loss for 3 months. There were circular and patchy alopecia with diffuse scaling on his scalp. Meanwhile, his mother also developed patchy erythema and scaling on her face. Several weeks later, the boy’s sister, a 4-year-old girl, was noted to have inconspicuous scaly plaques in the center of her scalp. The development of tinea capitis in the two children and tinea corporis in their mother were diagnosed based on the positive KOH examination. Morphologic characteristics and sequencing of the internal transcribed spacers 1 and 2, amplified from primary culture isolates, confirmed that their infections were caused by the zoophilic M. canis. Repetitive sequence-based molecular typing using the DiversiLab system secreted enzymatic activity analysis, and antifungal susceptibility indicated that these isolates might share the same source. The boy and girl were cured by the treatment with oral itraconazole and topical naftifine–ketoconazole cream after washing the hair with 2 % ketoconazole shampoo, and their mother was successfully treated by terbinafine orally in combination with topical application of naftifine–ketoconazole cream.     

Non-lethal method of DNA sampling in euglossine bees supported by mark–recapture experiments and microsatellite genotyping

Non-lethal sampling methods are of great interest for conservation genetic studies to prevent the death of individuals in populations that are threatened or in decline. With this aim, we tested a non-lethal method of partial antennae removal for DNA sampling in two euglossine bee species: Euglossa cordata and Eulaema nigrita. We validated the survival of the individuals through mark–recapture experiments during 16 months. The quality and quantity of the tissue for DNA analysis was verified through amplification and genotyping of nine and eleven microsatellite loci, respectively. Our results from the mark–recapture experiments showed equal recapture rates of individuals with intact and removed antennae (E. cordata χ² = 2.492, df = 1, p = 0.114; E. nigrita χ² = 1.683, df = 1, p = 0.194). Microsatellite loci were successfully genotyped in 97.1 and 97.6 % of the E. cordata and E. nigrita individuals, respectively. Our results validate the feasibility of using antennae tissue for DNA genetic analysis without compromising the survival of individual bees.     

Prevalence of Entamoeba nuttalli infection in wild rhesus macaques in Nepal and characterization of the parasite isolates

We have recently resurrected the name Entamoeba nuttalli Castellani, 1908 for a potentially virulent ameba isolate, P19-061405, obtained from a rhesus macaque in Kathmandu, Nepal. The ameba was morphologically indistinguishable from Entamoeba histolytica/Entamoeba dispar/Entamoeba moshkovskii, but located phylogenetically between E. histolytica and E. dispar. To evaluate the prevalence of E. nuttalli infection in wild rhesus macaques, 112 fecal samples were collected in four locations of the Kathmandu Valley. PCR analysis of DNA extracted from the feces showed positive rates of E. nuttalli, E. dispar, E. histolytica and E. moshkovskii of 51%, 12%, 0% and 0%, respectively. A total of 14 E. nuttalli isolates were obtained from four locations, of which 6 were established as axenic cultures. The sequences of the serine-rich protein gene of E. nuttalli isolates differed among four locations although no differences were found in the composition of sequence motifs. Isoenzyme pattern was analyzed in 8 isolates obtained from three locations. In hexokinase, the mobility of the slower migrating band was located between E. histolytica and E. dispar regardless of the culture conditions. These results demonstrate that E. nuttalli is highly prevalent in wild rhesus macaques in Nepal. Rhesus macaques appear to be one of the natural hosts and heterogeneity of the serine-rich protein gene might be useful for geographical typing of isolates.