Effect of protein kinase C inhibitors and activators on corneal re-epithelialization in the rat

PURPOSE: To examine the ability of protein kinase C (PKC) inhibitors and activators to influence the rate of corneal re-epithelialization in the rat. METHOD: Rat corneas with 3 mm diameter central epithelial abrasions were organ-cultured in control medium or in medium with inhibitors or activators of PKC. RESULTS: In control corneas, the defect was completely re-epithelialized by 25 hr. In the presence of the PKC inhibitors staurosporine (100 nM), sphinganine (50 mumol/l), or H-7 (100 mumol/l) there were significantly larger epithelial defects than in controls after 5-25 hr of incubation. Re-epithelialization rates were similar to control corneas when the incubation medium contained HA1004 (100 mumol/l), an analogue of H-7 that is a potent inhibitor of cyclic adenosine monophosphate- and cyclic guanosine monophosphate-dependent protein kinases and a weak inhibitor of PKC. Two PKC activators, 1-oleoyl-2-acetyl-sn-glycerol (OAG) and phorbol 12-myristate 13-acetate (PMA), were unable to enhance the rate of epithelial wound healing. CONCLUSIONS: Our results suggest that PKC activity is an important factor in regulating corneal epithelial wound healing, presumably by influencing cell migration. Moreover, the results with OAG and PMA suggest that PKC is maximally activated during re-epithelialization in this organ-culture assay

Academic motherhood and fieldwork: Juggling time, emotions and competing demands

The idea and practice of going ‘into the field’ to conduct research and gather data is a deeply rooted aspect of Geography as a discipline. For global North Development Geographers, amongst others, this usually entails travelling to, and spending periods of time in, often far-flung parts of the global South. Forging a successful academic career as a Development Geographer in the UK, is therefore to some extent predicated on mobility. This paper aims to critically engage with the gendered aspects of this expected mobility, focusing on the challenges and time constraints that are apparent when conducting overseas fieldwork as a mother, unaccompanied by her children. The paper emphasises the emotion work that is entailed in balancing the competing demands of overseas fieldwork and mothering, and begins to think through the implications of these challenges in terms of the types of knowledge we produce, as well as in relation to gender equality within the academy

Norovirus Detection and Genotyping for Children with Gastroenteritis, Brazil

During 1998–2005, we analyzed stool samples from 289 children in Rio de Janeiro to detect and genotype norovirus strains. Previous tests showed all samples to be negative for rotavirus and adenovirus. Of 42 (14.5%) norovirus-positive specimens, 20 (47.6%) were identified as genogroup GI and 22 (52.3%) as GII

The EarthCARE satellite: the next step forward in global measurements of clouds, aerosols, precipitation, and radiation

The collective representation within global models of aerosol, cloud, precipitation, and their radiative properties remains unsatisfactory. They constitute the largest source of uncertainty in predictions of climatic change and hamper the ability of numerical weather prediction models to forecast high-impact weather events. The joint European Space Agency (ESA)–Japan Aerospace Exploration Agency (JAXA) Earth Clouds, Aerosol and Radiation Explorer (EarthCARE) satellite mission, scheduled for launch in 2018, will help to resolve these weaknesses by providing global profiles of cloud, aerosol, precipitation, and associated radiative properties inferred from a combination of measurements made by its collocated active and passive sensors. EarthCARE will improve our understanding of cloud and aerosol processes by extending the invaluable dataset acquired by the A-Train satellites CloudSat, Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO), and Aqua. Specifically, EarthCARE’s cloud profiling radar, with 7 dB more sensitivity than CloudSat, will detect more thin clouds and its Doppler capability will provide novel information on convection, precipitating ice particle, and raindrop fall speeds. EarthCARE’s 355-nm high-spectral-resolution lidar will measure directly and accurately cloud and aerosol extinction and optical depth. Combining this with backscatter and polarization information should lead to an unprecedented ability to identify aerosol type. The multispectral imager will provide a context for, and the ability to construct, the cloud and aerosol distribution in 3D domains around the narrow 2D retrieved cross section. The consistency of the retrievals will be assessed to within a target of ±10 W m–2 on the (10 km)2 scale by comparing the multiview broadband radiometer observations to the top-of-atmosphere fluxes estimated by 3D radiative transfer models acting on retrieved 3D domains

Maximum occlusal force and medial mandibular flexure in relation to vertical facial pattern: a cross-sectional study

BACKGROUND: Vertical facial pattern may be related to the direction of pull of the masticatory muscles, yet its effect on occlusal force and elastic deformation of the mandible still is unclear. This study tested whether the variation in vertical facial pattern is related to the variation in maximum occlusal force (MOF) and medial mandibular flexure (MMF) in 51 fully-dentate adults. METHODS: Data from cephalometric analysis according to the method of Ricketts were used to divide the subjects into three groups: Dolichofacial (n = 6), Mesofacial (n = 10) and Brachyfacial (n = 35). Bilateral MOF was measured using a cross-arch force transducer placed in the first molar region. For MMF, impressions of the mandibular occlusal surface were made in rest (R) and in maximum opening (O) positions. The impressions were scanned, and reference points were selected on the occlusal surface of the contralateral first molars. MMF was calculated by subtracting the intermolar distance in O from the intermolar distance in R. Data were analysed by ANCOVA (fixed factors: facial pattern, sex; covariate: body mass index (BMI); alpha = 0.05). RESULTS: No significant difference of MOF or MMF was found among the three facial patterns (P = 0.62 and P = 0.72, respectively). BMI was not a significant covariate for MOF or MMF (P > 0.05). Sex was a significant factor only for MOF (P = 0.007); males had higher MOF values than females. CONCLUSION: These results suggest that MOF and MMF did not vary as a function of vertical facial pattern in this Brazilian sample

Characterization of Pseudomonas aeruginosa isolates: Occurrence rates, antimicrobial susceptibility patterns, and molecular typing in the global SENTRY Antimicrobial Surveillance Program, 1997-1999

During 1997–1999, a total of 70,067 isolates (6631 Pseudomonas aeruginosa isolates) were analyzed in the SENTRY program by geographic region and body site of infection. The respiratory tract was the most common source of P. aeruginosa. P. aeruginosa isolation rates increased during the study interval. Europe was the only region to show a significant decline in β-lactam and aminoglycoside susceptibility rates. There was a reduction in the rates of susceptibility of Canadian isolates to imipenem and of Latin American isolates to meropenem. A total of 218 multidrug-resistant P. aeruginosa isolates (MDR-PSA; resistant to piperacillin, ceftazidime, imipenem, and gentamicin) were observed; MDR-PSA occurrence rates (percentages of all isolates) ranged from 8.2% (Latin America) to 0.9% (Canada). No antimicrobial inhibited >50% of MDR-PSA strains. Molecular characterization of selected, generally resistant strains was performed. Isolates showing unique ribogroups were found in Europe, Latin America, and the United States, but clonal spread was documented in several medical centers.A. C. Gales, R. N. Jones, J. Turnidge, R. Rennie, and R. Rampha

Serological identification and expression analysis of gastric cancer-associated genes

Serological identification of tumour antigens by recombinant expression cloning has proved to be an effective strategy for the identification of cancer-associated genes having a relevance to cancer aetiology and progression, and for defining possible targets for immunotherapeutic intervention. In the present study we applied this technique to identify immunogenic proteins for gastric cancer that resulted in isolation of 14 distinct serum-reactive antigens. In order to evaluate their role in tumourigenesis and assess the immunogenicity of the identified antigens, we characterised each cDNA clone by DNA sequence analysis, mRNA tissue distribution, comparison of mRNA levels in cancerous and adjacent non-cancerous tissues and the frequency of antibody responses in allogeneic patient and control sera. Previously unknown splice variants of TACC1 and an uncharacterised gene Ga50 were identified. The expression of a newly identified TACC1 isoform is restricted to brain and gastric cancer tissues. Comparison of mRNA levels by semi-quantitative RT–PCR revealed a relative overexpression of three genes in cancer tissues, including growth factor granulin and Tbdn-1 – an orthologue of the mouse acetyltransferase gene which is associated with blood vessel development. An unusual DNA polymorphism – a three-nucleotide deletion was found in NUCB2 cDNA but its mRNA level was consistently decreased in gastric tumours compared with that in the adjacent non-cancerous tissues. This study has revealed several new gastric cancer candidate genes; additional studies are required to gain a deeper insight into their role in the tumorigenesis and their potential as therapeutic targets

CyBorD-DARA is potent initial induction for MM and enhances ADCP: Initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

CyBorD DARA as induction is well tolerated and induces deep responses when used in conjunction with ASCT for MM.Mechanism of action studies indicate that CyBorD DARA enhances macrophage activation, which may play a role in its clinical efficacy. Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was <10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810

Molecular Characteristics of Extended-Spectrum Beta-Lactamases and qnr Determinants in Enterobacter Species from Japan

The incidence of extended-spectrum β-lactamases (ESBLs) has been increasing worldwide, but screening criteria for detection of ESBLs are not standardized for AmpC-producing Enterobacteriaceae such as Enterobacter species. In this study, we investigated the prevalence of ESBLs and/or AmpC β-lactamases in Japanese clinical isolates of Enterobacter spp. and the association of plasmid-mediated quinolone resistance (PMQR) determinants with ESBL producers. A total of 364 clinical isolates of Enterobacter spp. collected throughout Japan between November 2009 and January 2010 were studied. ESBL-producing strains were assessed by the CLSI confirmatory test and the boronic acid disk test. PCR and sequencing were performed to detect CTX-M, TEM, and SHV type ESBLs and PMQR determinants. For ESBL-producing Enterobacter spp., pulsed-field gel electrophoresis (PFGE) was performed using XbaI restriction enzyme. Of the 364 isolates, 22 (6.0%) were ESBL producers. Seven isolates of Enterobacter cloacae produced CTX-M-3, followed by two isolates producing SHV-12. Two isolates of Enterobacter aerogenes produced CTX-M-2. Of the 22 ESBL producers, 21 had the AmpC enzyme, and six met the criteria for ESBL production in the boronic acid test. We found a significant association of qnrS with CTX-M-3-producing E. cloacae. The 11 ESBL-producing Enterobacter spp. possessing blaCTX-M, blaSHV, or blaTEM were divided into six unique PFGE types. This is the first report about the prevalence of qnr determinants among ESBL-producing Enterobacter spp. from Japan. Our results suggest that ESBL-producing Enterobacter spp. with qnr determinants are spreading in Japan

The human exosome: an autoantigenic complex of exoribonucleases in myositis and scleroderma

The anti-PM/Scl autoantibodies are known to characterize a subset of autoimmune patients with myositis, scleroderma (Scl), and the PM/Scl overlap syndrome. The major autoantigens that are recognized by anti-PM/Scl autoantibodies are designated PM/Scl-100 and PM/Scl-75. These autoantigens have been reported to associate into a large complex consisting of 11 to 16 proteins and to play a role in ribosome synthesis. Recently, it was discovered that the PM/Scl complex is the human counterpart of the yeast (Saccharomyces cerevisiae) exosome, which is an RNA-processing complex consisting of 11 3' → 5' exoribonucleases. To date, 10 human exosome components have been identified, although only some of these were studied in more detail. In this review, we discuss some recent advances in the characterization of the PM/Scl complex