Distribution and turnover of Langerhans cells during delayed immune responses in human skin

The changes in distribution and turnover of T6+ Langerhans cells (LC) in the skin during delayed immune responses to tuberculin, and in the lesions of tuberculoid leprosy and cutaneous Leishmaniasis were investigated. In each situation, there was a dermal accumulation of monocytes and T cells and epidermal thickening with keratinocyte Ia expression. In the tuberculin response a dramatic change in the distribution of LC was observed. By 41 h, T6+ LC were displaced to the upper zone of the thickening epidermis followed by an almost complete loss of LC from the epidermis by approximately 72 h. After 7 d, T6+ cells started to reappear in the epidermis, which regained almost normal numbers of T6+ LC by 14 d. After antigen administration and initiation of the delayed immune response, enhanced numbers of T6+ cells appeared in association with the mononuclear cell infiltrate of the upper dermal lesions. Their numbers peaked by 72 h, were reduced at 7 d, and again enhanced by 14 d, when the epidermis was being repopulated. Similar numbers of T6+ cells were found in the chronic lesions of tuberculoid leprosy and cutaneous Leishmaniasis but not lepromatous leprosy. The cells of the dermis were identified as typical LC by the presence of Birbeck granules and surface T6 antigen at the electron microscope level. These cells were closely associated with lymphocytes. We have quantified the number of LC, evaluated their directional flux into the epidermis and dermis, determined nearest neighbors, and made predictions as to their fate

Horizontal Vortex Tubes near a Simulated Tornado: Three-Dimensional Structure and Kinematics

Supercell thunderstorms can produce a wide spectrum of vortical structures, ranging from midlevel mesocyclones to small-scale suction vortices within tornadoes. A less documented class of vortices are horizontally-oriented vortex tubes near and/or wrapping about tornadoes, that are observed either visually or in high-resolution Doppler radar data. In this study, an idealized numerical simulation of a tornadic supercell at 100 m grid spacing is used to analyze the three-dimensional (3D) structure and kinematics of horizontal vortices (HVs) that interact with a simulated tornado. Visualizations based on direct volume rendering aided by visual observations of HVs in a real tornado reveal the existence of a complex distribution of 3D vortex tubes surrounding the tornadic flow throughout the simulation. A distinct class of HVs originates in two key regions at the surface: around the base of the tornado and in the rear-flank downdraft (RFD) outflow and are believed to have been generated via surface friction in regions of strong horizontal near-surface wind. HVs around the tornado are produced in the tornado outer circulation and rise abruptly in its periphery, assuming a variety of complex shapes, while HVs to the south-southeast of the tornado, within the RFD outflow, ascend gradually in the updraft.The first author is supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Grant number 88881.129505/2016-01 of the “Programa de Doutorado Pleno no Exterior” (DPE – 3830) under the Brazilian Ministry of Education. The second author is supported NSF Grant AGS-1261776 and NOAA VORTEX-SE Grant NA17OAR4590188. Open Access fees paid for in whole or in part by the University of Oklahoma Libraries.Ye

Microtubules regulate disassembly of epithelial apical junctions

BACKGROUND: Epithelial tight junction (TJ) and adherens junction (AJ) form the apical junctional complex (AJC) which regulates cell-cell adhesion, paracellular permeability and cell polarity. The AJC is anchored on cytoskeletal structures including actin microfilaments and microtubules. Such cytoskeletal interactions are thought to be important for the assembly and remodeling of apical junctions. In the present study, we investigated the role of microtubules in disassembly of the AJC in intestinal epithelial cells using a model of extracellular calcium depletion. RESULTS: Calcium depletion resulted in disruption and internalization of epithelial TJs and AJs along with reorganization of perijunctional F-actin into contractile rings. Microtubules reorganized into dense plaques positioned inside such F-actin rings. Depolymerization of microtubules with nocodazole prevented junctional disassembly and F-actin ring formation. Stabilization of microtubules with either docetaxel or pacitaxel blocked contraction of F-actin rings and attenuated internalization of junctional proteins into a subapical cytosolic compartment. Likewise, pharmacological inhibition of microtubule motors, kinesins, prevented contraction of F-actin rings and attenuated disassembly of apical junctions. Kinesin-1 was enriched at the AJC in cultured epithelial cells and it also accumulated at epithelial cell-cell contacts in normal human colonic mucosa. Furthermore, immunoprecipitation experiments demonstrated association of kinesin-1 with the E-cadherin-catenin complex. CONCLUSION: Our data suggest that microtubules play a role in disassembly of the AJC during calcium depletion by regulating formation of contractile F-actin rings and internalization of AJ/TJ proteins

Myosin II regulates the shape of three-dimensional intestinal epithelial cysts.

The development of luminal organs begins with the formation of spherical cysts composed of a single layer of epithelial cells. Using a model three-dimensional cell culture, this study examines the role of a cytoskeletal motor, myosin II, in cyst formation. Caco-2 and SK-CO15 intestinal epithelial cells were embedded into Matrigel, and myosin II was inhibited by blebbistatin or siRNA-mediated knockdown. Whereas control cells formed spherical cysts with a smooth surface, inhibition of myosin II induced the outgrowth of F-actin-rich surface protrusions. The development of these protrusions was abrogated after inhibition of F-actin polymerization or of phospholipase C (PLC) activity, as well as after overexpression of a dominant-negative ADF/cofilin. Surface protrusions were enriched in microtubules and their formation was prevented by microtubule depolymerization. Myosin II inhibition caused a loss of peripheral F-actin bundles and a submembranous extension of cortical microtubules. Our findings suggest that inhibition of myosin II eliminates the cortical F-actin barrier, allowing microtubules to reach and activate PLC at the plasma membrane. PLC-dependent stimulation of ADF/cofilin creates actin-filament barbed ends and promotes the outgrowth of F-actin-rich protrusions. We conclude that myosin II regulates the spherical shape of epithelial cysts by controlling actin polymerization at the cyst surface

Multiple interval mapping of QTLs and epistasis for iron toxicity tolerance in segregating population of Indica rice

The global average temperature has increased by approximately 0.5 °C, over a last few decades and is projected to continue to increase. Environmental stress factors such as, elevated temperature, salinity, toxic elements (Fe, Al, Cd, Cr, Pb, Zn and As), drought and rising CO2 affect plant growth and make a growing threat to agriculture. Rice is a primary food crop in the world and the establishment of rice crop in acidic soil and in marginal soil is a major goal for the improvement of rice production to fulfill the food security. Among environmental stresses, Fe2+ toxicity is one of the main stresses in limiting the cereal crops production. Tolerant rice genotypes that can tolerate the high concentration of Fe2+ toxicity are the potential source genes for rice tolerance improvement in Fe2+ toxicity. In this research work, the genetic basis of seed germination traits and growth traits was investigated in rice using (multiple interval mapping) MIM. Many rice genotypes serve as source of tolerant against toxic metal ion like Fe2+, could be an important factor in controlling the sever effect of Fe2+ toxicity on germination and seedling growth traits.  The F3 progenies of cross between Fe2+ toxicity tolerant cultivar ‘Pokkali’ and susceptible cultivar ‘Pak basmati’ were test against the optimized level of Fe2+ toxicity at germination, to determine the mode of inheritance to Fe2+ toxicity tolerance. Wide range of continues variation was found in F3 progenies. Among the 49 quantitative germination trait and 23 growth trait loci (QTLs) on chromosomes 1, 2, 4, 6, 8 and 9 linked with tolerance to Fe2+ toxicity was mapped. Additionally, 21 QTLs for germination traits and 9 QTLs for growth traits were classified as major QTLs using MIM. For germination and growth traits, notable epistasis between the chromosome 1, 2, 4, 6 and 11 was detected across germination and growth traits. Our results suggest that the tolerance mechanisms at germination and seedling phases could differ for Fe2+ toxicity. QTLs detected in this study for germination and seedling growth could be a source of new alleles for development of tolerance rice to Fe2+ toxicity varieties and transformation, gene cloning and gene editing in the futur

Drug-prescribing patterns during pregnancy in the tertiary care hospitals of Pakistan: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>The rationale for use of drugs during pregnancy requires a careful assessment as in addition to the mother, the health and life of her unborn child is also at stake. Information on the use of drugs during pregnancy is not available in Pakistan. The aim of this study was to evaluate the patterns of drug prescriptions to pregnant women in tertiary care hospitals of Pakistan.</p> <p>Methods</p> <p>This was a cross-sectional study conducted at five tertiary care hospitals of Pakistan. Copies of outpatient medicinal prescriptions given to pregnant patients attending the antenatal clinics were collected. The drugs were classified according to the pharmacological class and their teratogenic potential.</p> <p>Results</p> <p>All the pregnant women attending the antenatal clinics received a prescription containing at least one drug. A total of 3769 distinct prescriptions given to different women were collected. Majority of the women who received the prescriptions belonged to third trimester (55.4%) followed by second (33.6%) and first trimester (11.0%). On an average, each prescription contained 1.66 ± 0.14 drugs. The obstetricians at Civil Hospital, Karachi and Chandka Medical College Hospital, Larkana showed a tendency of prescribing lesser number of drugs compared to those in other hospitals. Anti-anemic drugs including iron preparations and vitamin and mineral supplements (79.4%) were the most frequently prescribed drugs followed by analgesics (6.2%) and anti-bacterials (2.2%). 739 women (19.6%) received prescriptions containing drugs other than vitamin or mineral supplements. Only 1275 (21.6%) of all the prescribed drugs (n = 6100) were outside this vitamin/mineral supplement class. Out of these 1275 drugs, 29 (2.3%) drugs were prescribed which are considered to be teratogenic. Misoprostol was the most frequently prescribed (n = 6) among the teratogenic drugs followed by carbimazole (n = 5) and methotrexate (n = 5). Twenty nine pregnant women (0.8% of all the women studied) were prescribed these teratogenic drugs.</p> <p>Conclusion</p> <p>Less than one percent of the pregnant women attending tertiary care hospitals in Pakistan are prescribed teratogenic drugs. The prescribing practices of Pakistani physicians are similar to those in western countries.</p

A Group Parenting Intervention for Depressed Fathers (LTP + Dads): A Feasibility Study from Pakistan

Introduction: In this study, we feasibility tested Learning Through Play Plus Dads (LTP+ Dads), a group parenting psychoeducation program adapted for depressed Pakistani fathers of children under three years of age. Methods: A total of 18 fathers with depression were recruited in Karachi, Pakistan for a pre-post feasibility study. Ten sessions of group LTP+ Dads were offered over three months. Clinical assessments were administered at baseline, 3 and 6 months and included the Edinburgh Postnatal Depression Scale, 17-item Hamilton Depression Rating Scale, Brief Disability Questionnaire, Multidimensional Scale of Perceived Social Support, Euro-Qol-5 Dimensions, Rosenberg Self-esteem Scale, Parenting Stress Index, and Knowledge, Attitude and Practices questionnaire. Results: The intervention was feasible to implement and acceptable based on a recruitment rate of 100% of eligible participants and a 100% attendance rate for 5 of the 10 sessions. Within this preliminary sample, fathers showed, on average, a reduction in depressive symptoms, an increase in most areas of fathers’ knowledge and positive attitudes about child development. Perceived social support, self-esteem and functioning scores also increased. Limitations: The small sample size and lack of control group are limitations of this study. Conclusions: In this first study of paternal depression in Pakistan, a low cost culturally adapted group intervention was found to be feasible and acceptable. Changes in depression, parenting-related and other outcomes are promising and inform a future larger trial. Keywords: Paternal depression, Cultural Adaptation, CBT, Parenting, Low and middle income countr

Structural, thermal and dissolution properties of MgO- and CaO-containing borophosphate glasses: effect of Fe2O3 addition

This paper investigated manufacture of high-durability phosphate glass fibres for biomedical applications. Five different borophosphate glass formulations in the systems of 45P2O5–5B2O3–5Na2O–(29 − x)CaO–16MgO–(x)Fe2O3 and 45P2O5–5B2O3–5Na2O–24CaO–(21 − x)MgO–(x)Fe2O3 where x = 5, 8 and 11 mol% were produced via melt quenching. The compositions and amorphous nature of the glasses were confirmed by ICP-MS and XRD, respectively. FTIR results indicated depolymerisation of the phosphate chains with a decrease in Q2 units with increasing Fe2O3 content. DSC analyses showed an increase in Tg by ~5 °C with an increment of 3 mol% in Fe2O3 content. The thermal properties were also used to calculate processing window (i.e. Tc,ons—Tg) and another parameter, Kgl, to determine the suitability for fibre drawing directly from melt, which equals (Tc,ons—Tg)/(Tl—Tc,ons). The degradation study conducted in PBS solution at 37 °C showed a decrease of 25–47% in degradation rate with increasing Fe2O3 content. This confirmed that the chemical durability of the glasses had increased, which was suggested to be due to Fe2O3 addition. Furthermore, the density measured via Archimedes method revealed a linear increase with increasing Fe2O3 content

What Point-of-Use Water Treatment Products Do Consumers Use? Evidence from a Randomized Controlled Trial among the Urban Poor in Bangladesh

BACKGROUND: There is evidence that household point-of-use (POU) water treatment products can reduce the enormous burden of water-borne illness. Nevertheless, adoption among the global poor is very low, and little evidence exists on why. METHODS: We gave 600 households in poor communities in Dhaka, Bangladesh randomly-ordered two-month free trials of four water treatment products: dilute liquid chlorine (sodium hypochlorite solution, marketed locally as Water Guard), sodium dichloroisocyanurate tablets (branded as Aquatabs), a combined flocculant-disinfectant powdered mixture (the PUR Purifier of Water), and a silver-coated ceramic siphon filter. Consumers also received education on the dangers of untreated drinking water. We measured which products consumers used with self-reports, observation (for the filter), and chlorine tests (for the other products). We also measured drinking water's contamination with E. coli (compared to 200 control households). FINDINGS: Households reported highest usage of the filter, although no product had even 30% usage. E. coli concentrations in stored drinking water were generally lowest when households had Water Guard. Households that self-reported product usage had large reductions in E. coli concentrations with any product as compared to controls. CONCLUSION: Traditional arguments for the low adoption of POU products focus on affordability, consumers' lack of information about germs and the dangers of unsafe water, and specific products not meshing with a household's preferences. In this study we provided free trials, repeated informational messages explaining the dangers of untreated water, and a variety of product designs. The low usage of all products despite such efforts makes clear that important barriers exist beyond cost, information, and variation among these four product designs. Without a better understanding of the choices and aspirations of the target end-users, household-based water treatment is unlikely to reduce morbidity and mortality substantially in urban Bangladesh and similar populations

Future research directions in pneumonia

Copyright © 2018 by the American Thoracic Society. Pneumonia is a complex pulmonary disease in need of new clinical approaches. Although triggered by a pathogen, pneumonia often results from dysregulations of host defense that likely precede infection. The coordinated activities of immune resistance and tissue resilience then dictate whether and how pneumonia progresses or resolves. Inadequate or inappropriate host responses lead to more severe outcomes such as acute respiratory distress syndrome and to organ dysfunction beyond the lungs and over extended time frames after pathogen clearance, some of which increase the risk for subsequent pneumonia. Improved understanding of such host responses will guide the development of novel approaches for preventing and curing pneumonia and for mitigating the subsequent pulmonary and extrapulmonary complications of pneumonia. The NHLBI assembled a working group of extramural investigators to prioritize avenues of host-directed pneumonia research that should yield novel approaches for interrupting the cycle of unhealthy decline caused by pneumonia. This report summarizes the working group’s specific recommendations in the areas of pneumonia susceptibility, host response, and consequences. Overarching goals include the development of more host-focused clinical approaches for preventing and treating pneumonia, the generation of predictive tools (for pneumonia occurrence, severity, and outcome), and the elucidation of mechanisms mediating immune resistance and tissue resilience in the lung. Specific areas of research are highlighted as especially promising for making advances against pneumonia