Increased Hematopoietic Extracellular RNAs and Vesicles in the Lung during Allergic Airway Responses.

Extracellular RNAs (exRNAs) can be released by numerous cell types in vitro, are often protected within vesicles, and can modify recipient cell function. To determine how the composition and cellular sources of exRNAs and the extracellular vesicles (EVs) that carry them change in vivo during tissue inflammation, we analyzed bronchoalveolar lavage fluid (BALF) from mice before and after lung allergen challenge. In the lung, extracellular microRNAs (ex-miRNAs) had a composition that was highly correlated with airway-lining epithelium. Using cell type-specific membrane tagging and single vesicle flow, we also found that 80% of detected vesicles were of epithelial origin. After the induction of allergic airway inflammation, miRNAs selectively expressed by immune cells, including miR-223 and miR-142a, increased and hematopoietic-cell-derived EVs also increased >2-fold. These data demonstrate that infiltrating immune cells release ex-miRNAs and EVs in inflamed tissues to alter the local extracellular environment

MicroRNA regulation of type 2 innate lymphoid cell homeostasis and function in allergic inflammation.

MicroRNAs (miRNAs) exert powerful effects on immunity through coordinate regulation of multiple target genes in a wide variety of cells. Type 2 innate lymphoid cells (ILC2s) are tissue sentinel mediators of allergic inflammation. We established the physiological requirements for miRNAs in ILC2 homeostasis and immune function and compared the global miRNA repertoire of resting and activated ILC2s and T helper type 2 (TH2) cells. After exposure to the natural allergen papain, mice selectively lacking the miR-17∼92 cluster in ILC2s displayed reduced lung inflammation. Moreover, miR-17∼92-deficient ILC2s exhibited defective growth and cytokine expression in response to IL-33 and thymic stromal lymphopoietin in vitro. The miR-17∼92 cluster member miR-19a promoted IL-13 and IL-5 production and inhibited expression of several targets, including SOCS1 and A20, signaling inhibitors that limit IL-13 and IL-5 production. These findings establish miRNAs as important regulators of ILC2 biology, reveal overlapping but nonidentical miRNA-regulated gene expression networks in ILC2s and TH2 cells, and reinforce the therapeutic potential of targeting miR-19 to alleviate pathogenic allergic responses

Kajian Pelaksanaan Pelayanan Cakupan K4 Di Puskesmas Baumata Tahun 2018

 K4 pregnant women services are complete antenatal services with a time of examination, namely one visit in the first trimester, one visit in the second trimester, and two visits in the third trimester. The Baumata Community Health Center experienced a decline in K4 coverage based on the Kupang District Health Office profile data and annual reports where in 2016 K4 coverage reached 60.7%, in 2017 it reached 51.8% and in 2018 it only reached 44.2%. This research is a combination of qualitative and quantitative research (mix method) with descriptive research. The purpose of this study is to examine the implementation of K4 coverage services at the Baumata community health center in 2018 which includes description of inputs (human resources, facilities, sources of funds, policies and Standard Operating Procedures), process descriptions (planning and organizing) as well as output descriptions (K4 coverage ). Informants in this study amounted to 13 people and respondents numbered 66 people consisting of the Head of the Family Health and Nutrition Section of the Kupang District Health Office, the Head of the Baumata community health center, the Midwife who provided K4 services and the mother who had a pregnancy (K4) at the community health center Baumata in 2018. The results showed that in terms of input at the Baumata community health center as a whole it was good but there was no Ultrasonography facility at the community health center and the limited space where there was no special room for maternal and child health services/ family planning/immunization, in terms of the process is good related to planning, organizing and forms of services received by pregnant women are in accordance with 10T standards, it's just a long time in the process of providing services due to poor management time and lack of awareness of pregnant women to check pregnancy to the facility. The nearest health bag is due to the lack of knowledge of pregnant women about the importance of antenatal care, while in terms of output based on document review it can be seen that in the past three years there has been a decline in achievement of the K4 target at the Baumata community health center. It is recommended that the Baumata community health center procure supporting facilities in the form of Ultrasonography and additional rooms, make time management so that pregnant women do not wait too long for the service process, and conduct socialization to the public about the importance of antenatal care

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change

Efficacy of a multimodal physiotherapy treatment program for hip osteoarthritis: a randomised placebo-controlled trial protocol

<p>Abstract</p> <p>Background</p> <p>Hip osteoarthritis (OA) is a common condition leading to pain, disability and reduced quality of life. There is currently limited evidence to support the use of conservative, non-pharmacological treatments for hip OA. Exercise and manual therapy have both shown promise and are typically used together by physiotherapists to manage painful hip OA. The aim of this randomised controlled trial is to compare the efficacy of a physiotherapy treatment program with placebo treatment in reducing pain and improving physical function.</p> <p>Methods</p> <p>The trial will be conducted at the University of Melbourne Centre for Health, Exercise and Sports Medicine. 128 participants with hip pain greater or equal to 40/100 on visual analogue scale (VAS) and evidence of OA on x-ray will be recruited. Treatment will be provided by eight community physiotherapists in the Melbourne metropolitan region. The active physiotherapy treatment will comprise a semi-structured program of manual therapy and exercise plus education and advice. The placebo treatment will consist of sham ultrasound and the application of non-therapeutic gel. The participants and the study assessor will be blinded to the treatment allocation. Primary outcomes will be pain measured by VAS and physical function recorded on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) immediately after the 12 week intervention. Participants will also be followed up at 36 weeks post baseline.</p> <p>Conclusions</p> <p>The trial design has important strengths of reproducibility and reflecting contemporary physiotherapy practice. The findings from this randomised trial will provide evidence for the efficacy of a physiotherapy program for painful hip OA.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry reference: ACTRN12610000439044</p

The influence of ethylene and ethylene modulators on shoot organogenesis in tomato

[EN] The influence of ethylene and ethylene modulators on the in vitro organogenesis of tomato was studied using a highly regenerating accession of the wild tomato Solanum pennellii and an F1 plant resulting from a cross between Solanum pennellii and Solanum lycopersicum cv. Anl27, which is known to have a low regeneration frequency. Four ethylene-modulating compounds, each at four levels, were used, namely: cobalt chloride (CoCl 2), which inhibits the production of ethylene; AgNO 3 (SN), which inhibits ethylene action; and Ethephon and the precursor 1-aminocyclopropane-1-carboxylic acid (ACC), which both promote ethylene synthesis. Leaf explants of each genotype were incubated on shoot induction medium supplemented with each of these compounds at 0, 10 or 15 days following bud induction. The results obtained in our assays indicate that ethylene has a significant influence on tomato organogenesis. Concentrations of ethylene lower than the optimum (according to genotype) at the beginning of the culture may decrease the percentage of explants with buds (B), produce a delay in their appearance, or indeed inhibit bud formation. This was observed in S. pennellii and the F1 explants cultured on media with SN (5.8-58.0 ¿M) as well as in the F1 explants cultured on medium with 21.0 ¿M CoCl 2. The percentage of explants with shoots (R) and the mean number of shoots per explant with shoots (PR) also diminished in media that contained SN. Shoots isolated from these explants were less developed compared to those isolated from control explants. On the other hand, ethylene supplementation may contribute to enhancing shoot development. The number of isolable shoots from S. pennellii explants doubled in media with ACC (9.8-98.0 ¿M). Shoots isolated from explants treated with ethylene releasing compounds showed a higher number of nodes when ACC and Ethephon were added at 10 days (in F1 explants) or at 15 days (in S. pennellii) after the beginning of culture. Thus, the importance of studying not only the concentration but also the timing of the application of regulators when developing regeneration protocols has been made manifest. An excess of ethylene supplementation may produce an inhibitory effect, as was observed when using Ethephon (17.2-69.0 ¿M). These results show the involvement of ethylene in tomato organogenesis and lead us to believe that ethylene supplementation may contribute to enhancing regeneration and shoot development in tomato. © 2012 Springer Science+Business Media B.V.Carlos Trujillo has a predoctoral fellowship from the Spanish 'Ministerio de Educacion y Ciencia'. This work has been funded by Universitat Politecnica de Valencia (PAID 05-10). The technical assistance of N. Palacios and the revision of the manuscript's English by J. Bergen are gratefully acknowledged.Trujillo Moya, C.; Gisbert Domenech, MC. (2012). The influence of ethylene and ethylene modulators on shoot organogenesis in tomato. Plant Cell, Tissue and Organ Culture. 111(1):141-148. https://doi.org/10.1007/s11240-012-0168-zS1411481111Abeles FB, Morgan PW, Saltveit ME (1992) Ethylene in plant biology. Academic Press, San DiegoBhatia P, Ashwath N, Senaratna T, David M (2004) Tissue culture studies of tomato (Lycopersicon esculentum). Plant Cell Tiss Org Cult 78:1–21Bhatia P, Ashwath N, Midmore DJ (2005) Effects of genotype, explant orientation, and wounding on shoot regeneration in tomato. In Vitro Cell Dev Biol-Plant 41:457–464Biddington NL (1992) The Influence of ethylene in plant-tissue culture. Plant Growth Regul 11:173–187Brown DC, Thorpe TA (1995) Crop improvement through tissue culture. 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Phenotype and Clinical Outcomes of Titin Cardiomyopathy

BACKGROUND: Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification. OBJECTIVES: The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM. METHODS: In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events. RESULTS: Of 716 subjects recruited (mean age 53.5 ± 14.3 years; 469 men [65.5%]; 577 [80.6%] New York Heart Association function class I/II), 83 (11.6%) had TTNtv. Patients with TTNtv were younger at enrollment (49.0 years vs. 54.1 years; p = 0.002) and had lower indexed left ventricular mass (5.1 g/m2 reduction; padjusted = 0.03) compared with patients without TTNtv. There was no difference in biventricular ejection fraction between TTNtv+/- groups. Overall, 78 of 604 patients (12.9%) met the primary endpoint (median follow-up 3.9 years; interquartile range: 2.0 to 5.8 years), including 9 of 71 patients with TTNtv (12.7%) and 69 of 533 (12.9%) without. There was no difference in the composite primary outcome of cardiovascular death, heart failure, or arrhythmic events, for patients with or without TTNtv (hazard ratio adjusted for primary endpoint: 0.92 [95% confidence interval: 0.45 to 1.87]; p = 0.82). CONCLUSIONS: In this large, prospective, genotype-phenotype study of ambulatory DCM patients, we show that prognostic factors for all-cause DCM also predict outcome in TTNtv DCM, and that TTNtv DCM does not appear to be associated with worse medium-term prognosis

Graphene Nano-, Micro-and Macro-Photonics

ABSTRACT Graphene has already become an established medium for novel photonic devices and their applications. In some cases, e.g. the use of graphene as a non-linear medium with saturable absorption properties, it is experimentally convenient to use the readily available form that is known as graphene oxide. Moreover, technological and scientific developments that are advancing control of the properties of graphene for electronic applications are also likely to be applicable in photonic and optoelectronic devices. This presentation will review research in the field of graphene photonics across the world. It will address, in particular, its application as a saturable absorber, e.g. for pulsed operation of fibre lasers -as well as work on materials characterisation of deposited graphene films. Patterning of graphene films with precision at the microand nano-scales will be an important requirement -and will be considered in this presentation