Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Novel treatment strategies are needed which allow preservation of GVL effects without causing GVHD. Using murine models, we show that targeting IL-2-inducible T cell kinase (ITK) in donor T cells reduces GVHD while preserving GVL effects. Both CD8+ and CD4+ donor T cells from Itk-/- mice produce less inflammatory cytokines and show decrease migration to GVHD target organs such as the liver and small intestine, while maintaining GVL efficacy against primary B-cell acute lymphoblastic leukemia (B-ALL). Itk-/- T cells exhibit reduced expression of IRF4 and decreased JAK/STAT signaling activity but upregulating expression of Eomesodermin (Eomes) and preserve cytotoxicity, necessary for GVL effect. Transcriptome analysis indicates that ITK signaling controls chemokine receptor expression during alloactivation, which in turn affects the ability of donor T cells to migrate to GVHD target organs. Our data suggest that inhibiting ITK could be a therapeutic strategy to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead

SignificanceIdentifying and explaining regional differences in tropical forest dynamics, structure, diversity, and composition are critical for anticipating region-specific responses to global environmental change. Floristic classifications are of fundamental importance for these efforts. Here we provide a global tropical forest classification that is explicitly based on community evolutionary similarity, resulting in identification of five major tropical forest regions and their relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. African and American forests are grouped, reflecting their former western Gondwanan connection, while Indo-Pacific forests range from eastern Africa and Madagascar to Australia and the Pacific. The connection between northern-hemisphere Asian and American forests is confirmed, while Dry forests are identified as a single tropical biome.

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

We determined cytokines (e.g. interleukin-8, 10, 12 and TNF-α) expression by peripheral blood mononuclear cells (PBMCs) and in rectal mucosa in diarrhoea-predominant irritable bowel syndrome (D-IBS) with Blastocystis spp. Eighty patients with D-IBS and Blastocystis spp. infection were classified as 'cases' and 80 with D-IBS without Blastocystis spp. infection were classified as 'control'. Cases were subdivided into D-IBS and Blastocystis sp. defined type 1 (subtype-specific primer SB83) and type 3 (SB227). Stool microscopy and culture were performed. Rectal biopsies were obtained for histology and cytokines by real-time PCR for mRNA expression of cytokines. PBMCs IL-8 was similar in different groups but in type 1, IL-8mRNA was increased compared with type 3 (P = 0·001) and control (P = 0·001). In type 1, IL-10 by PBMCs had a low mean value (14·5±1·6) compared with (16·7±1·5) type 3 and (16±2·3) in controls (P<0·001 and P<0·001, respectively). In Blastocystis sp. type 1, low IL-10 was associated with lymphocyte and plasma cell infiltration (P = 0·015 and P = 0·002, respectively). In Blastocystis sp. type 1 and type 3, IL-12 was associated with goblet cell depletion 23 (85%) (P<0·001) and 8 (29%) (P = 0·037), respectively. In Blastocystis sp. type 1, low IL-10 was associated with a proinflammatory response characterized by IL-8.

BACKGROUNDImportance of androgen receptor (AR) as an independent prognostic marker in Pakistani women with breast cancer (BCa) remains unexplored. Our aim was to identify the expression and potential prognostic value of AR, its upstream regulator (pAkt) and target gene (pPTEN) in invasive BCa.METHODSThis study used a cohort of 200 Pakistani women with invasive BCa diagnosed during 2002-2011. Expression of AR, pAkt and pPTEN was determined on formalin fixed paraffin embedded tissue sections by immunohistochemistry. The association of AR, pAkt and pPTEN with clinicopathological parameters was determined. Survival analyses were undertaken on patients with ≥ 5 years of follow-up (n = 82).RESULTSExpression of AR, pAkt and pPTEN was observed in 47.5%, 81.3% and 50.6% of patients, respectively. AR-expressing tumors were low or intermediate in grade (P < .001) and expressed ER (P = .002) and PR (P = .001). Patients with AR+ tumors had significantly higher OS (Mean OS = 10.2 ± 0.465 years) compared to patients with AR− tumors (Mean OS = 5.8 ± 0.348 years) (P = .047). Furthermore, AR-positivity was associated with improved OS in patients receiving endocrine therapy (P = .020). Patients with AR+ /pAkt+ /pPTEN− tumors, had increased OS (Mean OS = 7.1 ± 0.535 years) compared to patients with AR−/pAkt+/pPTEN− tumors (Mean OS = 5.1 ± 0.738 years).CONCLUSIONAR-expressing tumors are frequently characterized by low or intermediate grade tumors, expressing ER and PR. In addition, expression of AR, pAkt and pPTEN, could be considered in prognostication of patients with invasive BCa.

No abstract

The study of habitat variables of five rare pheasant species inhabiting the Himalayas, India, was carried out with the aim of evaluating niche overlap levels and explaining ecological separation among these coexisting species. The performed Discriminant Function Analysis revealed that altitude was a decisive discriminant factor in species segregation. The second function described pheasant habitats in terms of vegetation components (a higher percentage of grass cover and low herb density), while the third function represented forested areas varying from open to closed canopy forest with a simultaneous increase in the percentage of shrub cover. The study revealed that all the five pheasant species under study have fitted into a three-dimensional niche space in the habitat. A detailed discussion of each species study is presented.Ištirti penkių retų Indijos Himalajuose gyvenančių fazanų rūšių buveinių kintamieji, įvertintas ekologinių nišų persidengimas, pagrįstas šių koegzistuojančių rūšių ekologinis atskirtumas. Diskriminantinė analizė parodė, kad visas rūšis diferencijuojantis lemiamas veiksnys yra buveinės aukštis virš jūros lygio. Antroji diskriminantinė funkcija apibūdina fazanų buveinių augalijos komponentus (dominuojanti žolinė danga ir retai augantys žoliniai augalai). Trečioji funkcija apibūdina miškingas vietoves su skirtingo susivėrimo skliautu (nuo atviro iki susivėrusio) bei didėjančia krūmų dangos dalimi. Tyrimas parodė, kad visos fazanų rūšys turi savo trimatę nišą buveinėje.