When the going gets tough, the tough get going: Social identification and individual effort in intergroup competition.

Based on social identity theory, the authors predicted that in ongoing intergroup competition, people’s strength of social identification will have a positive impact on their behavioral efforts on behalf of an ingroup when its current status is low, whereas this will not be the case when its current status is high. In a first experiment, male participants showed the expected pattern of behavior. Female participants, however, tended to display opposite reactions. As a possible explanation, it was argued that the experimental procedure may have inadvertently evoked a gender-based stereotype threat for female participants. In an attempt to obtain more consistent support for their hypothesis, the authors therefore replicated the experiment with modifications to avoid such a threat. These changes proved to be effective in the sense that this time the predicted interaction effect between ingroup identification and current group status was obtained for both male and female participants

Transformasi Padi Indica Kultivar Batutegi dan Kasalath dengan Gen Regulator HD-Zip untuk Perakitan Varietas Toleran Kekeringan

Water deficiency. Genetic engineering at the level of transcription factors (TF) is particulary a promising strategy in developing drought tolerant rice cultivar. HD-Zip genes are TF that function in plant adaptation to some environmental stresses including water deficit. The recombinant plasmid pC1301H Oshox6 which contained HD-Zip Oshox6 gene was placed under a drought inducible promoter called LEA promoter, gusA and hpt genes were driven with CaMV promoter. The aim of research was to obtain indica rice transgenic plants of Batutegi and Kasalath cultivars using pC1301H Oshox6 plasmid. Recombinant plasmid was transformed into immature rice embryos using Agrobacterium tumefaciens. Kasalath cultivar showed a better capacity to form embryogenic calli compared to Batutegi. Transformation efficiency of Batutegi is lower (1.5 - 0.3%) than Kasalath (2.2-28.3%). Regeneration efficiency is 25-83.3% and 7.7-100% for Batutegi and Kasalath, respectively. Number of putative transformant plantlets of Batutegi and Kasalath are 63 and 48 plantlets, respectively. Southern blot analysis (using hpt probe) on 12 independent lines of each Batutegi and Kasalath cultivars showed different gene copy number, ranging from one to four copies of gene

Perbandingan Tiga Metode Transformasi Agrobacterium Untuk Pencarian Gen-gen Terkait Toleransi Kekeringan Menggunakan Transposon Ac/Ds Pada Padi CV. Batutegi

Transformation Strategy for Indonesian Indica Rice in Attempt to Discover Drought-TolerantRelated Genes Using of Transposon Ac/Ds. Attempt to identify, isolate the gene, and study forgene function for several agronomical traits have been done including some drought toleranttraits. Japonica rice cultivars have been used due to its higher efficiencies compared withindica cultivars. Two plasmids namely pNU400 and pUR224 were used to generate mutants ofthese cultivars (Batutegi dan Kasalath cultivars). Those plasmids contain an element calledActivator (Ac) and Dissociator (Ds) respectively. The pNU400 contains GFP (green flourescensprotein) as a selectable marker, whereas the pUR224 contains hygromycine resistant gene andgusA as a reporter gene. Each plasmid was transformed into rice genome of Batutegi andKasalath cultivars by Agrobacterium mediated transformation using three methods oftransformation (A, B and C). The transformation method A was not suitable for both cultivars,where none of plantlets were produced from pNU400 and pUR224 plasmids. The transformationmethod B produced some plantlets from the Kasalath cultivar only using pUR224 plasmid.The transformation method C was the best method to produce transgenic plants from bothcultivars (Batutegi and Kasalath), using both plasmids (pNU400 and pUR224). The PCR analysisshowed that 19 and 9 plants of Batutegi and Kasalath contained both gusA and hpt genesrespectively. None of those plants contained of gusA gene. Southern blot analysis revealed 3independent lines from Batutegi dan 7 independent lines from Kasalath. The integration of Actransposon was analyzed based on expression gfp gene when observed under UV dark reader.This research has proved that indica rice cultivars, especially the Batutegi cultivar of Indonesianorigin, could be transformed. The cultivar could be used as plant model for the indicatransformation

Determinants and clinical outcome of uptitration of ACE-inhibitor and beta-blocker in patients with heart failure:a prospective European study

Introduction: Despite clear guidelines recommendations, most patients with heart failure and reduced ejection–fraction (HFrEF) do not attain guideline-recommended target doses. We aimed to investigate characteristics and for treatment-indication-bias corrected clinical outcome of patients with HFrEF that did not reach recommended treatment doses of ACE-inhibitors/Angiotensin receptor blockers (ARBs) and/or beta-blockers. Methods and results: BIOSTAT-CHF was specifically designed to study uptitration of ACE-inhibitors/ARBs and/or beta-blockers in 2516 heart failure patients from 69 centres in 11 European countries who were selected if they were suboptimally treated while initiation or uptitration was anticipated and encouraged. Patients who died during the uptitration period (n = 151) and patients with a LVEF > 40% (n = 242) were excluded. Median follow up was 21 months. We studied 2100 HFrEF patients (76% male; mean age 68 ±12), of which 22% achieved the recommended treatment dose for ACE-inhibitor/ARB and 12% of beta-blocker. There were marked differences between European countries. Reaching <50% of the recommended ACE-inhibitor/ARB and beta-blocker dose was associated with an increased risk of death and/or heart failure hospitalization. Patients reaching 50–99% of the recommended ACE-inhibitor/ARB and/or beta-blocker dose had comparable risk of death and/or heart failure hospitalization to those reaching ≥100%. Patients not reaching recommended dose because of symptoms, side effects and non-cardiac organ dysfunction had the highest mortality rate (for ACE-inhibitor/ARB: HR 1.72; 95% CI 1.43–2.01; for beta-blocker: HR 1.70; 95% CI 1.36–2.05). Conclusion: Patients with HFrEF who were treated with less than 50% of recommended dose of ACE-inhibitors/ARBs and beta-blockers seemed to have a greater risk of death and/or heart failure hospitalization compared with patients reaching ≥100%

The Role of Cathepsin D in the Pathophysiology of Heart Failure and its Potentially Beneficial Properties:a translational approach

Aims: Cathepsin D is a ubiquitous lysosomal protease that is primarily secreted due to oxidative stress. The role of circulating cathepsin D in heart failure (HF) is unknown. The aim of this study is to determine the association between circulating cathepsin D levels and clinical outcomes in patients with HF and to investigate the biological settings that induce the release of cathepsin D in HF. Methods and results: Cathepsin D levels were studied in 2174 patients with HF from the BIOSTAT-CHF index study. Results were validated in 1700 HF patients from the BIOSTAT-CHF validation cohort. The primary combined outcome was all-cause mortality and/or HF hospitalizations. Human pluripotent stem cell-derived cardiomyocytes were subjected to hypoxic, pro-inflammatory signalling and stretch conditions. Additionally, cathepsin D expression was inhibited by targeted short hairpin RNAs (shRNA). Higher levels of cathepsin D were independently associated with diabetes mellitus, renal failure and higher levels of interleukin-6 and N-terminal pro-B-type natriuretic peptide (P < 0.001 for all). Cathepsin D levels were independently associated with the primary combined outcome [hazard ratio (HR) per standard deviation (SD): 1.12; 95% confidence interval (CI) 1.02–1.23], which was validated in an independent cohort (HR per SD: 1.23, 95% CI 1.09–1.40). In vitro experiments demonstrated that human stem cell-derived cardiomyocytes released cathepsin D and troponin T in response to mechanical stretch. ShRNA-mediated silencing of cathepsin D resulted in increased necrosis, abrogated autophagy, increased stress-induced metabolism, and increased release of troponin T from human stem cell-derived cardiomyocytes under stress. Conclusions: Circulating cathepsin D levels are associated with HF severity and poorer outcome, and reduced levels of cathepsin D may have detrimental effects with therapeutic potential in HF

Prognostic Significance of Changes in Heart Rate Following Uptitration of Beta-Blockers in Patients with Sub-Optimally Treated Heart Failure with Reduced Ejection Fraction in Sinus Rhythm versus Atrial Fibrillation

Background: In patients with heart failure with reduced ejection fraction (HFrEF) on sub-optimal doses of beta-blockers, it is conceivable that changes in heart rate following treatment intensification might be important regardless of underlying heart rhythm. We aimed to compare the prognostic significance of both achieved heart rate and change in heart rate following beta-blocker uptitration in patients with HFrEF either in sinus rhythm (SR) or atrial fibrillation (AF). Methods: We performed a post hoc analysis of the BIOSTAT-CHF study. We evaluated 1548 patients with HFrEF (mean age 67 years, 35% AF). Median follow-up was 21 months. Patients were evaluated at baseline and at 9 months. The combined primary outcome was all-cause mortality and heart failure hospitalisation stratified by heart rhythm and heart rate at baseline. Results: Despite similar changes in heart rate and beta-blocker dose, a decrease in heart rate at 9 months was associated with reduced incidence of the primary outcome in both SR and AF patients [HR per 10 bpm decrease—SR: 0.83 (0.75–0.91), p &lt; 0.001; AF: 0.89 (0.81–0.98), p = 0.018], whereas the relationship was less strong for achieved heart rate in AF [HR per 10 bpm higher—SR: 1.26 (1.10–1.46), p = 0.001; AF: 1.08 (0.94–1.23), p = 0.18]. Achieved heart rate at 9 months was only prognostically significant in AF patients with high baseline heart rates (p for interaction 0.017 vs. low). Conclusions: Following beta-blocker uptitration, both achieved and change in heart rate were prognostically significant regardless of starting heart rate in SR, however, they were only significant in AF patients with high baseline heart rate

The Clinical Significance of Interleukin-6 in Heart Failure:Results from the BIOSTAT-CHF Study

Aims: Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)‐α were largely unsuccessful. Interleukin (IL)‐6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL‐6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. Methods and results: Interleukin‐6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) ≤ 40%] of the BIOSTAT‐CHF cohort. The primary outcome was all‐cause mortality and HF hospitalization during 2 years, with all‐cause, cardiovascular (CV), and non‐CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL‐6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N‐terminal pro‐brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF‐α/IL‐1‐related biomarkers, or having iron deficiency, atrial fibrillation and LVEF &gt; 40% independently predicted elevated IL‐6 levels. IL‐6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11–1.21), P &lt; 0.001], all‐cause mortality [1.22 (1.16–1.29), P &lt; 0.001] and CV as well as non‐CV mortality [1.16 (1.09–1.24), P &lt; 0.001; 1.31 (1.18–1.45), P &lt; 0.001], but did not improve discrimination in previously published risk models. Conclusions: In a large, heterogeneous cohort of HF patients, elevated IL‐6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL‐6 as a potential therapeutic target in specific HF subpopulations

Identifying Pathophysiological Mechanisms in Heart Failure With Reduced Versus Preserved Ejection Fraction

Background: Information on the pathophysiological differences between heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF) is needed Objectives: The purpose of this study was to establish biological pathways specifically related to HFrEF and HFpEF. Methods: The authors performed a network analysis to identify unique biomarker correlations in HFrEF and HFpEF using 92 biomarkers from different pathophysiological domains in a cohort of 1,544 heart failure (HF) patients. Data were independently validated in 804 patients with HF. Networks were enriched with existing knowledge on protein–protein interactions and translated into biological pathways uniquely related to HFrEF, HF with a midrange ejection fraction, and HFpEF. Results: In the index cohort (mean age 74 years; 34% female), 718 (47%) patients had HFrEF (left ventricular ejection fraction [LVEF] <40%) and 431 (27%) patients had HFpEF (LVEF ≥50%). A total of 8 (12%) correlations were unique for HFrEF and 6 (9%) were unique to HFpEF. Central proteins in HFrEF were N-terminal B-type natriuretic peptide, growth differentiation factor-15, interleukin-1 receptor type 1, and activating transcription factor 2, while central proteins in HFpEF were integrin subunit beta-2 and catenin beta-1. Biological pathways in HFrEF were related to DNA binding transcription factor activity, cellular protein metabolism, and regulation of nitric oxide biosynthesis. Unique pathways in patients with HFpEF were related to cytokine response, extracellular matrix organization, and inflammation. Biological pathways of patients with HF with a midrange ejection fraction were in between HFrEF and HFpEF. Conclusions: Network analysis showed that biomarker profiles specific for HFrEF are related to cellular proliferation and metabolism, whereas biomarker profiles specific for HFpEF are related to inflammation and extracellular matrix reorganization. (The BIOlogy Study to TAilored Treatment in Chronic Heart Failure [BIOSTAT-CHF]; EudraCT 2010-020808-29