A protein phosphorylation/dephosphorylation network regulates a plant potassium channel

Potassium (K(+)) is an essential nutrient for plant growth and development. Plants often adapt to low K(+) conditions by increasing their K(+) uptake capability. Recent studies have led to the identification of a calcium signaling pathway that enables plants to act in this capacity. Calcium is linked to two calcineurin B-like calcium sensors (CBLs) and a target kinase (CBL-interacting protein kinase 23 or CIPK23) that, in turn, appears to phosphorylate and activate the potassium channel, Arabidopsis K(+) transporter 1 (AKT1), responsible for K(+) uptake in roots. Here, we report evidence that this regulatory mechanism is more elaborate than earlier envisaged. The recently described pathway is part of an extensive network whereby several CBLs interact with multiple CIPKs in the activation of the potassium channel, AKT1. The physical interactions among the CBL, CIPK, and AKT1 components provide a mechanism for specifying the members of the CBL and CIPK families functional in AKT1 regulation. The interaction between the CIPKs and AKT1 was found to involve the kinase domain of the CIPK component and the ankyrin repeat domain of the channel. Furthermore, we identified a 2C-type protein phosphatase that physically interacts and inactivates the AKT1 channel. These findings provide evidence that the calcium-sensitive CBL and CIPK families together with 2C-type protein phosphatases form a protein phoshporylation/dephosphorylation network that regulates the AKT1 channel for K(+) transport in plants.     

Distress overlaps with anxiety and depression in patients with head and neck cancer

Psychological problems in cancer patients often go unrecognized until they are specifically sought. This is more in patients with depression as they are reluctant to complain about their symptoms. The present study was carried out to evaluate the relation of distress with anxiety and depression in 123 patients with head and neck cancers using Distress Inventory for Cancer version 2 (DIC2) and the Hospital Anxiety and Depression scale (HADS). The mean DIC 2 scores were 24.6 while that of subscales ranged from 2.6 to 11.0. Fifteen patients were found to have clinical caseness for anxiety while 12 (10%) were caseness for depression. Total distress, emotional and social distress subscales were found to have positive correlation with anxiety and depression suggesting a possible overlap of two constructs. In multivariate analysis only belief in god was found to significantly affect the distress. Results of present study suggest significant psychological morbidity in head neck cancer patients undergoing curative treatment. This is the first study reporting on the psychometric properties of distress inventory on cancer version 2 since its validation, the results suggest a possible overlap of two constructs similar to that seen with other tools on distress and this may have major implications for clinical practice.     

Slow acetylator genotype of N-acetyl transferase2 (NAT2) is associated with increased susceptibility to gallbladder cancer: the cancer risk not modulated by gallstone disease

This study comprised 124 consecutive cases of proven GBC and 147 healthy controls. NAT2 polymorphisms were carried out using PCR-RFLP method. The NAT2 slow acetylator genotype was significantly associated with risk of GBC (OR 3.4, 95% CI =1.9-5.7 p = 0.000007). The NAT2 2*6 and 2*7 allele frequencies were higher in GBC and conferred significant risk of cancer (OR 1.9, 95% Cl = 1.2-2.9, p= 0.006; OR, 2.9, 95% Cl = 1.6-5.2, p = 0.0001). The haplotypes 2, 1, 1 and 1, 2, 1 were significantly higher (OR 3.7 95% Cl 2.1-7.0, p = 0.00001; OR 1.8 95% Cl =1.1-2.8, p = 0.008) in GBC. The risk of slow acetylator phenotype in GBC patients with or without gallstones was similar. These results suggest that NAT2 slow acetylator phenotype influences the susceptibility of gallbladder cancer and the risk is not modulated by gallstone disease.     

Rac1-mediated signaling plays a central role in secretion-dependent platelet aggregation in human blood stimulated by atherosclerotic plaque

Background  

Platelet activation requires rapid remodeling of the actin cytoskeleton which is regulated by small GTP-binding proteins. By using the Rac1-specific inhibitor NSC23766, we have recently found that Rac1 is a central component of a signaling pathway that regulates dephosphorylation and activation of the actin-dynamising protein cofilin, dense and α-granule secretion, and subsequent aggregation of thrombin-stimulated washed platelets.     

Lipoprotein receptor associated protein (LRPAP1) insertion/deletion polymorphism: association with gallbladder cancer susceptibility

Background Low-density lipoprotein receptor-related protein associated protein (LRPAP1) insertion/deletion polymorphism influences cholesterol homeostasis and may confer risk for gallstone disease and gallbladder carcinoma (GBC) incidence usually parallels with the prevalence of cholelithiosis. Aim We aimed to examine the role of LRPAP1 polymorphism in susceptibility to GBC. Methods Present case control study included 129 proven GBC patients, 183 gallstone patients, and 208 healthy controls. Genotyping was done by polymerase chain reaction–restriction fragment length polymorphism method. Results The D allele of LRPAP1 was significantly higher in GBC patients as compared to gallstone patients (p = 0.013; OR = 1.6, 95% CI = 1.1–2.4). However, II genotype and I allele was associated with reduced risk of GBC as compared to gallstone patients (p = 0.002; OR = 0.1, 95% CI = 0.1–0.6; p = 0.013; OR = 0.6, 95% CI = 0.4–0.8) The increased risk due to D allele was limited to female GBC patients (p = 0.021; OR = 1.8, 95% CI = 1.1–3.0). However, reduced risk due to II genotype and I allele was observed which was also confined to female GBC patients (p = 0.005; OR = 0.1, 95% CI = 0.1–0.6; p = 0.021; OR = 0.5, 95% CI = 0.3–0.8). On comparing GBC patients having gallstone with gallstone patients, high risk was observed in the GBC patients having gallstone due to the presence of D allele (p = 0.032; OR = 1.7, 95% CI = 1.0–2.8). However, low risk was observed because of I allele in GBC patients with gallstone in comparison to gallstone patients (p = 0.032, OR = 0.6, 95% CI = 0.4–0.9). Conclusion It appears that ‘D’ allele may modulate the susceptibility of GBC, and the risk is independent to genetic risk of gallstone.     

Antibodies to human cytomegalovirus protein UL83 in systemic sclerosis

OBJECTIVE: To determine whether elevated levels of antibodies to HCMV protein UL83 were present in patients with SSc and if their prevalence was associated with major SSc-associated autoantibodies. METHODS: The study population consisted of 253 Caucasian subjects (110 SSc patients and 143 controls). IgG antibodies to UL83 were measured by an enzyme-linked immunosorbent assay (ELISA). Antibodies to centromere and RNA polymerase (RNAP) were determined by indirect immunofluorescence and immnoprecipitation methods, respectively. RESULTS: The mean level of anti-UL83 antibodies in the sera of SSc patients as a whole was significantly higher than that in control subjects (14.75 vs 10.6 units/microl, p = 0.002). Both subgroups of patients contributed to this variation: compared to controls, anti-UL83 antibody levels were higher in diffuse (16.32 vs 10.6 units/microl, p = 0.012) as well as in those with the limited form of the disease (13.95 vs 10.6 units/microl, p = 0.015). Anti-UL83 antibodies were not associated with major SSc associated autoantibodies. CONCLUSION :Humoral immunity to HCMV protein UL83 may be relevant to the etiopathogenesis of scleroderma.     

Demonstration of interstitial cerebral edema with diffusion tensor MR imaging in type C hepatic encephalopathy

Brain water may increase in hepatic encephalopathy (HE). Diffusion tensor imaging was performed in patients with cirrhosis with or without HE to quantify the changes in brain water diffusivity and to correlate it with neuropsychological (NP) tests. Thirty-nine patients with cirrhosis, with minimal (MHE) or overt HE, were studied and compared to 18 controls. Mean diffusivity (MD) and fractional anisotropy (FA) were calculated in corpus callosum, internal capsule, deep gray matter nuclei, periventricular frontal, and occipital white matter regions in both cerebral hemispheres. The MD and FA values from different regions in different groups were compared using analysis of variance and Spearman's rank correlation test. In 10 patients with MHE, repeat studies were performed after 3 weeks of lactulose therapy to look for any change in MD, FA, and NP scores. Significantly increased MD was found with insignificant changes in FA in various regions of brain in patients with MHE or HE compared with controls, indicating an increase in interstitial water in the brain parenchyma without any microstructural changes. A significant correlation was found between MD values from corpus callosum, internal capsule, and NP test scores. After therapy, MD values decreased significantly and there was a corresponding improvement in NP test scores. Further analysis showed that MD values were different for different grades of minimal or overt HE. In conclusion, the increase in MD with no concomitant changes in FA in cirrhosis with minimal or early HE indicates the presence of reversible interstitial brain edema.     

Identification of insulin resistance in Asian Indian adolescents: classification and regression tree (CART) and logistic regression based classification rules

Objective Biochemical measures for assessment of insulin resistance are not cost‐effective in resource‐constrained developing countries. Using classification and regression tree (CART) and multivariate logistic regression, we aimed to develop simple predictive decision models based on routine clinical and biochemical parameters to predict insulin resistance in apparently healthy Asian Indian adolescents. Design Community based cross‐sectional study. Subjects and patients Data of apparently healthy 793 adolescents (aged 14–19 years) were used for analysis. WHO's multistage cluster sampling design was used for data collection. Methods and measurements Homeostasis Model of Assessment value > 75th centile was used as cut‐off for defining the main outcome variable insulin resistance. CART was used to develop the decision tree models and multivariate logistic regression used to develop the clinical prediction score. Results Three classification trees and an equation for prediction score were developed and internally validated. The three decision trees were termed as CART I, CART II and CART III, respectively. CART I based on anthropometric parameters alone has sensitivity 88·2%, specificity 50·1% and area under receiver operating characteristic curve (aROC) 77·8%. CART II based on anthropometric and routine biochemical parameters has sensitivity 94·5%, specificity 38·3% and aROC 73·6%. CART III based on all anthropometric, biochemical and clinical parameters together has sensitivity 70·7%, specificity 79·2% and aROC 77·4%. Prediction score for insulin resistance = 1 × (waist circumference) + 1·1 × (percentage body fat) + 1·6 × (triceps skin‐fold thickness) – 1·9 × (gender). A score cut‐off of > 0 (using values marked for each) was a marker of insulin resistance in the study population (sensitivity 82·4%, specificity 56·7%, and aROC 73·4%). Conclusion These simple and cost‐effective classification rules may be used to predict insulin resistance and implement population based preventive interventions in Asian Indian adolescents.     

Hippocampal cell proliferation regulation by repeated stress and antidepressants

A recent hypothesis suggests reduced hippocampal neurogenesis in depression. Here, we examined cell proliferation in the dentate gyrus and the subventricular zone of rats given repeated stress, a paradigm that prolongs learned helplessness behavior, and whether antidepressants modulate the learned helplessness-associated altered cell proliferation. Decreased cell proliferation, number of clusters, and cells/cluster were noted in the dentate gyrus, but not in the subventricular zone, of learned helplessness rats. Both fluoxetine and desipramine reversed the learned helplessness behavior and increased the cell proliferation and the number of clusters in learned helplessness rats; only fluoxetine did so significantly. Both fluoxetine and desipramine significantly increased the number of cells/cluster. Our results suggest modified hippocampal neurogenesis in prolonged depression and in the mechanism of antidepressant action.