3D-QSAR studies on natural acetylcholinesterase inhibitors of Sarcococca saligna by comparative molecular field analysis (CoMFA)

We have derived a comprehensive structure–activity relationship (SAR) picture for a new series of natural acetylcholinesterase inhibitors isolated from Sarcococca saligna. A set of 32 previously isolated and tested pregnane-type steroidal alkaloids inhibitors were investigated with respect to their IC₅₀ values (pIC₅₀) against the AChE enzyme in order to derive CoMFA models using atom-based alignment. A highly significant CoMFA model was obtained with r² value of 0.974. The q² (cross validation r²) value also confirms the statistical significance of our model.     

Burden of Visceral Leishmaniasis in Villages of Eastern Gedaref State, Sudan: An Exhaustive Cross-Sectional Survey

Background

Since December 2009, Médecins Sans Frontières has diagnosed and treated patients with visceral leishmaniasis (VL) in Tabarak Allah Hospital, eastern Gedaref State, one of the main endemic foci of VL in Sudan. A survey was conducted to estimate the VL incidence in villages around Tabarak Allah.

Methods

Between the 5^th of May and the 17^th of June 2011, we conducted an exhaustive door-to-door survey in 45 villages of Al-Gureisha locality. Deaths were investigated by verbal autopsies. All individuals with (i) fever of at least two weeks, (ii) VL diagnosed and treated in the previous year, and (iii) clinical suspicion of post-kala-azar dermal leishmaniasis (PKDL) were referred to medical teams for case ascertainment. A new case of VL was a clinical suspect with a positive rk39 rapid test or direct agglutination test (DAT).

Results

In the 45 villages screened, 17,702 households were interviewed, for a population of 94,369 inhabitants. The crude mortality rate over the mean recall period of 409 days was 0.13/10''000 people per day. VL was a possible or probable cause for 19% of all deaths. The VL-specific mortality rate was estimated at 0.9/1000 per year.The medical teams examined 551 individuals referred for a history of fever of at least two weeks. Out of these, 16 were diagnosed with primary VL. The overall incidence of VL over the past year was 7.0/1000 persons per year, or 7.9/1000 per year when deaths possibly or probably due to VL were included. Overall, 12.5% (11,943/95,609) of the population reported a past VL treatment episode.

Discussion and Conclusion

VL represents a significant health burden in eastern Gedaref State. Active VL case detection had a very low yield in this specific setting with adequate access to care and may not be the priority intervention to enhance control in similar contexts.     

Cyclic AMP-dependent protein kinase regulates 9G8-mediated alternative splicing of tau exon 10

Alternative splicing of tau exon 10 generates tau isoforms with three or four microtubule-binding repeats, named 3R- or 4R-tau. Normal adult human brain expresses equal levels of them. Imbalance of 3R-tau and 4R-tau associates with several tauopathies. Splicing factor 9G8 suppresses tau exon 10 inclusion and its function is regulated by phosphorylation. Here, we found that cyclic AMP-dependent protein kinase (PKA) phosphorylated 9G8. The catalytic subunits α and β of PKA interacted with 9G8, and activation of PKA enhanced the interaction. Up-regulation of PKA activity prevented 9G8 from inhibition of tau exon 10 inclusion. These findings provide novel insights into the regulation of tau exon 10 splicing and further our understanding of neurodegeneration associated with dysregulation of tau exon 10 splicing.     

Molecular detection of Colletotrichum falcatum causing red rot disease of sugarcane (Saccharum officinarum) using a SCAR marker

Red rot disease of sugarcane caused by Colletotrichum falcatum is one of the most destructive diseases of sugarcane (Saccharum officinarum) worldwide. The pathogen spreads primarily through infected sugarcane setts and hence the use of disease‐free planting materials is essential for preventing disease development in the field. In the present study a polymerase chain reaction (PCR) assay was developed for accurate and sensitive detection of C. falcatum in planting materials. Randomly amplified polymorphic DNA (RAPD) analysis identified a 566 bp PCR fragment that was specific to C. falcatum. The DNA sequence of this fragment was determined and used to design oligonucleotides amplifying a 442 bp sequence characterised amplified region (SCAR). The specificity of the SCAR primers was evaluated using purified DNA from C. falcatum and other Colletotrichum spp. as templates in PCR. The results indicated that the SCAR primers were highly specific to C. falcatum since the 442 bp fragment was amplified only from DNA of isolates and races of C. falcatum but not from any other Colletotrichum spp. tested. The detection sensitivity of C. falcatum was 0.1 ng for genomic DNA of C. falcatum and 5 ng for DNA extracted from infected sugarcane tissue. This new PCR‐based assay is a convenient tool for detection of this important pathogen in seed canes to ensure production of sugarcane.     

Clinical Picture Of Arrhythmogenic Right Ventricular Dysplasia / Cardiomyopathy Patients From Indian Origin

Objective

Among the inherited cardiomyopathies, Arrhythmogenic right ventricular dysplasia/cardiomyopathy is unique with a peculiar pathology of fibro-fatty replacement. Studies have been carried out all over the world and several groups have reported clinical heterogeneity in manifestation of ARVD/C related symptoms. Present study is an attempt to identify the clinical profile of ARVD/C patients from Asian Indian origin.

Methods

31 patients in the span of three years were diagnosed with ARVD/C. Diagnosis was based on proposed task force criteria.

Results

The mean age at diagnosis was 32.9 ± 16.4 years with slight tilt in male to female ratio (1.46). About 80% cases had palpitations, syncope in 45.16% and dyspnea in 22.5%, whereas 16% of patients were asymptomatic. About 50% of patients revealed a family history of confirmed ARVD/C or sudden death of a family member without any known cause. ECG showed T-wave inversion in about 60% cases, prolongation of QRS was observed in 20% cases. RV dilatation was observed in 80% of patients and 66.7% showed systolic dysfunction. RV free wall motion abnormalities were found in 33% patients. Most of the early onset cases with less than 30 years of age showed family history indicative of ARVD/C. Familial study in three patients indicated early onset of condition in younger generations in two families.

Conclusions

ARVD/C in India shows relatively early age at onset when compared with other Asian populations with more than half of patients showing the disease below the age of 30 years. History in most of the early onset cases revealed family history indicating strong genetic influence.     

Population energy use scales positively with body size in natural aquatic microcosms

Aim  We test the 'energetic equivalence rule' (EER) – the idea that the amount of energy used by a population per unit area per unit time is independent of body mass – in meio-invertebrate communities from a series of natural, multitrophic aquatic 'rock pool' microcosms. Our study represents the first rigorous test of the EER at local scales of observation in a community of naturally coexisting species.
Location  Discovery Bay, Jamaica.
Method  We estimated population energy use (PEU) for every occurrence of every species of meio-invertebrate fauna found in each of 29 microcosms (233 observations of 31 species) using estimates of population density obtained in January 2005 in combination with published metabolism–mass relations for closely related taxa.
Results  In the rock pool system as a whole, population density decreased ( ancova : b  = –0.38 (–0.55 to –0.19), r ² = 0.19, P  < 0.001) and PEU increased with body mass ( ancova : b  = 0.55 (0.36–0.73), r ² = 0.28, P  < 0.001).
Main conclusions  The positive PEU–body mass relation found here suggests that larger organisms are energetically dominant and points to the importance of size-structured competition in these systems. Our results contrast those obtained in the few other previously published tests of the EER and challenge the idea that all species use similar amounts of energy regardless of their size.     

Prolactin enhances production of interferon-gamma,interleukin-12, and interleukin-10, but not of tumor necrosis factor-alpha,in a stimulus-specific manner

Prolactin, an anterior pituitary hormone, has been shown to have a role in immunomodulation. Some reports have shown the importance of prolactin in activating lymphocytes and macrophages, while in hyperprolactinemia patients, prolactin was found to decrease lymphocyte activation and natural killer function. In the present work, at physiological (15ng/ml) and stress-induced levels (30ng/ml) of prolactin, interferon-gamma (IFN-gamma) and interleukin (IL)-12 p70 levels, but not of IL-10 and tumor necrosis factor-alpha (TNF-alpha), increased significantly (p<0.05-0.006) in phytohemeagglutinin (PHA)+lipopolysaccharide (LPS)-stimulated whole blood. However, no such effect was observed at high concentrations of prolactin (100-300ng/ml). In addition, 15ng/ml of prolactin reversed hydrocortisone suppressive effect on IFN-gamma, IL-12 p70, and IL-10 production in PHA+LPS-stimulated whole blood. On the other hand, in LPS-stimulated whole blood, prolactin enhanced significantly (p=0.027) the production levels of IL-10, but not of IFN-gamma, IL-12 p70, and TNF-alpha, in non-concentration-dependent manner. These results suggest that prolactin modulates cytokine response during antigenic response, and this modulation is stimulus specific.     

A divide-and-conquer approach to fragment assembly

MOTIVATION: One of the major problems in DNA sequencing is assembling the fragments obtained by shotgun sequencing. Most existing fragment assembly techniques follow the overlap-layout-consensus approach. This framework requires extensive computation in each phase and becomes inefficient with increasing number of fragments. RESULTS: We propose a new algorithm which solves the overlap, layout, and consensus phases simultaneously. The fragments are clustered with respect to their Average Mutual Information (AMI) profiles using the k-means algorithm. This removes the unnecessary burden of considering the collection of fragments as a whole. Instead, the orientation and overlap detection are solved efficiently, within the clusters. The algorithm has successfully reconstructed both artificial and real data. Availability: Available on request from the authors.