Response properties of visual neurons in the turtle nucleus isthmi

The optic tectum holds a central position in the tectofugal pathway of non-mammalian species and is reciprocally connected with the nucleus isthmi. Here, we recorded from individual nucleus isthmi pars parvocellularis (Ipc) neurons in the turtle eye-attached whole-brain preparation in response to a range of computer-generated visual stimuli. Ipc neurons responded to a variety of moving or flashing stimuli as long as those stimuli were small. When mapped with a moving spot, the excitatory receptive field was of circular Gaussian shape with an average half-width of less than 3°. We found no evidence for directional sensitivity. For moving spots of varying sizes, the measured Ipc response-size profile was reproduced by the linear Difference-of-Gaussian model, which is consistent with the superposition of a narrow excitatory center and an inhibitory surround. Intracellular Ipc recordings revealed a strong inhibitory connection from the nucleus isthmi pars magnocellularis (Imc), which has the anatomical feature to provide a broad inhibitory projection. The recorded Ipc response properties, together with the modulatory role of the Ipc in tectal visual processing, suggest that the columns of Ipc axon terminals in turtle optic tectum bias tectal visual responses to small dark changing features in visual scenes.     

Affinity maturation to improve human monoclonal antibody neutralization potency and breadth against hepatitis C virus

A potent neutralizing antibody to a conserved hepatitis C virus (HCV) epitope might overcome its extreme variability, allowing immunotherapy. The human monoclonal antibody HC-1 recognizes a conformational epitope on the HCV E2 glycoprotein. Previous studies showed that HC-1 neutralizes most HCV genotypes but has modest potency. To improve neutralization, we affinity-matured HC-1 by constructing a library of yeast-displayed HC-1 single chain Fv (scFv) mutants, using for selection an E2 antigen from one of the poorly neutralized HCVpp. We developed an approach by parallel mutagenesis of the heavy chain variable (VH) and κ-chain variable (Vk) genes separately, then combining the optimized VH and Vk mutants. This resulted in the generation of HC-1-related scFv variants exhibiting improved affinities. The best scFv variant had a 92-fold improved affinity. After conversion to IgG1, some of the antibodies exhibited a 30-fold improvement in neutralization activity. Both surface plasmon resonance and solution kinetic exclusion analysis showed that the increase in affinity was largely due to a lowering of the dissociation rate constant, Koff. Neutralization against a panel of HCV pseudoparticles and infectious 2a HCV virus improved with the affinity-matured IgG1 antibodies. Interestingly, some of these antibodies neutralized a viral isolate that was not neutralized by wild-type HC-1. Moreover, propagating 2a HCVcc under the selective pressure of WT HC-1 or affinity-matured HC-1 antibodies yielded no viral escape mutants and, with the affinity-matured IgG1, needed 100-fold less antibody to achieve complete virus elimination. Taken together, these findings suggest that affinity-matured HC-1 antibodies are excellent candidates for therapeutic development.     

Origin of the Koreans: a population genetic study.

A population genetic study was undertaken to investigate the origin of Koreans. Thirteen polymorphic and 7 monomorphic blood genetic markers (serum proteins and red cell enzymes) were studied in a group of 437 Koreans. Genetic distance analyses by both cluster and principal components models were performed between Koreans and eight other populations (Koreans in China, Japanese, Han Chinese, Mongolians, Zhuangs, Malays, Javanese, and Soviet Asians) on the basis of 47 alleles controlled by 15 polymorphic loci. A more detailed analysis using 65 alleles at 19 polymorphic loci was performed on six populations. Both analyses demonstrated genetic evidence of the origin of Koreans from the central Asian Mongolians. Further, the Koreans are more closely related to the Japanese and quite distant from the Chinese. The above evidence of the origin of Koreans fits well with the ethnohistoric account of the origin of Koreans and the Korean language. The minority Koreans in China also maintained their genetic identity.     

Impact of rapid urbanization on the rates of infection by Vibrio cholerae O1 and enterotoxigenic Escherichia coli in Dhaka, Bangladesh

Background

In Bangladesh, increases in cholera epidemics are being documented with a greater incidence and severity. The aim of this prospective study was to identify the prevalence and importance of V. cholerae O1 and enterotoxigenic Escherichia coli (ETEC) as causal agents of severe diarrhea in a high diarrhea prone urban area in Dhaka city.

Methodology

Systematic surveillance was carried out on all diarrheal patients admitted from Mirpur between March 2008 to February 2010 at the ICDDR, B hospital. Stool or rectal swabs were collected from every third diarrheal patient for microbiological evaluation.

Principal Findings

Of diarrheal patients attending the hospital from Mirpur, 41% suffered from severe dehydration with 39% requiring intravenous rehydration therapy. More diarrheal patients were above five years of age (64%) than those below five years of age (36%). About 60% of the patients above five years of age had severe dehydration compared with only 9% of patients under five years of age. The most prevalent pathogen isolated was Vibrio cholerae O1 (23%) followed by ETEC (11%). About 8% of cholera infection was seen in infants with the youngest children being one month of age while in the case of ETEC the rate was 11%. Of the isolated ETEC strains, the enterotoxin type were almost equally distributed; ST accounted for 31% of strains; LT/ST for 38% and LT for 31%.

Conclusion

V. cholerae O1 is the major bacterial pathogen and a cause of severe cholera disease in 23% of patients from Mirpur. This represents a socioeconomic group that best reflects the major areas of high cholera burden in the country. Vaccines that can target such high risk groups in the country and the region will hopefully be able to reduce the disease morbidity and the transmission of pathogens that impact the life and health of people.     

HIV and tuberculosis in India

The global impact of the converging dual epidemics of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major public health challenges of our time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common opportunistic infection in HIV-infected patients as well as the leading cause of death. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. The diagnosis of TB is based on sputum smear microscopy, a 100-year old technique and chest radiography, which has problems of specificity. Extra-pulmonary, disseminated and sputum smear negative manifestations are more common in patients with advanced immunosuppression. Newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-poor settings. Treatment of HIV-TB co-infection is complex and associated with high pill burden, overlapping drug toxicities, risk of immune reconstitution inflammatory syndrome (IRIS) and challenges related to adherence. From a programmatic point of view, screening of all HIV-infected persons for tuberculosis and vice-versa will help identify co-infected patients who require treatment for both infections. This requires good coordination and communication between the TB and AIDS control programs, in India.     

Efficient algorithms for polyploid haplotype phasing

Background

Inference of haplotypes, or the sequence of alleles along the same chromosomes, is a fundamental problem in genetics and is a key component for many analyses including admixture mapping, identifying regions of identity by descent and imputation. Haplotype phasing based on sequencing reads has attracted lots of attentions. Diploid haplotype phasing where the two haplotypes are complimentary have been studied extensively. In this work, we focused on Polyploid haplotype phasing where we aim to phase more than two haplotypes at the same time from sequencing data. The problem is much more complicated as the search space becomes much larger and the haplotypes do not need to be complimentary any more.

Results

We proposed two algorithms, (1) Poly-Harsh, a Gibbs Sampling based algorithm which alternatively samples haplotypes and the read assignments to minimize the mismatches between the reads and the phased haplotypes, (2) An efficient algorithm to concatenate haplotype blocks into contiguous haplotypes.

Conclusions

Our experiments showed that our method is able to improve the quality of the phased haplotypes over the state-of-the-art methods. To our knowledge, our algorithm for haplotype blocks concatenation is the first algorithm that leverages the shared information across multiple individuals to construct contiguous haplotypes. Our experiments showed that it is both efficient and effective.

     

An annotated checklist of Culicoides Latreille, 1809 (Insecta: Ceratopogonidae: Diptera) with incorporation of a vector species list from India

Culicoides Latreille, 1809 (Insecta : Diptera : Ceratopogonidae) are small nematocerous biological vectors of a wide range of pathogens of veterinary and medical importance. They are distributed worldwide but prefer warm, damp, and muddy areas. Female midges require blood for egg maturation. Studies on taxonomy, proper identification keys, and distribution patterns of these flies across different geographical regions of India of these flies are limited. This article provides an updated checklist of Culicoides spp. from India collected from various scattered publications, along with their synonyms and details on their subgenera, geographical distribution, and type locality. A compiled list of different Culicoides vectors from India has also been included separately in this article, along with the type of the diseases spread.     

Purification and characterization of a motility initiating protein from caprine epididymal plasma

Numerous reports have appeared on the occurrence of undefined protein factors in male reproductive fluids that promote motility of mature sperm and initiate forward motility in the immature (immotile) caput‐epididymal sperm. This study reports for the first time purification to apparent homogeneity of a motility initiating protein (MIP) from epididymal plasma and its characterization using the caprine sperm model. It is a 125 kDa (approximately) dimeric protein made up of two subunits: 70 and 54 kDa. MIP is an acidic protein with an isoelectric point of 4.75. The motility protein at 30 µg/ml (240 nM) level showed nearly maximal motility‐promoting activity. MIP is heat stable and it is maximally active at pH 8. It is a glycoprotein that binds with high affinity to concanavalin A and it contains mannose, galactose, and N‐acetyl glucosamine approximately in the ratios of 6:1:6. It is sensitive to the actions of α‐mannosidase and β‐N‐acetylglucoseaminidase thereby demonstrating that the sugar side chain of the glycoprotein is essential for its biological activity. Epididymal plasma is its richest source. It is also capable of enhancing forward motility of mature cauda‐sperm. Its antibody markedly inhibits sperm motility. MIP antibody is highly immunospecific and it recognizes both the subunits. MIP causes significant increase of the intrasperm level of cyclic AMP. MIP: the physiological motility‐activating protein has potential for use as a contraceptive vaccine and for solving some of the problems of human infertility and animal breeding. J. Cell. Physiol. 222:254–263, 2010. © 2009 Wiley‐Liss, Inc.