Rakesh K. Jain

Bio: Rakesh K. Jain is an academic researcher from Harvard University. The author has contributed to research in topics: Angiogenesis & Vascular endothelial growth factor. The author has an hindex of 200, co-authored 1467 publications receiving 177727 citations. Previous affiliations of Rakesh K. Jain include Government Medical College, Thiruvananthapuram & University of Oslo.

Measuring Vascular Permeability in Mice

Abstract: Noninvasive techniques have been developed for the assessment of vascular parameters, including vascular permeability, in normal and diseased tissues of mice. In this protocol, mice are injected with an appropriate fluorescent tracer. The effective average vascular permeability (P) of a region of vessels is measured by single-photon microscopy. Additionally, the vascular permeability of individual vessel segments within ~600 µm of a tumor/window interface is measured by multiphoton laser-scanning microscopy (MPLSM).

First Report of Occurrence of Papaya ring spot virus Infecting Papaya in Bangladesh

Abstract: Papaya (Carica papaya L.) is an important fruit crop in Bangladesh. During surveys conducted in Dhaka and Mymensingh regions from April to June 2003, >50% of papaya plants were observed to have leaf mottling, mosaic and mild distortion, and water-soaked streaks on petioles and stem, which are typical symptoms of Papaya ring spot virus (PRSV) infection. Electron-microscopic examination of negatively stained leaf-dip preparations from 10 symptomatic samples revealed the association of flexuous virus particles that were decorated with polyclonal antibodies raised to an isolate from India (PRSV-D). The identity of PRSV associated with the papaya disease in Bangladesh was further confirmed by reverse transcription polymerase chain reaction and sequence analysis (2). By using PRSV specific primers (2), the 3'-terminal region comprising a part of the nuclear inclusion b gene, the coat protein (CP) gene, and the untranslated region were amplified and sequenced (GenBank Accession No. AY423557). The CP gene consisted of 286 amino acids and the conserved regions common to the genus Potyvirus, such as WCIEN and QMKAA, were present. Like all known PRSV sequences (1), a stretch of glutamic acid and lysine repeats (EK region) after the aphid transmission motif (DAG) also was present. Comparative CP amino acid sequence analyses revealed that the virus infecting papaya in Bangladesh, designated as PRSV-Bd, shared 89 to 92% identity with PRSV isolates from India and 88 to 93% identity with isolates from other parts of the world. To our knowledge, this is the first report of occurrence of PRSV infecting papaya in Bangladesh. References: (1) M. F. Bateson et al. J. Gen. Virol. 83:2575, 2002. (2) R. K. Jain et al. Ann Appl. Biol. 132:413, 1998.

A Quantitative Analysis of Memantine in Human Plasma Using Ultra Performance Liquid Chromatography/Tandem Mass Spectrometry

Abstract: The aim of this study is to compare the single-dose oral bioavailability of memantine hydrochloride 10 mg tablets of Ranbaxy Laboratories Limited, with NAMENDA™ tablets (containing memantine hydrochloride 10 mg) of Forest Pharmaceuticals Inc. in healthy, adult, human subjects under fasting condition. The study was carried out as 2-way crossover design on 8 subjects in fasting and fed conditions. The plasma samples were obtained over a 72 h post dose in each period. Plasma memantine samples were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with positive ion electro spray ionization using multiple reactions monitoring (MRM). A sensitive, reproducible, accurate and validated LC-MS/MS method with limit of quantification (LOQ) 0.200 ng/mL was used to analyze memantine. Ln transformed AUC0-72 and Cmax were assessed for bioequivalence using 90% confidence interval (CI). 90% confidence intervals for the ratio of test and reference (Ratio of least-squares mean) for ln-transformed AUC0-72 and Cmax were within the regulatory acceptance criteria of 80-125%.

Can plant virus infect human being

Abstract: Numerous viruses infect plant, however, none of them so far is known as pathogen to animal and human beings Only three families, Bunyaviridae, Rhabdoviridae and Reoviridae contain viruses known to infect plant, animal and human Philippe Colson and coworkers from France reported in the recent issue of PLoS ONE that Pepper mild mottle virus (PMMoV), a plant virus might infecting human being [1] The findings trigger to reevaluate the dogmatic concept that plant viruses are safe to human health even though numerous viruses are consumed through various types of fresh foods and food-products Colson et al [1] tested stool samples of 304 adults and 137 children and 21 various food products containing chilli-pepper (Sauce, spicy powder ect) for the presence of PMMoV using real-time PCR, sequencing, and electron microscopy PMMoV was detected in 57% of food products, 72% of stool samples of adults and 07% of children Viral RNA sequence was recovered, virus particles were visualized and the virus present in food product was viable as it infected the host plants In the case-control study, fever, abdominal pains and pruritus were found significantly common in the patients detected with PMMoV Anti-PMMoV IgM antibodies were detected in all PMMoV positive patients indicating specific immune response to PMMoV Based on these findings, Colson et al [1] concluded that PMMoV might infect humans and cause clinical symptoms PMMoV, a rod-shaped non-envelop positive sense ssRNA virus belongs to the genus Tobamovirus and commonly infects chilli-pepper The members under the genus Tobamovirus are highly stable, contagious and require no specific insect-vector for transmission from one host to another host Tobacco mosaic virus, the type species of the genus Tobamovirus, is well known for its stability in dead tissues of tobacco (cigarette) and also in sputum and thoracentesis fluids of cigarette smokers [5] PMMoV has been shown widespread in wastewater in USA [6] Cucumber green mottle mosaic virus, another tobamovirus was detected in the water of Yamuna river in India and the recovered virus from water was infectious on several host plants [7] Several of such examples show that tobamoviruses are highly stable outside living host-cell Therefore, presence of biologically active PMMoV in food products and human stools are not surprising Prior to the work of Colson et al [1], PMMoV was shown as the major RNA virus in human stool by Zhang et al [8] The interesting observation of Colson et al is that PMMoV is not a mere gut-inhabitant flora in human being, it interacts with the immune system and generates anti-PMMoV IgM antibody Furthermore, PMMoV positive patients were correlated with specific clinical symptoms Although, as they also have pointed out, the symptoms like abdominal pain and fever may be due to spicy food Plant viruses, such as tospovirus, rhabdovirus, reovirus, begomovirus and nanovirus are expected to have some linkage beyond their plant-hosts to insect and animal hosts Tospoviruses, enveloped negative stranded ssRNA plant viruses, are worldwide distributed infecting numerous plants including a wide variety of freshly consumed vegetables, such as tomato, chilli-pepper, lettuce, onion, watermelon, muskmelon etc Tomato spotted wilt virus, the type species of the genus Tospovirus is known to replicate in insect-vector, thrips and in two human cell lines [3] Groundnut bud necrosis virus, one of the commonly occurring tospovirus in India, could be transmitted to tobacco plant from tissues of a ripen tomato fruit (unpublished results) (Fig 1) This means live tospoviruses are consumed while eating fresh salad To our opinion, tospoviruses are one group of plant viruses that may have potential for host-switching to human or higher animal Tomato yellow leaf curl virus, a begomovirus (ssDNA virus) affects tomato cultivation in several countries in the world is known to reduce the lifespan and fecundity of its insect-vector, Bemisia tabaci, and the virus is transmitted to the next generation through eggs of B tabaci Viruses undergo alteration to inhabit in a new niche Vertebrate-infecting ssDNA viruses, circoviruses are of such example, which have evolved from plant-infecting nanoviruses though host-switching event and then recombination with vertebrate-infecting virus [4] Recently, Dangre et al [2] predicted major histocompatibility complex (MHC) binding affinity of coat proteins from five species under the genus Nanovirus The MHC molecules are cell surface glycoproteins, which play an important role in the host immune system, autoimmunity and reproductive success The presence of MHC binding peptide in nanovirus prompted Dangre et al to forecast that man might be the future host of nanovirus Fig 1 Tomato fruit showing symptoms (rings and uneven ripening indicated by arrows) (a) of Groundnut bud necrosis virus (b) Plant based food and water are obvious route through plant viruses can get access to human body The other possible route of access of plant virus directly to human cells is through insects that feed on both plant and human The insect may be vector, host or both for a virus Mosquito is one possible insect that feed on both plant and human and is a carrier of viruses under the plant and human viruses containing families, Bunyaviridae, Rhabdoviridae and Reoviridae To establish plant virus as human pathogen, evidence of its entry into cell, replication therein and finally fulfillment of Koch’s postulation is necessary However, there is no rigid rule that plant virus can not break the barrier of their host kingdom and invade human or animal It is possible that some plant virus may have direct or indirect role as human pathogen, but at this moment, no such study is available to consider plant virus as human pathogen

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

Abstract: background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy. methods Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life. results The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progressionfree survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed. conclusions The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.