Herbal Remedies for Combating Irradiation: a Green Antiirradiation Approach

Plants play important roles in human life not only as suppliers of oxygen but also as a fundamental resource to sustain the human race on this earthly plane. Plants also play a major role in our nutrition by converting energy from the sun during photosynthesis. In addition, plants have been used extensively in traditional medicine since time immemorial. Information in the biomedical literature has indicated that many natural herbs have been investigated for their efficacy against lethal irradiation. Pharmacological studies by various groups of investigators have shown that natural herbs possess significant radioprotective activity. In view of the immense medicinal importance of natural product based radioprotective agents, this review aims at compiling all currently available information on radioprotective agents from medicinal plants and herbs, especially the evaluation methods and mechanisms of action. In this review we particularly emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action and toxicology. We also describe modern techniques for evaluating herbal samples as radioprotective agents. The usage of herbal remedies for combating lethal irradiation is a green antiirradiation approach for the betterment of human beings without high cost, side effects and toxicity

Rate of Convergence Towards Hartree Dynamics

We consider a system of N bosons interacting through a two-body potential with, possibly, Coulomb-type singularities. We show that the difference between the many-body Schr\"odinger evolution in the mean-field regime and the effective nonlinear Hartree dynamics is at most of the order 1/N, for any fixed time. The N-dependence of the bound is optimal.Comment: 26 page

Can computers be teammates?

This study investigated the claim that humans will readily form team relationships with computers . Drawing from the group dynamic literature in human -human interactions , a laboratory experiment ( n ϭ 56) manipulated identity and interdependence to create team af filiation in a human -computer interaction . The data show that subjects who are told they are interdependent with the computer af filiate with the computer as a team . The data also show that the ef fects of being in a team with a computer are the same as the ef fects of being in a team with another human : subjects in the interdependence conditions perceived the computer to be more similar to themselves , saw themselves as more cooperative , were more open to influence from the computer , thought the information from the computer was of higher quality , found the information from the computer friendlier , and conformed more to the computer's information . Subjects in the identity conditions showed neither team af filiation nor the ef fects of team af filiation

Accuracy and User-Acceptability of HIV Self-Testing Using an Oral Fluid-Based HIV Rapid Test

10.1371/journal.pone.0045168PLoS ONE79

A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression

Pancreatic ductal adenocarcinoma (PDAC) develops a pronounced stromal response reflecting an aberrant wound-healing process. This stromal reaction features transdifferentiation of tissue-resident pancreatic stellate cells (PSC) into activated cancer-associated fibroblasts, a process induced by PDAC cells but of unclear significance for PDAC progression. Here, we show that PSCs undergo a dramatic lipid metabolic shift during differentiation in the context of pancreatic tumorigenesis, including remodeling of the intracellular lipidome and secretion of abundant lipids in the activated, fibroblastic state. Specifically, stroma-derived lysophosphatidylcholines support PDAC cell synthesis of phosphatidylcholines, key components of cell membranes, and also facilitate production of the potent wound-healing mediator lysophosphatidic acid (LPA) by the extracellular enzyme autotaxin, which is overexpressed in PDAC. The autotaxin–LPA axis promotes PDAC cell proliferation, migration, and AKT activation, and genetic or pharmacologic autotaxin inhibition suppresses PDAC growth in vivo. Our work demonstrates how PDAC cells exploit the local production of wound-healing mediators to stimulate their own growth and migration. Significance: Our work highlights an unanticipated role for PSCs in producing the oncogenic LPA signaling lipid and demonstrates how PDAC tumor cells co-opt the release of wound-healing mediators by neighboring PSCs to promote their own proliferation and migration

Cyclic Tetrapyrrolic Photosensitisers from the leaves of Phaeanthus ophthalmicus

<p>Abstract</p> <p>Background</p> <p>Twenty-seven extracts from 26 plants were identified as photo-cytotoxic in the course of our bioassay guided screening program for photosensitisers from 128 extracts prepared from 64 terrestrial plants in two different collection sites in Malaysia - Royal Belum Forest Reserve in the State of Perak and Gunung Nuang in the State of Selangor. One of the photo-cytotoxic extracts from the leaves of <it>Phaeanthus ophtalmicus </it>was further investigated.</p> <p>Results</p> <p>The ethanolic extract of the leaves from <it>Phaeanthus ophtalmicus </it>was able to reduce the <it>in vitro </it>viability of leukaemic HL60 cells to < 50% when exposed to 9.6 J/cm²of a broad spectrum light at a concentration of 20 μg/mL. Dereplication of the photo-cytotoxic fractions from <it>P. ophthalmicus </it>extracts based on TLC R_fvalues and HPLC co-injection of reference tetrapyrrolic compounds enabled quick identification of known photosensitisers, pheophorbide-<it>a</it>, pheophorbide-<it>a </it>methyl ester, 13²-hydroxypheophorbide-<it>a </it>methyl ester, pheophytin-<it>a </it>and 15¹-hydroxypurpurin 7-lactone dimethyl ester. In addition, compound <b>1 </b>which was not previously isolated as a natural product was also identified as 7-formyl-15¹-hydroxypurpurin-7-lactone methyl ester using standard spectroscopic techniques.</p> <p>Conclusions</p> <p>Our results suggest that the main photosensitisers in plants are based on the cyclic tetrapyrrole structure and photosensitisers with other structures, if present, are present in very minor amounts or are not as active as those with the cyclic tetrapyrrole structure.</p

The epidemiology and transmission of methicillin-resistant Staphylococcus aureus in the community in Singapore: study protocol for a longitudinal household study.

BACKGROUND/AIM: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug-resistant organisms in healthcare settings worldwide, but little is known about MRSA transmission outside of acute healthcare settings especially in Asia. We describe the methods for a prospective longitudinal study of MRSA prevalence and transmission. METHODS: MRSA-colonized individuals were identified from MRSA admission screening at two tertiary hospitals and recruited together with their household contacts. Participants submitted self-collected nasal, axilla and groin (NAG) swabs by mail for MRSA culture at baseline and monthly thereafter for 6 months. A comparison group of households of MRSA-negative patients provided swab samples at one time point. In a validation sub-study, separate swabs from each site were collected from randomly selected individuals, to compare MRSA detection rates between swab sites, and between samples collected by participants versus those collected by trained research staff. Information on each participant's demographic information, medical status and medical history, past healthcare facilities usage and contacts, and personal interactions with others were collected using a self-administered questionnaire. DISCUSSION/CONCLUSION: Understanding the dynamics of MRSA persistence and transmission in the community is crucial to devising and evaluating successful MRSA control strategies. Close contact with MRSA colonized patients may to be important for MRSA persistence in the community; evidence from this study on the extent of community MRSA could inform the development of household- or community-based interventions to reduce MRSA colonization of close contacts and subsequent re-introduction of MRSA into healthcare settings. Analysis of longitudinal data using whole-genome sequencing will yield further information regarding MRSA transmission within households, with significant implications for MRSA infection control outside acute hospital settings

Dynamically-Driven Inactivation of the Catalytic Machinery of the SARS 3C-Like Protease by the N214A Mutation on the Extra Domain

Despite utilizing the same chymotrypsin fold to host the catalytic machinery, coronavirus 3C-like proteases (3CLpro) noticeably differ from picornavirus 3C proteases in acquiring an extra helical domain in evolution. Previously, the extra domain was demonstrated to regulate the catalysis of the SARS-CoV 3CLpro by controlling its dimerization. Here, we studied N214A, another mutant with only a doubled dissociation constant but significantly abolished activity. Unexpectedly, N214A still adopts the dimeric structure almost identical to that of the wild-type (WT) enzyme. Thus, we conducted 30-ns molecular dynamics (MD) simulations for N214A, WT, and R298A which we previously characterized to be a monomer with the collapsed catalytic machinery. Remarkably, three proteases display distinctive dynamical behaviors. While in WT, the catalytic machinery stably retains in the activated state; in R298A it remains largely collapsed in the inactivated state, thus implying that two states are not only structurally very distinguishable but also dynamically well separated. Surprisingly, in N214A the catalytic dyad becomes dynamically unstable and many residues constituting the catalytic machinery jump to sample the conformations highly resembling those of R298A. Therefore, the N214A mutation appears to trigger the dramatic change of the enzyme dynamics in the context of the dimeric form which ultimately inactivates the catalytic machinery. The present MD simulations represent the longest reported so far for the SARS-CoV 3CLpro, unveiling that its catalysis is critically dependent on the dynamics, which can be amazingly modulated by the extra domain. Consequently, mediating the dynamics may offer a potential avenue to inhibit the SARS-CoV 3CLpro

A Coevolutionary Residue Network at the Site of a Functionally Important Conformational Change in a Phosphohexomutase Enzyme Family

Coevolution analyses identify residues that co-vary with each other during evolution, revealing sequence relationships unobservable from traditional multiple sequence alignments. Here we describe a coevolutionary analysis of phosphomannomutase/phosphoglucomutase (PMM/PGM), a widespread and diverse enzyme family involved in carbohydrate biosynthesis. Mutual information and graph theory were utilized to identify a network of highly connected residues with high significance. An examination of the most tightly connected regions of the coevolutionary network reveals that most of the involved residues are localized near an interdomain interface of this enzyme, known to be the site of a functionally important conformational change. The roles of four interface residues found in this network were examined via site-directed mutagenesis and kinetic characterization. For three of these residues, mutation to alanine reduces enzyme specificity to ∼10% or less of wild-type, while the other has ∼45% activity of wild-type enzyme. An additional mutant of an interface residue that is not densely connected in the coevolutionary network was also characterized, and shows no change in activity relative to wild-type enzyme. The results of these studies are interpreted in the context of structural and functional data on PMM/PGM. Together, they demonstrate that a network of coevolving residues links the highly conserved active site with the interdomain conformational change necessary for the multi-step catalytic reaction. This work adds to our understanding of the functional roles of coevolving residue networks, and has implications for the definition of catalytically important residues