Polymicrobial infections in children with diarrhoea in a rural area of Jordan

Polymicrobial infections associated with diarrhoea are common in developing countries. Stool specimens were collected from 220 patient children and 100 controls. Potential pathogenic agents isolated from 143 (65%) children were identified by molecular and standard microbiological methods. Co-infections with two or more agents were detected in 50 (35%) cases. Escherichia coli, Shigella dysenteriae, Giardia and Entamoeba histolytica were found to be predominant. The etiologic agents could not be determined in 77 (35%) cases. The most significant risk factors were the age, the education level of the mother and the use of non-chlorinated water. The high infection rate of diarrhoeal diseases is a strong indication that these pathogens circulate easily through the population.     

Measuring Adult Mortality Using Sibling Survival: A New Analytical Method and New Results for 44 Countries, 1974–2006

Background

For several decades, global public health efforts have focused on the development and application of disease control programs to improve child survival in developing populations. The need to reliably monitor the impact of such intervention programs in countries has led to significant advances in demographic methods and data sources, particularly with large-scale, cross-national survey programs such as the Demographic and Health Surveys (DHS). Although no comparable effort has been undertaken for adult mortality, the availability of large datasets with information on adult survival from censuses and household surveys offers an important opportunity to dramatically improve our knowledge about levels and trends in adult mortality in countries without good vital registration. To date, attempts to measure adult mortality from questions in censuses and surveys have generally led to implausibly low levels of adult mortality owing to biases inherent in survey data such as survival and recall bias. Recent methodological developments and the increasing availability of large surveys with information on sibling survival suggest that it may well be timely to reassess the pessimism that has prevailed around the use of sibling histories to measure adult mortality.

Methods and Findings

We present the Corrected Sibling Survival (CSS) method, which addresses both the survival and recall biases that have plagued the use of survey data to estimate adult mortality. Using logistic regression, our method directly estimates the probability of dying in a given country, by age, sex, and time period from sibling history data. The logistic regression framework borrows strength across surveys and time periods for the estimation of the age patterns of mortality, and facilitates the implementation of solutions for the underrepresentation of high-mortality families and recall bias. We apply the method to generate estimates of and trends in adult mortality, using the summary measure ₄₅ q ₁₅—the probability of a 15-y old dying before his or her 60th birthday—for 44 countries with DHS sibling survival data. Our findings suggest that levels of adult mortality prevailing in many developing countries are substantially higher than previously suggested by other analyses of sibling history data. Generally, our estimates show the risk of adult death between ages 15 and 60 y to be about 20%–35% for females and 25%–45% for males in sub-Saharan African populations largely unaffected by HIV. In countries of Southern Africa, where the HIV epidemic has been most pronounced, as many as eight out of ten men alive at age 15 y will be dead by age 60, as will six out of ten women. Adult mortality levels in populations of Asia and Latin America are generally lower than in Africa, particularly for women. The exceptions are Haiti and Cambodia, where mortality risks are comparable to many countries in Africa. In all other countries with data, the probability of dying between ages 15 and 60 y was typically around 10% for women and 20% for men, not much higher than the levels prevailing in several more developed countries.

Conclusions

Our results represent an expansion of direct knowledge of levels and trends in adult mortality in the developing world. The CSS method provides grounds for renewed optimism in collecting sibling survival data. We suggest that all nationally representative survey programs with adequate sample size ought to implement this critical module for tracking adult mortality in order to more reliably understand the levels and patterns of adult mortality, and how they are changing. Please see later in the article for the Editors'' Summary     

Computational design of second‐site suppressor mutations at protein–protein interfaces

The importance of a protein–protein interaction to a signaling pathway can be established by showing that amino acid mutations that weaken the interaction disrupt signaling, and that additional mutations that rescue the interaction recover signaling. Identifying rescue mutations, often referred to as second‐site suppressor mutations, controls against scenarios in which the initial deleterious mutation inactivates the protein or disrupts alternative protein–protein interactions. Here, we test a structure‐based protocol for identifying second‐site suppressor mutations that is based on a strategy previously described by Kortemme and Baker. The molecular modeling software Rosetta is used to scan an interface for point mutations that are predicted to weaken binding but can be rescued by mutations on the partner protein. The protocol typically identifies three types of specificity switches: knob‐in‐to‐hole redesigns, switching hydrophobic interactions to hydrogen bond interactions, and replacing polar interactions with nonpolar interactions. Computational predictions were tested with two separate protein complexes; the G‐protein Gα_i1 bound to the RGS14 GoLoco motif, and UbcH7 bound to the ubiquitin ligase E6AP. Eight designs were experimentally tested. Swapping a buried hydrophobic residue with a polar residue dramatically weakened binding affinities. In none of these cases were we able to identify compensating mutations that returned binding to wild‐type affinity, highlighting the challenges inherent in designing buried hydrogen bond networks. The strongest specificity switches were a knob‐in‐to‐hole design (20‐fold) and the replacement of a charge–charge interaction with nonpolar interactions (55‐fold). In two cases, specificity was further tuned by including mutations distant from the initial design. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

Functional traits and life history diversity of the North Africa endemic Ebenus pinnata Aiton

Ebenus pinnata Aiton occurs in few localities along the Mediterranean coast of North Africa from Libya to Morocco. In Libya this species grows in few places of the northwestern coastal mountain escarpment, where it is rarely recorded. The study site was located one in Msallata National Park area, Libya, at an altitude of 200–300 m. Three growth types were recognized in E. pinnata: ephemeral (E), modular (M), and coppiced (C) life-forms (functional types). The intra-population variations in the plant's functional types are interpreted as a plasticity mechanism for survival and existence under the given soil texture and micronutrient heterogeneity.     

FAK/src-family dependent activation of the Ste20-like kinase SLK is required for microtubule-dependent focal adhesion turnover and cell migration

Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal.     

Adhesion,invasion, and translocation characteristics of Listeria monocytogenes serotypes in Caco-2 cell and mouse models

Adhesion is a crucial first step in Listeria monocytogenes pathogenesis. In this study, we examined how the adhesion properties of serotypes correlate with their invasion efficiencies in a cell culture model (Caco-2) and in a mouse model. Adhesion characteristics of all 13 serotypes of L. monocytogenes (25 strains) were analyzed, which yielded three distinct groups (P < 0.05) with high-, medium-, and low-level-adhesion profiles. The efficiency of these strains in invading the Caco-2 cell line was analyzed, which produced two groups; however, the overall correlation (R(2)) was only 0.1236. In the mouse bioassay, all selected strains, irrespective of their adhesion profiles, translocated to the liver and the spleen with almost equal frequencies that did not show any clear relationship with adhesion profiles. However, the serotypes with increased adhesion showed a slightly increased translocation to the brain (R(2) = 0.3371). Collectively, these results indicate that an in vitro adhesion profile might not be an accurate assessment of a strain's ability to invade a cultured cell line or organs or tissues in a mouse model.     

Structure-Activity Relationship of Pyrimidine Heterosubstituted Nucleoside Analogues

Abstract

The structure-activity relationship of sixteen 3-deaza, C-4 substituted pyrimidines and imidazo[1,2-c]pyrimidine bases of 1,3-oxathiolanes and 1,3-dioxolanes revealed good anti-HBV activity in 2.2.15 cells transfected with human hepatitis B virus of the imidazo[1,2-c]pyrimidine nucleosides 21, 25 and 29. Two procedures for the preparation of C-4 substituted analogues are reported based on nucleophilic displacement of a sulfonamide or imidazole by a variety of nitrogen nucleophiles.     

Chemokine receptor CCR1 disruption in bone marrow cells enhances atherosclerotic lesion development and inflammation in mice

Several chemokines or chemokine receptors are involved in atherogenesis. CCR1 is expressed by macrophages and lymphocytes, two major cell types involved in the progression of atherosclerosis, and binds to lesion-expressed ligands. We examined the direct role of the blood-borne chemokine receptor CCR1 in atherosclerosis by transplanting bone marrow cells from either CCR1+/+ or CCR1-/- mice into low-density lipoprotein-receptor (LDLr)-deficient mice. After exposure to an atherogenic diet for 8 weeks, no differences in fatty streak size or composition were detected between the 2 groups. After 12 weeks of atherogenic diet, however, an unexpected 70% increase in atherosclerotic lesion size in the thoracic aorta was detected in the CCR1-/- mice, accompanied by a 37% increase in the aortic sinus lesion area. CCR1-/- mice showed enhanced basal and concanavalin A-stimulated IFN-gamma production by spleen T cells and enhanced plaque inflammation. In conclusion, blood-borne CCR1 alters the immuno-inflammatory response in atherosclerosis and prevents excessive plaque growth and inflammation.