Density-related sterility in Eretmocerus mundus

While studying the reproductive capacity of Eretmocerus mundus Mercet (Hymenoptera: Aphelinidae) we found that varying numbers of females were sterile. Investigations showed that sterility occurred also in field populations, but at a very low rate. Laboratory sterility was significantly correlated with crowding of the parental females during oviposition. Whitefly hosts from which fertile of sterile females emerged did not differ in size, neither did the hind tibiae of fertile females differ in dimensions from those of sterile ones. Behavior of sterile females differed from that of the fertile ones in several parameters. They exhibited less leg drumming, used the ovipositor more frequently and for shorter durations, and changed more readily from probing to host stinging, and from a number of activities to walking. Altogether, their behavior appeared more restless and caused them to contact more hosts than fertile females. The possibility that the sterility is caused by crowding alone, or by the activity of microorganisms acting under crowded conditions, and the merits of the phenomenon for biological pest control are discussed.     

Structure-activity relationships of heparin-mimicking compounds in induction of bFGF release from extracellular matrix and inhibition of smooth muscle cell proliferation and heparanase activity

A series of nine synthetic polyaromatic compounds were synthesized by polymerization of aromatic ring monomers with formaldehyde, which yield substantially ordered backbones with different functional anionic groups (hydroxyl and carboxyl) on the phenol ring. These compounds were tested for their heparin-mimicking activity: (1) inhibition of heparanase activity; (2) inhibition of SMC proliferation; and (3) release of bFGF from the ECM. We demonstrate that compounds that have two hydroxyl groups para and ortho to the carboxylic group and a carboxylic group at a distance of two carbons from the phenol ring inhibit heparanase activity and SMC proliferation, as well as induced an almost complete release of bFGF from ECM. Addition of a methyl group next to the carboxylic group led to a preferential inhibition of heparanase activity. Similar results were obtained with a compound that contains one hydroxyl group para to the carboxylic group and an ether group near the carboxylic group on the phenol ring. Preferential inhibition of SMC proliferation was best achieved when the position of the hydroxyl group is para and ortho to the carboxylic group and the carboxylic group is at a distance of one carbon from the phenol ring. On the other hand, for maximal release of bFGF from ECM, the position of the carboxylic group should be three carbons away from the phenol ring. These new heparin-mimicking compounds may have a potential use in inhibition of tumor metastasis, arteriosclerosis, and inflammation.     

Ouabain-resistant Na+, K+ transport system in mouse NIH 3T3 cells

Summary It is shown that the ouabain-resistant (OR) furosemide-sensitive K⁺(Rb⁺) transport system performs a net efflux of K⁺ in growing mouse 3T3 cells. This conclusion is based on the finding that under the same assay conditions the furosemidesensitive K⁺(Rb⁺) efflux was found to be two- to threefold higher than the ouabain-resistant furosemide-sensitive K⁺(Rb⁺) influx. The oubain-resistant furosemide-sensitive influxes of both²²Na and⁸⁶Rb appear to be Cl^– dependent, and the data are consistent with coupled unidirectional furosemide-sensitive influxes of Na⁺, K⁺ and Cl^– with a ratio of 1 1 2. However, the net efflux of K⁺ performed by this transport system cannot be coupled to a ouabain-resistant net efflux of Na⁺ since the unidirectional ouabain-resistant efflux of Na⁺ was found to be negligible under physiological conditions. This latter conclusion was based on the fact that practically all the Na⁺ efflux appears to be ouabainsensitive and sufficient to balance the Na⁺ influx under such steady-state conditions. Therefore, it is suggested that the ouabain-resistant furosemide-sensitive transport system in growing cells performs a facilitated diffusion of K⁺ and Na⁺, driven by their respective concentration gradients: a net K⁺ efflux and a net Na⁺ influx.     

Inequalities in self rated health in the 1958 birth cohort: lifetime social circumstances or social mobility?

OBJECTIVE: To investigate explanations for social inequalities in health with respect to health related social mobility and cumulative socioeconomic circumstances over the first three decades of life. DESIGN: Longitudinal follow up. SETTING: Great Britain. SUBJECTS: Data from the 1958 birth cohort study (all children born in England, Wales, and Scotland during 3-9 March 1958) were used, from the original birth survey and from sweeps at 16, 23, and 33 years. MAIN OUTCOME MEASURES: Subjects'' own ratings of their health; social differences in self rated health at age 33. RESULTS: Social mobility varied by health status, with those reporting poor health at age 23 having higher odds of downward mobility than of staying in same social class. Men with poor health were also less likely to be upwardly mobile. Prevalence of poor health at age 33 increased with decreasing social class: from 8.5% in classes I and II to 17.7% in classes IV and V among men, and from 9.4% to 18.8% among women. These social differences remained significant after adjustment for effects of social mobility. Health inequalities attenuated when adjusted for social class at birth, at age 16, or at 23 or for self rated health at age 23. When adjusted for all these variables simultaneously, social differences in self rated health at age 33 were substantially reduced and no longer significant. CONCLUSIONS: Lifetime socioeconomic circumstances accounted for inequalities in self reported health at age 33, while social mobility did not have a major effect on health inequalities.     

Regulation of proto-oncogenic dbl by chaperone-controlled, ubiquitin-mediated degradation

The dbl proto-oncogene product is a prototype of a growing family of guanine nucleotide exchange factors (GEFs) that stimulate the activation of small GTP-binding proteins from the Rho family. Mutations that result in the loss of proto-Dbl's amino terminus produce a variant with constitutive GEF activity and high oncogenic potential. Here, we show that proto-Dbl is a short-lived protein that is kept at low levels in cells by efficient ubiquitination and degradation. The cellular fate of proto-Dbl is regulated by interactions with the chaperones Hsc70 and Hsp90 and the protein-ubiquitin ligase CHIP, and these interactions are mediated by the spectrin domain of proto-Dbl. We show that CHIP is the E3 ligase responsible for ubiquitination and proteasomal degradation of proto-Dbl, while Hsp90 functions to stabilize the protein. Onco-Dbl, lacking the spectrin homology domain, cannot bind these regulators and therefore accumulates in cells at high levels, leading to persistent stimulation of its downstream signaling pathways.     

A double-selective tissue culture system for isolation of wild-type poliovirus from sewage applied in a long-term environmental surveillance

We describe a simple, cost-efficient, double-selective method for isolation of wild-type poliovirus from sewage samples containing vaccine polioviruses and other enteroviruses, with a detection limit of 18 to 50 PFU per 1 to 2 liters of sewage. By this method we were able to process 1,700 sewage samples collected between 1991 and 1996, from which 10,472 plaques were isolated, 41 of them being identified as wild-type polioviruses.     

A virulence attenuated amoebapore-less mutant of Entamoeba histolytica and its interaction with host cells

Entamoeba histolytica, the protozoan parasite which causes amoebiasis, is an exclusively human pathogen so developing a vaccine could effectively impact the spread of the disease. Recently we developed a genetically modified avirulent strain, termed G3, from the virulent E. histolytica strain HM-1:IMSS. The new strain lacks the important virulence factor, the amoebapore-A. The objective of our current study was to investigate the avirulence of the attenuated strain as well as to examine the antigenic and immunogenic responses of these trophozoites as potential candidates for a live vaccine. Functional assays were conducted to characterise the virulent behaviour of the G3 strain. This behaviour was compared to the virulent strain HM-1:IMSS and the non-virulent strain Rahman. Western blots were conducted to confirm the lack of amoebapore-A in the E. histolytica G3 strain and to demonstrate that it had no influence on the presence of other virulence factors. Results of these two sets of tests proved the G3 strain to be phenotypically similar to the avirulent Rahman strain while antigenically identical to the virulent HM-1:IMSS, apart from the lack of the amoebapore-A protein. Intraperitoneal immunisation of hamsters with G3 trophozoites compared to sham immunised hamsters resulted in IgG anti-HM-1:IMSS antibodies. The level of humoral response was variable and further testing has to take place before introducing this new strain as a vaccine.     

H-Index Is Important for Postural Control for People with Impaired Foot Sole Sensation

Introduction

People with Peripheral Neuropathy (PN), especially those with impaired sensory inputs through the small-afferent fiber (type II afferent fibers) reflex loop (SAF), might depend more on the large-afferent fiber (type I afferent fibers) reflex loop (LAF) for postural control.

Purpose

To examine whether the function of the LAF reflex loop, reflected by the H-reflex and ankle joint proprioception, influences postural control when the SAF reflex loop is impaired, as indicated by reduced foot sole cutaneous sensation.

Methods

Thirteen participants (8 women, 5 men) diagnosed with PN and 12 age-matched controls (7 women, 5 men) completed the testing protocol. Measures of interest included the H-index, active (AAP) and passive (PAP) ankle proprioception, plantar pressure sensitivity (PPS), average sway velocity (V_AVG) and area (A₉₅) during 30 seconds eyes-closed standing, 6-minute walk distance (6MWD) and timed up-and-go duration (TUG).

Results

Statistically significant group-dependent regression was observed between V_AVG and H-index. Compared to the control group, the PN group demonstrated reduced PPS (2.0 ± 1.9 vs. 4.2 ± 1.2, P < .05) and H-index (63.6 ± 10.9 vs. 76.4 ± 16.0, P < .05), greater V_AVG (3.5 ± 2.1 vs. 1.6 ± 0.6cm/s, P < .05) and A₉₅ (10.0 ± 10.1 vs. 2.5 ± 1.5cm², P < .05), shorter 6MWD (442.2 ± 93.0 vs. 525.3 ± 68.2m, P < .05), and longer TUG (9.4 ± 1.6 vs. 6.5 ± 1.3s, P < .05). Within the PN group, but not the control group, the H-index was correlated with V_AVG (r = -.56, P < .05). Moreover, within the PN group only, PAP scores were correlated with 6MWD (r = -.68, P < .05) and TUG (r = -.59, P < .05) performance. No other statistically significant group difference, correlation or group-dependent regression was observed.

Conclusion

V_AVG, 6MWD, and TUG correlated with LAF reflex loop function observed among those with impaired functioning of the SAF reflex loop. This observation suggests that the LAF reflex loop may be critical to the control of balance in those individuals suffering from small-fiber PN.     

Assessing early child development and its association with stunting and schistosome infections in rural Zimbabwean children using the Griffiths Scales of Child Development

There is a paucity of reference early childhood development (ECD) data at community level in rural Africa. Our objective was to conduct a comprehensive assessment of ECD in rural Zimbabwe and determine the impact of stunting and schistosome infections on ECD. Using the Griffiths Scales of Child Development, we conducted a cross sectional assessment of Eye and Hand Coordination (EHC), Personal-Social-Emotional (PSE), Language and Communication (LC), Foundations of Learning (FL) and Gross Motor (GM) domains and the summary General Development (GD) in 166 children aged 6–72 months. The effects of stunting, malnutrition and Schistosoma haematobium infection on ECD was determined. The impact of praziquantel curative treatment of schistosome infection on the developmental scores was determined through a longitudinal follow up at 6 and 12 months. From an initial 166 children, 11 were found to have developmental deficits warranting further investigation. Of the remaining 155, 58.7% recorded a good (≥ average) score for the overall General Development (GD). Proportions of children scoring above the cut-off (≥ average) for each domain were GM (84.5%), PSE (80.6%), EHC (61.9%), FL (43.9%) and LC (44.5%). The prevalence of stunting was 26.8% (95% CI = 20.1%–34.8%) Scores for stunted children were significantly lower for EHC (p = 0.0042), GM (p = 0.0099), and GD (p = 0.0014) with the fraction of lower scores attributable to stunting being GM = 63.4%, GD = 46.6%, EHC = 45%, and LC = 21%. S. haematobium infection prevalence was 39.7% and mean infection intensity was 5.4 eggs/10 ml urine. Infected children had poorer cognitive performance scores for the FL (p = 0.0005) with 30.8% of poor FL attributable to the infection. Performance in all domains improved to the expected normal or above reference levels at 6 and 12 months post curative treatment of schistosome infections. Our study documented reference values for ECD in rural Zimbabwean children. The study detected deficiencies in the FL domain, which were more pronounced in children, infected with schistosomes, highlighting the need for provision of cognitive stimulation tools and access to early childhood foundation education. There is also need for improved child nutrition and treatment of schistosome infections to improve child development outcomes.