Effect of Spatial Inhomogeneities on the Membrane Surface on Receptor Dimerization and Signal Initiation

Important signal transduction pathways originate on the plasma membrane, where microdomains may transiently entrap diffusing receptors. This results in a non-random distribution of receptors even in the resting state, which can be visualized as “clusters” by high resolution imaging methods. Here, we explore how spatial in-homogeneities in the plasma membrane might influence the dimerization and phosphorylation status of ErbB2 and ErbB3, two receptor tyrosine kinases that preferentially heterodimerize and are often co-expressed in cancer. This theoretical study is based upon spatial stochastic simulations of the two-dimensional membrane landscape, where variables include differential distributions and overlap of transient confinement zones (“domains”) for the two receptor species. The in silico model is parameterized and validated using data from single particle tracking experiments. We report key differences in signaling output based on the degree of overlap between domains and the relative retention of receptors in such domains, expressed as escape probability. Results predict that a high overlap of domains, which favors transient co-confinement of both receptor species, will enhance the rate of hetero-interactions. Where domains do not overlap, simulations confirm expectations that homo-interactions are favored. Since ErbB3 is uniquely dependent on ErbB2 interactions for activation of its catalytic activity, variations in domain overlap or escape probability markedly alter the predicted patterns and time course of ErbB3 and ErbB2 phosphorylation. Taken together, these results implicate membrane domain organization as an important modulator of signal initiation, motivating the design of novel experimental approaches to measure these important parameters across a wider range of receptor systems

Reduction in acute filariasis morbidity during a mass drug administration trial to eliminate lymphatic filariasis in Papua New Guinea.

Background Acute painful swelling of the extremities and scrotum are debilitating clinical manifestations of Wuchereria bancrofti infection. The ongoing global program to eliminate filariasis using mass drug administration is expected to decrease this and other forms of filarial morbidity in the future by preventing establishment of new infections as a consequence of eliminating transmission by the mosquito vector. We examined whether mass treatment with anti-filarial drugs has a more immediate health benefit by monitoring acute filariasis morbidity in Papua New Guinean communities that participated in a 5-year mass drug administration trial. Methodology/Principal Findings Weekly active surveillance for acute filariasis morbidity defined by painful swelling of the extremities, scrotum and breast was performed 1 year before and each year after 4 annual mass administrations of anti-filarial drugs (16,480 person-years of observation). Acute morbidity events lasted <3 weeks in 92% of affected individuals and primarily involved the leg (74–79% of all annual events). The incidence for all communities considered together decreased from 0.39 per person-year in the pre-treatment year to 0.31, 0.15, 0.19 and 0.20 after each of 4 annual treatments (p<0.0001). Residents of communities with high pre-treatment transmission intensities (224–742 infective bites/person/year) experienced a greater reduction in acute morbidity (0.62 episodes per person-year pre-treatment vs. 0.30 in the 4th post-treatment year) than residents of communities with moderate pre-treatment transmission intensities (24–167 infective bites/person/year; 0.28 episodes per person-year pre-treatment vs. 0.16 in the 4th post-treatment year). Conclusions Mass administration of anti-filarial drugs results in immediate health benefit by decreasing the incidence of acute attacks of leg and arm swelling in people with pre-existing infection. Reduction in acute filariasis morbidity parallels decreased transmission intensity, suggesting that continuing exposure to infective mosquitoes is involved in the pathogenesis of acute filariasis morbidity

Feasibility and Effectiveness of Basic Lymphedema Management in Leogane, Haiti, an Area Endemic for Bancroftian Filariasis

Lymphatic filariasis is a parasitic disease that is spread by mosquitoes. In tropical countries where lymphatic filariasis occurs, approximately 14 million people suffer from chronic swelling of the leg, known as lymphedema. Repeated episodes of bacterial skin infection (acute attacks) cause lymphedema to progress to its disfiguring form, elephantiasis. To help achieve the goal of eliminating lymphatic filariasis globally, the World Health Organization recommends basic lymphedema management, which emphasizes hygiene, skin care, exercise, and leg elevation. Its effectiveness in reducing acute attack frequency, as well as the role of compressive bandaging, have not been adequately evaluated in filariasis-endemic areas. Between 1995 and 1998, we studied 175 people with lymphedema of the leg in Leogane, Haiti. During Phase I of the study, when compression bandaging was used to reduce leg volume, the average acute attack rate was 1.56 episodes per year; it was greater in people who were illiterate and those who used compression bandages. After March 1997, when hygiene and skin care were emphasized and bandaging discouraged, acute attack frequency significantly decreased to 0.48 episodes per year. This study highlights the effectiveness of hygiene and skin care, as well as limitations of compressive bandaging, in managing lymphedema in filariasis-endemic areas

A systematic review of population health interventions and Scheduled Tribes in India

<p>Abstract</p> <p>Background</p> <p>Despite India's recent economic growth, health and human development indicators of Scheduled Tribes (ST) or <it>Adivasi </it>(India's indigenous populations) lag behind national averages. The aim of this review was to identify the public health interventions or components of these interventions that are effective in reducing morbidity or mortality rates and reducing risks of ill health among ST populations in India, in order to inform policy and to identify important research gaps.</p> <p>Methods</p> <p>We systematically searched and assessed peer-reviewed literature on evaluations or intervention studies of a population health intervention undertaken with an ST population or in a tribal area, with a population health outcome(s), and involving primary data collection.</p> <p>Results</p> <p>The evidence compiled in this review revealed three issues that promote effective public health interventions with STs: (1) to develop and implement interventions that are low-cost, give rapid results and can be easily administered, (2): a multi-pronged approach, and (3): involve ST populations in the intervention.</p> <p>Conclusion</p> <p>While there is a growing body of knowledge on the health needs of STs, there is a paucity of data on how we can address these needs. We provide suggestions on how to undertake future population health intervention research with ST populations and offer priority research avenues that will help to address our knowledge gap in this area.</p

Carbon mitigation potential of different landuse systems in Northwest Himalayas of India

The alarming increase of CO2 from pre-industrial time has made scientists of every corner to evolve technology to harness this anthropogenic gas and balance the system. A landuse can be a source or sink for carbon depending on the process experienced by the system. The proportion of carbon stored in landuse varies widely depending on their components and climate conditions. More accurate estimates of global or continental CO2 emission from landuse/cover change can only be obtained from extrapolation of reliable local estimates. Northwest Himalayan region has variety of land management practices and landuse systems. In the present research at Department of Silviculture and Agroforestry, Dr. Y. S. Parmar University of Horticulture and Forestry, India, all possible land use systems of Northwestern Himalayas (India) viz.  Agri-silvi-horticulture (ASH), Agri-horti-silviculture (AHS), Agri-silviculture (AS), Agri-horticulture (AH), Silvi-pasture (SP), Pure agriculture  (PA), Pure grassland  (PG) and Abandoned land  (AL) / undisturbed lands were taken to assess the relative carbon mitigation (RCM) potential by calculating carbon mitigation in plant biomass as well as in soil component of the system. The carbon inventory in plants were estimated by calculating the above and below ground biomass using non-destructive method for different plant parts while in the soil the carbon expressed as mega grams per hectare (Mg/ha) for soil depths (0-20 cm and 0-40 cm) was computed by multiplying the soil organic carbon (g kg-1) with bulk density (g cm-3) and depth (cm). The results showed that all land use systems had higher relative carbon mitigation potential than agriculture system. For the soil layer 0-20 cm, the relative carbon mitigation potential ranged from 1.33-2.32 (taking value for agriculture LU system as 1). The lowest value was obtained for AH whereas, the maximum for abandoned land. Further, the study shows that the relative carbon mitigation potential of AL was obtained 2.32 times higher than agriculture followed by SP, ASH, AS, PG=AHS and AH. Considering the RCM values for cumulative soil layer 0-40 cm over 0-20 cm only, different land use systems showed slightly higher carbon mitigation potential values except PG. The different land use systems in terms of RCM potential were ranked as: AL &gt; SP &gt; ASH &gt; AS &gt; AH &gt; AHS &gt; PG and ranging from 1.16-2.40

Effect of INM and Biofertilizers on Growth, Yield and Quality of Eggplant (Solanum melogena)

This study aimed to determine the most effective combination of Integrated Nutrient Management (INM) and biofertilizers for enhancing the growth, yield, and quality of eggplants (Solanum melongena). A randomized block design with ten treatments was employed, incorporating various biofertilizers (Trichoderma harzanium, Azotobacter, and Rhizobacter) and INM components (vermicompost, farmyard manure, and poultry manure).The treatment combinations were&nbsp; T1 (100% Recommended Dose of Fertilizer - RDF), T2 (75% RDF + 25% Vermicompost + Azotobacter), T3 (50% RDF + 50% Vermicompost + Azotobacter), T4 (25% RDF + 75% Vermicompost + Azotobacter), T5 (75% RDF + 25% FYM + Trichoderma harzanium), T6 (50% RDF + 50% FYM + Trichoderma harzanium), T7 (25% RDF + 75% FYM + Trichoderma harzanium), T8 (75% RDF + 25% Poultry manure + Rhizobium), T9 (50% RDF + 50% Poultry manure + Rhizobium), and T10 (25% RDF + 75% Poultry manure + Rhizobium). The findings revealed that T1 exhibited the best performance in terms of growth parameters, while T10 demonstrated the highest yield. Regarding quality, T7 exhibited the most favourable outcomes. These results suggest that the appropriate combination of biofertilizers and INM components can significantly impact the growth, yield, and quality of egg plants. The significance and implications of these findings lie in their potential to enhance eggplant production through sustainable agricultural practices

Family level multimorbidity among older adults in India: looking through a syndemic lens

Background Most of the epidemiological reports on multimorbidity are drawn from individual level assessment despite the fact that the occurrence and outcomes of multimorbidity are modulated by the shared risk factors prevailing within household and family environment. Our study reports on the magnitude of family level multimorbidity and its healthcare expenditure among older adults using data from Longitudinal Ageing Study in India (LASI), wave-1. Methods LASI is a nationwide survey amongst older adults aged ≥45years conducted in 2017-2018. We included (n=22,526) families defined as two or more members co-residing in the same household. We propose two new terms “family level multimorbidity” defined as two or more members of a family having multimorbidity and “family level complex multimorbidity” defined as two or more members of a family having ≥3 chronic conditions in three or more organ systems. Multivariable logistic regression assessed correlates, expressed as adjusted odds ratio with 95% confidence interval. Findings Family level multimorbidity was prevalent among 44.46% families while 41.8% (both partners) had conjugal multimorbidity. Amongst siblings 42.86% and inter-generational (three generations) 46.07% reported multimorbidity. Family level complex multimorbidity was prevalent among 17.93% households. Family level multimorbidity was predominantly associated with urban and affluent class. Healthcare expenditure increased with more multimorbid individuals in a family. Interpretation Our study, reports on the novel concept of looking at multimorbidity by considering family or household as a unit. Multimorbidity is found to be increasingly prevalent in households thus, necessitating family centred intervention rather than individualized approach. Future studies should explore intermediaries of family level multimorbidity through a syndemic lens