Novel method to rescue a lethal phenotype through integration of target gene onto the X-chromosome.

The loss-of-function mutations of serine protease inhibitor, Kazal type 1 (SPINK1) gene are associated with human chronic pancreatitis, but the underlying mechanisms remain unknown. We previously reported that mice lacking Spink3, the murine homologue of human SPINK1, die perinatally due to massive pancreatic acinar cell death, precluding investigation of the effects of SPINK1 deficiency. To circumvent perinatal lethality, we have developed a novel method to integrate human SPINK1 gene on the X chromosome using Cre-loxP technology and thus generated transgenic mice termed "X-SPINK1". Consistent with the fact that one of the two X chromosomes is randomly inactivated, X-SPINK1 mice exhibit mosaic pattern of SPINK1 expression. Crossing of X-SPINK1 mice with Spink3+/- mice rescued perinatal lethality, but the resulting Spink3-/-;XXSPINK1 mice developed spontaneous pancreatitis characterized by chronic inflammation and fibrosis. The results show that mice lacking a gene essential for cell survival can be rescued by expressing this gene on the X chromosome. The Spink3-/-;XXSPINK1 mice, in which this method has been applied to partially restore SPINK1 function, present a novel genetic model of chronic pancreatitis

Effect of insecticide-treated bed net usage on under-five mortality in northern Ghana

BACKGROUND: Although under-five mortality rate seems to be declining in Ghana, the northern part of the country has higher levels of under-five mortality vis-à-vis the national rates. This research examines the correlates of the high under-five mortality among children in the northern part of Ghana, with emphasis on the usage of insecticide-treated bed net (ITN), as recommended by the World Health Organization. METHODS: A total of 3,839 under-five children sourced from the Ghana Demographic and Health Survey—was used for this study. Univariate descriptive statistics was employed to describe the variables used for the empirical estimation. The maximum likelihood estimation technique was used to estimate a logit model in other to determine the effect of insecticide treated bed net usage on under-five mortality. RESULTS: Insecticide-treated bed net usage among children enhances their survival rates. Thus, under-five mortality among children who sleep under treated bed nets is about 18.8% lower than among children who do not sleep under treated bed nets. While health facility delivery was found to reduce to reduce under-five mortality, child bearing among older women is detrimental to the survival of the child. CONCLUSIONS: The study, therefore, recommends that policies targeting reduction in under-five mortality in northern Ghana should consider not mere availability of ITNs in the household, but advocate the usage of these treated nets. The study recommends to the Ministry of Health to extend their services to unreached rural communities to encourage health facility delivery to reduce under-five mortality

Examination of consistency of marine gravity with land gravity in and around the Japanese Islands using a helicopter-borne gravimeter

Abstract This paper reports a finding that marine gravity data around the Japanese Islands are inconsistent with nearby land gravity data. The comparison between land and marine gravity was made possible by the gravity measurements from the air using a helicopter-borne gravimeter (SEGAWA Model) developed by the present authors. The ground/sea truth gravity anomaly can be checked against the gravity from the air, though it is not free air gravity anomaly but gravity disturbance. The newly-developed airborne gravimeter first manufactured in 1998 shows a good performance with a 1–2 mgal average repeatability of measurement under a 90-knot flight speed. Thus we have found disagreements between ground truth and sea truth gravity anomalies on the basis of airborne gravity data in the areas in Japan where we have so far made measurements. Among them we will report the case in the area from Saitama and Ibaraki offshore to the Kashima-Nada Sea, p]Japan. Our conclusion about this area is that the past marine gravity data obtained by surface ship gravimeters involve systematic errors of more than 10 mgals. This kind of inconsistency between marine and land gravity is expected to be found in a number of other areas around the Japanese Islands.</jats:p

A Longitudinal Analysis of Mosquito Net Ownership and Use in an Indigenous Batwa Population after a Targeted Distribution

Major efforts for malaria prevention programs have gone into scaling up ownership and use of insecticidal mosquito nets, particularly in sub-Saharan Africa where the malaria burden is high. Socioeconomic inequities in access to long lasting insecticidal nets (LLINs) are reduced with free distributions of nets. However, the relationship between social factors and retention of nets after a free distribution has been less studied, particularly using a longitudinal approach. Our research aimed to estimate the ownership and use of LLINs, and examine the determinants of LLIN retention, within an Indigenous Batwa population after a free LLIN distribution. Two LLINs were given free of charge to each Batwa household in Kanungu District, Uganda in November 2012. Surveyors collected data on LLIN ownership and use through six cross-sectional surveys pre- and post-distribution. Household retention, within household access, and individual use of LLINs were assessed over an 18-month period. Socioeconomic determinants of household retention of LLINs post-distribution were modelled longitudinally using logistic regression with random effects. Direct house-to-house distribution of free LLINs did not result in sustainable increases in the ownership and use of LLINs. Three months post-distribution, only 73% of households owned at least one LLIN and this period also saw the greatest reduction in ownership compared to other study periods. Eighteen-months post distribution, only a third of households still owned a LLIN. Self-reported age-specific use of LLINs was generally higher for children under five, declined for children aged 6–12, and was highest for older adults aged over 35. In the model, household wealth was a significant predictor of LLIN retention, controlling for time and other variables. This research highlights on-going socioeconomic inequities in access to malaria prevention measures among the Batwa in southwestern Uganda, even after free distribution of LLINs, and provides critical information to inform local malaria programs on possible intervention entry-points to increase access and use among this marginalized population

TNF-α induces vascular insulin resistance via positive modulation of PTEN and decreased Akt/eNOS/NO signaling in high fat diet-fed mice

Abstract\ud \ud Background\ud High fat diet (HFD) induces insulin resistance in various tissues, including the vasculature. HFD also increases plasma levels of TNF-α, a cytokine that contributes to insulin resistance and vascular dysfunction. Considering that the enzyme phosphatase and tension homologue (PTEN), whose expression is increased by TNF-α, reduces Akt signaling and, consequently, nitric oxide (NO) production, we hypothesized that PTEN contributes to TNF-α-mediated vascular resistance to insulin induced by HFD. Mechanisms underlying PTEN effects were determined.\ud \ud \ud Methods\ud Mesenteric vascular beds were isolated from C57Bl/6J and TNF-α KO mice submitted to control or HFD diet for 18 weeks to assess molecular mechanisms by which TNF-α and PTEN contribute to vascular dysfunction.\ud \ud \ud Results\ud Vasodilation in response to insulin was decreased in HFD-fed mice and in ex vivo control arteries incubated with TNF-α. TNF-α receptors deficiency and TNF-α blockade with infliximab abolished the effects of HFD and TNF-α on insulin-induced vasodilation. PTEN vascular expression (total and phosphorylated isoforms) was increased in HFD-fed mice. Treatment with a PTEN inhibitor improved insulin-induced vasodilation in HFD-fed mice. TNF-α receptor deletion restored PTEN expression/activity and Akt/eNOS/NO signaling in HFD-fed mice.\ud \ud \ud Conclusion\ud TNF-α induces vascular insulin resistance by mechanisms that involve positive modulation of PTEN and inhibition of Akt/eNOS/NO signaling. Our findings highlight TNF-α and PTEN as potential targets to limit insulin resistance and vascular complications associated with obesity-related conditions.This work was supported by grants from Fundação de Amparo à Pesquisa\ud do Estado de São Paulo (FAPESP 2013/08216-2-CRID), Coordenação de Aper‑\ud feiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de\ud Desenvolvimento Científico e Tecnológico (CNPq), Brazil

Evaluation of mechanical properties of esthetic brackets

Plastic brackets, as well as ceramic brackets, are used in various cases since they have excellent esthetics. However, their mechanical properties remain uncertain. The purpose of this study was to determine how deformation and stress distribution in esthetic brackets differ among materials under the same wire load. Using the digital image correlation method, we discovered the following: (1) the strain of the wings of plastic brackets is within 0.2% and that of ceramic and metal brackets is negligible, (2) polycarbonate brackets having a stainless steel slot show significantly smaller displacement than other plastic brackets, and (3) there is a significant difference between plastic brackets and ceramic and stainless steel brackets in terms of the displacement of the bracket wing

Airborne gravimetry? a new gravimeter system and test results

© ASEG 2003Success of airborne gravity surveys mainly depends on determining the three-dimensional (3D) position of the moving platform. Recent advances in technology, especially the Global Positioning System (GPS), have made it possible to determine the velocity and position of the moving platform more frequently and with greater accuracy. Taking advantage of these advances in GPS technology, and using a newly developed system, helicopter-borne gravity measurements were successfully carried out over the Kanto and Tokai districts of Japan. This new gravimeter system is composed of servo accelerometer sensors, a stabilised platform, an optical-fibre gyroscope to control the stabilised platform, GPS receivers, and a data processor. The 3D position of the helicopter at every second was accurately determined by the interferometric GPS method. These GPS data were also used to compute various correction factors which are applied to the measured gravity acceleration. Real-time differential GPS positioning was also conducted using a separate receiver mounted on the helicopter. These real-time positioning data were used for controlling the optical-fibre gyroscope. The gravity acceleration data were processed and all necessary corrections were applied. Numerical filtering was carried out to remove high-frequency noise in the data. The observed free-air gravity anomalies were then compared with upward continuation of the ground gravity data to the flight altitude. We also compiled an airborne gravity anomaly map from the airborne data, which was compared with upward-continued ground gravity data.E. John Joseph, Jiro Segawa, Shigekazu Kusumoto, Eiji Nakayama, Takemi Ishihara, Masao Komazawa, Sadomi Sakum