Time-dependent effects of exposure to static magnetic field on glucose and lipid metabolism in rat

In the following study, we investigate the effects of static magnetic field (SMF) (128 mT, 1 h/day during 5 or 15 consecutive days) on anthropometric parameters, glucose and lipid metabolism in rats. Exposure to SMF during 5 days induced a decrease (-8%, p < 0.05) in relative liver weight and serum insulin concentration (-56%, p < 0.001), while blood glucose level was increased (+10%, p < 0.001). By contrast, the same treatment failed to alter body weight, relative kidney weight and levels of lactate, cholesterol, triglycerides and phospholipids. Exposure to SMF during 15 days induced a decrease (-15 %, p < 0.001) in body weight, liver weight (-15 %, p < 0.05), insulin concentration (-63%, p < 0.001), plasmatic lactate level (-55%, p < 0.05) and increased glucose (+24%, p < 0.001), cholesterol (+30%, p < 0.01,) and phospholipids levels (+58%, p < 0.001), whereas, triglycerides decreased (-28%, p < 0.001). These results showed that SMF effects on glucose and lipid metabolism are time-dependent.     

Large duplication 4q25-q34 with mild clinical effect

We report on a 5-year-old Tunisian boy with particular dysmorphic features and mild mental retardation limited in delayed and poor language acquisition. Cytogenetic analysis using RHG banding and FISH using whole chromosome four painting probe showed a partial duplication in the long arm of chromosome four. Locus specific probes and CGH confirmed the presence of a 'pure' partial trisomy 4q due to de novo direct tandem dup(4)(q25q34). Comparative analysis of our case with those published previously, suggests that region 4q31-q33 may be involved in the development of the 4q characteristic dysmorphic features and the distal band 4q35 may be involved in the development of microcephaly and severe mental and growth retardation.     

Evaluating germinability of eight desert halophytes under long-term seed storage: Implications for conservation

Ex situ conservation in seed banks is a potential complementary conservation strategy for native plant species.It is well established that ex situ seed banking of native wild plants prolongs seed viability and thereby preserves genetic and species diversity for future use.We evaluated ex situ storage potential of eight halophytic species from deserts in the United Arab Emirates(UAE)by studying seed germination.Specifically,we examined the germinability of freshly collected seeds and seeds stored for three years in a seed bank.We also examined the effect of light conditions on fresh and stored seed germination.Fresh seeds of seven of the eight species tested had a higher germination rates under 12/12 h light/dark fluctuations than did those exposed to total darkness.Storage reduced light sensitivity in Halocnemum strobilaceum,Suaeda aegyptiaca,Salsola drummondii and Salsola imbricata,but increased the requirement for light in Arthrocnemum macrostachyum.In Anabasis setifera,storage decreased germination percentage when there was a 12-hour light/dark fluctuation,but increased germination rate when exposed to the dark treatment.Storage significantly reduced germination in both the light/dark and dark treatments in Suaeda vermiculata and S.aegyptiaca.Germination speed also responded differently to storage;whereas Timson's index significantly increased in A.macrostachyum and H.strobilaceum,it significantly decreased for S.drummondii,S.aegyptiaca and S.vermiculata.Germination of these species at a range of temperatures requires further testing;additionally,we strongly suggest that these laboratory findings be complemented by field studies.     

SHIP1 and Lyn Kinase Negatively Regulate Integrin alpha IIb beta 3 signaling in platelets

Integrin alpha(IIb)beta(3) plays a critical role in platelet function, promoting a broad range of functional responses including platelet adhesion, spreading, aggregation, clot retraction, and platelet procoagulant function. Signaling events operating downstream of this receptor (outside-in signaling) are important for these responses; however the mechanisms negatively regulating integrin alpha(IIb)beta(3) signaling remain ill-defined. We demonstrate here a major role for the Src homology 2 domain-containing inositol 5-phosphatase (SHIP1) and Src family kinase, Lyn, in this process. Our studies on murine SHIP1 knockout platelets have defined a major role for this enzyme in regulating integrin alpha(IIb)beta(3)-dependent phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) accumulation, necessary for a cytosolic calcium response and platelet spreading. SHIP1 phosphorylation and PtdIns(3,4,5)P(3) metabolism is partially regulated through Lyn kinase, resulting in an enhanced calcium flux and spreading response in Lyn-deficient mouse platelets. Analysis of platelet adhesion dynamics under physiological blood flow conditions revealed an important role for SHIP1 in regulating platelet adhesion on fibrinogen. Specifically, SHIP1-dependent PtdIns(3,4,5)P(3) metabolism down-regulates the stability of integrin alpha(IIb)beta(3)-fibrinogen adhesive bonds, leading to a decrease in the proportion of platelets forming shear-resistant adhesion contacts. These studies define a major role for SHIP1 and Lyn as negative regulators of integrin alpha(IIb)beta(3) adhesive and signaling function.     

Is Abnormal Urine Protein/Osmolality Ratio Associated with Abnormal Renal Function in Patients Receiving Tenofovir Disoproxil Fumarate?

Background

Risk factors for and optimal surveillance of renal dysfunction in patients on tenofovir disoproxil fumarate (TDF) remain unclear. We investigated whether a urine protein-osmolality (P/O) ratio would be associated with renal dysfunction in HIV-infected persons on TDF.

Methods

This retrospective, single-center study investigated the relationship between parameters of renal function (estimated glomerular filtration rate (eGFR) and P/O-ratio) and risk factors for development of kidney dysfunction. Subjects were HIV-infected adults receiving TDF with at least one urinalysis and serum creatinine performed between 2010 and 2013. Regression analyses were used to analyze risk factors associated with abnormal P/O-ratio and abnormal eGFR during TDF therapy.

Results

Patients were predominately male (81%); (65%) were Caucasian. Mean age was 45.1(±11.8) years; median [IQR] TDF duration was 3.3 years. [1.5–7.6]. Median CD4+ T cell count and HIV viral load were 451 cells/μL [267.5–721.5] and 62 copies/mL [0–40,150], respectively. Abnormal P/O-ratio was not associated with low eGFR. 68% of subjects had an abnormal P/O-ratio and 9% had low eGFR. Duration of TDF use, age, diabetes and hypertension were associated with renal dysfunction in this study. After adjustment for age, subjects on TDF > 5 years had almost a four-fold increased likelihood of having an abnormal P/O-ratio than subjects on TDF for < 1yr (OR 3.9; 95% CI 1.2–14.0; p = 0.024).

Conclusion

Abnormal P/O-ratio is common in HIV-infected patients on TDF but was not significantly associated with low eGFR, suggesting that abnormal P/O-ratio may be a very early biomarker of decreased renal function in HIV infected patients.     

PI 3-kinase p110beta: a new target for antithrombotic therapy

Platelet activation at sites of vascular injury is essential for the arrest of bleeding; however, excessive platelet accumulation at regions of atherosclerotic plaque rupture can result in the development of arterial thrombi, precipitating diseases such as acute myocardial infarction and ischemic stroke. Rheological disturbances (high shear stress) have an important role in promoting arterial thrombosis by enhancing the adhesive and signaling function of platelet integrin alpha(IIb)beta(3) (GPIIb-IIIa). In this study we have defined a key role for the Type Ia phosphoinositide 3-kinase (PI3K) p110beta isoform in regulating the formation and stability of integrin alpha(IIb)beta(3) adhesion bonds, necessary for shear activation of platelets. Isoform-selective PI3K p110beta inhibitors have been developed which prevent formation of stable integrin alpha(IIb)beta(3) adhesion contacts, leading to defective platelet thrombus formation. In vivo, these inhibitors eliminate occlusive thrombus formation but do not prolong bleeding time. These studies define PI3K p110beta as an important new target for antithrombotic therapy.