The Adaptor Protein SH2B3 (Lnk) Negatively Regulates Neurite Outgrowth of PC12 Cells and Cortical Neurons

SH2B adaptor protein family members (SH2B1-3) regulate various physiological responses through affecting signaling, gene expression, and cell adhesion. SH2B1 and SH2B2 were reported to enhance nerve growth factor (NGF)-induced neuronal differentiation in PC12 cells, a well-established neuronal model system. In contrast, SH2B3 was reported to inhibit cell proliferation during the development of immune system. No study so far addresses the role of SH2B3 in the nervous system. In this study, we provide evidence suggesting that SH2B3 is expressed in the cortex of embryonic rat brain. Overexpression of SH2B3 not only inhibits NGF-induced differentiation of PC12 cells but also reduces neurite outgrowth of primary cortical neurons. SH2B3 does so by repressing NGF-induced activation of PLCγ, MEK-ERK1/2 and PI3K-AKT pathways and the expression of Egr-1. SH2B3 is capable of binding to phosphorylated NGF receptor, TrkA, as well as SH2B1β. Our data further demonstrate that overexpression of SH2B3 reduces the interaction between SH2B1β and TrkA. Consistent with this finding, overexpressing the SH2 domain of SH2B3 is sufficient to inhibit NGF-induced neurite outgrowth. Together, our data demonstrate that SH2B3, unlike the other two family members, inhibits neuronal differentiation of PC12 cells and primary cortical neurons. Its inhibitory mechanism is likely through the competition of TrkA binding with the positive-acting SH2B1 and SH2B2

Obesity and the microvasculature

Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber. Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m(2) increase in BMI was associated with a difference of 0.07 μm [95% CI: -0.08; -0.06] in arteriolar caliber and 0.22 μm [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children. Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists

Mechanical Characterization of Rabbit Pulmonary Vein Sleeves in In Vitro Intact Ring Preparation

BackgroundPulmonary vein (PV) sleeves, composed of cardiomyocytes, play certain roles in arrhythmogenesis. In the literature, it has been frequently reported that PV sleeves possess intrinsic spontaneous pacemaking activity and triggered activity in normal dogs and rabbits. In contrast, other research groups presented totally opposite findings which showed absence of such pacemakers in dogs, rabbits and rats. The present study was designed to clarify this puzzle and contradiction.MethodsA novel methodology using in vitro experimentation was used to examine the electromechanical activity of whole segments of PV sleeves. The ring preparation was composed of a small piece of left atrial (LA) free wall, PV ostium and sleeve from rabbits. A circumferential contraction of the PV sleeve was measured when the preparation was electrically driven from the LA free wall. Mechanical force of the ring preparation was measured using a force transducer. The action potentials were recorded using conventional intracellular recording technique in strip preparation.ResultsIn 15 rabbits, no spontaneous pacemaking activity or triggered activity was found in the in vitro ring preparation of PV sleeve. The circumferential contraction of PV sleeves was external calcium-dependent. Frequency-force relation displayed a negative staircase at 0.1–0.5 Hz and a positive staircase at 1–5 Hz. Post-rest potentiation was prominent between 15 s and 120 s. Intracellular action potential recording did not display any automaticity or triggered activity in PV sleeves.ConclusionIn an intact ring preparation of rabbit PV sleeves, intrinsic spontaneous pacemaking activity or triggered activity was not found

Obesity and the Microvasculature: A Systematic Review and Meta-Analysis

10.1371/journal.pone.0052708PLoS ONE82

Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).</p> <p>Methods</p> <p>Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.</p> <p>Results</p> <p>HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.</p> <p>Conclusion</p> <p>Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.</p

Application of Ground LiDAR for The Investigation of Outcrop Discontinuities and Estimation of Associated Engineering Characteristics

Reliable and direct information about rock slope materials and discontinuity parameters from field investigation are keys to engineering design, structure maintenance and soil/water conservation. Under the impact of global climate change and the surge in extreme weather events, rapid and accurate equipment or procedures for geological engineering surveys are necessary to harmonize engineering facilities with natural environment. This study utilizes 3D laser scanning technology (also known as ground LiDAR), which obtains the coordinates of surface geometry rapidly in point clouds, to survey two outcrops. Applying ground LiDAR in a geological survey, we compare the results with those provided by the International Society of Rock Mechanics, and analyze the slope stability. This study also discusses the applicability and limitations of ground LiDAR technology in discontinuity investigation and estimation of rock mass engineering characteristics. Suggested operating procedures for the use of ground LiDAR technology in outcrop surveys are provided accordingly. The results show that ground LiDAR technology reduces the in-situ operation time significantly, thus facilitating efficient discontinuity surveys and outcrop parameters evaluation. However, the quantities of office work and the accuracy of point clouds depend on the velocity and accuracy of ground LiDAR surveys. Therefore, inspection of survey results and output parameter, along with the application and operating specifications of geological surveys, including point cloud resolution, reasonable error of superimposition, inspection procedures and data analysis, still await further research.岩石工程道路邊坡經現地調查獲得可靠、直接的岩石材料種類與不連續面參數，為確保工程設計施工、設施營運維護及環境水土保持之關鍵資訊。在近年全球氣候變遷與極端氣候事件規模與頻率加大的衝擊下，迅速、精準的工程地質調查工具與作業方法，為落實工程設施與自然環境永續發展的不二法門。本研究利用三維雷射掃描技術 (又稱光達技術，|iDAR)，運用其可快速取得露頭表面幾何坐標描述點雲的特性，透過2處露頭現地地質調查，探討地面光達在工址地質調查之應用，並比較國際岩石力學學會建議工址現地調查作業方法所獲得的參數，分析評估邊坡的穩定特性，據以提出地面光達應用於露頭不連續面調查與岩體工程特性評估的適用性與限制，並提出地面光達應用於露頭調查的作業程序。研究結果顯示，地面光達技術可大幅縮減現地調查作業時間，為露頭不連續面調查與參數評估的新利器，由於室內分析工作量和點雲的精度決定了|iDAR應用於露頭不連續面調查的速度與精準度，未來針對調查成果與產出參數的檢核、在地質調查的應用與作業規範，包括點雲解析度、疊合容許誤差以及資料分析與檢核程序等，有待進一步深入研究

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

10.1038/ng.3405Nature Genetics47111282-1293GUSTO (Growing up towards Healthy Outcomes

Language barrier and its relationship to diabetes and diabetic retinopathy

10.1186/1471-2458-12-781BMC Public Health121

Impact of Migration and Acculturation on Prevalence of Type 2 Diabetes and Related Eye Complications in Indians Living in a Newly Urbanised Society

Background: Health of migrants is a major public health challenge faced by governments and policy makers. Asian Indians are among the fastest growing migration groups across Asia and the world, but the impact of migration and acculturation on diabetes and diabetes-related eye complications among Indians living in urban Asia remains unclear. Methodologies/Principal Findings: We evaluated the influence of migration and acculturation (i.e., migration status and length of residence) on the prevalence of type-2 diabetes mellitus (T2DM) and diabetes-related eye complications (diabetic retinopathy (DR) and cataract), among first-generation (defined as participant born in India with both parents born in India, n = 781) and second-generation (participants born in Singapore with both parents born in India, n = 1,112) Indian immigrants from a population-based study of Adult Indians in Singapore. Diabetes was defined as HbA1c≥6.5%, use of diabetic medication or a physician diagnosis of diabetes. Retinal and lens photographs were graded for the presence of DR and cataract. Compared to first generation immigrants, second generation immigrants had a higher age- and gender-standardized prevalence of T2DM (34.4% versus 29.0%, p<0.001), and, in those with T2DM, higher age- and gender-standardized prevalence of DR (31.7% versus 24.8%, p<0.001), nuclear cataract (13.6% versus 11.6%, p<0.001), and posterior sub-capsular cataract (6.4% versus 4.6%, p<0.001). Among first generation migrants, longer length of residence was associated with significantly younger age of diagnosis of diabetes and greater likelihood of having T2DM and diabetes-related eye complications. Conclusion: Second generation immigrant Indians and longer length of residence are associated with higher prevalence of diabetes and diabetes-related complications (i.e., DR and cataract) among migrant Indians living in Singapore. These data highlight potential worldwide impacts of migration patterns on the risk and burden of diabetes