LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages

Mutations in the human LIS1 gene cause the smooth brain disease classical lissencephaly. To understand the underlying mechanisms, we conducted in situ live cell imaging analysis of LIS1 function throughout the entire radial migration pathway. In utero electroporation of LIS1 small interference RNA and short hairpin dominant negative LIS1 and dynactin cDNAs caused a dramatic accumulation of multipolar progenitor cells within the subventricular zone of embryonic rat brains. This effect resulted from a complete failure in progression from the multipolar to the migratory bipolar state, as revealed by time-lapse analysis of brain slices. Surprisingly, interkinetic nuclear oscillations in the radial glial progenitors were also abolished, as were cell divisions at the ventricular surface. Those few bipolar cells that reached the intermediate zone also exhibited a complete block in somal translocation, although, remarkably, process extension persisted. Finally, axonal growth also ceased. These results identify multiple distinct and novel roles for LIS1 in nucleokinesis and process dynamics and suggest that nuclear position controls neural progenitor cell division

Ectopic cervical thymoma in a patient with Myasthenia gravis

Ectopic cervical thymoma is rare and is often misdiagnosed as a thyroid tumor or other malignancy. Ectopic thymic tissue can be found along the entire thymic descent path during embryogenesis. However, a thymoma arising from such ectopic thymic tissue is extremely rare. Herein we report a patient with ectopic cervical thymoma and myasthenia gravis (MG) and discuss the management

Vitamin D Status during Pregnancy and the Risk of Gestational Diabetes Mellitus: A Longitudinal Study in a Multiracial Cohort

Aims Emerging evidence suggests that maternal vitamin D status may be associated with gestational diabetes (GDM). However, the temporal relation remains unclear due to the lack of longitudinal data on vitamin D over pregnancy. We aimed to prospectively and longitudinally investigate vitamin D status during early to mid‐pregnancy in relation to GDM risk. Methods In a nested case‐control study of 107 GDM cases and 214 controls within the Fetal Growth Studies‐Singleton Cohort, plasma levels of 25‐hydroxyvitamin D2 and D3 (25(OH)D) and vitamin D binding protein were measured at gestational weeks 10‐14, 15‐26, 23‐31, and 33‐39; we further calculated total, free, and bioavailable 25(OH)D. Conditional logistic regression models and linear mixed‐effects models were used. Results We observed a threshold effect for the relation of vitamin D biomarkers with GDM risk. Vitamin D deficiency (<50 nmol/L) at 10‐14 gestational weeks was associated with a 2.82‐fold increased risk for GDM [odds ratio (OR) =2.82, 95% confidence interval (CI): 1.15‐6.93]. Women with persistent vitamin D deficiency at 10‐14 and 15‐26 weeks of gestation had a 4.46‐fold elevated risk for GDM compared to women persistently non‐deficient (OR=4.46, 95% CI: 1.15‐17.3). Conclusions Maternal vitamin D deficiency as early as the first trimester of pregnancy was associated with an elevated risk of GDM. The association was stronger for women who were persistently deficient through the 2nd trimester. Assessment of vitamin D status in early pregnancy may be clinically important and valuable for improving risk stratification and developing effective interventions for the primary prevention of GDM

Perspective of monochromatic gamma-ray line detection with the High Energy cosmic-Radiation Detection (HERD) facility onboard China's Space Station

HERD is the High Energy cosmic-Radiation Detection instrument proposed to operate onboard China's space station in the 2020s. It is designed to detect energetic cosmic ray nuclei, leptons and photons with a high energy resolution ($\sim1\%$ for electrons and photons and $20\%$ for nuclei) and a large geometry factor ($>3\,{ m^2\,sr}$ for electrons and diffuse photons and $>2\,{ m^2\,sr}$ for nuclei). In this work we discuss the capability of HERD to detect monochromatic $\gamma$-ray lines, based on simulations of the detector performance. It is shown that HERD will be one of the most sensitive instruments for monochromatic $\gamma$-ray searches at energies between $\sim10$ to a few hundred GeV. Above hundreds of GeV, Cherenkov telescopes will be more sensitive due to their large effective area. As a specific example, we show that a good portion of the parameter space of a supersymmetric dark matter model can be probed with HERD.Comment: 9 pages, 7 figures, matches version published in Astropart.Phy

Anti-Bladder-Tumor Effect of Baicalein from Scutellaria baicalensis Georgi and Its Application In Vivo

Some phytochemicals with the characteristics of cytotoxicity and/or antimetastasis have generated intense interest among the anticancer studies. In this study, a natural flavonoid baicalein was evaluated in bladder cancer in vitro and in vivo. Baicalein inhibits 5637 cell proliferation. It arrests cells in G1 phase at 100 μM and in S phase below 75 μM. The protein expression of cyclin B1 and cyclin D1 is reduced by baicalein. Baicalein-induced p-ERK plays a minor role in cyclin B1 reduction. Baicalein-inhibited p65NF-κB results in reduction of cell growth. Baicalein-induced pGSK(ser9) has a little effect in increasing cyclin B1/D1 expression instead. The translation inhibitor cycloheximide blocks baicalein-reduced cyclin B1, suggesting that the reduction is caused by protein synthesis inhibition. On the other hand, neither cycloheximide nor proteasome inhibitor MG132 completely blocks baicalein-reduced cyclin D1, suggesting that baicalein reduces cyclin D1 through protein synthesis inhibition and proteasomal degradation activation. In addition, baicalein also inhibits cell invasion by inhibiting MMP-2 and MMP-9 mRNA expression and activity. In mouse orthotopic bladder tumor model, baicalein slightly reduces tumor size but with some hepatic toxicity. In summary, these results demonstrate the anti-bladder-tumor properties of the natural compound baicalein which shows a slight anti-bladder-tumor effect in vivo

Contributions of Animal Models to the Mechanisms and Therapies of Transthyretin Amyloidosis

Transthyretin amyloidosis (ATTR amyloidosis) is a fatal systemic disease caused by amyloid deposits of misfolded transthyretin, leading to familial amyloid polyneuropathy and/or cardiomyopathy, or a rare oculoleptomeningeal amyloidosis. A good model system that mimic the disease phenotype is crucial for the development of drugs and treatments for this devastating degenerative disorder. The present models using fruit flies, worms, rodents, non-human primates and induced pluripotent stem cells have helped researchers understand important disease-related mechanisms and test potential therapeutic options. However, the challenge of creating an ideal model still looms, for these models did not recapitulates all symptoms, particularly neurological presentation, of ATTR amyloidosis. Recently, knock-in techniques was used to generate two humanized ATTR mouse models, leading to amyloid deposition in the nerves and neuropathic manifestation in these models. This review gives a recent update on the milestone, progress, and challenges in developing different models for ATTR amyloidosis research