CTSB promotes porcine preadipocytes differentiation by degrading fibronectin and attenuating the Wnt/β-catenin signaling pathway

The process of preadipocytes differentiation plays a vital role in adipose tissue expansion and many factors are involved in this event. Cathepsin B (CTSB), secreted from lysosome, has been reported in regulating a variety of physiological processes. In this study, we demonstrated CTSB promotes lipid accumulation and adipogenic genes expression in porcine primary preadipocytes by degrading fibronectin (Fn), a key component of extracellular matrix. Lithium chloride (LiCl) is an activator of Wnt/β-catenin signaling through stabilizing β-catenin. We found that CTSB can relieve the anti-adipogenic effects of LiCl, indicating that CTSB could impact Wnt/β-catenin signaling pathway. Interestingly, Fn is an important target gene of Wnt/β-catenin. So we considered that CTSB promote preadipocytes differentiation by suppressing these two pathways.     

The plant glycosyltransferase clone collection for functional genomics

The glycosyltransferases (GTs) are an important and functionally diverse family of enzymes involved in glycan and glycoside biosynthesis. Plants have evolved large families of GTs which undertake the array of glycosylation reactions that occur during plant development and growth. Based on the Carbohydrate‐Active enZymes (CAZy) database, the genome of the reference plant Arabidopsis thaliana codes for over 450 GTs, while the rice genome (Oryza sativa) contains over 600 members. Collectively, GTs from these reference plants can be classified into over 40 distinct GT families. Although these enzymes are involved in many important plant specific processes such as cell‐wall and secondary metabolite biosynthesis, few have been functionally characterized. We have sought to develop a plant GTs clone resource that will enable functional genomic approaches to be undertaken by the plant research community. In total, 403 (88%) of CAZy defined Arabidopsis GTs have been cloned, while 96 (15%) of the GTs coded by rice have been cloned. The collection resulted in the update of a number of Arabidopsis GT gene models. The clones represent full‐length coding sequences without termination codons and are Gateway^® compatible. To demonstrate the utility of this JBEI GT Collection, a set of efficient particle bombardment plasmids (pBullet) was also constructed with markers for the endomembrane. The utility of the pBullet collection was demonstrated by localizing all members of the Arabidopsis GT14 family to the Golgi apparatus or the endoplasmic reticulum (ER). Updates to these resources are available at the JBEI GT Collection website http://www.addgene.org/ .     

Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention

Broadly neutralizing antibodies (bNAbs) are promising agents to prevent HIV infection and achieve HIV remission without antiretroviral therapy (ART). As with ART, bNAb combinations are likely needed to cover HIV’s extensive diversity. Not all bNAbs are identical in terms of their breadth, potency, and in vivo longevity (half-life). Given these differences, it is important to optimally select the composition, or dose ratio, of combination bNAb therapies for future clinical studies. We developed a model that synthesizes 1) pharmacokinetics, 2) potency against a wide HIV diversity, 3) interaction models for how drugs work together, and 4) correlates that translate in vitro potency to clinical protection. We found optimization requires drug-specific balances between potency, longevity, and interaction type. As an example, tradeoffs between longevity and potency are shown by comparing a combination therapy to a bi-specific antibody (a single protein merging both bNAbs) that takes the better potency but the worse longevity of the two components. Then, we illustrate a realistic dose ratio optimization of a triple combination of VRC07, 3BNC117, and 10–1074 bNAbs. We apply protection estimates derived from both a non-human primate (NHP) challenge study meta-analysis and the human antibody mediated prevention (AMP) trials. In both cases, we find a 2:1:1 dose emphasizing VRC07 is nearly optimal. Our approach can be immediately applied to optimize the next generation of combination antibody prevention and cure studies.     

Effect of silicon-doped calcium phosphate cement on angiogenesis based on controlled macrophage polarization

Vascularization is an important early indicator of osteogenesis involving biomaterials.Bone repair and new bone formation are associated with extensive neovascu...     

Which Urban Migrants Default from Tuberculosis Treatment in Shanghai,China?

Background

Migration is a major challenge to tuberculosis (TB) control worldwide. TB treatment requires multiple drugs for at least six months. Some TB patients default before completing their treatment regimen, which can lead to ongoing infectiousness and drug resistance.

Methods

We conducted a retrospective analysis of 29,943 active TB cases among urban migrants that were reported between 2000 to 2008 in Shanghai, China. We used logistic regression models to identify factors independently associated with treatment defaults in TB patients among urban migrants during 2005-2008.

Results

Fifty-two percent of the total TB patients reported in Shanghai during the study period were among urban migrants. Three factors increased the odds of a treatment default: case management using self-administered therapy (OR, 5.84, 95% CI, 3.14-10.86, p<0.0005), being a retreatment case (OR, 1.47, 95% CI, 1.25-1.71, p<0.0005), and age >60 years old (OR, 1.33, 95% CI, 1.05-1.67, p=0.017). The presence of a cavity in the initial chest radiograph decreased the odds for a treatment default (OR, 0.87, 95% CI, 0.77-0.97, p=0.015), as did migration from central China (OR, 0.85, 95% CI, 0.73-0.99, p=0.042), case management by family members (OR, 0.73, 95% CI 0.66-0.81, p<0.0005), and the combination of case detection by a required physical exam and case management by health care staff (OR, 0.64, 95% CI, 0.45-0.93, p=0.019).

Conclusion

Among TB patients who were urban migrants in Shanghai, case management using self-administered therapy was the strongest modifiable risk factor that was independently associated with treatment defaults. Interventions that target retreated TB cases could also reduce treatment defaults among urban migrants. Health departments should develop effective measures to prevent treatment defaults among urban migrants, to ensure completion of therapy among urban migrants who move between cities and provinces, and to improve reporting of treatment outcomes.