Engineering extracellular matrix structure in 3D multiphase tissues

In native tissues, microscale variations in the extracellular matrix (ECM) structure can drive different cellular behaviors. Although control over ECM structure could prove useful in tissue engineering and in studies of cellular behavior, isotropic 3D matrices poorly replicate variations in local microenvironments. In this paper, we demonstrate a method to engineer local variations in the density and size of collagen fibers throughout 3D tissues. The results showed that, in engineered multiphase tissues, the structures of collagen fibers in both the bulk ECM phases (as measured by mesh size and width of fibers) as well as at tissue interfaces (as measured by density of fibers and thickness of tissue interfaces) could be modulated by varying the collagen concentrations and gelling temperatures. As the method makes use of a previously published technique for tissue bonding, we also confirmed that significant adhesion strength at tissue interfaces was achieved under all conditions tested. Hence, this study demonstrates how collagen fiber structures can be engineered within all regions of a multiphase tissue scaffold by exploiting knowledge of collagen assembly, and presents an approach to engineer local collagen structure that complements methods such as flow alignment and electrospinning.     

Cigarette smoke induces p-benzoquinone-albumin adduct in blood serum: Implications on structure and ligand binding properties

Earlier we had reported that irrespective of the source cigarette smoke (CS) contains substantial amounts of p-benzosemiquinone, which is readily converted to p-benzoquinone (p-BQ) by disproportionation and oxidation by transition metal containing proteins. Here we show that after CS-exposure, p-BQ-protein adducts are formed in the lungs as well as serum albumin of guinea pigs. We also show that serum of human smokers contains p-BQ-albumin adduct. It is known that human serum albumin (HSA) plays a very important role in binding and transport of a variety of ligands, including fatty acids and drugs. We show in vitro that p-BQ forms covalent adducts with free amino groups of all twenty amino acids as well as ?-amino groups of lysine residues of HSA in a concentration dependent manner. When HSA is incubated with p-BQ in the molar ratio of 1:1, the number of p-BQ incorporated is 1. At the molar ratio of 1:60, the number of p-BQ incorporated is 40. The formation of HSA-p-BQ adduct has been demonstrated by absorption spectroscopy, MALDI-MS and MALDI-TOF-TOF-MS analyses. Upon complexation with p-BQ, the secondary structure and conformation of HSA are altered, as evidenced by steady state and time-resolved fluorescence, circular dichroism, 8-anilino-1-napthalenesulfonic acid binding and differential scanning calorimetry. Alteration of the structure and conformation of HSA results in impairment of its ligand binding properties with respect to myristic acid, quercitin and paracetamol. This might be one of the reasons why transport and distribution of lipids and drugs are impaired in smokers.     

Injection behaviors among injection drug users in treatment: the role of hepatitis C awareness

Background

Injection drug use (IDU) is a primary vector for blood-borne infections. Awareness of Hepatitis C virus (HCV) infection status may affect risky injection behaviors. This study determines the prevalence of risky injection practices and examines associations between awareness of positive HCV status and risky injection behaviors.

Methods

We surveyed individuals seeking treatment for substance use at 12 community treatment programs as part of a national HIV screening trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Participants reported socio-demographic characteristics, substance use, risk behaviors, and HCV status. We used multivariable logistic regression to test associations between participant characteristics and syringe/needle sharing.

Results

The 1281 participants included 244 (19.0%) individuals who reported injecting drugs in the past 6 months and 37.7% of IDUs reported being HCV positive. During the six months preceding baseline assessment, the majority of IDUs reported obtaining sterile syringes from pharmacies (51.6%) or syringe exchange programs (25.0%), but fewer than half of IDUs always used a sterile syringe (46.9%). More than one-third (38.5%) shared syringe/needles with another injector in the past 6 months. Awareness of positive HCV vs. negative/unknown status was associated with increased recent syringe/needle sharing (aOR 2.37, 95% CI 1.15, 4.88) in multivariable analysis.

Conclusions

Risky injection behaviors remain prevalent and awareness of HCV infection was associated with increased risky injection behaviors. New approaches are needed to broadly implement HCV prevention interventions for IDUs seeking addiction treatment.     

Vagus nerve stimulation as a strategy to prevent and manage metabolic syndrome

An increase in pro-inflammatory cytokines, decrease in endothelial nitric oxide (eNO) and adiponectin levels and an alteration in hypothalamic peptides and gastrointestinal hormones such as incretins and cholecystokinin that regulate satiety, hunger, and food intake occur in metabolic syndrome. Thus, metabolic syndrome is a low-grade systemic inflammatory condition and could be due to inappropriate cross-talk between the peripheral tissues and the hypothalamic centers implying that methods designed to restore these two abnormalities to normal could be of significant benefit in metabolic syndrome. Vagus nerve stimulation has been shown to suppress inflammation and acetylcholine, the principal vagal neurotransmitter, modulates the actions of several hypothalamic peptides and incretins and cholecystokinin. Based on these evidences, it is proposed that vagus nerve stimulation could be of significant benefit in the management of the metabolic syndrome.     

Extra-corporeal membrane oxygenation in the management of 2009 influenza A (H1N1) refractory respiratory failure

Rapidly progressive acute respiratory failure attributed to 2009 H1N1 influenza A infection has been reported worldwide-3. Refractory hypoxaemia despite conventional mechanical ventilation and lung protective strategies has resulted in the use a combination of rescue therapies, such as conservative fluid management, prone positioning, inhaled nitric oxide, high frequency oscillatory ventilation and extracorporeal membrane oxygenation (ECMO)4. ECMO allows for pulmonary or cardiopulmonary support as an adjunct to respiratory and cardiac failure, minimising ventilator-associated lung injury (VALI). This permits treatment of the underlying disease process, while concurrently allowing for recovery of the acute lung injury. This case documents a previously healthy twenty-two year old Asian male patient with confirmed pandemic (H 1N1) 2009 influenza A who was successfully managed with ECMO in the setting of severe refractory hypoxaemia and progressive hypercapnia.     

JNK regulates FoxO-dependent autophagy in neurons

The cJun N-terminal kinase (JNK) signal transduction pathway is implicated in the regulation of neuronal function. JNK is encoded by three genes that play partially redundant roles. Here we report the creation of mice with targeted ablation of all three Jnk genes in neurons. Compound JNK-deficient neurons are dependent on autophagy for survival. This autophagic response is caused by FoxO-induced expression of Bnip3 that displaces the autophagic effector Beclin-1 from inactive Bcl-XL complexes. These data identify JNK as a potent negative regulator of FoxO-dependent autophagy in neurons.     

Comparative genomic analysis of simple sequence repeats in three Plasmodium species

Simple sequence repeats (SSRs) are known to be responsible for genetic complexities and play major roles in gene and genome evolution. To this respect, malaria parasites are known to have rapidly evolving and complex genomes with complicated and differential pathogenic behaviors. Hence, by studying the whole genome comparative SSRs patterns, one can understand genomic complexities and differential evolutionary patterns of these species. We herein utilized the whole genome sequence information of three Plasmodium species, Plasmodium falciparum, Plasmodium vivax, and Plasmodium knowlesi, to comparatively analyze genome-wide distribution of SSRs. The study revealed that despite having the smallest genome size, P. falciparum bears the highest SSR content among the three Plasmodium species. Furthermore, distribution patterns of different SSRs types (e.g., mono, di, tri, tetra, penta, and hexa) in term of relative abundance and relative density provide evidences for greater accumulation of di-repeats and marked decrease of mono-repeats in P. falciparum in comparison to other two species. Overall, the types and distribution of SSRs in P. falciparum genome was found to be different than that of P. vivax and P. knowlesi. The latter two species have quite similar SSR organizations in many aspects of the data. The results were discussed in terms of comparative SSR patterns among the three Plasmodium species, uniqueness of P. falciparum in SSR organization and general pattern of evolution of SSRs in Plasmodium.