Recent Advances of Efficient Design of Terahertz Quantum-Cascade Lasers

Terahertz (THz) quantum cascade lasers (QCLs) are electrically pumped and heterostructure based semiconductor laser sources with intersubband transitions of electrons in different layers of the quantum wells and barriers. The THz QCLs have high output power in THz region which make them important from application point of view. Recently intensive research has been carried out by researchers for obtaining efficient designs of THz sources. Most of the researchers have investigated the THz frequency range between 0.1 and 3 THz; however, the output power of the THz sources in the frequency range 3–5 THz is small because of transit time and resistance-capacitance effects. Nevertheless, the present review is focused for the development of efficient THz QCL sources in the frequency range from 3 to 5 THz where one of the major problem of thermal backfilling of the carriers has to be overcome by engineering the heterostructure.

     

Burden of Invasive Pneumococcal Disease in Children Aged 1 Month to 12 Years Living in South Asia: A Systematic Review

Objective

The primary objective was to estimate the burden of invasive pneumococcal disease (IPD) in children aged 1 month to 12 years in South Asian countries.

Methods

We searched three electronic databases (PubMed, Embase and the Cochrane Library) using a comprehensive search strategy, we manually searched published databases (Index Medicus and Current Contents) and we also searched the bibliographies of the included studies and retrieved reviews. The searches were current through June 2013. Eligible studies (community-based and hospital-based) were pooled and a separate analysis for India was also completed. A meta-regression analysis and heterogeneity analysis were performed. The protocol was registered with PROSPERO registration number CRD42013004483.

Results

A total of 22 studies surveying 36,714 children were included in the systematic review. Hospital-based prospective studies from South Asia showed that 3.57% of children had IPD, and 15% of all bacterial pneumonia cases were due to Streptococcus pneumoniae. Indian studies showed that the incidence of IPD was 10.58% in children admitted to hospitals with suspected invasive bacterial diseases, and 24% of all bacterial pneumonia cases were due to S. pneumonia. Population-based studies from South Asian countries showed that 12.8% of confirmed invasive bacterial diseases were caused by S. pneumonia whereas retrospective hospital-based studies showed that 28% of invasive bacterial diseases were due to S. pneumoniae. Meta-regression showed that there was a significant influence of the antigen testing method for diagnosing IPD on IPD prevalence.

Conclusion

S. pneumoniae is responsible for a substantial bacterial disease burden in children of South Asian countries including India despite the presence of high heterogeneity in this meta-analysis. Treatment guidelines must be formulated, and preventive measures like vaccines must also be considered.     

Synthesis of β-ionone derived chalcones as potent antimicrobial agents

A series of chalcones (3a–v) have been synthesized by condensation of β-ionone (1) with a variety of aldehydes (2a–v). The synthesized compounds have been screened for their in vitro antimicrobial activity against five bacterial and five fungal strains, using disc diffusion assay. The evaluated compounds display a wide range of activities, from completely inactive to the highly active compounds. Some of the compounds are also active against methicillin resistant staphylococcus aureus (MRSA).     

Survivin-specific T-cell reactivity correlates with tumor response and patient survival: a phase-II peptide vaccination trial in metastatic melanoma

Background

Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets.

Patients and methods

This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS).

Results

Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR?+?PR?+?SD) more often showed SSTRs than patients with disease progression (p?=?0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6?months; p?=?0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p?=?0.013). The induction of SSTRs was associated with gender (female vs. male; p?=?0.014) and disease stage (M1a/b vs. M1c; p?=?0.010), but not with patient age, HLA type, performance status, or vaccination regimen.

Conclusion

Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.     

A synopsis of the species of Myxobolus Bütschli, 1882 (Myxozoa: Bivalvulida) parasitising Indian fishes and a revised dichotomous key to myxosporean genera

A synopsis of 131 nominal species of Myxobolus Bütschli, 1882 (Myxozoa: Myxosporea: Myxobolidae) reported from India is presented. For each species, the relevant morphometric and morphological data are indicated, as well as the host(s), site(s) of infection within the host and locality data. A revised dichotomous key of 59 genera of the class Myxosporea has also been included. This key incorporates 10 additional genera to that proposed in 1991 by Lom & Dyková.     

Cadherin-11, a marker of the mesenchymal phenotype, regulates glioblastoma cell migration and survival in vivo

Glioblastoma multiforme (GBM) is the most malignant and lethal form of astrocytoma. The GBM patient survival time of approximately 1 year necessitates the identification of novel molecular targets and more effective therapeutics. Cadherin-11, a calcium-dependent cell-cell adhesion molecule and mesenchymal marker, plays a role in both normal tissue development and in cancer cell migration. The functional significance of cadherin-11 in GBM has not been investigated. Here, we show that cadherin-11 is expressed in human GBM tumors and human glioma stem-like cells by immunohistochemical labeling. In addition, we show that cadherin-11 is expressed in human glioma cell lines by immunoblotting. Short hairpin RNA-mediated knockdown of cadherin-11 expression in human glioma cell lines results in decreased migration and growth factor-independent cell survival in vitro. More importantly, knockdown of cadherin-11 inhibits glioma cell survival in heterotopic and orthotopic mouse xenograft models. Together, our results show the functional significance of cadherin-11 expression in GBM and provide evidence for a novel role of cadherin-11 in promoting glioma cell survival in an in vivo environment. Thus, our studies suggest cadherin-11 is a viable molecular target for therapeutic intervention in GBM.     

Inhibition of the Host Proteasome Facilitates Papaya Ringspot Virus Accumulation and Proteosomal Catalytic Activity Is Modulated by Viral Factor HcPro

The ubiquitin/26S proteasome system plays an essential role not only in maintaining protein turnover, but also in regulating many other plant responses, including plant–pathogen interactions. Previous studies highlighted different roles of the 20S proteasome in plant defense during virus infection, either indirectly through viral suppressor-mediated degradation of Argonaute proteins, affecting the RNA interference pathway, or directly through modulation of the proteolytic and RNase activity of the 20S proteasome, a component of the 20S proteasome, by viral proteins, affecting the levels of viral proteins and RNAs. Here we show that MG132, a cell permeable proteasomal inhibitor, caused an increase in papaya ringspot virus (PRSV) accumulation in its natural host papaya (Carica papaya). We also show that the PRSV HcPro interacts with the papaya homologue of the Arabidopsis PAA (α1 subunit of the 20S proteasome), but not with the papaya homologue of Arabidopsis PAE (α5 subunit of the 20S proteasome), associated with the RNase activity, although the two 20S proteasome subunits interacted with each other. Mutated forms of PRSV HcPro showed that the conserved KITC54 motif in the N-terminal domain of HcPro was necessary for its binding to PAA. Co-agroinfiltration assays demonstrated that HcPro expression mimicked the action of MG132, and facilitated the accumulation of bothtotal ubiquitinated proteins and viral/non-viral exogenous RNA in Nicotiana benthamiana leaves. These effects were not observed by using an HcPro mutant (KITS54), which impaired the HcPro – PAA interaction. Thus, the PRSV HcPro interacts with a proteasomal subunit, inhibiting the action of the 20S proteasome, suggesting that HcPro might be crucial for modulating its catalytic activities in support of virus accumulation.     

Distinct role of CD80 and CD86 in the regulation of the activation of B cell and B cell lymphoma.

To date, not much has been known regarding the role of CD80 and CD86 molecules in signaling of B cells. The CD28/CTLA4 ligands, CD80 (B7-1) and CD86 (B7-2), are expressed on the surface of freshly isolated splenic B cells, and their expression is up-regulated by lipopolysaccharides. In the present study, we have investigated whether signaling via CD80/CD86 could alter the proliferation and immunoglobulin synthesis of B cells. Splenic B cells were stimulated with lipopolysaccharides in the presence of anti-B7-1 (16-10A1) and anti-B7-2 (GL1) monoclonal antibodies (mAbs). Exciting features observed during the study were that cross-linking of CD86 with GL1 enhanced the proliferation and production of IgG1 and IgG2a isotypes. In contrast, anti-B7-1 (16-10A1) mAb could efficiently block the proliferation and production of IgG1 and IgG2a. Furthermore, GL1 mAb could also induce the secretion of IgG isotypes from B cell lymphomas. Importantly, 16-10A1 could retard the growth of lymphomas and favored the up-regulation of pro-apoptotic molecules caspase-3, caspase-8, Fas, FasL, Bak, and Bax and down-regulation of anti-apoptotic molecule Bcl-x(L). In contrast, GL1 augmented the level of anti-apoptotic molecules Bcl-w and Bcl-x(L) and decreased the levels of pro-apoptotic molecule caspase-8, thereby providing a novel insight into the mechanism whereby triggering through CD80 and CD86 could deliver regulatory signals. Thus, this study is the first demonstration of a distinct signaling event induced by CD80 and CD86 molecules in B cell lymphoma. Finally, the significance of the finding is that CD80 provided negative signal for the proliferation and IgG secretion of normal B cells and B cell lymphomas. In contrast, CD86 encouraged the activity of B cells.     

Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels

Ligand-gated ion channels underlie synaptic communication in the nervous system¹. In mammals there are three families of ligand-gated channels: the cys loop, the glutamate-gated and the P2X receptor channels². In each case binding of transmitter leads to the opening of a pore through which ions flow down their electrochemical gradients. Many ligand-gated channels are also permeable to calcium ions^{3, 4}, which have downstream signaling roles⁵ (e.g. gene regulation) that may exceed the duration of channel opening. Thus ligand-gated channels can signal over broad time scales ranging from a few milliseconds to days. Given these important roles it is necessary to understand how ligand-gated ion channels themselves are regulated by proteins, and how these proteins may tune signaling. Recent studies suggest that many, if not all, channels may be part of protein signaling complexes⁶. In this article we explain how to identify the proteins that bind to the C-terminal aspects of the P2X2 receptor cytosolic domain.P2X receptors are ATP-gated cation channels and consist of seven subunits (P2X1-P2X7). P2X receptors are widely expressed in the brain, where they mediate excitatory synaptic transmission and presynaptic facilitation of neurotransmitter release⁷. P2X receptors are found in excitable and non-excitable cells and mediate key roles in neuronal signaling, inflammation and cardiovascular function⁸. P2X2 receptors are abundant in the nervous system⁹ and are the focus of this study. Each P2X subunit is thought to possess two membrane spanning segments (TM1 & TM2) separated by an extracellular region⁷ and intracellular N and C termini (Fig 1a)⁷. P2X subunits¹⁰ (P2X1-P2X7) show 30-50% sequence homology at the amino acid level¹¹. P2X receptors contain only three subunits, which is the simplest stoichiometry among ionotropic receptors. The P2X2 C-terminus consists of 120 amino acids (Fig 1b) and contains several protein docking consensus sites, supporting the hypothesis that P2X2 receptor may be part of signaling complexes. However, although several functions have been attributed to the C-terminus of P2X2 receptors⁹ no study has described the molecular partners that couple to the intracellular side of this protein via the full length C-terminus. In this methods paper we describe a proteomic approach to identify the proteins which interact with the full length C-terminus of P2X2 receptors.Open in a separate windowClick here to view.^{(104M, flv)}     

28-Homobrassinolide potential for oxidative interface in <Emphasis Type="Italic">Brassica juncea</Emphasis> under temperature stress

Exploration of scavenging potential of 28-homobrassinolide (28-homoBL) in mitigating the oxidative stress caused by free radicals (·O₂ ^?, H₂O₂, ·NO, OH^?) produced due to temperature stress (4, 44 °C) in Brassica juncea L. was made in the present research. Brassica juncea var. RLC-1 seeds were given pre-sowing soaking of different concentrations of 10^?9 M 28-homoBL for 8 h. Seeds were sown in bedded petri plates lined with 10 No. What’s man filter paper under controlled laboratory conditions. Temperature of 4 and 44 °C, taken as low- and high-temperature stress, suppressed membrane stability and overall growth of the seedlings, while cell death was triggered. Accumulation of malondialdehyde (MDA), hydrogen peroxide (H₂O₂), and nitric oxide (NO) was boosted which resulted in enhanced oxidative stress on the 10th day after sowing. Activity level of antioxidant enzymes viz. superoxide dismutase (SOD), catalase (CAT), guaiacol peroxidase (GPOX), and ascorbate peroxidase (APOX) was enhanced which was ensued for up-regulation of total antioxidant potential in 10-day-old plants exposed to negative effect of temperature stress. Priming treatment of 28-homoBL at seed level helped in maintaining the growth of seedlings to higher level as compared to only stressed as well as from control double distilled water-raised seedlings. 10^?9 M 28-HBL found to be the best in enhancing the enzymatic activities of SOD, CAT, GPOX, and APOX and thus maintained antioxidant potential at higher level which accounted for alleviating oxidative stress caused due to extreme temperature stress. Dead cell formation reduced significantly in 28-homoBL-treated plants, membrane stability was upturned, while production of MDA, H₂O_2, and NO was under control. These results suggested and try to establish 28-homoBL as effective stress protector for B. juncea particularly from the oxidative damage induced by extreme temperatures.