Self-assembled GaInNAs/GaAsN quantum dot lasers: solid source molecular beam epitaxy growth and high-temperature operation

Self-assembled GaInNAs quantum dots (QDs) were grown on GaAs (001) substrate using solid-source molecular-beam epitaxy (SSMBE) equipped with a radio-frequency nitrogen plasma source. The GaInNAs QD growth characteristics were extensively investigated using atomic-force microscopy (AFM), photoluminescence (PL), and transmission electron microscopy (TEM) measurements. Self-assembled GaInNAs/GaAsN single layer QD lasers grown using SSMBE have been fabricated and characterized. The laser worked under continuous wave (CW) operation at room temperature (RT) with emission wavelength of 1175.86 nm. Temperature-dependent measurements have been carried out on the GaInNAs QD lasers. The lowest obtained threshold current density in this work is ∼1.05 kA/cm2from a GaInNAs QD laser (50 × 1,700 µm2) at 10 °C. High-temperature operation up to 65 °C was demonstrated from an unbonded GaInNAs QD laser (50 × 1,060 µm2), with high characteristic temperature of 79.4 K in the temperature range of 10–60 °C

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment

Prediction of Protein Domain with mRMR Feature Selection and Analysis

The domains are the structural and functional units of proteins. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop effective methods for predicting the protein domains according to the sequences information alone, so as to facilitate the structure prediction of proteins and speed up their functional annotation. However, although many efforts have been made in this regard, prediction of protein domains from the sequence information still remains a challenging and elusive problem. Here, a new method was developed by combing the techniques of RF (random forest), mRMR (maximum relevance minimum redundancy), and IFS (incremental feature selection), as well as by incorporating the features of physicochemical and biochemical properties, sequence conservation, residual disorder, secondary structure, and solvent accessibility. The overall success rate achieved by the new method on an independent dataset was around 73%, which was about 28–40% higher than those by the existing method on the same benchmark dataset. Furthermore, it was revealed by an in-depth analysis that the features of evolution, codon diversity, electrostatic charge, and disorder played more important roles than the others in predicting protein domains, quite consistent with experimental observations. It is anticipated that the new method may become a high-throughput tool in annotating protein domains, or may, at the very least, play a complementary role to the existing domain prediction methods, and that the findings about the key features with high impacts to the domain prediction might provide useful insights or clues for further experimental investigations in this area. Finally, it has not escaped our notice that the current approach can also be utilized to study protein signal peptides, B-cell epitopes, HIV protease cleavage sites, among many other important topics in protein science and biomedicine

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

Multiple Causes for Delay in Arrival at Hospital in Acute Stroke Patients in Aydin, Turkey

This descriptive, hospital-based study, performed in western Turkey, was designed to assess the level of pre-hospital delay and reasons for such delay in acute stroke patients, taking into consideration certain factors such as socioeconomic status, availability of transport options at onset of symptoms. Data were collected from hospital records, and a questionnaire was administered that included questions about socio-demographics, self-reported risk factors and questions related to hospital arrival. The rate of patients arriving at the hospital more than 3 hours after symptom onset was found to be 31.6% for this study. Approximately 1/3 of patients delayed going to the hospital because they were waiting for symptoms to go away while 1/3 of patients were not aware of the importance of seeking immediate medical help. There was a significant relationship between the use of ambulance transportation and length of time before arrival at the hospitals, though there was no statistically significantly relationship between the existence of stroke risk factors and hospital arrival delay. These results will likely be helpful to health care decision makers as they develop a model for stroke health care and community based training

Worth the ‘EEfRT’? The Effort Expenditure for Rewards Task as an Objective Measure of Motivation and Anhedonia

Background: Of the putative psychopathological endophenotypes in major depressive disorder (MDD), the anhedonic subtype is particularly well supported. Anhedonia is generally assumed to reflect aberrant motivation and reward responsivity. However, research has been limited by a lack of objective measures of reward motivation. We present the Effort-Expenditure for Rewards Task (EEfRT or ‘‘effort’’), a novel behavioral paradigm as a means of exploring effort-based decision-making in humans. Using the EEfRT, we test the hypothesis that effort-based decision-making is related to trait anhedonia. Methods/Results: 61 undergraduate students participated in the experiment. Subjects completed self-report measures of mood and trait anhedonia, and completed the EEfRT. Across multiple analyses, we found a significant inverse relationship between anhedonia and willingness to expend effort for rewards. Conclusions: These findings suggest that anhedonia is specifically associated with decreased motivation for rewards, and provide initial validation for the EEfRT as a laboratory-based behavioral measure of reward motivation and effort-base

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians

BACKGROUND: Although vitamin D receptor (VDR) polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG (f allele), abolishing the first translation initiation site and resulting in a peptide lacking the first three amino acids (F allele). We examined the role of this polymorphism in insulin sensitivity and beta cell function. This study included 49 healthy Caucasian subjects (28 females, age 28 ± 1 years old, body mass index 24.57 ± 0.57 kg/m(2), waist-hip ratio 0.81 ± 0.01 cm/cm). They were all normotensive (less than 140/90 mmHg) and glucose tolerant, which was determined by a standard 75-gm oral glucose tolerance test. Their beta cell function (%B) and insulin sensitivity (%S) were calculated based on the Homeostasis Model Assessment (HOMA). Their genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism analysis. Phenotypes were compared between genotypic groups. RESULTS: There were 18 FF, 21 Ff, and 10 ff subjects. Since only 10 ff subjects were identified, they were pooled with the Ff subjects during analyses. The FF and Ff/ff groups had similar glucose levels at each time point before and after a glucose challenge. The Ff/ff group had higher insulin levels than the FF group at fasting (P=0.006), 30 minutes (P=0.009), 60 minutes (P=0.049), and 90 minutes (P=0.042). Furthermore, the Ff/ff group also had a larger insulin area under the curve than the FF group (P=0.009). While no difference was noted in %B, the Ff/ff group had a lower %S than the FF group (0.53 vs. 0.78, P=0.006). A stepwise regression analysis confirmed that the Fok I polymorphism was an independent determinant for %S, accounting for 29.3% of variation in %S when combined with waist-hip ratio. CONCLUSIONS: We report that the Fok I polymorphism at the VDR gene locus is associated with insulin sensitivity, but has no influence on beta cell function in healthy Caucasians. Although this polymorphism has been shown to affect the activation of vitamin D-dependent transcription, the molecular basis of the association between this polymorphism and insulin resistance remains to be determined

Quality of reporting according to the CONSORT, STROBE and Timmer instrument at the American Burn Association (ABA) annual meetings 2000 and 2008

<p>Abstract</p> <p>Background</p> <p>The quality of oral and poster conference presentations differ. We hypothesized that the quality of reporting is better in oral abstracts than in poster abstracts at the American Burn Association (ABA) conference meeting.</p> <p>Methods</p> <p>All 511 abstracts (2000: N = 259, 2008: N = 252) from the ABA annual meetings in year 2000 and 2008 were screened. RCT's and obervational studies were analyzed by two independent examiners regarding study design and quality of reporting for randomized-controlled trials (RCT) by CONSORT criteria, observational studies by the STROBE criteria and additionally the Timmer instrument.</p> <p>Results</p> <p>Overall, 13 RCT's in 2000 and 9 in 2008, 77 observational studies in 2000 and 98 in 2008 were identified. Of the presented abstracts, 5% (oral; 7%(n = 9) vs. poster; 3%(n = 4)) in 2000 and 4% ((oral; 5%(n = 7) vs. poster; 2%(n = 2)) in 2008 were randomized controlled trials. The amount of observational studies as well as experimental studies accepted for presentation was not significantly different between oral and poster in both years. Reporting quality of RCT was for oral vs. poster abstracts in 2000 (CONSORT; 7.2 ± 0.8 vs. 7 ± 0, p = 0.615, CI -0.72 to 1.16, Timmer; 7.8 ± 0.7 vs. 7.5 ± 0.6,) and 2008 (CONSORT; 7.2 ± 1.4 vs. 6.5 ± 1, Timmer; 9.7 ± 1.1 vs. 9.5 ± 0.7). While in 2000, oral and poster abstracts of observational studies were not significantly different for reporting quality according to STROBE (STROBE; 8.3 ± 1.7 vs. 8.9 ± 1.6, p = 0.977, CI -37.3 to 36.3, Timmer; 8.6 ± 1.5 vs. 8.5 ± 1.4, p = 0.712, CI -0.44 to 0.64), in 2008 oral observational abstracts were significantly better than posters (STROBE score; 9.4 ± 1.9 vs. 8.5 ± 2, p = 0.005, CI 0.28 to 1.54, Timmer; 9.4 ± 1.4 vs. 8.6 ± 1.7, p = 0.013, CI 0.32 to 1.28).</p> <p>Conclusions</p> <p>Poster abstract reporting quality at the American Burn Association annual meetings in 2000 and 2008 is not necessarily inferior to oral abstracts as far as study design and reporting quality of clinical trials are concerned. The primary hypothesis has to be rejected. However, endorsement for the comprehensive use of the CONSORT and STROBE criteria might further increase the quality of reporting ABA conference abstracts in the future.</p

Triclosan Disrupts SKN-1/Nrf2- Mediated Oxidative Stress Response in C. elegans and Human Mesenchymal Stem Cells

Triclosan (TCS), an antimicrobial chemical with potential endocrine-disrupting properties, may pose a risk to early embryonic development and cellular homeostasis during adulthood. Here, we show that TCS induces toxicity in both the nematode C. elegans and human mesenchymal stem cells (hMSCs) by disrupting the SKN-1/Nrf2-mediated oxidative stress response. Specifically, TCS exposure affected C. elegans survival and hMSC proliferation in a dose-dependent manner. Cellular analysis showed that TCS inhibited the nuclear localization of SKN-1/Nrf2 and the expression of its target genes, which were associated with oxidative stress response. Notably, TCS-induced toxicity was significantly reduced by either antioxidant treatment or constitutive SKN-1/Nrf2 activation. As Nrf2 is strongly associated with aging and chemoresistance, these findings will provide a novel approach to the identification of therapeutic targets and disease treatment