The effects of temperature on nitrous oxide and oxygen mixture homogeneity and stability

<p>Abstract</p> <p>Background</p> <p>For many long standing practices, the rationale for them is often lost as time passes. This is the situation with respect to the storage and handling of equimolar 50% nitrous oxide and 50% oxygen volume/volume (v/v) mixtures.</p> <p>Methods</p> <p>A review was undertaken of existing literature to examine the developmental history of nitrous oxide and oxygen mixtures for anesthesia and analgesia and to ascertain if sufficient bibliographic data was available to support the position that the contents of a cylinder of a 50%/50% volume/volume (v/v) mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage and if justification could be found for the standard instructions given for handling before use.</p> <p>Results</p> <p>After ranking and removing duplicates, a total of fifteen articles were identified by the various search strategies and formed the basis of this literature review. Several studies were identified that confirmed that 50%/50% v/v mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage. The effect of temperature on the change of phase of the nitrous oxide in this mixture was further examined by several authors. These studies demonstrated that although it is possible to cause condensation and phase separation by cooling the cylinder, by allowing the cylinder to rewarm to room temperature for at least 48 hours, preferably in a horizontal orientation, and inverting it three times before use, the cylinder consistently delivered the proper proportions of the component gases as a homogenous mixture.</p> <p>Conclusions</p> <p>The contents of a cylinder of a 50%/50% volume/volume (v/v) mixture of nitrous oxide and oxygen is in a homogenous single gas phase in a filled cylinder under normal conditions of handling and storage. The standard instructions given for handling before are justified based on previously conducted studies.</p

BRCA1-deficient mammary tumor cells are dependent on EZH2 expression and sensitive to Polycomb Repressive Complex 2-inhibitor 3-deazaneplanocin A

10.1186/bcr2354Breast Cancer Research114R6

Assessment of risk factors related to healthcare-associated methicillin-resistant Staphylococcus aureus infection at patient admission to an intensive care unit in Japan

<p>Abstract</p> <p>Background</p> <p>Healthcare-associated methicillin-resistant <it>Staphylococcus aureus </it>(HA-MRSA) infection in intensive care unit (ICU) patients prolongs ICU stay and causes high mortality. Predicting HA-MRSA infection on admission can strengthen precautions against MRSA transmission. This study aimed to clarify the risk factors for HA-MRSA infection in an ICU from data obtained within 24 hours of patient ICU admission.</p> <p>Methods</p> <p>We prospectively studied HA-MRSA infection in 474 consecutive patients admitted for more than 2 days to our medical, surgical, and trauma ICU in a tertiary referral hospital in Japan. Data obtained from patients within 24 hours of ICU admission on 11 prognostic variables possibly related to outcome were evaluated to predict infection risk in the early phase of ICU stay. Stepwise multivariate logistic regression analysis was used to identify independent risk factors for HA-MRSA infection.</p> <p>Results</p> <p>Thirty patients (6.3%) had MRSA infection, and 444 patients (93.7%) were infection-free. Intubation, existence of open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission, were detected as independent prognostic indicators. Patients with intubation or open wound comprised 96.7% of MRSA-infected patients but only 57.4% of all patients admitted.</p> <p>Conclusions</p> <p>Four prognostic variables were found to be risk factors for HA-MRSA infection in ICU: intubation, open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission. Preemptive infection control in patients with these risk factors might effectively decrease HA-MRSA infection.</p

Large Scale Gene Expression Profiles of Regenerating Inner Ear Sensory Epithelia

Loss of inner ear sensory hair cells (HC) is a leading cause of human hearing loss and balance disorders. Unlike mammals, many lower vertebrates can regenerate these cells. We used cross-species microarrays to examine this process in the avian inner ear. Specifically, changes in expression of over 1700 transcription factor (TF) genes were investigated in hair cells of auditory and vestibular organs following treatment with two different damaging agents and regeneration in vitro. Multiple components of seven distinct known signaling pathways were clearly identifiable: TGFβ, PAX, NOTCH, WNT, NFKappaB, INSULIN/IGF1 and AP1. Numerous components of apoptotic and cell cycle control pathways were differentially expressed, including p27KIP and TFs that regulate its expression. A comparison of expression trends across tissues and treatments revealed identical patterns of expression that occurred at identical times during regenerative proliferation. Network analysis of the patterns of gene expression in this large dataset also revealed the additional presence of many components (and possible network interactions) of estrogen receptor signaling, circadian rhythm genes and parts of the polycomb complex (among others). Equal numbers of differentially expressed genes were identified that have not yet been placed into any known pathway. Specific time points and tissues also exhibited interesting differences: For example, 45 zinc finger genes were specifically up-regulated at later stages of cochlear regeneration. These results are the first of their kind and should provide the starting point for more detailed investigations of the role of these many pathways in HC recovery, and for a description of their possible interactions

Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns

Introduction: Five different molecular subtypes of breast cancer have been identified through gene expression profiling. Each subtype has a characteristic expression pattern suggested to partly depend on cellular origin. We aimed to investigate whether the molecular subtypes also display distinct methylation profiles. Methods: We analysed methylation status of 807 cancer-related genes in 189 fresh frozen primary breast tumours and four normal breast tissue samples using an array-based methylation assay. Results: Unsupervised analysis revealed three groups of breast cancer with characteristic methylation patterns. The three groups were associated with the luminal A, luminal B and basal-like molecular subtypes of breast cancer, respectively, whereas cancers of the HER2-enriched and normal-like subtypes were distributed among the three groups. The methylation frequencies were significantly different between subtypes, with luminal B and basal-like tumours being most and least frequently methylated, respectively. Moreover, targets of the polycomb repressor complex in breast cancer and embryonic stem cells were more methylated in luminal B tumours than in other tumours. BRCA2-mutated tumours had a particularly high degree of methylation. Finally, by utilizing gene expression data, we observed that a large fraction of genes reported as having subtype-specific expression patterns might be regulated through methylation. Conclusions: We have found that breast cancers of the basal-like, luminal A and luminal B molecular subtypes harbour specific methylation profiles. Our results suggest that methylation may play an important role in the development of breast cancers

Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer

The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators with an expanding tumor suppressor function. KLF2 is one of the prominent members of the family because of its diminished expression in malignancies and its growth-inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the Polycomb group protein Enhancer of Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5′-end of KLF2 is also associated with a gain of trimethylated lysine 27 histone H3 and a depletion of phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A, the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. In this last setting, KLF2 transfection was also associated with decreased dissemination and lower mortality rate. In EZH2-depleted cells, which characteristically have lower tumorigenicity, the induction of KLF2 depletion ‘rescued' partially the oncogenic phenotype, suggesting that KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival

Transgenic technologies to induce sterility

The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes

Transgenic technologies to induce sterility

The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes

Polycomb Target Genes Are Silenced in Multiple Myeloma

Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enriched for previously defined H3K27-tri-methylated genes, targets of the Polycomb group (PcG) proteins in human embryonic fibroblasts. Additionally, the silenced gene signature was more pronounced in ISS stage III MM compared to stage I and II. Using chromatin immunoprecipitation (ChIP) assay on purified CD138+ cells from four MM patients and on two MM cell lines, we found enrichment of H3K27me3 at genes selected from the profile. As the data implied that the Polycomb-targeted gene profile would be highly relevant for pharmacological treatment of MM, we used two compounds to chemically revert the H3K27-tri-methylation mediated gene silencing. The S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin (DZNep) and the histone deacetylase inhibitor LBH589 (Panobinostat), reactivated the expression of genes repressed by H3K27me3, depleted cells from the PRC2 component EZH2 and induced apoptosis in human MM cell lines. In the immunocompetent 5T33MM in vivo model for MM, treatment with LBH589 resulted in gene upregulation, reduced tumor load and increased overall survival. Taken together, our results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex. The importance of the underexpressed gene profile in MM tumor initiation and progression should be subjected to further studies

Global cooling as a driver of diversification in a major marine clade

Climate is a strong driver of global diversity and will become increasingly important as human influences drive temperature changes at unprecedented rates. Here we investigate diversification and speciation trends within a diverse group of aquatic crustaceans, the Anomura. We use a phylogenetic framework to demonstrate that speciation rate is correlated with global cooling across the entire tree, in contrast to previous studies. Additionally, we find that marine clades continue to show evidence of increased speciation rates with cooler global temperatures, while the single freshwater clade shows the opposite trend with speciation rates positively correlated to global warming. Our findings suggest that both global cooling and warming lead to diversification and that habitat plays a role in the responses of species to climate change. These results have important implications for our understanding of how extant biota respond to ongoing climate change and are of particular importance for conservation planning of marine ecosystems