Murine Neural Stem/Progenitor Cells Protect Neurons against Ischemia by HIF-1α–Regulated VEGF Signaling

Focal cerebral ischemia following middle cerebral artery occlusion (MCAO) stimulates a robust cytogenic response from the adult subventricular zone (SVZ) that includes massive proliferation of neural stem/progenitor cells (NSPCs) and cellular migration into the injury area. To begin to explore beneficial roles of NSPCs in this response, we investigated the ability of embryonic and postnatal NSPCs to promote neuronal survival under conditions of in vivo and in vitro ischemia. Intracerebral transplantation of NSPCs attenuated neuronal apoptosis in response to focal ischemia induced by transient MCAO, and prevented neuronal cell death of cortical neurons in response to oxygen-glucose deprivation (OGD) in culture. NSPC-mediated neuroprotection was blocked by the pharmacological inhibitors of vascular endothelial growth factor (VEGF), SU1498 and Flt-1Fc. Embryonic and postnatal NSPCs were both intrinsically resistant to brief OGD exposure, and constitutively expressed both hypoxia-inducible factor 1α (HIF-1α) transcription factor and its downstream target, VEGF. Genomic deletion of HIF-1α by Cre-mediated excision of exon 2 in NSPC cultures resulted in >50% reduction of VEGF production and ablation of NSPC-mediated neuroprotection. These findings indicate that NSPCs promote neuronal survival under ischemic conditions via HIF-1α-VEGF signaling pathways and support a role for NSPCs in promotion of neuronal survival following stroke

Deoxydehydration of vicinal diols and polyols catalyzed by pyridinium perrhenate salts

Simple ammonium and pyridinium perrhenate salts were evaluated as catalysts for the deoxydehydration (DODH) of diols into alkenes. Pyridinium perrhenates were found to be effective catalysts at much lower temperatures than those in previous reports, outperforming primary, secondary, and tertiary ammonium salts, while quaternary ammonium salts are effectively inactive. The mechanism of reaction was studied computationally using DFT calculations which indicate that proton shuttling between the ion pair is intrinsic to the mechanism and that the reduction of rhenium by the phosphine occurs before the diol condensation

Is geographical variation driving the transcriptomic responses to multiple stressors in the kelp Saccharina latissima

Background: Kelps (Laminariales, Phaeophyceae) are brown macroalgae of utmost ecological, and increasingly economic, importance on temperate to polar rocky shores. Omics approaches in brown algae are still scarce and knowledge of their acclimation mechanisms to the changing conditions experienced in coastal environments can benefit from the application of RNA-sequencing. Despite evidence of ecotypic differentiation, transcriptomic responses from distinct geographical locations have, to our knowledge, never been studied in the sugar kelp Saccharina latissima so far. Results: In this study we investigated gene expression responses using RNA-sequencing of S. latissima from environments with contrasting temperature and salinity conditions – Roscoff, in temperate eastern Atlantic, and Spitsbergen in the Arctic. Juvenile sporophytes derived from uniparental stock cultures from both locations were pre-cultivated at 8 °C and SA 30. Sporophytes acclimated to 0 °C, 8 °C and 15 °C were exposed to a low salinity treatment (SA 20) for 24 h. Hyposalinity had a greater impact at the transcriptomic level than the temperature alone, and its effects were modulated by temperature. Namely, photosynthesis and pigment synthesis were extensively repressed by low salinity at low temperatures. Although some responses were shared among sporophytes from the different sites, marked differences were revealed by principal component analysis, differential expression and GO enrichment. The interaction between low temperature and low salinity drove the largest changes in gene expression in sporophytes from Roscoff while specimens from Spitsbergen required more metabolic adjustment at higher temperatures. Moreover, genes related to cell wall adjustment were differentially expressed between Spitsbergen and Roscoff control samples. Conclusions: Our study reveals interactive effects of temperature and salinity on transcriptomic profiles in S. latissima. Moreover, our data suggest that under identical culture conditions sporophytes from different locations diverge in their transcriptomic responses. This is probably connected to variations in temperature and salinity in their respective environment of origin. The current transcriptomic results support the plastic response pattern in sugar kelp which is a species with several reported ecotypes. Our data provide the baseline for a better understanding of the underlying processes of physiological plasticity and may help in the future to identify strains adapted to specific environments and its genetic control

Genomic sequence and analysis of a vaccinia virus isolate from a patient with a smallpox vaccine-related complication

BACKGROUND: Vaccinia virus (VACV)-DUKE was isolated from a lesion on a 54 year old female who presented to a doctor at the Duke University Medical Center. She was diagnosed with progressive vaccinia and treated with vaccinia immune globulin. The availability of the VACV-DUKE genome sequence permits a first time genomic comparison of a VACV isolate associated with a smallpox vaccine complication with the sequence of culture-derived clonal isolates of the Dryvax vaccine. RESULTS: This study showed that VACV-DUKE is most similar to VACV-ACAM2000 and CLONE3, two VACV clones isolated from the Dryvax(® )vaccine stock confirming VACV-DUKE as an isolate from Dryvax(®). However, VACV-DUKE is unique because it is, to date, the only Dryvax(® )clone isolated from a patient experiencing a vaccine-associated complication. The 199,960 bp VACV-DUKE genome encodes 225 open reading frames, including 178 intact genes and 47 gene fragments. Between VACV-DUKE and the other Dryvax(® )isolates, the major genomic differences are in fragmentation of the ankyrin-like, and kelch-like genes, presence of a full-length Interferon-α/β receptor gene, and the absence of a duplication of 12 ORFs in the inverted terminal repeat. Excluding this region, the DNA sequence of VACV-DUKE differs from the other two Dryvax(® )isolates by less than 0.4%. DNA sequencing also indicated that there was little heterogeneity in the sample, supporting the hypothesis that virus from an individual lesion is clonal in origin despite the fact that the vaccine is a mixed population. CONCLUSION: Virus in lesions that result from progressive vaccinia following vaccination with Dryvax are likely clonal in origin. The genomic sequence of VACV-DUKE is overall very similar to that of Dryvax(® )cell culture-derived clonal isolates. Furthermore, with the sequences of multiple clones from Dryvax(® )we can begin to appreciate the diversity of the viral population in the smallpox vaccine

Bis(2,2′-bipyridine-κ2 N,N′)(maleato-κ2 O 1,O 1′)nickel(II) 7.34-hydrate

The title compound, [Ni(C4H2O4)(C10H8N2)2]·7.34H2O, was obtained by crystallization from an aqueous ethano­lic reaction mixture containing nickel(II) acetate, maleic acid, bipyridine, sodium hydroxide and ammonia. The asymmetric unit contains one independent complex mol­ecule and 7.34 water mol­ecules occupying eight crystallographically independent positions. Two of these water molecules are disordered. The nickel(II) atom is coordinated in a distorted octa­hedral geometry by two O atoms from one carboxyl­ate group of the maleato ligand and by four N atoms from two 2,2′-bipyridine (bipy) ligands. The water mol­ecules, along with the O atoms of the uncoordinated carboxyl­ate group, form an extended hydro­philic three-dimensional hydrogen-bonded system with large cavities in which the hydro­phobic bipy ligands are located. One H atom of the maleate ligand is involved in a weak hydrogen bond of the C—H⋯O type. Stacking inter­actions between the pyridyl rings of the bipy ligands [centroid–centroid distance = 3.549 (15) Å] lead to the formation of pairs of complex mol­ecules

Matrix Theory Description of Schwarzschild Black Holes in the Regime N >> S

We study the description of Schwarzschild black holes, of entropy S, within matrix theory in the regime $N \ge S \gg 1$. We obtain the most general matrix theory equation of state by requiring that black holes admit a description within this theory. It has a recognisable form in various cases. In some cases a D dimensional black hole can plausibly be thought of as a $\tilde{D} = D + 1$ dimensional black hole, described by another auxiliary matrix theory, but in its $\tilde{N} \sim S$ regime. We find what appears to be a matrix theory generalisation to higher dynamical branes of the normalisation of dynamical string tension, seen in other contexts. We discuss a further possible generalisation of the matrix theory equation of state. In a special case, it is governed by $N^3$ dynamical degrees of freedom.Comment: 22 pages. Latex fil

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

The next detectors for gravitational wave astronomy

This paper focuses on the next detectors for gravitational wave astronomy which will be required after the current ground based detectors have completed their initial observations, and probably achieved the first direct detection of gravitational waves. The next detectors will need to have greater sensitivity, while also enabling the world array of detectors to have improved angular resolution to allow localisation of signal sources. Sect. 1 of this paper begins by reviewing proposals for the next ground based detectors, and presents an analysis of the sensitivity of an 8 km armlength detector, which is proposed as a safe and cost-effective means to attain a 4-fold improvement in sensitivity. The scientific benefits of creating a pair of such detectors in China and Australia is emphasised. Sect. 2 of this paper discusses the high performance suspension systems for test masses that will be an essential component for future detectors, while sect. 3 discusses solutions to the problem of Newtonian noise which arise from fluctuations in gravity gradient forces acting on test masses. Such gravitational perturbations cannot be shielded, and set limits to low frequency sensitivity unless measured and suppressed. Sects. 4 and 5 address critical operational technologies that will be ongoing issues in future detectors. Sect. 4 addresses the design of thermal compensation systems needed in all high optical power interferometers operating at room temperature. Parametric instability control is addressed in sect. 5. Only recently proven to occur in Advanced LIGO, parametric instability phenomenon brings both risks and opportunities for future detectors. The path to future enhancements of detectors will come from quantum measurement technologies. Sect. 6 focuses on the use of optomechanical devices for obtaining enhanced sensitivity, while sect. 7 reviews a range of quantum measurement options

Is the giant radio galaxy M 87 a TeV gamma-ray emitter?

For the first time an excess of photons above an energy threshold of 730 GeV from the giant radio galaxy M 87 has been measured at a significance level above 4 σ. The data have been taken during the years 1998 and 1999 with the HEGRA stereoscopic system of 5 imaging atmospheric Cherenkov telescopes. The excess of 107.4 ± 26.8 events above 730 GeV corresponds to an integral flux of 3.3% of the Crab flux or Nγ (E > 730 GeV) = (0.96 ± 0.23) × 10-12 phot cm-2 s-1. M 87 is located at the center of the Virgo cluster of galaxies at a relatively small redshift of z = 0.00436 and is a promising candidate among the class of giant radio galaxies for the emission of TeV γ-radiation. The detection of TeV γ-rays from M 87 - if confirmed - would establish a new class of extragalactic source in this energy regime since all other AGN detected to date at TeV energies are BL Lac type objects.F. A. Aharonian ...G. P. Rowell...et al