Induction of Anti-Hebbian LTP in CA1 Stratum Oriens Interneurons: Interactions between Group I Metabotropic Glutamate Receptors and M1 Muscarinic Receptors

An anti-Hebbian form of LTP is observed at excitatory synapses made with some hippocampal interneurons. LTP induction is facilitated when postsynaptic interneurons are hyperpolarized, presumably because Ca(2+) entry through Ca(2+)-permeable glutamate receptors is enhanced. The contribution of modulatory transmitters to anti-Hebbian LTP induction remains to be established. Activation of group I metabotropic receptors (mGluRs) is required for anti-Hebbian LTP induction in interneurons with cell bodies in the CA1 stratum oriens. This region receives a strong cholinergic innervation from the septum, and muscarinic acetylcholine receptors (mAChRs) share some signaling pathways and cooperate with mGluRs in the control of neuronal excitability.We therefore examined possible interactions between group I mGluRs and mAChRs in anti-Hebbian LTP at synapses which excite oriens interneurons in rat brain slices. We found that blockade of either group I mGluRs or M1 mAChRs prevented the induction of anti-Hebbian LTP by pairing presynaptic activity with postsynaptic hyperpolarization. Blocking either receptor also suppressed long-term effects of activation of the other G-protein coupled receptor on interneuron membrane potential. However, no crossed blockade was detected for mGluR or mAchR effects on interneuron after-burst potentials or on the frequency of miniature EPSPs. Paired recordings between pyramidal neurons and oriens interneurons were obtained to determine whether LTP could be induced without concurrent stimulation of cholinergic axons. Exogenous activation of mAChRs led to LTP, with changes in EPSP amplitude distributions consistent with a presynaptic locus of expression. LTP, however, required noninvasive presynaptic and postsynaptic recordings

The p21 cip1/waf1 cyclin-dependent kinase inhibitor enhances the cytotoxic effect of cisplatin in human ovarian carcinoma cells

The seriousness of ovarian cancer, which is related to the observed link between recurrency and cell cycle control defect, prompted us to explore the effect of ectopic expression of the cdk inhibitor p21cip1/waf1 on ovarian carcinoma chemosensitivity. The transfection of p21cip1/waf1 cDNA into SKOV3 and OVCAR3 cells led to reduction of tumor cell growth, enhanced susceptibility to cisplatin-induced apoptosis, and abolition of recurrency after cisplatin exposure. p21cip1/waf1 gene transfer allowed a marked reduction of the cisplatin concentration needed to erradicate the tumor cell population. These results suggest exploring the possible use of p21cip1/waf1 as an adjunctive to conventional chemotherapy

Targeting the Replication Initiator of the Second Vibrio Chromosome: Towards Generation of Vibrionaceae-Specific Antimicrobial Agents

The Vibrionaceae is comprised of numerous aquatic species and includes several human pathogens, such as Vibrio cholerae, the cause of cholera. All organisms in this family have two chromosomes, and replication of the smaller one depends on rctB, a gene that is restricted to the Vibrionaceae. Given the increasing prevalence of multi-drug resistance in pathogenic vibrios, there is a need for new targets and drugs to combat these pathogens. Here, we carried out a high throughput cell-based screen to find small molecule inhibitors of RctB. We identified a compound that blocked growth of an E. coli strain bearing an rctB-dependent plasmid but did not influence growth of E. coli lacking this plasmid. This compound, designated vibrepin, had potent cidal activity against V. cholerae and inhibited the growth of all vibrio species tested. Vibrepin blocked RctB oriCII unwinding, apparently by promoting formation of large non-functional RctB complexes. Although vibrepin also appears to have targets other than RctB, our findings suggest that RctB is an attractive target for generation of novel antibiotics that only block growth of vibrios. Vibrio-specific agents, unlike antibiotics currently used in clinical practice, will not engender resistance in the normal human flora or in non-vibrio environmental microorganisms

New infrared star clusters in the Northern and Equatorial Milky Way with 2MASS

We carried out a survey of infrared star clusters and stellar groups on the 2MASS J, H and K_s all-sky release Atlas in the Northern and Equatorial Milky Way (350 < l < 360, 0 < l < 230). The search in this zone complements that in the Southern Milky Way (Dutra et al. 2003a). The method concentrates efforts on the directions of known optical and radio nebulae. The present study provides 167 new infrared clusters, stellar groups and candidates. Combining the two studies for the whole Milky Way, 346 infrared clusters, stellar groups and candidates were discovered, whereas 315 objects were previously known. They constitute an important new sample for future detailed studies.Comment: Accepted to Astronomy and Astrophysic

SPI observations of the diffuse 60Fe emission in the Galaxy

Gamma-ray line emission from radioactive decay of 60Fe provides constraints on nucleosynthesis in massive stars and supernovae. The spectrometer SPI on board INTEGRAL has accumulated nearly three years of data on gamma-ray emission from the Galactic plane. We have analyzed these data with suitable instrumental-background models and sky distributions to produce high-resolution spectra of Galactic emission. We detect the gamma-ray lines from 60Fe decay at 1173 and 1333 keV, obtaining an improvement over our earlier measurement of both lines with now 4.9 sigma significance for the combination of the two lines. The average flux per line is (4.4 \pm 0.9) \times 10^{-5} ph cm^{-2} s^{-1} rad^{-1} for the inner Galaxy region. Deriving the Galactic 26Al gamma-ray line flux with using the same set of observations and analysis method, we determine the flux ratio of 60Fe/26Al gamma-rays as 0.148 \pm 0.06. The current theoretical predictions are still consistent with our result.Comment: 10 pages, 7 figures, 2 tables, A&A in pres

The Scientific Performance of the Microchannel X-ray Telescope on board the SVOM Mission

The Microchannel X-ray Telescope (MXT) will be the first focusing X-ray telescope based on a "Lobster-Eye" optical design to be flown on Sino-French mission SVOM. SVOM will be dedicated to the study of Gamma-Ray Bursts and more generally time-domain astrophysics. The MXT telescope is a compact (focal length ~ 1.15 m) and light (< 42 kg) instrument, sensitive in the 0.2--10 keV energy range. It is composed of an optical system, based on micro-pore optics (MPOs) of 40 micron pore size, coupled to a low-noise pnCDD X-ray detector. In this paper we describe the expected scientific performance of the MXT telescope, based on the End-to-End calibration campaign performed in fall 2021, before the integration of the SVOM payload on the satellite.Comment: 22 pages, 12 figures, accepted for publication in Experimental Astronom

PLM in SME, what are we missing? an alternative view on PLM implementation for SME

Part 10: PLM Maturity, Implementation and AdoptionInternational audienceToday, the concept of Product Lifecycle Management (PLM) is widely accepted as strategically important. It is used to manage the increasing complexity of products, processes and organizations. The need to adopt PLM is growing rapidly for Small to Medium-sized Enterprises (SME). PLM implementations are costly and require a lot of effort. The business impact and financial risks are high for SME. Also, SMEs seem to have relatively more difficulties to benefit from PLM. The study at hand addresses the question, based on literature research, why these difficulties exist and how they can be overcome. To answer that question, three sub questions are discussed in this paper. (1) A generic PLM implementation process structure. (2) A list of identified PLM implementation challenges, specific for SME. (3) A classification of PLM research for SME, related to the common PLM implementation process structure. A hypothesis for a PLM implementation failure mechanism in SMEs is formulated, based on the findings. Also, a potential research gap on operational implementation knowledge in SMEs is identified

New infrared star clusters in the southern Milky Way with 2MASS

We carried out a 2MASS J, H and K_s survey of infrared star clusters in the Milky Way sector 230$^{\circ}$ $< \ell <$ 350$^{\circ}$. This zone was the least studied in the literature, previously including only 12 infrared clusters or stellar groups with $|b|<$ 10$^{\circ}$, according to the recent catalogue by Bica et al. (2003). We concentrated efforts on embedded clusters, which are those expected in the areas of known radio and optical nebulae. The present study provides 179 new infrared clusters and stellar groups, which are interesting targets for detailed future infrared studies. The sample of catalogued infrared clusters and stellar groups in the Galaxy is now increased by 63%.Comment: 8 pages, 10 figures, accepted to A&A. Tables 3 and 4 available in eletronic form at CD

Power-to-Hydrogen and Hydrogen-to-X pathways: opportunities for next generation energy systems

Energy systems are evolving rapidly around the world, driven mainly by CO2-e reduction targets. This has led to opportunities for integrated low carbon electricity-and-fuel systems founded on large scale “Power-to-Hydrogen, Hydrogen-to-X” (PtH-HtX). Power-to-Hydrogen (PtH) refers to large scale electrolysis. Hydrogen-to-X (HtX) refers to a range of high value products and services. If these pathways start with low-carbon electricity, then the fuel consumed at the downstream end also low-carbon. Use of intermittently low valued power lowers all production costs. This paper specifically identifies the main pathways and interconnections in a way that overcomes the ambiguities inherent in the term “Power-to-Gas”. In turn, this provides solid and easier to understand foundations for building legal and regulatory frameworks for new business opportunities along the lengths of the numerous pathways from supply to consumption.<br/

Regulatory Cross-Talk Links Vibrio cholerae Chromosome II Replication and Segregation

There is little knowledge of factors and mechanisms for coordinating bacterial chromosome replication and segregation. Previous studies have revealed that genes (and their products) that surround the origin of replication (oriCII) of Vibrio cholerae chromosome II (chrII) are critical for controlling the replication and segregation of this chromosome. rctB, which flanks one side of oriCII, encodes a protein that initiates chrII replication; rctA, which flanks the other side of oriCII, inhibits rctB activity. The chrII parAB2 operon, which is essential for chrII partitioning, is located immediately downstream of rctA. Here, we explored how rctA exerts negative control over chrII replication. Our observations suggest that RctB has at least two DNA binding domains—one for binding to oriCII and initiating replication and the other for binding to rctA and thereby inhibiting RctB's ability to initiate replication. Notably, the inhibitory effect of rctA could be alleviated by binding of ParB2 to a centromere-like parS site within rctA. Furthermore, by binding to rctA, ParB2 and RctB inversely regulate expression of the parAB2 genes. Together, our findings suggest that fluctuations in binding of the partitioning protein ParB2 and the chrII initiator RctB to rctA underlie a regulatory network controlling both oriCII firing and the production of the essential chrII partitioning proteins. Thus, by binding both RctB and ParB2, rctA serves as a nexus for regulatory cross-talk coordinating chrII replication and segregation