Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus

Several neurotransmitters, including GABA acting at presynaptic GABAB receptors, modulate glutamate release at synapses between hippocampal mossy fibers and CA3 pyramidal neurons. This phenomenon gates excitation of the hippocampus and may therefore prevent limbic seizure propagation. Here we report that status epilepticus, triggered by either perforant path stimulation or pilocarpine administration, was followed 24 hr later by a loss of GABAB receptor-mediated heterosynaptic depression among populations of mossy fibers. This was accompanied by a decrease in the sensitivity of mossy fiber transmission to the exogenous GABAB receptor agonist baclofen. Autoradiography revealed a reduction in GABAB receptor binding in the stratum lucidum after status epilepticus. Failure of GABAB receptor-mediated modulation of mossy fiber transmission at mossy fibers may contribute to the development of spontaneous seizures after status epilepticus

Photorefractive planar waveguides in BaTiO₃ fabricated by ion-beam implantation

For the first time to our knowledge, photorefractive properties have been observed in planar waveguides fabricated by the technique of ion-beam implantation in BaTiO3 single crystals. The implantation was carried out by using 1.5 MeV H+ ions at a dose of 10-16 ions/cm2. For a given input power, a decrease in the effective photo-refractive two-beam coupling response time of ≥102 has been observed, owing to a combination of optical confinement within the waveguide and possible modification of charge-transport properties induced through implantation. Experiments carried out on the two-beam coupling gain show that the gain direction has been reversed in the waveguide compared with that of the bulk crystal

BaTiO₃ waveguide self-pumped phase conjugator

For the first time to our knowledge, self-pumped phase conjugation is reported in a planar waveguide structure in a BaTiO3 single crystal. The waveguide was fabricated by the technique of ion implantation, with 1.5-MeV H+ ions at a dose of 1016 ions/cm2. Phase-conjugate reflectivities >20% have been measured for waveguide self-pumped phase conjugation, and, for a given input power, an order-of-magnitude reduction in the response time is observed in the waveguide compared with the bulk. The fidelity of phase conjugation in the guide is also discussed

Clinical delineation and natural history of the PIK3CA-related overgrowth spectrum.

Somatic mutations in the phosphatidylinositol/AKT/mTOR pathway cause segmental overgrowth disorders. Diagnostic descriptors associated with PIK3CA mutations include fibroadipose overgrowth (FAO), Hemihyperplasia multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, Scoliosis/skeletal and spinal (CLOVES) syndrome, macrodactyly, and the megalencephaly syndrome, Megalencephaly-Capillary malformation (MCAP) syndrome. We set out to refine the understanding of the clinical spectrum and natural history of these phenotypes, and now describe 35 patients with segmental overgrowth and somatic PIK3CA mutations. The phenotypic data show that these previously described disease entities have considerable overlap, and represent a spectrum. While this spectrum overlaps with Proteus syndrome (sporadic, mosaic, and progressive) it can be distinguished by the absence of cerebriform connective tissue nevi and a distinct natural history. Vascular malformations were found in 15/35 (43%) and epidermal nevi in 4/35 (11%) patients, lower than in Proteus syndrome. Unlike Proteus syndrome, 31/35 (89%) patients with PIK3CA mutations had congenital overgrowth, and in 35/35 patients this was asymmetric and disproportionate. Overgrowth was mild with little postnatal progression in most, while in others it was severe and progressive requiring multiple surgeries. Novel findings include: adipose dysregulation present in all patients, unilateral overgrowth that is predominantly left-sided, overgrowth that affects the lower extremities more than the upper extremities and progresses in a distal to proximal pattern, and in the most severely affected patients is associated with marked paucity of adipose tissue in unaffected areas. While the current data are consistent with some genotype-phenotype correlation, this cannot yet be confirmed

Observational diagnostics of gas in protoplanetary disks

Protoplanetary disks are composed primarily of gas (99% of the mass). Nevertheless, relatively few observational constraints exist for the gas in disks. In this review, I discuss several observational diagnostics in the UV, optical, near-IR, mid-IR, and (sub)-mm wavelengths that have been employed to study the gas in the disks of young stellar objects. I concentrate in diagnostics that probe the inner 20 AU of the disk, the region where planets are expected to form. I discuss the potential and limitations of each gas tracer and present prospects for future research.Comment: Review written for the proceedings of the conference "Origin and Evolution of Planets 2008", Ascona, Switzerland, June 29 - July 4, 2008. Date manuscript: October 2008. 17 Pages, 6 graphics, 134 reference

Tackling transition:the value of peer mentoring

This paper is aimed at those interested in the promotion of student retention in higher education; particularly those with an interest in peer mentoring as a means of student support. It critically discusses the results of an exploratory study analysing the perceptions of peer mentors and mentees within five universities in the United Kingdom. The aim of the study was to analyse how student peer mentoring can aid transition into university by focusing specifically on how senior students can support their junior counterparts in their first year at university. The paper discusses the results of a survey which was completed by 329 student peer mentors and mentees. Focusing on the benefits and outcomes of participation in Mentoring Programmes, the survey was distinctive in that it asked mentors and mentees similar questions. From a theoretical perspective, the paper contributes to debates about peer support in higher education showing that participation in such programmes can have positive outcomes from both social and pedagogic perspectives. Practically speaking, the results have important implications for Higher Education Institutions as the research highlights the importance of putting into place formally structured Peer Mentoring Programmes which facilitate student support at a time when new students are most at risk of ‘dropping out’

A Historiometric Examination of Machiavellianism and a New Taxonomy of Leadership

Although researchers have extensively examined the relationship between charismatic leadership and Machiavellianism (Deluga, 2001; Gardner & Avolio, 1995; House & Howell, 1992), there has been a lack of investigation of Machiavellianism in relation to alternative forms of outstanding leadership. Thus, the purpose of this investigation was to examine the relationship between Machiavellianism and a new taxonomy of outstanding leadership comprised of charismatic, ideological, and pragmatic leaders. Using an historiometric approach, raters assessed Machiavellianism via the communications of 120 outstanding leaders in organizations across the domains of business, political, military, and religious institutions. Academic biographies were used to assess twelve general performance measures as well as twelve general controls and five communication specific controls. The results indicated that differing levels of Machiavellianism is evidenced across the differing leader types as well as differing leader orientation. Additionally, Machiavellianism appears negatively related to performance, though less so when type and orientation are taken into account.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts infectivity and fusogenicity

The SARS-CoV-2 Omicron BA.1 variant emerged in 20211 and has multiple mutations in its spike protein2. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Imaging the rotationally state-selected NO(A,n) product from the predissociation of the A state of the NO-Ar van der Waals cluster

The origin of the resonant structures in the spectrum of the predissociative part of the A state in the NO-Ar van der Waals cluster has been investigated. We have employed direct excitation to the predissociative part of the NO-Ar A state followed by rotational state selective ionization of the NO fragment. Velocity map imaging of the NO ion yields the recoil energy of the rotational state-selected fragment. A substantial contribution of rotational hotbands to the resonant structures is observed. Our data indicate that a centrifugal barrier as the origin of these resonances can be ruled out. We hypothesize that after the NO-Ar cluster is excited to the A state sufficient mixing within the rotating cluster takes place as it changes geometry from being T shaped in the NO (X) -Ar state to linear in the NO (A) -Ar state. This mixing allows the low energy and high angular momentum (J≈4.5) tumbling motion of the initially populated hotbands in the ground state NO (X) -Ar complex to be converted into NO (A,n=2) spinning rotation in the A state of the complex. The electronically excited spinning complex falls apart adiabatically producing rotationally excited NO (A,n=2) at the energetic threshold. This interpretation indicates that the resonances can be attributed to some type of vibrational Feshbach resonance. The appearance energy for the formation of NO (A,n=0) +Ar is found to be 44294.3±1.4 cm-1. © 2009 American Institute of Physics