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Discovery of Procognitive Antipsychotics by Combining Muscarinic M1 Receptor Structure-Activity Relationship with Systems Response Profiles in Zebrafish Larvae

Current antipsychotic drugs are notably ineffective at addressing the cognitive deficits associated with schizophrenia. N-Desmethylclozapine (NDMC), the major metabolite of clozapine, displays muscarinic M1 receptor (M1) agonism, an activity associated with improvement in cognitive functioning. Preclinical and clinical data support that M1 agonism may be a desired activity in antipsychotic drugs.

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally

Preeclampsia is Associated with Sex-Specific Transcriptional and Proteomic Changes in Fetal Erythroid Cells

Preeclampsia (PE) has been associated with placental dysfunction, resulting in fetal hypoxia, accelerated erythropoiesis, and increased erythroblast count in the umbilical cord blood (UCB). Although the detailed effects remain unknown, placental dysfunction can also cause inflammation, nutritional, and oxidative stress in the fetus that can affect erythropoiesis. Here, we compared the expression o

On norovirus outbreaks and transmission in hospitals

Abstract Noroviruses are now the leading cause of gastroenteritis worldwide. Noroviruses are effectively transmitted due to a low infectious dose, viral shedding in high concentrations, environmental stability, and they induce only a limited immunity after infection. Especially, the norovirus variants of genotype II.4 (GII.4) have seemed greatly adapted for pandemic spread. The high infectivity of

Lin28b controls a neonatal to adult switch in B cell positive selection

The ability of B-1 cells to become positively selected into the mature B cell pool, despite being weakly self-reactive, has puzzled the field since its initial discovery. Here, we explore changes in B cell positive selection as a function of developmental time by exploiting a link between CD5 surface levels and the natural occurrence of self-reactive B cell receptors (BCRs) in BCR wild-type mice.

Leading with a cool head and a warm heart : trait-based leadership resources linked to task performance, perceived stress, and work engagement

Leaders of today need to achieve well in terms of task performance, perceiving low stress, and having high levels of work engagement. One may ask whether trait-based leadership resource factors can be identified and how such resource factors might relate to task performance, perceived stress, and work engagement. Our aim was to test the hypothesis, derived from Hobfoll’s motivational Conservation

Infrared Photodetectors based on InSb and InAs Nanostructures via Heterogeneous Integration-Rapid Melt Growth and Template Assisted Selective Epitaxy

Monolithic heterogeneous integration of III-V semiconductors with the contemporary Si Complementary Metal Oxide Semiconductor (CMOS) technology has instigated a wide range of possibilities and functionalities in the semiconductor industry, in the field of digital circuits, optical sensors, light emitters, and high-frequency communication devices. However, the integration of III-V semiconductors is

Are there trans and queer methodologies? Methodological negotiations on gender and sexuality

Are there research methods and methodologies that are inherently queer or transfeminist in empirical research? This is a question I wrestle with often. And I am not alone, although methodological discussions are less central in queer and transfeminist knowledge production than in the wider feminist field. Transfeminist discussions of methodology often set our from a research ethics starting point;

Generating GABAergic interneurons through reprogramming and differentiation strategies : English

In recent years reprogramming techniques, differentiation protocols, and sequencing analysis have opened a field for generating and studying human-derived neurons with greater potential than ever before. This has generated a large number of studies with the goal of deriving bona fide neurons. Both direct reprogramming and differentiation have benefits and drawbacks, while direct reprogramming can

Investigating Design Rules for Photoinduced Electron Transfer Quenching in Triangulenium Probes

Fluorescent probes based on photoinduced electron transfer (PET) quenching of long lifetime triangulenium fluorophores have found multiple applications. For such probes a successful design relies on the right balance between the rate of PET quenching and fluorescence. In a series of ADOTA (A) and DAOTA (D) triangulenium fluorophores appended with aniline-like quencher moieties, we have investigate

Solvent-Dependent Structural Dynamics in the Ultrafast Photodissociation Reaction of Triiodide Observed with Time-Resolved X-ray Solution Scattering

Resolving the structural dynamics of bond breaking, bond formation, and solvation is required for a deeper understanding of solution-phase chemical reactions. In this work, we investigate the photodissociation of triiodide in four solvents using femtosecond time-resolved X-ray solution scattering following 400 nm photoexcitation. Structural analysis of the scattering data resolves the solvent-depe

Intermediate states in Andreev bound state fusion

Hybridization is one of the most fundamental quantum mechanical phenomena, with the text book example of binding two hydrogen atoms in a hydrogen molecule. Here we report tunnel spectroscopy experiments illustrating the hybridization of another type of discrete quantum states, namely of superconducting subgap states that form in segments of a semiconducting nanowire in contact with superconducting

Ultrafast Jahn-Teller Photoswitching in Cobalt Single-Ion Magnets

Single-ion magnets (SIMs) constitute the ultimate size limit in the quest for miniaturizing magnetic materials. Several bottlenecks currently hindering breakthroughs in quantum information and communication technologies could be alleviated by new generations of SIMs displaying multifunctionality. Here, ultrafast optical absorption spectroscopy and X-ray emission spectroscopy are employed to track

Self-Heating in Gate-All-Around Vertical III-V InAs/InGaAs MOSFETs

We investigate self-heating in vertical, gate-all-around III-V InAs/InGaAs nanowire MOSFETs using pulsed IV measurements at various temperatures. Low temperature measurements reveal a negative output conductance indicating self-heating in the transistor. Under pulsed measurements, an increase in drain current (15%) and transconductance (30%) are observed at room temperature, with values influenced

Energetics of Microwaves Probed by Double Quantum Dot Absorption

We explore the energetics of microwaves interacting with a double quantum dot photodiode and show wave-particle aspects in photon-assisted tunneling. The experiments show that the single-photon energy sets the relevant absorption energy in a weak-drive limit, which contrasts the strong-drive limit where the wave amplitude determines the relevant-energy scale and opens up microwave-induced bias tri

Preparation of colloidal molecules with temperature-tunable interactions from oppositely charged microgel spheres

The self-assembly of small colloidal clusters, so-called colloidal molecules, into crystalline materials has proven extremely challenging, the outcome often being glassy, amorphous states where positions and orientations are locked. In this paper, a new type of colloidal molecule is therefore prepared, assembled from poly(N-isopropylacrylamide) (PNIPAM)-based microgels that due to their well docum

The Effect of Canthotomy on Blood Perfusion During the Repair of Lower Eyelid Defects

PURPOSE: Canthotomy is frequently used to mobilize extra tissue when repairing larger lower eyelid defects. The aim of this study was to explore the effect of canthotomy on blood perfusion and oxygen tension.METHODS: Eight pigs underwent a wedge resection of the lower eyelid and canthotomy (with cantholysis involving the lateral palpebral artery). The wedge resection was performed 8, 6, and 4 mm f