Biochemistry and Pharmacokinetics Thiamine functions as a coenzyme in more than 24 enzymes, most importantly pyruvate dehydrogenase (for energy production in the Krebs cycle), transketolase (for lipid and glucose metabolism, production of branched chain amino acids, and production and maintenance of myelin sheath), and 2-oxo-glucarate dehydrogenase (for synthesis of acetylcholine, GABA, and glu...

The capability to conditionally inactivate gene function is essential for understanding themolecular basis of development. In geneandmRNA targeting approaches, protein products can perdure, complicating genetic analysis. Current methods for selective protein degradation require drug treatment or take hours for protein removal, limiting their utility in studying rapid developmental processes in ...

D ow noad A key property of modern cities is increasing returns to scale—the finding that many socioeconomic outputs increase more rapidly than their population size. Recent theoretical work proposes that this phenomenon is the result of general network effects typical of human social networks embedded in space and, thus, is not necessarily limited to modern settlements. We examine the extent t...

KChIPs coassemble with pore-forming Kv4 a subunits to form a native complex in the brain and heart and regulate the expression and gating properties of Kv4 K1 channels, but the mechanisms underlying these processes are unknown. Here we report a co-crystal structure of the complex of human Kv4.3 N-terminus and KChIP1 at a 3.2-Å resolution. The structure reveals a unique clamping action of the co...

Primary objective: To examine the predictive associations of family satisfaction, functional impairment, pain, and depression on health-related quality-of-life (HRQoL) among persons with traumatic brain injury (TBI) through structural equation modelling (SEM). Research design: Participants were part of a larger longitudinal study of adjustment following TBI. Direct and indirect effects of predi...

Objectives. Evidence regarding the cost-effectiveness of joint protection and hand exercises for the management of hand OA is not well established. The primary aim of this study is to assess the costeffectiveness (cost-utility) of these management options. In addition, given the absence of consensus regarding the conduct of economic evaluation alongside factorial trials, we compare different an...

Changes in activity-dependent calcium flux through voltage-gated calcium channels (CaVs) drive two self-regulatory calciumdependent feedback processes that require interaction between Ca2+/calmodulin (Ca2+/CaM) and a CaV channel consensus isoleucine-glutamine (IQ) motif: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF). Here, we report the high-resolution structure ...

The formation of a laminar structure such as the mammalian neocortex relies on the coordinated migration of different subtypes of excitatory pyramidal neurons in specific layers. Cyclin-dependent kinase 5 (Cdk5) is a master regulator of pyramidal neuron migration. Recently, we have shown that Cdk5 binds to the serotonin 6 receptor (5-HT6R), a G protein-coupled receptor (GPCR). Here, we investig...

The basolateral amygdala (BLA) mediates the facilitating effects of emotions on memory. The BLA’s enhancing influence extends to various types of memories, including striatal-dependent habit formation. To shed light on the underlying mechanisms, we carried out unit and local field potential (LFP) recordings in BLA, striatum, auditory cortex and intralaminar thalamus in cats trained on a stimulu...

Methods and Results-—Within the prospective Cardiac Arrest Registry to Enhance Survival (CARES), we identified children (age <18 years) with an OHCA from October 2005 to December 2013. Survival to hospital discharge by age (categorized as infants [0 to 1 year], younger children [2 to 7 years], older children [8 to 12 years], and teenagers [13 to 17 years]), sex, and race was assessed using modi...