Tremor markedly reduces quality of life and causes a significant psychological burden for patients who are severely affected by this movement disorder. Pharmacologic and surgical treatments for tremor exist, but for patients who have failed medical therapy and are not surgical candidates, stereotactic radiosurgery is the only available treatment option. Of available stereotactic radiosurgical techniques for intractable tremor, the authors chose to evaluate the safety and efficacy of gamma knife stereotactic radiosurgical thalamotomy.
View Article and Find Full Text PDFUsing RNA interference, we have selectively perturbed neurotransmitter-related features of the larval swimming behavior of Oikopleura dioica, a tunicate with a central nervous system comprising about 130 neurons. We injected dsRNA into fertilized eggs to knockdown the expression of the genes, respectively, encoding ChAT (choline acetyltransferase) and GAD (glutamic acid decarboxylase), enzymes critical for the biosynthesis of acetylcholine and GABA. These two neurotransmitters have conserved roles during evolution, particularly within chordate motor systems, where they mediate respectively neuromuscular and central inhibitory signals.
View Article and Find Full Text PDFHouses have often been used as comparison stimuli in face-processing studies because of the many attributes they share with faces (e.g., distinct members of a basic category, consistent internal features, mono-orientation, and relative familiarity).
View Article and Find Full Text PDFMany intracellular protein-protein interactions are mediated by the phosphorylation of serine, and phosphoserine-containing peptides can inhibit these interactions. However, hydrolysis of the phosphate by phosphatases, and the poor cell permeability associated with phosphorylated peptides has limited their utility in cellular and in vivo contexts. Compounding the problem, strategies to replace phosphoserine in peptide inhibitors with easily accessible mimetics (such as Glu or Asp) routinely fail.
View Article and Find Full Text PDFV3 spinal interneurons (INs) are a group of excitatory INs that play a crucial role in producing balanced and stable gaits in vertebrate animals. In the developing mouse spinal cord, V3 INs arise from the most ventral progenitor domain and form anatomically distinctive subpopulations in adult spinal cords. They are marked by the expression of transcription factor Sim1 postmitotically, but the function of Sim1 in V3 development remains unknown.
View Article and Find Full Text PDFBackground: Inactivating germline mutations in the tumour suppressor gene BRCA1 are associated with a significantly increased risk of developing breast and ovarian cancer. A large number (>1500) of unique BRCA1 variants have been identified in the population and can be classified as pathogenic, non-pathogenic or as variants of unknown significance (VUS). Many VUS are rare missense variants leading to single amino acid changes.
View Article and Find Full Text PDFBackground: Survival rates of patients with osteosarcoma have remained stagnant over the last thirty years. Better understanding of biology, new therapeutics, and improved biomarkers are needed. The Children's Oncology Group (COG) addressed this need by developing one of the largest osteosarcoma biorepositories ever, containing over 15,000 tumor and tissue samples from over 1,500 patients.
View Article and Find Full Text PDFUltra-thin curved transmission crystals operating in the Cauchois spectrometer geometry were evaluated for the purpose of achieving high spectral resolution in the 6-13 keV x-ray energy range. The crystals were silicon (111) and sapphire R-cut wafers, each 18 μm thick, and a silicon (100) wafer of 50-μm thickness. The W Lα(1) spectral line at 8.
View Article and Find Full Text PDFBackground: Severe mental illness (SMI), including schizophrenia, bipolar disorder and severe depression, is responsible for a substantial proportion of disability in the population. This article describes the aims and design of a research study that takes a novel approach to targeted prevention of SMI. It is based on the rationale that early developmental antecedents to SMI are likely to be more malleable than fully developed mood or psychotic disorders and that low-risk interventions targeting antecedents may reduce the risk of SMI.
View Article and Find Full Text PDFRev Sci Instrum
November 2014
A high resolution crystal spectrometer utilizing a crystal in transmission geometry has been developed and experimentally optimized to measure the widths of emission lines in the 10-60 keV energy range with eV accuracy. The spectrometer achieves high spectral resolution by utilizing crystal planes with small lattice spacings (down to 2d = 0.099 nm), a large crystal bending radius and Rowland circle diameter (965 mm), and an image plate detector with high spatial resolution (60 μm in the case of the Fuji TR image plate).
View Article and Find Full Text PDFInitiation of the DNA damage and innate immune responses is dependent upon the flow of chemical information through coupled protein-protein interaction networks and driven by the synthesis and recognition of Lys 63 linked polyubiquitin (polyUb) chains on adaptor proteins. The central chemical step in Lys 63-linked protein ubiquitination involves the reaction of a specific lysine on a target protein with Ub that is covalently attached as a thioester conjugate to the Ub conjugating enzyme (E2) Ubc13. The active site cysteine of Ubc13, and E2 enzymes in general, is buttressed by a flexible loop.
View Article and Find Full Text PDFBackground: Surgical site infection (SSI) following joint arthroplasty increases length of stay, hospital cost, and leads to patient and healthcare provider dissatisfaction. Due to the presence of non-biologic implants (the prosthetic joint) in these procedures, infection is often devastating and treatment of the infection is more difficult. For this reason, prevention of SSI is of crucial importance in this population.
View Article and Find Full Text PDFThe emergence of bone as an endocrine regulator has prompted a re-evaluation of the role of bone mineralization factors in the development of metabolic disease. Ectonucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) controls bone mineralization through the generation of pyrophosphate, and levels of NPP1 are elevated both in dermal fibroblast cultures and muscle of individuals with insulin resistance. We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 (Enpp1(-/-) mice).
View Article and Find Full Text PDFIn the F family of conjugative plasmids, TraJ is an essential transcriptional activator of the tra operon that encodes most of the proteins required for conjugation. Here we report for the first time the X-ray crystal structures of the TraJ N-terminal domains from the prototypic F plasmid (TraJF(11-130)) and from the Salmonella virulence plasmid pSLT (TraJpSLT(1-128)). Both structures contain similar Per-ARNT-Sim (PAS) folds, which further homodimerize through the N-terminal helix and the structurally conserved β-sheet of the PAS fold from each protomer.
View Article and Find Full Text PDFUsing optical recording of synaptically mediated calcium transients and selective spinal lesions, we investigated the pattern of activation of spinal motoneurons (MNs) by the pontine reticulospinal projection in isolated brain stem-spinal cord preparations from the neonatal mouse. Stimulation sites throughout the region where the pontine reticulospinal neurons reside reliably activated MNs at cervical, thoracic, and lumbar levels. Activation was similar in MNs ipsi- and contralateral to the stimulation site, similar in medial and lateral motor columns that contain trunk and limb MNs, respectively, and similar in the L2 and L5 segments that predominantly contain flexor and extensor MNs, respectively.
View Article and Find Full Text PDFObjectives: In preparation for a pediatric randomized controlled trial on thromboprophylaxis, we determined the frequency of catheter-related thrombosis in children. We also systematically reviewed the pediatric trials on thromboprophylaxis to evaluate its efficacy and to identify possible pitfalls in the conduct of these trials.
Patients/methods: We searched MEDLINE, EMBASE, Web of Science and the Cochrane Central Register for Controlled Trials for articles published until December 2013.
Developmental and evolutionary data from vertebrates are beginning to elucidate the origin of the sensorimotor pathway that links gravity and motion detection to image-stabilizing eye movements--the vestibulo-ocular reflex (VOR). Conserved transcription factors coordinate the development of the vertebrate ear into three functional sensory compartments (graviception/translational linear acceleration, angular acceleration and sound perception). These sensory components connect to specific populations of vestibular and auditory projection neurons in the dorsal hindbrain through undetermined molecular mechanisms.
View Article and Find Full Text PDFJ Res Natl Inst Stand Technol
November 2015
In recent times, ionizing radiation has been used around the world to screen persons for non-medical purposes, namely to detect bulk explosives or other contraband hidden on the body including materials not registered by metal detectors. In contrast to conventional transmission or projection imaging, backscatter and forward-scatter systems employ a "flying spot" of x rays and large-area detectors. A small spot is rastered across an individual and the Compton scatter signal collected by these detectors is quickly integrated and assigned to a pixel value in an image corresponding to the transient location of the small flying spot.
View Article and Find Full Text PDFBackground: Antenatal corticosteroids and surfactant replacement therapy have dramatically reduced mortality caused by lung disease in premature babies. Knowledge about mechanisms regulating epithelial differentiation of the respiratory membrane is limited, as are effects of pharmacological interventions. The chicken fetus is a valuable model for exploring pharmacological actions on developing organs.
View Article and Find Full Text PDFWomen in their reproductive years are at risk of experiencing depressive and anxiety disorders. As such, it is likely that pregnant women will undergo treatment with antidepressants. We review the risk of adverse birth outcomes and neonatal complications subsequent to antidepressant use in pregnancy.
View Article and Find Full Text PDFThis article discusses characteristic factors in the presentation of depressive disorders in persons older than age 65 years. Clinical presentation is discussed along with risk and protective factors. Detailed descriptions of tests useful for screening and diagnosis of depression in the elderly are presented.
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