Glycine is a major neurotransmitter that activates inhibitory glycine receptors and is a co-agonist for excitatory glutamatergic N-methyl-D-aspartate (NMDA) receptors. Two transporters, GLYT1 and ...GLYT2, regulate extracellular glycine concentrations within the CNS. Dysregulation of the extracellular glycine has been associated with hyperekplexia and nonketotic hyperglycinemia. Here, we report four individuals from two families who presented at birth with facial dysmorphism, encephalopathy, arthrogryposis, hypotonia progressing to hypertonicity with startle-like clonus, and respiratory failure. Only one individual survived the respiratory failure and was weaned off ventilation but has significant global developmental delay. Mildly elevated cerebrospinal fluid (CSF) glycine and normal serum glycine were observed in two individuals. In both families, we identified truncating mutations in SLC6A9, encoding GLYT1. We demonstrate that pharmacologic or genetic abolishment of GlyT1 activity in mice leads to mildly elevated glycine in the CSF but not in blood. Additionally, previously reported slc6a9-null mice and zebrafish mutants also display phenotypes consistent with the affected individuals we examined. Our data suggest that truncating SLC6A9 mutations lead to a distinct human neurological syndrome hallmarked by mildly elevated CSF glycine and normal serum glycine.
The default mode network (DMN) has been implicated in an array of social-cognitive functions, including self-referential processing, theory of mind, and mentalizing. Yet, the properties of the ...external stimuli that elicit DMN activity in relation to these domains remain unknown. Previous studies suggested that motion kinematics is utilized by the brain for social-cognitive processing. Here, we used functional MRI to examine whether the DMN is sensitive to parametric manipulations of observed motion kinematics. Preferential responses within core DMN structures differentiating non-biological from biological kinematics were observed for the motion of a realistically looking, human-like avatar, but not for an abstract object devoid of human form. Differences in connectivity patterns during the observation of biological versus non-biological kinematics were additionally observed. Finally, the results additionally suggest that the DMN is coupled more strongly with key nodes in the action observation network, namely the STS and the SMA, when the observed motion depicts human rather than abstract form. These findings are the first to implicate the DMN in the perception of biological motion. They may reflect the type of information used by the DMN in social-cognitive processing.
Background
Infectious diseases have been associated with increased risk of type 1 diabetes (T1D). The objective of this case‐crossover was to quantify the role of infectious diseases as triggers for ...T1D, 1 and 2 yr preceding disease diagnosis.
Methods
All children aged 2–18 yr diagnosed with T1D between 2004 and 2009 among a two million member Israeli healthcare organization were identified (n = 368). For each patient, visits to physicians with symptomatic infectious diseases during 1 and 2 yr before T1D diagnosis were collected and compared. A similar analysis was conducted in a population of non‐diabetic members matched on exact date of birth, sex and socioeconomic status (n = 307).
Results
The rate of systemic viral infections was significantly higher in the year before T1D onset, as compared to the prior year 27 vs. 7%, respectively, odds ratio (OR) = 4.7, 95% confidence intervals (CI): 2.9–8.2. This difference was most significant among patients diagnosed with T1D at the age of 2 to 6 (5 vs. 46%, respectively, OR = 27.0, 95% CI: 4.5–1105.4). Among non‐T1D patients of the same age group, no difference was found in the proportion of patients with viral diseases 1 and 2 yr prior to T1D diagnosis (44 vs. 49%, respectively, OR = 0.8, 95% CI: 0.4–1.6). This unique association was limited only to viral diseases and to patients diagnosed with T1D at young age.
Conclusions
Our results indicate that T1D occurring in toddlers is characterized with a relatively low incidence of viral disease 2 yr prior to diagnosis and a much higher incidence in the subsequent year.
מטרת המחקר הייתה להשוות בין שתי קבוצות של חולות סרטן השד, כאשר ההבדל היחיד בין שתי הקבוצות היה גיל הנשים בהן: חולות בנות 70 ומעלה וחולות מתחת לגיל 70. במחקר השתתפו 187 חולות בנות 70 ומעלה ו- 609 ...חולות מתחת לגיל 70. החוקרים הגיעו למסקנה שלא היו שינויים משמעותיים במחלת הסרטן בין שתי הקבוצות.
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