A brainwide atlas of synapses across the mouse life span

Synapses connect neurons together to form the circuits of the brain, and their molecular composition controls innate and learned behavior. We analyzed the molecular and morphological diversity of 5 billion excitatory synapses at single-synapse resolution across the mouse brain from birth to old age. A continuum of changes alters synapse composition in all brain regions across the life span. Expansion in synapse diversity produces differentiation of brain regions until early adulthood, and compositional changes cause dedifferentiation in old age. The spatiotemporal synaptome architecture of the brain potentially accounts for life-span transitions in intellectual ability, memory, and susceptibility to behavioral disorders

Architecture of the Mouse Brain Synaptome

Synapses are found in vast numbers in the brain and contain complex proteomes. We developed genetic labeling and imaging methods to examine synaptic proteins in individual excitatory synapses across all regions of the mouse brain. Synapse catalogs were generated from the molecular and morphological features of a billion synapses. Each synapse subtype showed a unique anatomical distribution, and each brain region showed a distinct signature of synapse subtypes. Whole-brain synaptome cartography revealed spatial architecture from dendritic to global systems levels and previously unknown anatomical features. Synaptome mapping of circuits showed correspondence between synapse diversity and structural and functional connectomes. Behaviorally relevant patterns of neuronal activity trigger spatiotemporal postsynaptic responses sensitive to the structure of synaptome maps. Areas controlling higher cognitive function contain the greatest synapse diversity, and mutations causing cognitive disorders reorganized synaptome maps. Synaptome technology and resources have wide-ranging application in studies of the normal and diseased brain

The failure of the floating cover of a vertical cylindrical tank

The location of oil tanks for the storage of volatile hydrocarbons could be done in geographical areas where the standard unit weight of the snow layer on the horizontal surface of the land reached 1500 ... 2000 N / m2 . The snow layer deposited on the floating cover under heavy weather conditions can cause a compressive force between 4500 and 6000 N / m2 . This creates problems in the operation of the tank and consequently the constructive structure of the floating cover can not bear this unitary load from the snow load, inevitably causing the damage. The capacities of the floating cover should be considered not only in terms of limitations on load-bearing considerations in general, but also in terms of the distribution of loads on the surface of the floating cover. The paper presents the aspect of the failure of a floating cover of a vertical cylindrical tank used to store liquid hydrocarbons under heavy climatic conditions

Considerations on damage to bulb turbine shafts from iron Gates II

During operation, the turbine bulb shaft is subjected to static specific stresses (tension, compression, torsion) and dynamic (fatigue, random vibrations). These stresses are the effect of hydraulic forces and moments developed on the rotor blade, the weight of the rotor (with or without oil) in the console and inevitable vibrations, which creates a rotating mass unevenly distributed over the axis of symmetry of the turbine. Observations made on the turbine bulb shafts of the Iron Gate II CHE have revealed cracks in the connection area of a shaft flange that engages it with the turbine rotor. Examination of these cracks leads to the conclusion that they are specific to the inevitable fatigue demands in exploiting the tree and enhancing the environment in which they work. Therefore, in the paper, a presentation and analysis of the damage of bulb turbine shafts from CHE Porţile de Fier II, after a significant number of hours of operation

Analysis and management of avariation to a fluvial transport vessel caused by collision

In general, the body of the ship is a welded metal structure made up of the shell and bone. The paper aims is to analyze and present the solution for the collision damage to a river transport vessel. The problem is treated as in the case of a typical failure of welded constructions. In this regard, the fault will be described, after which the stages of the fault remedy will be presented

Architecture of the Mouse Brain Synaptome

Synapses are found in vast numbers in the brain and contain complex proteomes. We developed genetic labeling and imaging methods to examine synaptic proteins in individual excitatory synapses across all regions of the mouse brain. Synapse catalogs were generated from the molecular and morphological features of a billion synapses. Each synapse subtype showed a unique anatomical distribution, and each brain region showed a distinct signature of synapse subtypes. Whole-brain synaptome cartography revealed spatial architecture from dendritic to global systems levels and previously unknown anatomical features. Synaptome mapping of circuits showed correspondence between synapse diversity and structural and functional connectomes. Behaviorally relevant patterns of neuronal activity trigger spatiotemporal postsynaptic responses sensitive to the structure of synaptome maps. Areas controlling higher cognitive function contain the greatest synapse diversity, and mutations causing cognitive disorders reorganized synaptome maps. Synaptome technology and resources have wide-ranging application in studies of the normal and diseased brain

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

miR-16 Targets Transcriptional Corepressor SMRT and Modulates NF-kappaB-Regulated Transactivation of Interleukin-8 Gene

The signaling pathways associated with the Toll-like receptors (TLRs) and nuclear factor-kappaB (NF-κB) are essential to pro-inflammatory cytokine and chemokine expression, as well as initiating innate epithelial immune responses. The TLR/NF-κB signaling pathways must be stringently controlled through an intricate network of positive and negative regulatory elements. MicroRNAs (miRNAs) are non-coding small RNAs that regulate the stability and/or translation of protein-coding mRNAs. Herein we report that miR-16 promotes NF-κB-regulated transactivation of the IL-8 gene by suppression of the silencing mediator for retinoid and thyroid hormone receptor (SMRT). LPS stimulation activated miR-16 gene transcription in human monocytes (U937) and biliary epithelial cells (H69) through MAPK-dependent mechanisms. Transfection of cells with the miR-16 precursor promoted LPS-induced production of IL-8, IL-6, and IL-1α, without a significant effect on their RNA stability. Instead, an increase in NF-κB-regulated transactivation of the IL-8 gene was confirmed in cells following transfection of miR-16 precursor. Importantly, miR-16 targeted the 3′-untranslated region of SMRT and caused translational suppression of SMRT. LPS decreased SMRT expression via upregulation of miR-16. Moreover, functional manipulation of SMRT altered NF-κB-regulated transactivation of LPS-induced IL-8 expression. These data suggest that miR-16 targets SMRT and modulates NF-κB-regulated transactivation of the IL-8 gene

Klotho Lacks a Vitamin D Independent Physiological Role in Glucose Homeostasis, Bone Turnover, and Steady-State PTH Secretion In Vivo

Apart from its function as co-receptor for fibroblast growth factor-23 (FGF23), Klotho is thought to regulate insulin signaling, intracellular oxidative stress, and parathyroid hormone (PTH) secretion in an FGF23 independent fashion. Here, we crossed Klotho deficient (Kl−/−) mice with vitamin D receptor (VDR) mutant mice to examine further vitamin D independent functions of Klotho. All mice were fed a rescue diet enriched with calcium, phosphorus, and lactose to prevent hyperparathyroidism in VDR mutants, and were killed at 4 weeks of age after double fluorochrome labeling. Kl−/− mice displayed hypercalcemia, hyperphosphatemia, dwarfism, organ atrophy, azotemia, pulmonary emphysema, and osteomalacia. In addition, glucose and insulin tolerance tests revealed hypoglycemia and profoundly increased peripheral insulin sensitivity in Kl−/− mice. Compound mutants were normocalcemic and normophosphatemic, did not show premature aging or organ atrophy, and were phenocopies of VDR mutant mice in terms of body weight, bone mineral density, bone metabolism, serum calcium, serum phosphate, serum PTH, gene expression in parathyroid glands, as well as urinary calcium and phosphate excretion. Furthermore, ablation of vitamin D signaling in double mutants completely normalized glucose and insulin tolerance, indicating that Klotho has no vitamin D independent effects on insulin signaling. Histomorphometry of pancreas islets showed similar beta cell volume per body weight in all groups of animals. In conclusion, our findings cast doubt on a physiologically relevant vitamin D and Fgf23 independent function of Klotho in the regulation of glucose metabolism, bone turnover, and steady-state PTH secretion in vivo