U4SSC - City Snapshot - Averøy, Norway

U4SSC - City Snapshot - Fjord, Norway

U4SSC - City Snapshot - Gjemnes, Norway

U4SSC - City Snapshot - Herøy, Norway

U4SSC - City Snapshot - Hustadvika, Norway

U4SSC - City Snapshot - Ørsta, Norway

U4SSC - City Snapshot - Rauma, Norway

U4SSC - City Snapshot - Sande, Norway

U4SSC - City Snapshot - Smøla, Norway

U4SSC - City Snapshot - Stranda, Norway

U4SSC - City Snapshot - Sunndal, Norway

U4SSC - City Snapshot - Surnadal, Norway

U4SSC - City Snapshot - Sykkylven, Norway

U4SSC - City Snapshot - Tingvoll, Norway

U4SSC - City Snapshot - Ulstein, Norway

U4SSC - City Snapshot - Vanylven, Norway

U4SSC - City Snapshot - Vestnes, Norway

U4SSC - City Snapshot - Volda, Norway

U4SSC - City Snapshot - Hareid, Norway

U4SSC - City Snapshot - More og Romsdal, Norway

U4SSC - City Snapshot - Larvik, Norway

U4SSC - Snapshot - Mashhad, Iran

U4SSC - City Snapshot - Daegu, Korea

U4SSC - City Snapshot - Narvik, Norway

U4SSC - City Snapshot - TROMSØ, NORWAY

U4SSC - Snapshot - Geneva, Switzerland

U4SSC - City Snapshot - Kyebi, Ghana

U4SSC - City Snapshot - Anyang, Korea (Republic of)

Roofing Services Solutions, a Dunes Point Capital portfolio company, has acquired Earl W. Johnston Roofing, expanding its Florida presence to 10 locations and 200 employees.

WikiLeaks: 2009-12-15: 09STOCKHOLM779: Snapshot of Muslim Communities in Sweden

Look back at Volume 2024 through photos from our photographers Volume Music Festival's return after five years was nothing short of epic…

The one-third of Jonas Brothers admits he is 'so thankful and grateful' to be able to spend time at home with wife Sophie Turner and daughter Willa during the coronavirus pandemic.

Nathan MacKinnon had his most productive night of the season to pull the Colorado Avalanche out of a funk, but the club's extraordinary injury crisis may have somehow reached a new level.

Perception is everything.

Jonathan C. Trinidad
Aug 1, 2012; 11:215-229
Research

Highly engineered phytases, which sequentially hydrolyze the hexakisphosphate ester of inositol known as phytic acid, are routinely added to the feeds of monogastric animals to improve phosphate bioavailability. New phytases are sought as starting points to further optimize the rate and extent of dephosphorylation of phytate in the animal digestive tract. Multiple inositol polyphosphate phosphatases (MINPPs) are clade 2 histidine phosphatases (HP2P) able to carry out the stepwise hydrolysis of phytate. MINPPs are not restricted by a strong positional specificity making them attractive targets for development as feed enzymes. Here, we describe the characterization of a MINPP from the Gram-positive bacterium Bifidobacterium longum (BlMINPP). BlMINPP has a typical HP2P-fold but, unusually, possesses a large α-domain polypeptide insertion relative to other MINPPs. This insertion, termed the U-loop, spans the active site and contributes to substrate specificity pockets underpopulated in other HP2Ps. Mutagenesis of U-loop residues reveals its contribution to enzyme kinetics and thermostability. Moreover, four crystal structures of the protein along the catalytic cycle capture, for the first time in an HP2P, a large ligand-driven α-domain motion essential to allow substrate access to the active site. This motion recruits residues both downstream of a molecular hinge and on the U-loop to participate in specificity subsites, and mutagenesis identified a mobile lysine residue as a key determinant of positional specificity of the enzyme. Taken together, these data provide important new insights to the factors determining stability, substrate recognition, and the structural mechanism of hydrolysis in this industrially important group of enzymes.

α-Neurexins are essential and highly expressed presynaptic cell-adhesion molecules that are frequently linked to neuropsychiatric and neurodevelopmental disorders. Despite their importance, how the elaborate extracellular sequences of α-neurexins contribute to synapse function is poorly understood. We recently characterized the presynaptic gain-of-function phenotype caused by a missense mutation in an evolutionarily conserved extracellular sequence of neurexin-3α (A687T) that we identified in a patient diagnosed with profound intellectual disability and epilepsy. The striking A687T gain-of-function mutation on neurexin-3α prompted us to systematically test using mutants whether the presynaptic gain-of-function phenotype is a consequence of the addition of side-chain bulk (i.e., A687V) or polar/hydrophilic properties (i.e., A687S). We used multidisciplinary approaches in mixed-sex primary hippocampal cultures to assess the impact of the neurexin-3α^A687 residue on synapse morphology, function and ligand binding. Unexpectedly, neither A687V nor A687S recapitulated the neurexin-3α A687T phenotype. Instead, distinct from A687T, molecular replacement with A687S significantly enhanced postsynaptic properties exclusively at excitatory synapses and selectively increased binding to neuroligin-1 and neuroligin-3 without changing binding to neuroligin-2 or LRRTM2. Importantly, we provide the first experimental evidence supporting the notion that the position A687 of neurexin-3α and the N-terminal sequences of neuroligins may contribute to the stability of α-neurexin–neuroligin-1 trans-synaptic interactions and that these interactions may specifically regulate the postsynaptic strength of excitatory synapses.

Impaired inhibitory synapse development is suggested to drive neuronal hyperactivity in autism spectrum disorders (ASD) and epilepsy. We propose a novel mechanism by which astrocytes control the development of parvalbumin (PV)-specific inhibitory synapses in the hippocampus, implicating ephrin-B/EphB signaling. Here, we utilize genetic approaches to assess functional and structural connectivity between PV and pyramidal cells (PCs) through whole-cell patch–clamp electrophysiology, optogenetics, immunohistochemical analysis, and behaviors in male and female mice. While inhibitory synapse development is adversely affected by PV-specific expression of EphB2, a strong candidate ASD risk gene, astrocytic ephrin-B1 facilitates PV->PC connectivity through a mechanism involving EphB signaling in PV boutons. In contrast, the loss of astrocytic ephrin-B1 reduces PV->PC connectivity and inhibition, resulting in increased seizure susceptibility and an ASD-like phenotype. Our findings underscore the crucial role of astrocytes in regulating inhibitory circuit development and discover a new role of EphB2 receptors in PV-specific inhibitory synapse development.

Experience- and activity-dependent transcription is a candidate mechanism to mediate development and refinement of specific cortical circuits. Here, we demonstrate that the activity-dependent transcription factor myocyte enhancer factor 2C (MEF2C) is required in both presynaptic layer (L) 4 and postsynaptic L2/3 mouse (male and female) somatosensory (S1) cortical neurons for development of this specific synaptic connection. While postsynaptic deletion of Mef2c weakens L4 synaptic inputs, it has no effect on inputs from local L2/3, contralateral S1, or the ipsilateral frontal/motor cortex. Similarly, homozygous or heterozygous deletion of Mef2c in presynaptic L4 neurons weakens L4 to L2/3 excitatory synaptic inputs by decreasing presynaptic release probability. Postsynaptic MEF2C is specifically required during an early postnatal, experience-dependent, period for L4 to L2/3 synapse function, and expression of transcriptionally active MEF2C (MEF2C-VP16) rescues weak L4 to L2/3 synaptic strength in sensory-deprived mice. Together, these results suggest that experience- and/or activity-dependent transcriptional activation of MEF2C promotes development of L4 to L2/3 synapses. Additionally, MEF2C regulates the expression of many pre- and postsynaptic genes in postnatal cortical neurons. Interestingly, MEF2C was necessary for activity-dependent expression of many presynaptic genes, including those that function in transsynaptic adhesion and neurotransmitter release. This work provides mechanistic insight into the experience-dependent development of specific cortical circuits.

Download the data from Education Week showing how over 900 school districts provided instruction on their first day of the school year.

Title: AHA News: Study of Sleep in Older Adults Suggests Nixing Naps, Striving for 7-9 Hours a Night
Category: Health News
Created: 7/26/2022 12:00:00 AM
Last Editorial Review: 7/27/2022 12:00:00 AM

Title: Could Long Naps Shorten Your Life?
Category: Health News
Created: 8/26/2020 12:00:00 AM
Last Editorial Review: 8/27/2020 12:00:00 AM

Missing or inaccessible lung function measurements, gathered over time, have the potential to stagnate or impair clinical care decisions being made. This jeopardises patient safety and often contributes to excessive resource utilisation. Data integration is fundamental to clinical decision-making and entails amalgamating lung function data from multiple sources in a user-friendly format. Despite this, current systems for recording lung function data are suboptimal, with copious gaps in the clinical picture arising from missing or inaccessible lung function measurements. This article discusses the importance of data integration for lung function, with a call to action for key stakeholders involved in the performance, management and interpretation of such tests.

Smart TVs from Samsung and LG monitor what you are watching even when you are using the screens to display a feed from a connected laptop or video game console

Enterprise spending on cloud services continues to go up, up, up — to the tune of $675 billion this year — thanks to organizations’ firm embrace of software-as-a-service, the popularity of distributed working, and the arrival of compute-intensive tech like AI. A startup called PointFive believes it has found a better way to get a […]

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Casual mobile games have reached a fever pitch of interest with consumers, and so too with investors, who are rushing to back the biggest and most promising startups building these quick hits of engagement and diversion. In the latest development, a startup out of London called Tripledot — the company behind a popular Solitaire app, […]

© 2024 TechCrunch. All rights reserved. For personal use only.

The rapid progress of Synapse comes at a time when there is a growing desire from organisations to train and redevelop talent