Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence

The evolution of complex nervous systems was accompanied by the expansion of numerous protein families, including cell-adhesion molecules, surface receptors, and their ligands. These proteins mediate axonal guidance, synapse targeting, and other neuronal wiring-related functions. Recently, 32 interacting cell surface proteins belonging to two newly defined families of the Ig superfamily (IgSF) in fruit flies were discovered to label different subsets of neurons in the brain and ventral nerve cord. They have been shown to be involved in synaptic targeting and morphogenesis, retrograde signaling, and neuronal survival. Here, we show that these proteins, Dprs and DIPs, are members of a widely distributed family of two- and three-Ig domain molecules with neuronal wiring functions, which we refer to as Wirins. Beginning from a single ancestral Wirin gene in the last common ancestor of Bilateria, numerous gene duplications produced the heterophilic Dprs and DIPs in protostomes, along with two other subfamilies that diversified independently across protostome phyla. In deuterostomes, the ancestral Wirin evolved into the IgLON subfamily of neuronal receptors. We show that IgLONs interact with each other and that their complexes can be broken by mutations designed using homology models based on Dpr and DIP structures. The nematode orthologs ZIG-8 and RIG-5 also form heterophilic and homophilic complexes, and crystal structures reveal numerous apparently ancestral features shared with Dpr-DIP complexes. The evolutionary, biochemical, and structural relationships we demonstrate here provide insights into neural development and the rise of the metazoan nervous system

Family of neural wiring receptors in bilaterians defined by phylogenetic, biochemical, and structural evidence

The evolution of complex nervous systems was accompanied by the expansion of numerous protein families, including cell-adhesion molecules, surface receptors, and their ligands. These proteins mediate axonal guidance, synapse targeting, and other neuronal wiring-related functions. Recently, 32 interacting cell surface proteins belonging to two newly defined families of the Ig superfamily (IgSF) in fruit flies were discovered to label different subsets of neurons in the brain and ventral nerve cord. They have been shown to be involved in synaptic targeting and morphogenesis, retrograde signaling, and neuronal survival. Here, we show that these proteins, Dprs and DIPs, are members of a widely distributed family of two- and three-Ig domain molecules with neuronal wiring functions, which we refer to as Wirins. Beginning from a single ancestral Wirin gene in the last common ancestor of Bilateria, numerous gene duplications produced the heterophilic Dprs and DIPs in protostomes, along with two other subfamilies that diversified independently across protostome phyla. In deuterostomes, the ancestral Wirin evolved into the IgLON subfamily of neuronal receptors. We show that IgLONs interact with each other and that their complexes can be broken by mutations designed using homology models based on Dpr and DIP structures. The nematode orthologs ZIG-8 and RIG-5 also form heterophilic and homophilic complexes, and crystal structures reveal numerous apparently ancestral features shared with Dpr-DIP complexes. The evolutionary, biochemical, and structural relationships we demonstrate here provide insights into neural development and the rise of the metazoan nervous system

The Possible and the Accessible: Epistasis and Contingency in Protein Sequence Space

Epistatic interactions determine the phenotypic consequences of mutations and shape the course of evolution. However, little is known about the pattern of epistatic interactions among the possible mutations within a protein and the extent and temporal dynamics with which the effects of mutations change during evolution. By using a novel method to analyze experimental mutational datasets, I show that the architecture of epistatic interactions within a protein is surprisingly simple: Knowing only the context-independent effects and pairwise interactions of amino acids is sufficient to predict the phenotype with high accuracy. I then combine ancestral protein reconstruction with deep mutational scanning to experimentally reconstruct how the effect of every possible point mutation in a protein changed during long-term evolution. The effects of most mutations changed gradually and randomly at a rate characteristic to each mutation—a pattern I call epistatic drift. Epistatic drift randomized the effects of most mutations during evolution, making the outcome of evolution highly unpredictable. The statistical regularity of epistatic drift, however, means that this unpredictability can be quantified: A probability distribution for the future effect of a mutation—therefore the timescale at which evolution becomes unpredictable—can be calculated from the rate of epistatic drift. Overall, my work reveals a simple architecture and statistical regularity of epistasis and demonstrates the pervasive historical contingency of protein evolution

A Method for Accessing the Non-Slip Function of Socks in an Acute Maneuver

The shoe upper hides the foot motion on the insole, so it has been challenging to measure the non-slip function of socks in a dynamic motor task. The study aimed to propose a method to estimate the non-slip function of socks in an acute maneuver. Participants performed a shuttle run task while wearing three types of socks with different frictional properties. The forces produced by foot movement on the upper during the task were measured by pressure sensors installed at the upper. A force platform was also used to measure the ground reaction force at the outsole and ground. Peak force and impulse values computed by using forces measured by the pressure sensors were significantly different between the sock conditions, while there were no such differences in those values computed by using ground reaction forces measured by a force platform. The results suggested that the non-slip function of socks could be quantified by measuring forces at the foot-upper interface. The method could be an affordable option to measure the non-slip function of socks with minimal effects from skin artifacts and shoe upper integrity

Molecular basis of force-from-lipids gating in the mechanosensitive channel MscS

Prokaryotic mechanosensitive (MS) channels open by sensing the physical state of the membrane. As such, lipid-protein interactions represent the defining molecular process underlying mechanotransduction. Here, we describe cryo-electron microscopy (cryo-EM) structures of the E. coli small-conductance mechanosensitive channel (MscS) in nanodiscs (ND). They reveal a novel membrane-anchoring fold that plays a significant role in channel activation and establish a new location for the lipid bilayer, shifted ~14 Å from previous consensus placements. Two types of lipid densities are explicitly observed. A phospholipid that ‘hooks’ the top of each TM2-TM3 hairpin and likely plays a role in force sensing, and a bundle of acyl chains occluding the permeation path above the L105 cuff. These observations reshape our understanding of force-from-lipids gating in MscS and highlight the key role of allosteric interactions between TM segments and phospholipids bound to key dynamic components of the channel

Hybrid Antenna Module Concept for 28 GHz 5G Beamsteering Cellular Devices

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Combination of rhIL-7-hyFc and anti-PD-L1xCD3e bispecific antibody enhances antitumor response in mice

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Guideline of optimum interfacial layers in metal-ferroelectric-insulator-semiconductor structure for gate stack and ferroelectric tunnel junction

To investigate metal-ferroelectric-insulator-semiconductor (MFIS) stack design guidelines for its applications, the ferroelectricity in various IL thicknesses were investigated. As a result, IL has leaky insulator characteristics rather than an ideal dielectric and the MFIS stack shows a critical difference in ferroelectric characteristics.N

Epistasis facilitates functional evolution in an ancient transcription factor

A protein’s genetic architecture – the set of causal rules by which its sequence produces its functions – also determines its possible evolutionary trajectories. Prior research has proposed that the genetic architecture of proteins is very complex, with pervasive epistatic interactions that constrain evolution and make function difficult to predict from sequence. Most of this work has analyzed only the direct paths between two proteins of interest – excluding the vast majority of possible genotypes and evolutionary trajectories – and has considered only a single protein function, leaving unaddressed the genetic architecture of functional specificity and its impact on the evolution of new functions. Here, we develop a new method based on ordinal logistic regression to directly characterize the global genetic determinants of multiple protein functions from 20-state combinatorial deep mutational scanning (DMS) experiments. We use it to dissect the genetic architecture and evolution of a transcription factor’s specificity for DNA, using data from a combinatorial DMS of an ancient steroid hormone receptor’s capacity to activate transcription from two biologically relevant DNA elements. We show that the genetic architecture of DNA recognition consists of a dense set of main and pairwise effects that involve virtually every possible amino acid state in the protein-DNA interface, but higher-order epistasis plays only a tiny role. Pairwise interactions enlarge the set of functional sequences and are the primary determinants of specificity for different DNA elements. They also massively expand the number of opportunities for single-residue mutations to switch specificity from one DNA target to another. By bringing variants with different functions close together in sequence space, pairwise epistasis therefore facilitates rather than constrains the evolution of new functions

Review on Sensor Cloud and Its Integration with Arduino Based Sensor Network

The expansion of embedded ICT infrastructure has resulted in the deployment of a wide range of embedded systems in our environment which indicate the need for reusable, manageable and flexible Wireless Sensor Network. Integration of WSN infrastructure with Cloud simplifies the system operation and maintenance as well as the cost and capable of providing services to multiple end users. The integration offers benefits whereby common processing, computational and analytical tasks can be hosted on cloud service and freeing the devices from running heavy applications, hence reducing power consumption and maximizing the lifetime of power units as well as the network itself. The sensor clouds are therefore gaining popularity for providing an open, flexible and a reconfigurable platform for many monitoring and controlling applications. This paper looks at the benefits and basic features of Senor Cloud Services and how Ethernet enabled Arduino microcontroller based sensor network can be integrated to send sensor data to them by looking at three popular cloud services