MS -Pushing the Limits for Biomolecular Mass Spectrometry.

Electrospray mass spectrometry has become indispensable in many disciplines including the classic "omics" techniques such as proteomics or lipidomics, as well as other life science applications in molecular, cellular, and structural biology. However, a limiting factor that often arises for the detection of biomolecular analytes is their poor ionization efficiency in the ion source. Here, we present an add-on device for the electrospray source, termed MS (MS Spectral Impurity Eliminator & Value Enhancer), which is placed between the electrospray needle and the cone of the mass spectrometer.

Vascular FLRT2 regulates venous-mediated angiogenic expansion and CNS barriergenesis.

Veins have emerged as the origin of all other endothelial cell subtypes needed to expand vascular networks during developmental and pathological neoangiogenesis. Here, we uncover the role of the angioneurin Fibronectin Leucine Rich Transmembrane protein (FLRT) 2 in central nervous system (CNS) vascular development in the mouse. Early postnatal FLRT2 deletion reveals specific defects in retinal veins, impacting endothelial cell proliferation, sprouting and polarity that result in reduced tip cells at the vascular front.

Central pattern generator control of a vertebrate ultradian sleep rhythm.

The mechanisms underlying the mammalian ultradian sleep rhythm-the alternation of rapid-eye-movement (REM) and slow-wave (SW) states-are not well understood but probably depend, at least in part, on circuits in the brainstem. Here, we use perturbation experiments to probe this ultradian rhythm in sleeping lizards (Pogona vitticeps) and test the hypothesis that it originates in a central pattern generator-circuits that are typically susceptible to phase-dependent reset and entrainment by external stimuli. Using light pulses, we find that Pogona's ultradian rhythm can be reset in a phase-dependent manner, with a critical transition from phase delay to phase advance in the middle of SW.

"Neural correlates of social signaling in rodents: An acoustic perspective".

Despite the abundance and variety of rodent species worldwide, historically few have been used to study the neurobiology of social signaling. In recent years, the diversity of rodent behaviors has been leveraged to advance our understanding of neural circuits underlying social behaviors, and in particular those related to acoustic communication. Here we highlight recent work investigating vocal behaviors across social contexts in multiple rodent species and discuss how these studies reveal both shared and distinct neural circuits.

In situ structure and rotary states of mitochondrial ATP synthase in whole cells.

Cells depend on a continuous supply of adenosine triphosphate (ATP), the universal energy currency. In mitochondria, ATP is produced by a series of redox reactions, whereby an electrochemical gradient is established across the inner mitochondrial membrane. The ATP synthase harnesses the energy of the gradient to generate ATP from adenosine diphosphate (ADP) and inorganic phosphate.

Interdomain-linkers control conformational transitions in the SLC23 elevator transporter UraA.

Uptake of nucleobases and ascorbate is an essential process in all living organisms mediated by SLC23 transport proteins. These transmembrane carriers operate via the elevator alternating-access mechanism, and are composed of two rigid domains whose relative motion drives transport. The lack of large conformational changes within these domains suggests that the interdomain-linkers act as flexible tethers.

Barriers to therapy adherence in narcolepsy.

Background: Treatment adherence (TA) in narcolepsy is a complex phenomenon influenced by various factors beyond patient-related aspects. The management of narcolepsy involves non-pharmacological and symptomatic pharmacological treatment. Factors such as chronic daytime sleepiness, cognitive deficits, psychiatric comorbidities and adverse effects of pharmacological treatment are aspects of narcolepsy that could undermine TA, impacting patients' ability or willingness to consistently follow treatment plans.

Tonically active GABAergic neurons in the dorsal periaqueductal gray control instinctive escape in mice.

Escape behavior is a set of locomotor actions that move an animal away from threat. While these actions can be stereotyped, it is advantageous for survival that they are flexible. For example, escape probability depends on predation risk and competing motivations, and flight to safety requires continuous adjustments of trajectory and must terminate at the appropriate place and time.

Identification and structural analysis for the first mutation in the cystic fibrosis transmembrane conductance regulator protein in Iran: case report and developmental insight using microsatellite markers.

Cystic fibrosis (CF) is an autosomal recessive disease caused by the inheritance of two mutant cystic fibrosis transmembrane conductance regulator (CFTR) alleles, one from each parent. Autosomal recessive disorders are rarely associated with germline mutations or mosaicism. Here, we propose a case of paternal germline mutation causing CF.

Synapse-type-specific competitive Hebbian learning forms functional recurrent networks.

Cortical networks exhibit complex stimulus-response patterns that are based on specific recurrent interactions between neurons. For example, the balance between excitatory and inhibitory currents has been identified as a central component of cortical computations. However, it remains unclear how the required synaptic connectivity can emerge in developing circuits where synapses between excitatory and inhibitory neurons are simultaneously plastic.

Bactericidal effect of tetracycline in E. coli strain ED1a may be associated with ribosome dysfunction.

Ribosomes translate the genetic code into proteins. Recent technical advances have facilitated in situ structural analyses of ribosome functional states inside eukaryotic cells and the minimal bacterium Mycoplasma. However, such analyses of Gram-negative bacteria are lacking, despite their ribosomes being major antimicrobial drug targets.

A conserved brainstem region for instinctive behaviour control: The vertebrate periaqueductal gray.

Instinctive behaviours have evolved across animal phyla and ensure the survival of both the individual and species. They include behaviours that achieve defence, feeding, aggression, sexual reproduction, or parental care. Within the vertebrate subphylum, the brain circuits that support instinctive behaviour output are evolutionarily conserved, being present in the oldest group of living vertebrates, the lamprey.

Top-down modulation in canonical cortical circuits with short-term plasticity.

Cortical dynamics and computations are strongly influenced by diverse GABAergic interneurons, including those expressing parvalbumin (PV), somatostatin (SST), and vasoactive intestinal peptide (VIP). Together with excitatory (E) neurons, they form a canonical microcircuit and exhibit counterintuitive nonlinear phenomena. One instance of such phenomena is response reversal, whereby SST neurons show opposite responses to top-down modulation via VIP depending on the presence of bottom-up sensory input, indicating that the network may function in different regimes under different stimulation conditions.

RoboEM: automated 3D flight tracing for synaptic-resolution connectomics.

Mapping neuronal networks from three-dimensional electron microscopy (3D-EM) data still poses substantial reconstruction challenges, in particular for thin axons. Currently available automated image segmentation methods require manual proofreading for many types of connectomic analysis. Here we introduce RoboEM, an artificial intelligence-based self-steering 3D 'flight' system trained to navigate along neurites using only 3D-EM data as input.

Rigorous science demands support of transgender scientists.

To build a just, equitable, and diverse academy, scientists and institutions must address systemic barriers that sex and gender minorities face. This Commentary summarizes (1) critical context informing the contemporary oppression of transgender people, (2) how this shapes extant research on sex and gender, and (3) actions to build an inclusive and rigorous academy for all.

Structure and function of the hippocampal CA3 module.

The hippocampal formation is crucial for learning and memory, with submodule CA3 thought to be the substrate of pattern completion. However, the underlying synaptic and computational mechanisms of this network are not well understood. Here, we perform circuit reconstruction of a CA3 module using three dimensional (3D) electron microscopy data and combine this with functional connectivity recordings and computational simulations to determine possible CA3 network mechanisms.

Spike desensitisation as a mechanism for high-contrast selectivity in retinal ganglion cells.

In the vertebrate retina, several dozens of parallel channels relay information about the visual world to the brain. These channels are represented by the different types of retinal ganglion cells (RGCs), whose responses are rendered selective for distinct sets of visual features by various mechanisms. These mechanisms can be roughly grouped into synaptic interactions and cell-intrinsic mechanisms, with the latter including dendritic morphology as well as ion channel complement and distribution.

Guiding axon regeneration: Instructions from blood vessels.

In this issue of Neuron, Bhat et al. unveil the temporary reawakening of an embryonic guidance program, which facilitates the alignment of blood neovessels, creating a supportive "bridge" microenvironment for axon regrowth and tissue regeneration after peripheral nervous system (PNS) injury.