Long-range projections of oxytocin neurons in the marmoset brain.

The neurohormone oxytocin (OT) has become a major target for the development of novel therapeutic strategies to treat psychiatric disorders such as autism spectrum disorder because of its integral role in governing many facets of mammalian social behavior. Whereas extensive work in rodents has produced much of our knowledge of OT, we lack basic information about its neurobiology in primates making it difficult to interpret the limited effects that OT manipulations have had in human patients. In fact, previous studies have revealed only limited OT fibers in primate brains.

Long range projections of oxytocin neurons in the marmoset brain.

The neurohormone oxytocin (OT) has become a major target for the development of novel therapeutic strategies to treat psychiatric disorders such as autism spectrum disorder because of its integral role in governing many facets of mammalian social behavior. Whereas extensive work in rodents has produced much of our knowledge of OT, we lack basic information about its neurobiology in primates making it difficult to interpret the limited effects that OT manipulations have had in human patients. In fact, previous studies have revealed only limited OT fibers in primate brains.

Identification of inhibitors targeting the energy-coupling factor (ECF) transporters.

The energy-coupling factor (ECF) transporters are a family of transmembrane proteins involved in the uptake of vitamins in a wide range of bacteria. Inhibition of the activity of these proteins could reduce the viability of pathogens that depend on vitamin uptake. The central role of vitamin transport in the metabolism of bacteria and absence from humans make the ECF transporters an attractive target for inhibition with selective chemical probes.

CGCompiler: Automated Coarse-Grained Molecule Parametrization via Noise-Resistant Mixed-Variable Optimization.

Coarse-grained force fields (CG FFs) such as the Martini model entail a predefined, fixed set of Lennard-Jones parameters (building blocks) to model virtually all possible nonbonded interactions between chemically relevant molecules. Owing to its universality and transferability, the building-block coarse-grained approach has gained tremendous popularity over the past decade. The parametrization of molecules can be highly complex and often involves the selection and fine-tuning of a large number of parameters (e.

Expulsion mechanism of the substrate-translocating subunit in ECF transporters.

Energy-coupling factor (ECF)-type transporters mediate the uptake of micronutrients in many bacteria. They consist of a substrate-translocating subunit (S-component) and an ATP-hydrolysing motor (ECF module) Previous data indicate that the S-component topples within the membrane to alternately expose the binding site to either side of the membrane. In many ECF transporters, the substrate-free S-component can be expelled from the ECF module.

Martini 3 Coarse-Grained Force Field for Carbohydrates.

The Martini 3 force field is a full reparametrization of the Martini coarse-grained model for biomolecular simulations. Due to the improved interaction balance, it allows for a more accurate description of condensed phase systems. In the present work, we develop a consistent strategy to parametrize carbohydrate molecules accurately within the framework of Martini 3.

The human posterior cingulate, retrosplenial, and medial parietal cortex effective connectome, and implications for memory and navigation.

The human posterior cingulate, retrosplenial, and medial parietal cortex are involved in memory and navigation. The functional anatomy underlying these cognitive functions was investigated by measuring the effective connectivity of these Posterior Cingulate Division (PCD) regions in the Human Connectome Project-MMP1 atlas in 171 HCP participants, and complemented with functional connectivity and diffusion tractography. First, the postero-ventral parts of the PCD (31pd, 31pv, 7m, d23ab, and v23ab) have effective connectivity with the temporal pole, inferior temporal visual cortex, cortex in the superior temporal sulcus implicated in auditory and semantic processing, with the reward-related vmPFC and pregenual anterior cingulate cortex, with the inferior parietal cortex, and with the hippocampal system.

Modelling structural properties of cyanine dye nanotubes at coarse-grained level.

Self-assembly is a ubiquitous process spanning from biomolecular aggregates to nanomaterials. Even though the resulting aggregates can be studied through experimental techniques, the dynamic pathways of the process and the molecular details of the final structures are not necessarily easy to resolve. Consequently, rational design of self-assembling aggregates and their properties remains extremely challenging.

The Fate of Epidermal Tight Junctions in the : Their Involvement in the Regulation of Desquamation and Phenotypic Expression of Certain Skin Conditions.

We evaluated the presence of tight junction (TJ) remnants in the (SC) of in vitro reconstructed human epidermis and human skin explants subjected or not to an aggressive topical treatment with beta-lipohydroxy salicylic acid (LSA) for 24 h. LSA-treated samples showed an increased presence of TJ remnants in the two lowermost layers of the SC, as quantified with standard electron microscopy. The topical aggression-induced overexpression of TJ-like cell-cell envelope fusions may influence SC functions: (1) directly, through an enhanced cohesion, and (2) indirectly, by impeding accessibility of peripheral corneodesmosomes to extracellular hydrolytic enzymes and, thus, slowing down desquamation.

Polyply; a python suite for facilitating simulations of macromolecules and nanomaterials.

Molecular dynamics simulations play an increasingly important role in the rational design of (nano)-materials and in the study of biomacromolecules. However, generating input files and realistic starting coordinates for these simulations is a major bottleneck, especially for high throughput protocols and for complex multi-component systems. To eliminate this bottleneck, we present the polyply software suite that provides 1) a multi-scale graph matching algorithm designed to generate parameters quickly and for arbitrarily complex polymeric topologies, and 2) a generic multi-scale random walk protocol capable of setting up complex systems efficiently and independent of the target force-field or model resolution.

Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage.

The signal peptidase complex (SPC) is an essential membrane complex in the endoplasmic reticulum (ER), where it removes signal peptides (SPs) from a large variety of secretory pre-proteins with exquisite specificity. Although the determinants of this process have been established empirically, the molecular details of SP recognition and removal remain elusive. Here, we show that the human SPC exists in two functional paralogs with distinct proteolytic subunits.

Territorial blueprint in the hippocampal system.

As we skillfully navigate through familiar places, neural computations of distances and coordinates escape our attention. However, we perceive clearly the division of space into socially meaningful territories. 'My space' versus 'your space' is a distinction familiar to all of us.

Martini 3: a general purpose force field for coarse-grained molecular dynamics.

The coarse-grained Martini force field is widely used in biomolecular simulations. Here we present the refined model, Martini 3 ( http://cgmartini.nl ), with an improved interaction balance, new bead types and expanded ability to include specific interactions representing, for example, hydrogen bonding and electronic polarizability.

Author Correction: 2600-years of stratospheric volcanism through sulfate isotopes.

The authors became aware of a mistake in the data and axis labeling in Fig. 2 in the original version of the Article. Specifically, the authors mistakenly copied and pasted a formula for background correction instead of the actual values.

Membrane Asymmetry Imposes Directionality on Lipid Droplet Emergence from the ER.

During energy bursts, neutral lipids fabricated within the ER bilayer demix to form lipid droplets (LDs). LDs bud off mainly in the cytosol where they regulate metabolism and multiple biological processes. They indeed become accessible to most enzymes and can interact with other organelles.

Measuring spontaneous mentalizing with a ball detection task: putting the attention-check hypothesis by Phillips and colleagues (2015) to the test.

Theory of Mind (ToM) or mentalizing refers to the ability to attribute mental states (such as desires, beliefs or intentions) to oneself or others. ToM has been argued to operate in an explicit and an implicit or a spontaneous way. In their influential paper, Kovács et al.

2600-years of stratospheric volcanism through sulfate isotopes.

High quality records of stratospheric volcanic eruptions, required to model past climate variability, have been constructed by identifying synchronous (bipolar) volcanic sulfate horizons in Greenland and Antarctic ice cores. Here we present a new 2600-year chronology of stratospheric volcanic events using an independent approach that relies on isotopic signatures (ΔS and in some cases ΔO) of ice core sulfate from five closely-located ice cores from Dome C, Antarctica. The Dome C stratospheric reconstruction provides independent validation of prior reconstructions.

Transferable MARTINI Model of Poly(ethylene Oxide).

Motivated by the deficiencies of the previous MARTINI models of poly(ethylene oxide) (PEO), we present a new model featuring a high degree of transferability. The model is parametrized on (a) a set of 8 free energies of transfer of dimethoxyethane (PEO dimer) from water to solvents of varying polarity; (b) the radius of gyration in water at high dilution; and (c) matching angle and dihedral distributions from atomistic simulations. We demonstrate that our model behaves well in five different areas of application: (1) it produces accurate densities and phase behavior or small PEO oligomers and water mixtures; (2) it yields chain dimensions in good agreement with the experiment in three different solvents (water, diglyme, and benzene) over a broad range of molecular weights (∼1.

Modeling Linguistic Variables With Regression Models: Addressing Non-Gaussian Distributions, Non-independent Observations, and Non-linear Predictors With Random Effects and Generalized Additive Models for Location, Scale, and Shape.

As statistical approaches are getting increasingly used in linguistics, attention must be paid to the choice of methods and algorithms used. This is especially true since they require assumptions to be satisfied to provide valid results, and because scientific articles still often fall short of reporting whether such assumptions are met. Progress is being, however, made in various directions, one of them being the introduction of techniques able to model data that cannot be properly analyzed with simpler linear regression models.

Lathyrol and epoxylathyrol derivatives: Modulation of Cdr1p and Mdr1p drug-efflux transporters of Candida albicans in Saccharomyces cerevisiae model.

Macrocyclic diterpenes were previously found to be able to modulate the efflux pump activity of Candida albicans multidrug transporters. Most of these compounds were jatrophanes, but only a few number of lathyrane-type diterpenes was evaluated. Therefore, the aim of this study was to evaluate the ability of nineteen structurally-related lathyrane diterpenes (1-19) to overcome the drug-efflux activity of Cdr1p and Mdr1p transporters of C.

Effect of allergens and irritants on levels of natural moisturizing factor and corneocyte morphology.

Background: The irritant sodium lauryl sulfate (SLS) is known to cause a decrease in the stratum corneum level of natural moisturizing factor (NMF), which in itself is associated with changes in corneocyte surface topography.

Objective: To explore this phenomenon in allergic contact dermatitis.

Methods: Patch testing was performed on patients with previously positive patch test reactions to potassium dichromate (Cr), nickel sulfate (Ni), methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI), or p-phenylenediamine.

Gaze-informed, task-situated representation of space in primate hippocampus during virtual navigation.

To elucidate how gaze informs the construction of mental space during wayfinding in visual species like primates, we jointly examined navigation behavior, visual exploration, and hippocampal activity as macaque monkeys searched a virtual reality maze for a reward. Cells sensitive to place also responded to one or more variables like head direction, point of gaze, or task context. Many cells fired at the sight (and in anticipation) of a single landmark in a viewpoint- or task-dependent manner, simultaneously encoding the animal's logical situation within a set of actions leading to the goal.

Overcoming Multidrug Resistance in Candida albicans: Macrocyclic Diterpenes from Euphorbia Species as Potent Inhibitors of Drug Efflux Pumps.

Thirteen macrocyclic diterpenes (1-13) of the jatrophane and lathyrane types, either isolated from Euphorbia species or obtained by chemical derivatization, were evaluated for their ability to inhibit the drug efflux activity of Candida albicans CaCdr1p and CaMdr1p multidrug transporters overexpressed in a Saccharomyces cerevisiae strain. Their inhibitory potential was assessed through a functional assay of Nile Red accumulation monitored by flow cytometry. A chemosensitization assay, using the checkerboard method, was also performed with the active compounds in order to evaluate their type of interaction with fluconazole.

Structural and biochemical characterization of the β-N-acetylglucosaminidase from Thermotoga maritima: toward rationalization of mechanistic knowledge in the GH73 family.

Members of the GH73 glycosidase family cleave the β-1,4-glycosidic bond between the N-acetylglucosaminyl (GlcNAc) and N-acetylmuramyl (MurNAc) moieties in bacterial peptidoglycan. A catalytic mechanism has been proposed for members FlgJ, Auto, AcmA and Atl(WM) and the structural analysis of FlgJ and Auto revealed a conserved α/β fold reminiscent of the distantly related GH23 lysozyme. Comparison of the active site residues reveals variability in the nature of the catalytic general base suggesting two distinct catalytic mechanisms: an inverting mechanism involving two distant glutamate residues and a substrate-assisted mechanism involving anchimeric assistance by the C2-acetamido group of the GlcNAc moiety.