Timing of maternal exposure and fetal sex determine the effects of low-level chemical mixture exposure on the fetal neuroendocrine system in sheep

We have shown that continuous maternal exposure to the complex mixture of environmental chemicals (ECs) found in human biosolids (sewage sludge), disrupts mRNA expression of genes crucial for development and long-term regulation of hypothalamo-pituitary gonadal (HPG) function in sheep. This study investigated whether exposure to ECs only during preconceptional period or only during pregnancy perturbed key regulatory genes within the hypothalamus and pituitary gland and whether these effects were different from chronic (life-long) exposure to biosolid ECs. The findings demonstrate that the timing and duration of maternal EC exposure influences the subsequent effects on the fetal neuroendocrine system in a sex-specific manner. Maternal exposure prior to conception or during pregnancy only, altered the expression of key fetal neuroendocrine regulatory systems such as GnRH and kisspeptin to a greater extent than when maternal exposure was ‘life-long’. Furthermore, hypothalamic gene expression was affected to a greater extent in males than in females, and following EC exposure, male fetuses expressed more “female-like” mRNA levels for some key neuroendocrine genes. This is the first study to show that “real-life” maternal exposure to low levels of a complex cocktail of chemicals prior to conception can subsequently affect the developing fetal neuroendocrine system. These findings demonstrate that the developing neuroendocrine system is sensitive to EC mixtures in a sex-dimorphic manner likely to predispose to reproductive dysfunction in later life

VAMP7 modulates ciliary biogenesis in kidney cells

Epithelial cells elaborate specialized domains that have distinct protein and lipid compositions, including the apical and basolateral surfaces and primary cilia. Maintaining the identity of these domains is required for proper cell function, and requires the efficient and selective SNARE-mediated fusion of vesicles containing newly synthesized and recycling proteins with the proper target membrane. Multiple pathways exist to deliver newly synthesized proteins to the apical surface of kidney cells, and the post-Golgi SNAREs, or VAMPs, involved in these distinct pathways have not been identified. VAMP7 has been implicated in apical protein delivery in other cell types, and we hypothesized that this SNARE would have differential effects on the trafficking of apical proteins known to take distinct routes to the apical surface in kidney cells. VAMP7 expressed in polarized Madin Darby canine kidney cells colocalized primarily with LAMP2-positive compartments, and siRNA-mediated knockdown modulated lysosome size, consistent with the known function of VAMP7 in lysosomal delivery. Surprisingly, VAMP7 knockdown had no effect on apical delivery of numerous cargoes tested, but did decrease the length and frequency of primary cilia. Additionally, VAMP7 knockdown disrupted cystogenesis in cells grown in a three-dimensional basement membrane matrix. The effects of VAMP7 depletion on ciliogenesis and cystogenesis are not directly linked to the disruption of lysosomal function, as cilia lengths and cyst morphology were unaffected in an MDCK lysosomal storage disorder model. Together, our data suggest that VAMP7 plays an essential role in ciliogenesis and lumen formation. To our knowledge, this is the first study implicating an R-SNARE in ciliogenesis and cystogenesis. © 2014 Szalinski et al

Structural and functional analyses of the DMC1-M200V polymorphism found in the human population

The M200V polymorphism of the human DMC1 protein, which is an essential, meiosis-specific DNA recombinase, was found in an infertile patient, raising the question of whether this homozygous human DMC1-M200V polymorphism may cause infertility by affecting the function of the human DMC1 protein. In the present study, we determined the crystal structure of the human DMC1-M200V variant in the octameric-ring form. Biochemical analyses revealed that the human DMC1-M200V variant had reduced stability, and was moderately defective in catalyzing in vitro recombination reactions. The corresponding M194V mutation introduced in the Schizosaccharomyces pombe dmc1 gene caused a significant decrease in the meiotic homologous recombination frequency. Together, these structural, biochemical and genetic results provide extensive evidence that the human DMC1-M200V mutation impairs its function, supporting the previous interpretation that this single-nucleotide polymorphism is a source of human infertility

Trace Element Emissions Vary With Lava Flow Age and Thermal Evolution During the Fagradalsfjall 2021–2023 Eruptions, Iceland

Basaltic fissure eruptions emit volatile and environmentally reactive gases and particulate matter (PM) into the lower troposphere (e.g., SO2, HCl, and HF in the gas phase; Se, As, Pb as complexes in the PM phase). Lava flows from fissure eruptions can be spatially extensive, but the composition and fluxes of their emissions are poorly characterized compared to those from main vent(s). Using uncrewed aircraft systems-mounted (drone) samplers and ground-based remote Fourier Transform Infrared Spectroscopy, we investigated the down-flow compositional evolution of emissions from active lava flows during the Fagradalsfjall 2021–2023 eruptions. The calculated fluxes of volatile trace metals from lava flows are considerable relative to both main vent degassing and anthropogenic fluxes in Iceland. We demonstrate a fractionation in major gas emissions with decreasing S/halogen ratio down-flow. This S-Cl fractionation is reflected in the trace element degassing profile, where the abundance of predominantly sulfur-complexing elements (e.g., Se, Te, As, Pb) decreases more rapidly in down-flow emissions relative to elements complexing as chlorides (e.g., Cu, Rb, Cs), oxides (e.g., La, Ce) and hydroxides (e.g., Fe, Mg, Al, Ti). Using thermochemical modeling, we explain this relationship through temperature and composition dependent element speciation as the lava flow ages and cools. As a result, some chloride-complexing elements (such as Cu) become relatively more abundant in emissions further down-flow, compared to emissions from the main vent or more proximal lava flows. This variability in down-flow element fluxes suggests that the output of metals to the environment may change depending on lava flow age and thermal evolution

Adaptive real-time dual-comb spectroscopy

With the advent of laser frequency combs, coherent light sources that offer equally-spaced sharp lines over a broad spectral bandwidth have become available. One decade after revolutionizing optical frequency metrology, frequency combs hold much promise for significant advances in a growing number of applications including molecular spectroscopy. Despite its intriguing potential for the measurement of molecular spectra spanning tens of nanometers within tens of microseconds at Doppler-limited resolution, the development of dual-comb spectroscopy is hindered by the extremely demanding high-bandwidth servo-control conditions of the laser combs. Here we overcome this difficulty. We experimentally demonstrate a straightforward concept of real-time dual-comb spectroscopy, which only uses free-running mode-locked lasers without any phase-lock electronics, a posteriori data-processing, or the need for expertise in frequency metrology. The resulting simplicity and versatility of our new technique of adaptive dual-comb spectroscopy offer a powerful transdisciplinary instrument that may spark off new discoveries in molecular sciences.Comment: 10 pages, 5 figure

Optimality of Human Contour Integration

For processing and segmenting visual scenes, the brain is required to combine a multitude of features and sensory channels. It is neither known if these complex tasks involve optimal integration of information, nor according to which objectives computations might be performed. Here, we investigate if optimal inference can explain contour integration in human subjects. We performed experiments where observers detected contours of curvilinearly aligned edge configurations embedded into randomly oriented distractors. The key feature of our framework is to use a generative process for creating the contours, for which it is possible to derive a class of ideal detection models. This allowed us to compare human detection for contours with different statistical properties to the corresponding ideal detection models for the same stimuli. We then subjected the detection models to realistic constraints and required them to reproduce human decisions for every stimulus as well as possible. By independently varying the four model parameters, we identify a single detection model which quantitatively captures all correlations of human decision behaviour for more than 2000 stimuli from 42 contour ensembles with greatly varying statistical properties. This model reveals specific interactions between edges closely matching independent findings from physiology and psychophysics. These interactions imply a statistics of contours for which edge stimuli are indeed optimally integrated by the visual system, with the objective of inferring the presence of contours in cluttered scenes. The recurrent algorithm of our model makes testable predictions about the temporal dynamics of neuronal populations engaged in contour integration, and it suggests a strong directionality of the underlying functional anatomy

Polarisation dynamics of vector soliton molecules in mode locked fibre laser

Two fundamental laser physics phenomena - dissipative soliton and polarisation of light are recently merged to the concept of vector dissipative soliton (VDS), viz. train of short pulses with specific state of polarisation (SOP) and shape defined by an interplay between anisotropy, gain/loss, dispersion, and nonlinearity. Emergence of VDSs is both of the fundamental scientific interest and is also a promising technique for control of dynamic SOPs important for numerous applications from nano-optics to high capacity fibre optic communications. Using specially designed and developed fast polarimeter, we present here the first experimental results on SOP evolution of vector soliton molecules with periodic polarisation switching between two and three SOPs and superposition of polarisation switching with SOP precessing. The underlying physics presents an interplay between linear and circular birefringence of a laser cavity along with light induced anisotropy caused by polarisation hole burning