Characterization of larval habitats of Anopheles (Nyssorhynchus) darlingi and associated species in malaria areas in western Brazilian Amazon.

BACKGROUND: Anopheles darlingi is the most efficient vector of malaria parasites in the Neotropics. Nevertheless, the specificities of its larval habitats are still poorly known. OBJECTIVES: Characterize permanent larval habitats, and population dynamics of An. darlingi and other potential vectors in relation to climate, physicochemical variables, insect fauna and malaria cases. METHODS: A 14-month longitudinal study was conducted in Porto Velho, Rondônia, western Brazilian Amazon. Monthly, 21 permanent water bodies were sampled. Immature anophelines and associated fauna were collected, physicochemical characteristics, and climate variables were recorded and analyzed. FINDINGS: Five types of habitats were identified: lagoon, stream, stream combined with lagoon, stream combined with dam, and fishpond. A total of 60,927 anophelines were collected. The most abundant species in all habitats were Anopheles braziliensis and An. darlingi. The highest density was found in the lagoon, while streams had the highest species richness. Abundance was higher during the transition period wet-dry season. There was a lag of respectively four and five months between the peak of rainfall and the Madeira River level and the highest abundance of An. darlingi larvae, which were positively correlated with habitats partially shaded, pH close to neutrality, increase dissolved oxygen and sulphates. MAIN CONCLUSIONS: The present study provides data on key factors defining permanent larval habitats for the surveillance of An. darlingi and other potential vectors as well as a log-linear Negative Binomial model based on immature mosquito abundance and climate variables to predict the increase in the number of malaria cases.

Comparative gene retention analysis in barley, wild emmer, and bread wheat pangenome lines reveals factors affecting gene retention following gene duplication.

BACKGROUND: Gene duplication is a prevalent phenomenon and a major driving force underlying genome evolution. The process leading to the fixation of gene duplicates following duplication is critical to understand how genome evolves but remains fragmentally understood. Most previous studies on gene retention are based on gene duplicate analyses in single reference genome. No population-based comparative gene retention analysis has been performed to date. RESULTS: Taking advantage of recently published genomic data in Triticeae, we dissected a divergent homogentisate phytyltransferase (HPT2) lineage caught in the middle stage of gene fixation following duplication. The presence/absence of HPT2 in barley (diploid), wild emmer (tetraploid), and bread wheat (hexaploid) pangenome lines appears to be associated with gene dosage constraint and environmental adaption. Based on these observations, we adopted a phylogeny-based orthology inference approach and performed comparative gene retention analyses across barley, wild emmer, and bread wheat. This led to the identification of 326 HPT2-pattern-like genes at whole genome scale, representing a pool of gene duplicates in the middle stage of gene fixation. Majority of these HPT2-pattern-like genes were identified as small-scale duplicates, such as dispersed, tandem, and proximal duplications. Natural selection analyses showed that HPT2-pattern-like genes have experienced relaxed selection pressure, which is generally accompanied with partial positive selection and transcriptional divergence. Functional enrichment analyses showed that HPT2-pattern-like genes are over-represented with molecular-binding and defense response functions, supporting the potential role of environmental adaption during gene retention. We also observed that gene duplicates from larger gene family are more likely to be lost, implying a gene dosage constraint effect. Further comparative gene retention analysis in barley and bread wheat pangenome lines revealed combined effects of species-specific selection and gene dosage constraint. CONCLUSIONS: Comparative gene retention analyses at the population level support gene dosage constraint, environmental adaption, and species-specific selection as three factors that may affect gene retention following gene duplication. Our findings shed light on the evolutionary process leading to the retention of newly formed gene duplicates and will greatly improve our understanding on genome evolution via duplication.

Radical-Based Enantioconvergent Reductive Couplings of Racemic Allenes and Aldehydes.

Transition metal-catalyzed radical-based enantioconvergent reactions have become a powerful strategy to synthesize enantiopure compounds from racemic starting materials. However, existing methods primarily address precursors with central chirality, neglecting those with axial chirality. Herein, we describe the enantioconvergent reductive coupling of racemic allenes with aldehydes, facilitated by a photoredox, chromium, and cobalt triple catalysis system. This method selectively affords one product from sixteen possible regio- and stereoisomers. The protocol leverages CoIII-H mediated hydrogen atom transfer (MHAT) and Cr-catalyzed radical-polar crossover for efficient stereoablation of axial chirality and asymmetric addition, respectively. Supported by mechanistic insights from control experiments, deuterium labeling, and DFT calculations, our approach offers synthetic chemists a valuable tool for creating enantioenriched chiral homoallylic alcohols, promising to advance radical-based strategies for synthesizing complex chiral molecules.

Homogeneity Test of the First-Order Agreement Coefficient in a Stratified Design.

Gwet's first-order agreement coefficient (AC1) is widely used to assess the agreement between raters. This paper proposes several asymptotic statistics for a homogeneity test of stratified AC1 in large sample sizes. These statistics may have unsatisfactory performance, especially for small samples and a high value of AC1. Furthermore, we propose three exact methods for small pieces. A likelihood ratio statistic is recommended in large sample sizes based on the numerical results. The exact E approaches under likelihood ratio and score statistics are more robust in the case of small sample scenarios. Moreover, the exact E method is effective to a high value of AC1. We apply two real examples to illustrate the proposed methods.

Superconducting Cavity Electromechanics: The Realization of an Acoustic Frequency Comb at Microwave Frequencies.

We present a nonlinear multimode superconducting electroacoustic system, where the interplay between superconducting kinetic inductance and piezoelectric strong coupling establishes an effective Kerr nonlinearity among multiple acoustic modes at 10 GHz that could hardly be achieved via intrinsic mechanical nonlinearity. By exciting this multimode Kerr system with a single microwave tone, we further demonstrate a coherent electroacoustic frequency comb and provide theoretical understanding of multimode nonlinear interaction in the superstrong coupling limit. This nonlinear superconducting electroacoustic system sheds light on the active control of multimode resonator systems and offers an enabling platform for the dynamic study of microcombs at microwave frequencies.

Quantum Microwave Radiometry with a Superconducting Qubit.

The interaction of photons and coherent quantum systems can be employed to detect electromagnetic radiation with remarkable sensitivity. We introduce a quantum radiometer based on the photon-induced dephasing process of a superconducting qubit for sensing microwave radiation at the subunit photon level. Using this radiometer, we demonstrate the radiative cooling of a 1 K microwave resonator and measure its mode temperature with an uncertainty ∼0.01 K. We thus develop a precise tool for studying the thermodynamics of quantum microwave circuits, which provides new solutions for calibrating hybrid quantum systems and detecting candidate particles for dark matter.

Radiative Cooling of a Superconducting Resonator.

Cooling microwave resonators to near the quantum ground state, crucial for their operation in the quantum regime, is typically achieved by direct device refrigeration to a few tens of millikelvin. However, in quantum experiments that require high operation power such as microwave-to-optics quantum transduction, it is desirable to operate at higher temperatures with non-negligible environmental thermal excitations, where larger cooling power is available. In this Letter, we present a radiative cooling protocol to prepare a superconducting microwave mode near its quantum ground state in spite of warm environment temperatures for the resonator. In this proof-of-concept experiment, the mode occupancy of a 10 GHz superconducting resonator thermally anchored at 1.02 K is reduced to 0.44±0.05 from 1.56 by radiatively coupling to a 70 mK cold load. This radiative cooling scheme allows high-operation-power microwave experiments to work in the quantum regime, and opens possibilities for routing microwave quantum states to elevated temperatures.

Proposal for Heralded Generation and Detection of Entangled Microwave-Optical-Photon Pairs.

Quantum state transfer between microwave and optical frequencies is essential for connecting superconducting quantum circuits to optical systems and extending microwave quantum networks over long distances. However, establishing such a quantum interface is extremely challenging because the standard direct quantum transduction requires both high coupling efficiency and small added noise. We propose an entanglement-based scheme-generating microwave-optical entanglement and using it to transfer quantum states via quantum teleportation-which can bypass the stringent requirements in direct quantum transduction and is robust against loss errors. In addition, we propose and analyze a counterintuitive design-suppress the added noise by placing the device at a higher temperature environment-which can improve both the device quality factor and power handling capability. We systematically analyze the generation and verification of entangled microwave-optical-photon pairs. The parameter for entanglement verification favors the regime of cooperativity mismatch and can tolerate certain thermal noises. Our scheme is feasible given the latest advances on electro-optomechanics, and can be generalized to various physical systems.

The effect of P85 on neuronal proliferation and differentiation during development of mouse cerebral cortex.

Proliferation of neural stem cells and differentiation of newly generated cells are crucial steps during the development of mammalian neocortex, which are able to generate suitable number of neurons and glial cells to ensure normal formation of cortex. Any disturbance in these processes leads to structural and functional abnormalities of cerebral cortex, such as epilepsy or intellectual disability. Numerous molecules involved in the development of disorders of the nervous system have been discovered in the recent years. The PI3K/AKT signaling pathway has been shown to be widely involved in the corticogenesis. Recently we could show that overexpression of regulatory subunit P85 of PI3K disrupts neuronal migration. However, it remains unclear whether the regulatory subunit P85 plays a role in the proliferation of neural stem cells and differentiation of newly generated cells during mouse brain development. Here, by using in utero electroporation and immunohistochemistry, we show that overexpression of P85 inhibited proliferation of neural progenitor cells and neuronal differentiation. By using 5-bromo-2-deoxyuridine (BrdU) labeling, we reveal that overexpression of P85 extended the cell cycle duration, which may result in developmental retardation during mouse corticogenesis.

Soliton microcomb generation at 2 µm in z-cut lithium niobate microring resonators.

Chip-based soliton frequency combs have been demonstrated on various material platforms, offering broadband, mutually coherent, and equally spaced frequency lines desired for many applications. Lithium niobate (LN), possessing both second- and third-order optical nonlinearities, as well as integrability on insulating substrates, has emerged as a novel source for microcomb generation and controlling. Here we demonstrate mode-locked soliton microcombs generated around 2 µm in a high-Q z-cut LN microring resonator. The intracavity photorefractive effect is found to be still dominant over the thermal effect in the 2 µm region, which facilitates direct accessing soliton states in the red-detuned regime, as reported in the telecom band. We also find that intracavity stimulated Raman scattering is greatly suppressed when moving the pump wavelength from the telecom band to 2 µm, thus alleviating Raman-Kerr comb competition. This Letter expands mode-locked LN microcombs to 2 µm, and could enable a variety of potential applications based on LN nanophotonic platform.

P85 regulates neuronal migration through affecting neuronal morphology during mouse corticogenesis.

In mammalian developing embryonic cortex, projection neurons migrate from the ventricular zone to the cortical plate, guided by radial glial cells with a transformation between bipolar and multipolar morphology. Previous studies have demonstrated that the PI3K-Akt-mTOR signal plays a critical role in brain development. However, the function of P85 in cortical development is still unclear. In the present study, we found that overexpression of P85 impaired cortical neuronal migration. Using in utero electroporation, we revealed that the length of the leading process in P85 overexpressed neurons became shorter than that in the control group but with more branches. Using markers for new-born neurons, we further found that overexpression of P85 did not affect the ultimate fate of these cortical neurons. These findings indicated that the P85 subunit plays an essential role in neuronal migration and neuronal morphology during mouse corticogenesis.

Developmental exposure of decabromodiphenyl ether impairs subventricular zone neurogenesis and morphology of granule cells in mouse olfactory bulb.

Polybrominated diphenyl ethers (PBDEs) are additive flame retardants widely used in various products (e.g., textiles, consumer electronics, and plastics). Strong evidence indicates that PBDEs are developmental neurotoxicants that can cause neurodevelopmental disabilities and cognitive defects. Currently, decabromodiphenyl ether (BDE 209) is the only PBDE permitted for production in most countries. This study investigated the impact of BDE 209 on postnatal neurogenesis in the subventricular zone (SVZ) of ICR mice. For this purpose, pregnant ICR mice were orally administrated a daily dose of 0, 20 or 100 mg/kg BDE 209 from gestation day 6 to postnatal day 16. Bromodeoxyuridine (BrdU) incorporation and in vivo postnatal electroporation were performed to label the newly generated cells in the SVZ. On PND 16, a reduction of type-B stem cells was found in the 100 mg/kg group. BDE 209 also decreased the number of newborn cells and Calretinin+ interneurons in granule cell layer at the dose of 100 mg/kg. In addition, we observed impaired neuronal migration and dendritic development of newborn olfactory granule cells in both 20 and 100 mg/kg groups. In conclusion, developmental exposure to BDE 209 produces adverse effects on SVZ neurogenesis and dendritic growth of mouse offspring. These findings suggest a potential risk of BDE 209 in human neurodevelopment.

Lapsed El Niño impact on Atlantic and Northwest Pacific tropical cyclone activity in 2023.

A typical El Niño event often results in suppressed tropical cyclone (TC) genesis frequency (TCGF) over the North Atlantic (NA) and a distinct northwest-southeast dipole pattern in TCGF anomaly over the western North Pacific (WNP). The 2023 saw a strong El Niño event but surprisingly active NA and suppressed WNP TC activities. Here, we present that these unprecedented deviations were driven by the record-warm NA, a record-breaking negative phase of the Pacific Meridional Mode (PMM), and background global warming. Results from high-resolution global model experiments demonstrate that extraordinary Atlantic warming dominated the increased NA TCGF and contributed equally with the PMM to the suppressed WNP TCGF, overshadowing El Niño's impact. Global warming also contributed to the observed TCGF anomalies. Our findings demonstrate that the typical influence of strong El Niño events on regional TC activity could be markedly altered by other climate modes, highlighting the complexity of TC genesis in a warming world.

Single-neuron projectomes of mouse paraventricular hypothalamic nucleus oxytocin neurons reveal mutually exclusive projection patterns.

Oxytocin (OXT) plays important roles in autonomic control and behavioral modulation. However, it is unknown how the projection patterns of OXT neurons align with underlying physiological functions. Here, we present the reconstructed single-neuron, whole-brain projectomes of 264 OXT neurons of the mouse paraventricular hypothalamic nucleus (PVH) at submicron resolution. These neurons hierarchically clustered into two groups, with distinct morphological and transcriptional characteristics and mutually exclusive projection patterns. Cluster 1 (177 neurons) axons terminated exclusively in the median eminence (ME) and have few collaterals terminating within hypothalamic regions. By contrast, cluster 2 (87 neurons) sent wide-spread axons to multiple brain regions, but excluding ME. Dendritic arbors of OXT neurons also extended outside of the PVH, suggesting capability to sense signals and modulate target regions. These single-neuron resolution observations reveal distinct OXT subpopulations, provide comprehensive analysis of their morphology, and lay the structural foundation for better understanding the functional heterogeneity of OXT neurons.

Vapor Growth of All-Inorganic 2D Ruddlesden-Popper Lead- and Tin-Based Perovskites.

The 2D Ruddlesden-Popper (RP) perovskites Cs2PbI2Cl2 (Pb-based, n = 1) and Cs2SnI2Cl2 (Sn-based, n = 1) stand out as unique and rare instances of entirely inorganic constituents within the more expansive category of organic/inorganic 2D perovskites. These materials have recently garnered significant attention for their strong UV-light responsiveness, exceptional thermal stability, and theoretically predicted ultrahigh carrier mobility. In this study, we synthesized Pb and Sn-based n = 1 2D RP perovskite films covering millimeter-scale areas for the first time, utilizing a one-step chemical vapor deposition (CVD) method under atmospheric conditions. These films feature perovskite layers oriented horizontally relative to the substrate. Multilayered Cs3Pb2I3Cl4 (Pb-based, n = 2) and Cs3Sn2I3Cl4 (Sn-based, n = 2) films were also obtained for the first time, and their crystallographic structures were refined by combining X-ray diffraction (XRD) and density functional theory (DFT) calculations. DFT calculations and experimental optical spectroscopy support band-gap energy shifts related to the perovskite layer thickness. We demonstrate bias-free photodetectors using the Sn-based, n = 1 perovskite with reproducible photocurrent and a fast 84 ms response time. The present work not only demonstrates the growth of high-quality all-inorganic multilayered 2D perovskites via the CVD method but also suggests their potential as promising candidates for future optoelectronic applications.

Experimental and Numerical Investigation on Fatigue Properties of Carbon Fiber Cross-Ply Laminates in Hygrothermal Environments.

The fatigue properties of composite materials are degraded seriously in hygrothermal environments, so taking into account their influence is very important when evaluating the fatigue life of composite structures. Tensile fatigue experiments of carbon fiber reinforced resin composite cross-ply laminates were conducted in room temperature/dry (RTD), cool temperature/dry (CTD) and elevated temperature/wet (ETW) conditions. The S-N curves and fatigue failure modes of the cross-ply laminates were obtained in three conditions. On this basis, a finite element model was established to discuss the influence of temperature and moisture content on the fatigue properties, as well as a method for determining environmental factors of fatigue life of cross-ply laminates was established. The results show that the saturation moisture absorption and temperature have a significant influence on the tensile fatigue properties of cross-ply laminates. The high-cycle fatigue property is weakened significantly by the saturation moisture absorption and high temperature, but the low-cycle fatigue properties were strengthened in cool temperature conditions. The delamination failure mode in ETW is the most severe, presenting with an obvious necking phenomenon. The influence of temperature has a greater effect than that of moisture content, but moisture absorption would play its affect obviously when temperature exceeds 40 °C.

Single-cell transcriptomic profiling of the hypothalamic median eminence during aging.

Aging is a slow and progressive natural process that compromises the normal functions of cells, tissues, organs, and systems. The aging of the hypothalamic median eminence (ME), a structural gate linking neural and endocrine systems, may impair hormone release, energy homeostasis, and central sensing of circulating molecules, leading to systemic and reproductive aging. However, the molecular and cellular features of ME aging remain largely unknown. Here, we describe the transcriptional landscape of young and middle-aged mouse ME at single-cell resolution, revealing the common and cell type-specific transcriptional changes with age. The transcriptional changes in cell-intrinsic programs, cell-cell crosstalk, and cell-extrinsic factors highlight five molecular features of ME aging and also implicate several potentially druggable targets at cellular, signaling, and molecular levels. Importantly, our results suggest that vascular and leptomeningeal cells may lead the asynchronized aging process among diverse cell types and drive local inflammation and cellular senescence via a unique secretome. Together, our study uncovers how intrinsic and extrinsic features of each cell type in the hypothalamic ME are changed by the aging process, which will facilitate our understanding of brain aging and provide clues for efficient anti-aging intervention at the middle-aged stage.

ASH1L haploinsufficiency results in autistic-like phenotypes in mice and links Eph receptor gene to autism spectrum disorder.

ASD-associated genes are enriched for synaptic proteins and epigenetic regulators. How those chromatin modulators establish ASD traits have remained unknown. We find haploinsufficiency of Ash1l causally induces anxiety and autistic-like behavior, including repetitive behavior, and alters social behavior. Specific depletion of Ash1l in forebrain induces similar ASD-associated behavioral defects. While the learning ability remains intact, the discrimination ability of Ash1l mutant mice is reduced. Mechanistically, deletion of Ash1l in neurons induces excessive synapses due to the synapse pruning deficits, especially during the post-learning period. Dysregulation of synaptic genes is detected in Ash1l mutant brain. Specifically, Eph receptor A7 is downregulated in Ash1l+/- mice through accumulating EZH2-mediated H3K27me3 in its gene body. Importantly, increasing activation of EphA7 in Ash1l+/- mice by supplying its ligand, ephrin-A5, strongly promotes synapse pruning and rescues discrimination deficits. Our results suggest that Ash1l haploinsufficiency is a highly penetrant risk factor for ASD, resulting from synapse pruning deficits.

Evolutionarily conservative and non-conservative regulatory networks during primate interneuron development revealed by single-cell RNA and ATAC sequencing.

The differences in size and function between primate and rodent brains, and the association of disturbed excitatory/inhibitory balance with many neurodevelopmental disorders highlight the importance to study primate ganglionic eminences (GEs) development. Here we used single-cell RNA and ATAC sequencing to characterize the emergence of cell diversity in monkey and human GEs where most striatal and cortical interneurons are generated. We identified regional and temporal diversity among progenitor cells which give rise to a variety of interneurons. These cells are specified within the primate GEs by well conserved gene regulatory networks, similar to those identified in mice. However, we detected, in human, several novel regulatory pathways or factors involved in the specification and migration of interneurons. Importantly, comparison of progenitors between our human and published mouse GE datasets led to the discovery and confirmation of outer radial glial cells in GEs in human cortex. Our findings reveal both evolutionarily conservative and nonconservative regulatory networks in primate GEs, which may contribute to their larger brain sizes and more complex neural networks compared with mouse.

Hierarchical deployment of Tbx3 dictates the identity of hypothalamic KNDy neurons to control puberty onset.

The neuroendocrine system consists of a heterogeneous collection of neuropeptidergic neurons in the brain, among which hypothalamic KNDy neurons represent an indispensable cell subtype controlling puberty onset. Although neural progenitors and neuronal precursors along the cell lineage hierarchy adopt a cascade diversification strategy to generate hypothalamic neuronal heterogeneity, the cellular logic operating within the lineage to specify a subtype of neuroendocrine neurons remains unclear. As human genetic studies have recently established a link between TBX3 mutations and delayed puberty onset, we systematically studied Tbx3-derived neuronal lineage and Tbx3-dependent neuronal specification and found that Tbx3 hierarchically established and maintained the identity of KNDy neurons for triggering puberty. Apart from the well-established lineage-dependent fate determination, we uncovered rules of interlineage interaction and intralineage retention operating through neuronal differentiation in the absence of Tbx3. Moreover, we revealed that human TBX3 mutations disturbed the phase separation of encoded proteins and impaired transcriptional regulation of key neuropeptides, providing a pathological mechanism underlying TBX3-associated puberty disorders.