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Stimuli‐responsive molecules with dynamic covalent bonds show physicochemical changes in response to external stimuli but also exhibit active molecular motions and poor luminescent properties. Hence, the manipulation and balance of dynamic and static behaviors are crucial for the development of multifunctional materials. In this work, a series of hydrazone‐based compounds with aggregation‐induced emission characteristics and hydrogen‐halogen interactions are designed and synthesized. Among them, TPAHPyCl showed the highest quantum yield of 54.0% and morphology‐dependent mechanochromic properties due to the strong chlorine‐hydrogen interactions and other multiple intermolecular interactions in the aggregate state. With the help of the turn‐on emission response to the non‐polar environment of lipid droplets, TPAHPyCl is also utilized for high‐resolution latent fingerprint detection and intracellular lipid‐droplet imaging, demonstrating multiple functions with dynamic and static properties. This work highlights the role of halogen‐hydrogen interactions and provides a new strategy to develop stimuli‐responsive materials with dynamic and static features. [ABSTRACT FROM AUTHOR]

Photoactivatable agent is a powerful tool in biomedicine studies due to high‐precision spatiotemporal control of light. However, those previously reported agents generally suffer from short wavelength, fluorescence self‐quenching effect, and the lack of photosensitizing property, which severely restrict their practical applications. To address these issues, molecular engineering of 1,4‐dihydropyridine derivatives is conducted to obtain an optimized agent, namely TPA‐DHPy‐Py, which exhibits low oxidation potential, high photoactivation efficiency, and excellent type I/II combined photodynamic activity. Concurrently, its photoactivated counterpart is featured by aggregation‐induced near‐infrared emission and remarkable reactive oxygen species (ROS) production efficiency. Upon photoactivation, TPA‐DHPy‐Py is capable of precisely identifying cancer cells from co‐culturing cancer cells and normal cells without the assistance of any extra targeting units, and in situ monitoring lipid droplets and endoplasmic reticulum alteration under ROS stress, as well as achieving fluorescent visualization of tumor in vivo with supremely high imaging contrast. Furthermore, the unprecedented performance on photodynamic cancer therapy is demonstrated by the significant inhibition of tumor growth. Therefore, the photoactivatable TPA‐DHPy‐Py with dual‐organelle‐targeted and excellent photodynamic activity associated with self‐monitoring ability is highly promising for cancer theranostics in clinical trials. [ABSTRACT FROM AUTHOR]

Microbial pathogens, including bacteria, fungi and viruses, greatly threaten the global public health. For pathogen infections, early diagnosis and precise treatment are essential to cut the mortality rate. The emergence of aggregation‐induced emission (AIE) biomaterials provides an effective and promising tool for the theranostics of pathogen infections. In this review, the recent advances about AIE biomaterials for anti-pathogen theranostics are summarized. With the excellent sensitivity and photostability, AIE biomaterials have been widely applied for precise diagnosis of pathogens. Besides, different types of anti-pathogen methods based on AIE biomaterials will be presented in detail, including chemotherapy and phototherapy. Finally, the existing deficiencies and future development of AIE biomaterials for anti-pathogen applications will be discussed. [ABSTRACT FROM AUTHOR]

The olfactory organ of tetrapods, with few exceptions, comprises the main and accessory organs: olfactory epithelium (OE) and vomeronasal organ (VNO). Unlike tetrapods, teleost fish lack a VNO. However, lungfish, a type of sarcopterygian fish closely related to tetrapods, possesses a lamellar OE similar to the OE of teleosts and a recess epithelium (RecE) resembling the amphibian VNO. The RecE has been hypothesized as a primordial VNO. Olfactory receptors in tetrapods are distinctively expressed in the OE and VNO. For instance, type 2 vomeronasal receptors (V2Rs) in Xenopus are categorized into those exclusively expressed in the OE and those solely expressed in the VNO. It remains unclear whether V2Rs are differentially expressed between the lamellar OE and RecE in lungfish. This study investigated V2R expression in the lamellar OE and RecE of the African lungfish, Protopterus annectens. P. annectens V2Rs were categorized into three groups: those exclusively expressed in the lamellar OE, those exclusively expressed in the RecE, and those expressed in both the lamellar OE and RecE. V2Rs exclusively expressed in the RecE and those expressed in both the lamellar OE and RecE formed a distinct clade in the phylogenetic tree, whereas others were solely expressed in the lamellar OE. These findings suggest that lungfish V2R expression represents an intermediate stage toward complete segregation between V2Rs expressed in the OE and those expressed in the VNO. [ABSTRACT FROM AUTHOR]

• Structure prediction for intrinsically disordered protein complexes benchmarked. • Proposed and used multiple levels of model evaluation metrics. • IDP-LZerD, CABS-Dock, and Alphafold-Multimer were benchmarked. • Binding residues are in general well identified by the three methods. • Alphafold-Multimer performed well at atom level but still room for improvement. Intrinsically Disordered Proteins (IDPs) are a class of proteins in which at least some region of the protein does not possess any stable structure in solution in the physiological condition but may adopt an ordered structure upon binding to a globular receptor. These IDP-receptor complexes are thus subject to protein complex modeling in which computational techniques are applied to accurately reproduce the IDP ligand-receptor interactions. This often exists in the form of protein docking, in which the 3D structures of both the subunits are known, but the position of the ligand relative to the receptor is not. Here, we evaluate the performance of three IDP-receptor modeling tools with metrics that characterize the IDP-receptor interface at various resolutions. We show that all three methods are able to properly identify the general binding site, as identified by lower resolution metrics, but begin to struggle with higher resolution metrics that capture biophysical interactions. [ABSTRACT FROM AUTHOR]

In addition to C, H and O, some biomass is also rich in mineral elements. The recovery and utilization of special mineral elements is of great significance to prepare functional materials and alleviate the current energy shortage. Herein, we describe a facile strategy for making full use of the chemical composition (C, Fe) and special structure of red blood cells (RBCs) from waste pig blood to fabricate a dual metal (Fe, Co)-nitrogen (N)-doped porous carbon catalyst by pyrolysis of a mixture of RBCs biomass, cobaltous acetate, and melamine. The porous catalyst displays a comparable activity for oxygen reduction reaction (ORR) to that of commercial Pt/C catalyst, with a half-wave potential of 0.821 VvsRHE in alkaline media and 0.672 VvsRHE in acid electrolyte. Especially, the as-prepared catalyst shows excellent methanol tolerance and stability in both acidic and alkaline electrolytes, which is superior to commercial Pt/C catalysts. The excellent ORR activity of FeCo-N/C(RBC) can be ascribed to the porous morphology and the cooperation between metal and nitrogen species. This work provides a novel idea of exploiting the composition of renewable biomass to modulate the activity and stability of carbon-based ORR catalysts. [ABSTRACT FROM AUTHOR]

Wearable robotic devices are receiving rapidly growing attentions for human-centered scenarios from medical, rehabilitation, to industrial applications. Supernumerary robotic limbs have been widely investigated for the augmentation of human limb functions, both as fingers and manipulator arms. Soft robotics offers an alternative approach to conventional motor-driven robot limbs toward safer and lighter systems, while pioneering soft supernumerary limbs are strongly limited in payload and dexterity by the soft robotic design approach, as well as the fabrication techniques. In this article, we proposed a wearable supernumerary soft robot for the human forearm, inspired by the fore flippers of otariids (eared seals). A flat flipper design was adopted, differing from the finger- or arm-shaped state-of-the-art works, with multiple soft actuators embedded as different joints for manipulation dexterity. The soft actuators were designed following origami (paper folding) patterns, reinforced by kirigami (paper cutting) fabrics. With this new approach, the proposed soft flipper incorporated eight independent muscles, achieving over 20 times payload to self-weight ratio, while weighing less than 500 g. The versatility, dexterity, and payload capability were experimentally demonstrated using a fabricated prototype with proprietary actuation and control. This article demonstrates the feasibility and unique advantages of origami + kirigami soft robots as a new approach to strong, dexterous, and yet safe and lightweight wearable robotic devices. [ABSTRACT FROM AUTHOR]

With the continuous development of power electronics technology, variable-speed offshore wind turbines that penetrated the grid system caused the problem of inertia reduction. This study investigates the frequency stability of synchronous, offshore wind-farm integration through a modular-multilevel-converter high-voltage direct-current (MMC–HVDC) transmission system. When full-scale converter wind turbines (type 4) penetrate the AC grid, the AC system debilitates, and it becomes difficult to maintain the AC system frequency stability. In this paper, we present an improved inertial-response-control method to solve this problem. The mathematical model of the synchronous generator is based on the swing equation and is theoretically derived by establishing a MMC–HVDC. Based on the above model, the inertia constant is analyzed using a model that integrates the MMC–HVDC and offshore synchronous generator. With the new improved control method, a more sensitive and accurate inertia index can be obtained using the formula related to the effective short-circuit ratio of the AC system. Moreover, it is advantageous to provide a more accurate inertial control evaluation for AC systems under various conditions. Furthermore, the impact of the MMC–HVDC on system safety is assessed based on the capacitor time constant. This simulation was implemented using the PSCAD/EMTDC platform. [ABSTRACT FROM AUTHOR]

The vomeronasal organ (VNO) plays a key role in sensing pheromonal cues, which elicits social and reproductive behaviors. Although the VNO is highly conserved across mammals, it has been lost in some species that have evolved alternate sensing systems during diversification. In this study, we investigate a newly identified VNO-specific gene, ancV1R , in the extant 261 species of mammals to examine the correlation between genotype (ancV1R) and phenotype (VNO). As a result, we found signatures for the relaxation of purifying selection (inactivating mutations and the elevation of d N /d S) on ancV1R s in VNO-lacking mammals, such as catarrhine primates, cetaceans, the manatees, and several bat lineages, showing the distinct correlation between genotype and phenotype. Interestingly, we further revealed signatures for the relaxation of purifying selection on ancV1R in true seals, otters, the fossa, the owl monkey, and alcelaphine antelopes in which the existence of a functional VNO is still under debate. Our additional analyses on TRPC2 , another predictive marker gene for the functional VNO, showed a relaxation of purifying selection, supporting the possibility of VNO loss in these species. The results of our present study invite more in-depth neuroanatomical investigation in mammals for which VNO function remains equivocal. [ABSTRACT FROM AUTHOR]

A brain-machine interface (BMI) is a neuroprosthetic device that can restore motor function of individuals with paralysis. Although the feasibility of BMI control of upper-limb neuroprostheses has been demonstrated, a BMI for the restoration of lower-limb motor functions has not yet been developed. The objective of this study was to determine if gait-related information can be captured from neural activity recorded from the primary motor cortex of rats, and if this neural information can be used to stimulate paralysed hindlimb muscles after complete spinal cord transection. Neural activity was recorded from the hindlimb area of the primary motor cortex of six female Sprague Dawley rats during treadmill locomotion before and after mid-thoracic transection. Before spinal transection there was a strong association between neural activity and the step cycle. This association decreased after spinal transection. However, the locomotive state (standing vs. walking) could still be successfully decoded from neural recordings made after spinal transection. A novel BMI device was developed that processed this neural information in real-time and used it to control electrical stimulation of paralysed hindlimb muscles. This system was able to elicit hindlimb muscle contractions that mimicked forelimb stepping. We propose this lower-limb BMI as a future neuroprosthesis for human paraplegics. [ABSTRACT FROM AUTHOR]

Patients with damage to the medial temporal lobe show deficits in forming new declarative memories but can still recall older memories, suggesting that the medial temporal lobe is necessary for encoding memories in the neocortex. Here, we found that cortical projection neurons in the perirhinal and entorhinal cortices were mostly immunopositive for cholecystokinin (CCK). Local infusion of CCK in the auditory cortex of anesthetized rats induced plastic changes that enabled cortical neurons to potentiate their responses or to start responding to an auditory stimulus that was paired with a tone that robustly triggered action potentials. CCK infusion also enabled auditory neurons to start responding to a light stimulus that was paired with a noise burst. In vivo intracellular recordings in the auditory cortex showed that synaptic strength was potentiated after two pairings of presynaptic and postsynaptic activity in the presence of CCK. Infusion of a CCKB antagonist in the auditory cortex prevented the formation of a visuo-auditory association in awake rats. Finally, activation of the entorhinal cortex potentiated neuronal responses in the auditory cortex, which was suppressed by infusion of a CCKB antagonist. Together, these findings suggest that the medial temporal lobe influences neocortical plasticity via CCK-positive cortical projection neurons in the entorhinal cortex. [ABSTRACT FROM AUTHOR]

Reporter genes have contributed to advancements in molecular biology. Binding of an upstream regulatory protein to a downstream reporter promoter allows quantification of the activity of the upstream protein produced from the corresponding gene. In studies of synthetic biology, analyses of reporter gene activities ensure control of the cell with synthetic genetic circuits, as achieved using a combination of in silico and in vivo experiments. However, unexpected effects of downstream reporter genes on upstream regulatory genes may interfere with in vivo observations. This phenomenon is termed as retroactivity. Using in silico and in vivo experiments, we found that a different copy number of regulatory protein-binding sites in a downstream gene altered the upstream dynamics, suggesting retroactivity of reporters in this synthetic genetic oscillator. Furthermore, by separating the two sources of retroactivity (titration of the component and competition for degradation), we showed that, in the dual-feedback oscillator, the level of the fluorescent protein reporter competing for degradation with the circuits' components is important for the stability of the oscillations. Altogether, our results indicate that the selection of reporter promoters using a combination of in silico and in vivo experiments is essential for the advanced design of genetic circuits. [ABSTRACT FROM AUTHOR]

Summary Corticospinal neurons (CSNs) represent the direct cortical outputs to the spinal cord and play important roles in motor control across different species. However, their organizational principle remains unclear. By using a retrograde labeling system, we defined the requirement of CSNs in the execution of a skilled forelimb food-pellet retrieval task in mice. In vivo imaging of CSN activity during performance revealed the sequential activation of topographically ordered functional ensembles with moderate local mixing. Region-specific manipulations indicate that CSNs from caudal or rostral forelimb area control reaching or grasping, respectively, and both are required in the transitional pronation step. These region-specific CSNs terminate in different spinal levels and locations, therefore preferentially connecting with the premotor neurons of muscles engaged in different steps of the task. Together, our findings suggest that spatially defined groups of CSNs encode different movement modules, providing a logic for parallel-ordered corticospinal circuits to orchestrate multistep motor skills. [ABSTRACT FROM AUTHOR]

The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular “uncaging”, or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the “turning assay” and “collapse assay”, which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo , which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research. [ABSTRACT FROM AUTHOR]

Summary Many human spinal cord injuries are anatomically incomplete but exhibit complete paralysis. It is unknown why spared axons fail to mediate functional recovery in these cases. To investigate this, we undertook a small-molecule screen in mice with staggered bilateral hemisections in which the lumbar spinal cord is deprived of all direct brain-derived innervation, but dormant relay circuits remain. We discovered that a KCC2 agonist restored stepping ability, which could be mimicked by selective expression of KCC2, or hyperpolarizing DREADDs, in the inhibitory interneurons between and around the staggered spinal lesions. Mechanistically, these treatments transformed this injury-induced dysfunctional spinal circuit to a functional state, facilitating the relay of brain-derived commands toward the lumbar spinal cord. Thus, our results identify spinal inhibitory interneurons as a roadblock limiting the integration of descending inputs into relay circuits after injury and suggest KCC2 agonists as promising treatments for promoting functional recovery after spinal cord injury. [ABSTRACT FROM AUTHOR]

Summary A major hurdle for functional recovery after both spinal cord injury and cortical stroke is the limited regrowth of the axons in the corticospinal tract (CST) that originate in the motor cortex and innervate the spinal cord. Despite recent advances in engaging the intrinsic mechanisms that control CST regrowth, it remains to be tested whether such methods can promote functional recovery in translatable settings. Here we show that post-lesional AAV-assisted co-expression of two soluble proteins, namely insulin-like growth factor 1 (IGF1) and osteopontin (OPN), in cortical neurons leads to robust CST regrowth and the recovery of CST-dependent behavioral performance after both T10 lateral spinal hemisection and a unilateral cortical stroke. In these mice, a compound able to increase axon conduction, 4-aminopyridine-3-methanol, promotes further improvement in CST-dependent behavioral tasks. Thus, our results demonstrate a potentially translatable strategy for restoring cortical dependent function after injury in the adult. [ABSTRACT FROM AUTHOR]

Studying the genetic regulation of protein expression (through protein quantitative trait loci (pQTLs)) offers a deeper understanding of regulatory variants uncharacterized by mRNA expression regulation (expression QTLs (eQTLs)) studies. Here we report cis-eQTL and cis-pQTL statistical fine-mapping from 1,405 genotyped samples with blood mRNA and 2,932 plasma samples of protein expression, as part of the Japan COVID-19 Task Force (JCTF). Fine-mapped eQTLs (n = 3,464) were enriched for 932 variants validated with a massively parallel reporter assay. Fine-mapped pQTLs (n = 582) were enriched for missense variations on structured and extracellular domains, although the possibility of epitope-binding artifacts remains. Trans-eQTL and trans-pQTL analysis highlighted associations of class I HLA allele variation with KIR genes. We contrast the multi-tissue origin of plasma protein with blood mRNA, contributing to the limited colocalization level, distinct regulatory mechanisms and trait relevance of eQTLs and pQTLs. We report a negative correlation between ABO mRNA and protein expression because of linkage disequilibrium between distinct nearby eQTLs and pQTLs., (© 2024. The Author(s).)

Creating durable, motion-compliant neural interfaces is crucial for accessing dynamic tissues under in vivo conditions and linking neural activity with behaviors. Utilizing the self-alignment of nano-fillers in a polymeric matrix under repetitive tension, here, we introduce conductive carbon nanotubes with high aspect ratios into semi-crystalline polyvinyl alcohol hydrogels and create electrically anisotropic percolation pathways through cyclic stretching. The resulting anisotropic hydrogel fibers (diameter of 187 ± 13 µm) exhibit fatigue resistance (20,000 cycles at 20% strain) with a stretchability of 64.5 ± 7.9%, and low electrochemical impedance (900 ± 149 kΩ @ 1kHz). We observe the re-constructed nanofillers' axial alignment and a corresponding anisotropic impedance decrease along the direction of cyclic stretching. We fabricate fiber-shaped hydrogels into bioelectronic devices and implant them into wild-type and transgenic Thy1-ChR2-EYFP mice to record electromyographic signals from muscles in anesthetized and freely moving conditions. These hydrogel fibers effectively enable the simultaneous recording of electrical signals from ventral spinal cord neurons and the tibialis anterior muscles during optogenetic stimulation. Importantly, the devices maintain functionality with repeatable recording results over eight months after implantation, demonstrating their durability and potential for long-term monitoring in neurophysiological studies.

Protein-protein interactions are involved in almost all processes in a living cell and determine the biological functions of proteins. To obtain mechanistic understandings of protein-protein interactions, the tertiary structures of protein complexes have been determined by biophysical experimental methods, such as X-ray crystallography and cryogenic electron microscopy. However, as experimental methods are costly in resources, many computational methods have been developed that model protein complex structures. One of the difficulties in computational protein complex modeling (protein docking) is to select the most accurate models among many models that are usually generated by a docking method. This article reviews advances in protein docking model assessment methods, focusing on recent developments that apply deep learning to several network architectures., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

We present the results for CAPRI Round 54, the 5th joint CASP-CAPRI protein assembly prediction challenge. The Round offered 37 targets, including 14 homodimers, 3 homo-trimers, 13 heterodimers including 3 antibody-antigen complexes, and 7 large assemblies. On average ~70 CASP and CAPRI predictor groups, including more than 20 automatics servers, submitted models for each target. A total of 21 941 models submitted by these groups and by 15 CAPRI scorer groups were evaluated using the CAPRI model quality measures and the DockQ score consolidating these measures. The prediction performance was quantified by a weighted score based on the number of models of acceptable quality or higher submitted by each group among their five best models. Results show substantial progress achieved across a significant fraction of the 60+ participating groups. High-quality models were produced for about 40% of the targets compared to 8% two years earlier. This remarkable improvement is due to the wide use of the AlphaFold2 and AlphaFold2-Multimer software and the confidence metrics they provide. Notably, expanded sampling of candidate solutions by manipulating these deep learning inference engines, enriching multiple sequence alignments, or integration of advanced modeling tools, enabled top performing groups to exceed the performance of a standard AlphaFold2-Multimer version used as a yard stick. This notwithstanding, performance remained poor for complexes with antibodies and nanobodies, where evolutionary relationships between the binding partners are lacking, and for complexes featuring conformational flexibility, clearly indicating that the prediction of protein complexes remains a challenging problem., (© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

Organelle-targeted therapy guided by fluorescence imaging is promising for precise cancer treatment. However, most current organelle-targeted therapeutics can only destruct single organelles, which suffer from limited therapeutic efficacy. To address this challenge, a photoactivatable probe was developed for sequential photodynamic destruction of multiorganelles in cancer cells, including lysosomes, lipid droplets, and mitochondria. This photoactivatable probe not only exhibits efficient cancer cell eradication in vitro but also can suppress tumor growth in vivo . Simultaneously, the photoactivatable probe enables sequential destruction of multiple organelles in cancer cells, which can be observed in situ through the conversion of green-to-red fluorescence facilitated by a photooxidative dehydrogenation reaction. We believe this photoactivatable probe for sequential destruction of multiple organelles associated with fluorescence color conversion provides a new strategy for cancer treatment with greatly improved efficacy.

The Plant-Conserved Region (P-CR) and the Class-Specific Region (CSR) are two plant-unique sequences in the catalytic core of cellulose synthases (CESAs) for which specific functions have not been established. Here, we used site-directed mutagenesis to replace amino acids and motifs within these sequences predicted to be essential for assembly and function of CESAs. We developed an in vivo method to determine the ability of mutated CesA1 transgenes to complement an Arabidopsis (Arabidopsis thaliana) temperature-sensitive root-swelling1 (rsw1) mutant. Replacement of a Cys residue in the CSR, which blocks dimerization in vitro, rendered the AtCesA1 transgene unable to complement the rsw1 mutation. Examination of the CSR sequences from 33 diverse angiosperm species showed domains of high-sequence conservation in a class-specific manner but with variation in the degrees of disorder, indicating a nonredundant role of the CSR structures in different CESA isoform classes. The Cys residue essential for dimerization was not always located in domains of intrinsic disorder. Expression of AtCesA1 transgene constructs, in which Pro417 and Arg453 were substituted for Ala or Lys in the coiled-coil of the P-CR, were also unable to complement the rsw1 mutation. Despite an expected role for Arg457 in trimerization of CESA proteins, AtCesA1 transgenes with Arg457Ala mutations were able to fully restore the wild-type phenotype in rsw1. Our data support that Cys662 within the CSR and Pro417 and Arg453 within the P-CR of Arabidopsis CESA1 are essential residues for functional synthase complex formation, but our data do not support a specific role for Arg457 in trimerization in native CESA complexes., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

White Matter Hyperintensities (WMH) are the most common manifestation of cerebral small vessel disease (cSVD) on the brain MRI. Accurate WMH segmentation algorithms are important to determine cSVD burden and its clinical con-sequences. Most of existing WMH segmentation algorithms require both fluid attenuated inversion recovery (FLAIR) images and T1-weighted images as inputs. However, T1-weighted images are typically not part of standard clinical scans which are acquired for patients with acute stroke. In this paper, we propose a novel brain atlas guided attention U-Net (BAGAU-Net) that leverages only FLAIR images with a spatially-registered white matter (WM) brain atlas to yield competitive WMH segmentation performance. Specifically, we designed a dual-path segmentation model with two novel connecting mechanisms, namely multi-input attention module (MAM) and attention fusion module (AFM) to fuse the information from two paths for accurate results. Experiments on two publicly available datasets show the effectiveness of the proposed BAGAU-Net. With only FLAIR images and WM brain atlas, BAGAU-Net outperforms the state-of-the-art method with T1-weighted images, paving the way for effective development of WMH segmentation. Availability: https://github.com/Ericzhang1/BAGAU-Net., (©2021 AMIA - All rights reserved.)

The revision of the sub-order Microchiroptera is one of the most intriguing outcomes in recent mammalian molecular phylogeny. The unexpected sister-taxon relationship between rhinolophoid microbats and megabats, with the exclusion of other microbats, suggests that megabats arose in a relatively short period of time from a microbat-like ancestor. In order to understand the genetic mechanism underlying adaptive evolution in megabats, we determined the whole-genome sequences of two rousette megabats, Leschenault's rousette (Rousettus leschenaultia) and the Egyptian fruit bat (R. aegyptiacus). The sequences were compared with those of 22 other mammals, including nine bats, available in the database. We identified that megabat genomes are distinct in that they have extremely low activity of SINE retrotranspositions, expansion of two chemosensory gene families, including the trace amine receptor (TAAR) and olfactory receptor (OR), and elevation of the dN/dS ratio in genes for immunity and protein catabolism. The adaptive signatures discovered in the genomes of megabats may provide crucial insight into their distinct evolution, including key processes such as virus resistance, loss of echolocation, and frugivorous feeding., (© The Author(s) 2020. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.)