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IntroductionThe media’s recent focus on possible negative health outcomes following sports- related concussion has increased awareness as well as anxiety among parents and athletes. However, the literature on concussion outcomes is equivocal and limited by a variety of diagnostic approaches.MethodsThe current study used a rigorous, open- access concussion identification method—the Ohio State University Traumatic Brain Injury Identification method (OSU TBI-ID) to identify concussion and periods of repeated, subclinical head trauma in 108 young adult athletes who also underwent a comprehensive protocol of cognitive tests, mood/anxiety questionnaires, and high-angular-resolution diffusion-weighted brain imaging to evaluate potential changes in white matter microstructure.ResultsAnalyses showed that athletes with a history of repetitive, subclinical impacts to the head performed slightly worse on a measure of inhibitory impulse control and had more anxiety symptoms compared to those who never sustained any type of head injury but were otherwise the same as athletes with no history of concussion. Importantly, there were no group differences in cerebral white matter as measured by tract- based spatial statistics (TBSS), nor were there any associations between OSU TBI-ID measures and whole-brain principal scalars and free-water corrected scalars.DiscussionOur results provide support for the hypothesis that it is not concussion per se, but repetitive head impacts that beget worse outcomes.

Episodic memory relies on the coordination of widespread brain regions that reconstruct spatiotemporal details of an episode. These topologically dispersed brain regions can rapidly communicate through structural pathways. Research in animal and human lesion studies implicate the fornix—the major output pathway of the hippocampus—in supporting various aspects of episodic memory. Because episodic memory undergoes marked changes in early childhood, we tested the link between the fornix and episodic memory in an age window of robust memory development (ages 4–8 years). Children were tested on the stories subtest from the Children’s Memory Scale, a temporal order memory task, and a source memory task. Fornix streamlines were reconstructed using probabilistic tractography to estimate fornix microstructure. In addition, we measured fornix macrostructure and computed free water. To assess selectivity of our findings, we also reconstructed the uncinate fasciculus. Findings show that children’s memory increases from ages 4 to 8 and that fornix micro- and macrostructure increases between ages 4 and 8. Children’s memory performance across nearly every memory task correlated with individual differences in fornix, but not uncinate fasciculus, white matter. These findings suggest that the fornix plays an important role in supporting the development of episodic memory, and potentially semantic memory, in early childhood.

Seminal work in the 1990’s found alterations in the cerebellum of individuals with social disorders including autism spectrum disorder and schizophrenia. In healthy populations, distinct portions of the posterior cerebellum are consistently activated in fMRI studies of social cognition and it has been hypothesized that the cerebellum plays an essential role in social cognition, particularly in theory of mind. Here we review the lesion literature and find that the effect of cerebellar damage on social cognition is strongly linked to the age of insult, with dramatic impairments observed after prenatal insult, strong deficits observed after childhood damage, and mild and inconsistent deficits observed following damage to the adult cerebellum. To explain the developmental gradient, we propose that early in life, the forward model dominates cerebellar computations. The forward model learns and uses errors to help build schemas of our interpersonal worlds. Subsequently, we argue that once these schemas have been built up, the inverse model, which is the foundation of automatic processing, becomes dominant. We provide suggestions for how to test this, and also outline directions for future research.

Systems consolidation theories posit that consolidation occurs primarily through a coordinated communication between hippocampus and neocortex (McClelland and O’Reilly 1995; Kumaran et al., 2016; Moscovitch and Gilboa, 2022). Recent sleep studies in rodents have shown that hippocampus and visual cortex replay the same information at temporal proximity (“co-replay”) (Ji & Wilson, 2007; Lansink et al., 2009; Wierzynski et al., 2009; Peyrache et al., 2009). We developed a novel TR-based co-reactivation (TRCR) analysis method to study hippocampal-cortical co-replays in humans using functional MRI. Thirty-six young adults completed an image (face or scene)-location paired associate encoding task in the scanner, which were preceded and followed by resting state scans. We identified post-encoding rest TRs (+/− 1) that showed neural reactivation of each image-location trials in both hippocampus (HPC) and category-selective cortex (fusiform face area, FFA). This allowed us to characterize temporally proximal coordinated reactivations (“co-reactivations”) between HPC and FFA. Moreover, we found that increased HPC-FFA co-reactivations were associated with incorrectly recognized trials after a 1-week delay (p= 0.004). Finally, we found that these HPC-FFA co-reactivations were also associated with trials that were initially correctly recognized immediately after encoding but were later forgotten in 1-day (p= 0.043) and 1-week delay period (p= 0.031). We discuss these results from a trace transformation perspective (Winocur and Moscovitch, 2011; Sekeres et al., 2018) and speculate that HPC-FFA co-reactivations may be integrating related events, at the expense of disrupting event-specific details, hence leading to forgetting.

The ongoing stream of sensory experience is so complex and ever-changing that we tend to parse this experience at “event boundaries”, which structures and strengthens memory. Memory processes undergo profound change across early childhood. Whether young children also divide their ongoing processing along event boundaries, and if those boundaries relate to memory, could provide important insight into the development of memory systems. In Study 1, 4-7-year-old children and adults segmented a cartoon, and we tested their memory. Children’s event boundaries were more variable than adults’ and differed in location and consistency of agreement. Older children’s event segmentation was more adult-like than younger children’s, and children who segmented events more like adults had better memory for those events. In Study 2, we asked whether these developmental differences in event segmentation had their roots in distinct neural representations. A separate group of 4-8-year-old children watched the same cartoon while undergoing an fMRI scan. In the right hippocampus, greater pattern dissimilarity across event boundaries compared to within events was evident for both child and adult behavioral boundaries, suggesting children and adults share similar event cognition. However, the boundaries identified by a data-driven Hidden Markov Model found that a different brain region—the left and right angular gyri—aligned only with event boundaries defined by children. Overall, these data suggest that children’s event cognition is reasonably well-developed by age 4 but continues to become more adult-like across early childhood.

Vibrio species play a crucial role in maintaining the carbon and nitrogen balance between the oceans and the land through their ability to employ chitin as a sole source of energy. This study describes the structural basis for the action of the GH20 β‐N‐acetylglucosaminidase (VhGlcNAcase) in chitin metabolism by Vibrio campbellii (formerly V. harveyi) strain ATCC BAA‐1116. Crystal structures of wild‐type VhGlcNAcase in the absence and presence of the sugar ligand, and of the unliganded D437A mutant, were determined. VhGlcNAcase contains three distinct domains: an N‐terminal carbohydrate‐binding domain linked to a small α+β domain and a C‐terminal (β/α)8 catalytic domain. The active site of VhGlcNAcase has a narrow, shallow pocket that is suitable for accommodating a small chitooligosaccharide. VhGlcNAcase is a monomeric enzyme of 74 kDa, but its crystal structures show two molecules of enzyme per asymmetric unit, in which Gln16 at the dimeric interface of the first molecule partially blocks the entrance to the active site of the neighboring molecule. The GlcNAc unit observed in subsite −1 makes exclusive hydrogen bonds to the conserved residues Arg274, Tyr530, Asp532 and Glu584, while Trp487, Trp546, Trp582 and Trp505 form a hydrophobic wall around the −1 GlcNAc. The catalytic mutants D437A/N and E438A/Q exhibited a drastic loss of GlcNAcase activity, confirming the catalytic role of the acidic pair (Asp437–Glu438)., Crystal structures of a GH20 β‐N‐acetylglucosaminidase from V. campbellii reveal substrate specificity in chitin utilization.

Titanlib is a library of functions for the automatic quality control of meteorological observations and it is publicly available on github:https://github.com/metno/titanlibTitanlib builds upon the experience of running TITAN (Båserud et al., 2020) for the quality control of temperature and precipitation serving operational applications, such as the production of automatic weather forecasts (Yr.no) and observational gridded datasets (seNorge.no).We aim to manage titanlib as an open project that will eventually incorporate contributions from different working groups.The distinctive feature of titanlib is the use of spatial quality control methods. A wide range of spatial checks are made available, from buddy-checks among neighbouring observations to spatial consistency tests (SCTs) based on more sophisticated statistical interpolation.This presentation focuses on tuning the parameters of a generic titanlib function. In particular, a general approach to this problem will be presented. A set of reference observations is identified among all available observations. The reference observations are considered good observations. For the sake of simplicity, we call good observations those that are not affected by gross measurement errors, and bad observations those with gross errors. Synop stations constitute the natural reference set; however, other choices are possible. The quality control routine is always applied to the whole set of observations and the statistics are collected only over the reference observations. First, the routine is applied in the “unperturbed” mode and we count the number of: correct negatives (i.e. reference observations flagged as good ones), and false alarms (i.e. reference observations flagged as bad ones). Secondly the routine is applied on “perturbed” reference observations, by introducing known errors, and we count: misses (i.e. perturbed observations flagged as good ones), and hits (i.e. perturbed observations flagged as bad ones).The combination of “perturbed” and “unperturbed” experiments for different settings of the QC routine allows us to obtain several contingency tables that we use to determine the optimal combination of parameters in an original way. In order to define the cost function, the user is required to specify the prior knowledge on: the expected probability of having a bad observation in the network, and the relative cost of a false alarm for the application considered.The method is described by Alerskans et al. (2022), where it has been applied to QC of hourly temperature measured from crowdsourced observations. Furthermore, we will present an application for QC of hourly precipitation.References:Båserud, L., Lussana, C., Nipen, T. N., Seierstad, I. A., Oram, L., and Aspelien, T.: TITAN automatic spatial quality control of meteorological in-situ observations, Adv. Sci. Res., 17, 153–163, https://doi.org/10.5194/asr-17-153-2020, 2020 Alerskans, E., Lussana, C., Nipen, T. N., Seierstad, I. A.,: Optimizing spatial quality control for a dense network of meteorological stations, accepted for publication in Journal of Atmospheric and Oceanic Technology (JTECH), 2022

This chapter is a review of the success and possible development of digital education. It details the impact of technology on the approach to learning and teaching, how it produced an educational shift in providing ubiquitous access to information. It highlights as well the shift in the role of teachers and the rise of a more holistic acceptance of education simultaneously with a new form of student-centered approach. Teaching skills, creativity, innovation, critical global thinking are now central concepts that are discussed here. The review also reflects on the current techniques and tools to facilitate academic learning online (i.e., research, simulation, and gamification). It surveys their strengths, weaknesses, and potential for growth. The second half of the chapter provides guidelines for implementations. It analyses the roles of the innovation directors, students, teachers, and the LMS and suggests protocols to facilitate a smooth and successful implementation and running of digital innovation in schools.

Here, we report the draft genome sequence of Nereida sp. strain MMG025, isolated from the surface of giant kelp and assembled and analyzed by undergraduate students participating in a marine microbial genomics course. A genomic comparison suggests that MMG025 is a novel species, providing a resource for future microbiology and biotechnology investigations.

The scaffolding protein RbAp48 is part of several epigenetic regulation complexes and is overexpressed in a variety of cancers. In order to develop tool compounds for the study of RbAp48 function, we have developed peptide inhibitors targeting the protein–protein interaction interface between RbAp48 and the scaffold protein MTA1. Based on a MTA1‐derived linear peptide with low micromolar affinity and informed by crystallographic analysis, a bicyclic peptide was developed that inhibits the RbAp48/MTA1 interaction with a very low nanomolar K D value of 8.56 nM, and which showed appreciable stability against cellular proteases. Design included exchange of a polar amide cyclization strategy to hydrophobic aromatic linkers enabling mono‐ and bicyclization by means of cysteine alkylation, which improved affinity by direct interaction of the linkers with a hydrophobic residue on RbAp48. Our results demonstrate that stepwise evolution of a structure‐based design is a suitable strategy for inhibitor development targeting PPIs., Potent bicyclic peptide inhibitors of the RbAp48‐MTA1 interaction were developed by structure based stepwise optimization of the cyclization linker. The strategy exemplifies design of peptide derived inhibitors of protein–protein interactions involving large surface areas.

Background: The fornix is the primary axonal tract of the hippocampus, connecting it to modulatory subcortical structures. This review reveals that fornix damage causes cognitive deficits that closely mirror those resulting from hippocampal lesions. Methods: We reviewed the literature on the fornix, spanning non-human animal lesion research, clinical case studies of human patients with fornix damage, as well as diffusion-weighted imaging (DWI) work that evaluates fornix microstructure in vivo. Results: The fornix is essential for memory formation because it serves as the conduit for theta rhythms and acetylcholine, as well as providing mnemonic representations to deep brain structures that guide motivated behavior, such as when and where to eat. In rodents and non-human primates, fornix lesions lead to deficits in conditioning, reversal learning, and navigation. In humans, damage to the fornix manifests as anterograde amnesia. DWI research reveals that the fornix plays a key role in mild cognitive impairment and Alzheimer's Disease, and can potentially predict conversion from the former to the latter. Emerging DWI findings link perturbations in this structure to schizophrenia, mood disorders, and eating disorders. Cutting-edge research has investigated how deep brain stimulation of the fornix can potentially attenuate memory loss, control epileptic seizures, and even improve mood. Conclusions: The fornix is essential to a fully functioning memory system and is implicated in nearly all neurological functions that rely on the hippocampus. Future research needs to use optimized DWI methods to study the fornix in vivo, which we discuss, given the difficult nature of fornix reconstruction. IMPACT STATEMENT: The fornix is a white matter tract that connects the hippocampus to several subcortical brain regions and is pivotal for episodic memory functioning. Functionally, the fornix transmits essential neurotransmitters, as well as theta rhythms, to the hippocampus. In addition, it is the conduit by which memories guide decisions. The fornix is biomedically important because lesions to this tract result in irreversible anterograde amnesia. Research using in vivo imaging methods has linked fornix pathology to cognitive aging, mild cognitive impairment, psychosis, epilepsy, and, importantly, Alzheimer's Disease.

Here, we report the draft genome sequence of

Neurobiological models of receptive language have focused on the left-hemisphere perisylvian cortex with the assumption that the cerebellum supports peri-linguistic cognitive processes such as verbal working memory. The goal of this study was to identify language-sensitive regions of the cerebellum then map the structural connectivity profile of these regions. Functional imaging data and diffusion-weighted imaging data from the Human Connectome Project (HCP) were analyzed. We found that (a) working memory, motor activity, and language comprehension activated partially overlapping but mostly unique subregions of the cerebellum; (b) the linguistic portion of the cerebello-thalamo-cortical circuit was more extensive than the linguistic portion of the cortico-ponto-cerebellar tract; (c) there was a frontal-lobe bias in the connectivity from the cerebellum to the cerebrum; (d) there was some degree of specificity; and (e) for some cerebellar tracts, individual differences in picture identification ability covaried with fractional anisotropy metrics. These findings yield insights into the structural connectivity of the cerebellum as relates to the uniquely human process of language comprehension.

Over the past five decades, there has been a tremendous effort to better understand the nature of memory in infancy and early childhood. These findings are beginning to address the puzzle of how it is possible to build an impressive semantic memory during periods of development when episodic memories for events are unlikely to be retained (infantile amnesia, 0-2 years) or are fragile and fragmentary (childhood amnesia, 2-8 years). We discuss three relevant issues: (i) how the nontrivial mnemonic capacities of infants fit with the facts of infantile amnesia; (ii) the contribution of changes in key component processes of episodic memory to the lifting of childhood amnesia between ages 2 and 8 years; and (iii) what we know about the development of the neural underpinnings of memory. We highlight the importance of the reciprocal relationship between research on memory development and theories and models of mature memory systems; that is, how current knowledge about development may constrain building viable models, and how contemporary models provide guidance for understanding memory development.

Symbol systems have a profound influence on human behavior, spanning countless modalities such as natural language, clothing styles, monetary systems, and gestural conventions (e.g., handshaking). Selective impairments in understanding and manipulating symbols are collectively known as asymbolia. Here we address open questions about the nature of asymbolia in the context of both historical and contemporary approaches to human symbolic cognition. We describe a tripartite perspective on symbolic cognition premised upon (1) mental representation of a concept, (2) a stored pool of symbols segregated from their respective referents, and (3) fast and accurate mapping between concepts and symbols. We present an open-source toolkit for assessing symbolic knowledge premised upon matching animated video depictions of abstract concepts to their corresponding verbal and nonverbal symbols. Animations include simple geometric shapes (e.g., filled circles, squares) moving in semantically meaningful ways. For example, a rectangle bending under the implied weight of a large square denotes "heaviness." We report normative data for matching words and images to these target animations. In a second norming study, participants rated target animations across a range of semantic dimensions (e.g., valence, dominance). In a third study, we normed a set of concepts familiar to American English speakers but lacking verbal labels (e.g., the feeling of a Sunday evening). We describe how these tools may be used to assess human symbolic processing and identify asymbolic deficits across the span of human development.

The cerebellum is one-third the size of the cerebrum yet holds twice the number of neurons. Historically, its sole function was thought to be in the calibration of smooth movements through the creation and ongoing modification of motor programs. This traditional viewpoint has been challenged by findings showing that cerebellar damage can lead to striking changes in non-motor behavior, including emotional changes. In this manuscript, we review the literature on clinical and subclinical affective disturbances observed in individuals with lesions to the cerebellum. Disorders include pathological laughing and crying, bipolar disorder, depression and mixed mood changes. We propose a theoretical model based on cerebellar connectivity to explain how the cerebellum calibrates affect. We conclude with actionable steps for future researchers to test this model and improve upon the limitations of past literature.

Seminal work in the 1990’s found alterations in the cerebellum of individuals with social disorders including autism spectrum disorder and schizophrenia. In neurotypical populations, distinct portions of the posterior cerebellum are consistently activated in fMRI studies of social cognition and it has been hypothesized that the cerebellum plays an essential role in social cognition, particularly in theory of mind. Here we review the lesion literature and find that the effect of cerebellar damage on social cognition is strongly linked to the age of insult, with dramatic impairments observed after prenatal insult, strong deficits observed after childhood damage, and mild and inconsistent deficits observed following damage to the adult cerebellum. To explain the developmental gradient, we propose that early in life, the forward model dominates cerebellar computations. The forward model learns and uses errors to help build schemas of our interpersonal worlds. Subsequently, we argue that once these schemas have been built up, the inverse model, which is the foundation of automatic processing, becomes dominant. We provide suggestions for how to test this, and also outline directions for future research.

In Parkinson’s disease (PD), neurodegeneration of dopaminergic neurons occurs in the midbrain, specifically targeting the substantia nigra (SN), while leaving the ventral tegmental area (VTA) relatively spared in early phases of the disease. Although the SN and VTA are known to be functionally dissociable in healthy adults, it remains unclear how this dissociation is altered in PD. To examine this issue, we performed a whole-brain analysis to compare functional connectivity in PD to healthy adults using resting-state functional magnetic resonance imaging (rs-fMRI) data compiled from three independent datasets. Our analysis showed that across the sample, the SN had greater connectivity with the precuneus, anterior cingulate gyrus, and areas of the occipital cortex, partially replicating our previous work in healthy young adults. Notably, we also found that, in PD, VTA-right cerebellum connectivity was higher than SN-right cerebellum connectivity, whereas the opposite trend occurred in healthy controls. This double dissociation may reflect a compensatory role of the cerebellum in PD and could provide a potential target for future study and treatment.

Centromeres are specialized chromosome loci that seed the kinetochore, a large protein complex that effects chromosome segregation. A 16-subunit complex, the constitutive centromere associated network (CCAN), connects between the specialized centromeric chromatin, marked by the histone H3 variant CENP-A, and the spindle-binding moiety of the kinetochore. Here, we report a cryo-electron microscopy structure of human CCAN. We highlight unique features such as the pseudo GTPase CENP-M and report how a crucial CENP-C motif binds the CENP-LN complex. The CCAN structure has implications for the mechanism of specific recognition of the CENP-A nucleosome. A model consistent with our structure depicts the CENP-C-bound nucleosome as connected to the CCAN through extended, flexible regions of CENP-C. An alternative model identifies both CENP-C and CENP-N as specificity determinants but requires CENP-N to bind CENP-A in a mode distinct from the classical nucleosome octamer. in press

UV-induced mutagenesis is, to greater extent, a phenomenon dependent on translesion synthesis (TLS) and regulated by the SOS response in bacteria. Caulobacter crescentus, like many bacterial species, employs the ImuABC (ImuAB DnaE2) pathway in TLS. To have a better understanding of the characteristics of UV-induced mutagenesis in this organism, we performed a whole genome analysis of mutations present in survivors after an acute UVC exposure (300 J/m

Centromeres are specialized chromosome loci that seed the kinetochore, a large protein complex that effects chromosome segregation. The organization of the interface between the kinetochore and the specialized centromeric chromatin, marked by the histone H3 variant CENP-A, remains incompletely understood. A 16-subunit complex, the constitutive centromere associated network (CCAN), bridges CENP-A to the spindle-binding moiety of the kinetochore. Here, we report a cryo-electron microscopy structure of human CCAN. We highlight unique features such as the pseudo GTPase CENP-M and report how a crucial CENP-C motif binds the CENP-LN complex. The CCAN structure has also important implications for the mechanism of specific recognition of the CENP-A nucleosome. A supported model depicts the interaction as fuzzy and identifies the disordered CCAN subunit CENP-C as only determinant of specificity. A more speculative model identifies both CENP-C and CENP-N as specificity determinants, but implies CENP-A may be in a hemisome rather than in a classical octamer.

In their GTP-bound (active) form, Rab proteins interact with effector proteins that control downstream signaling. One such Rab15 effector is Rep15, which is known to have a role in receptor recycling from the endocytic recycling compartment but otherwise remains poorly characterized. Here, we report the characterization of the Rep15:Rab15 interaction and identification of Rab3 paralogs and Rab34 as Rep15 interacting partners from a yeast two-hybrid assay. Biochemical validation of the interactions is presented and crystal structures of the Rep15:Rab3B and Rep15:Rab3C complexes provide additional mechanistic insight. We find that Rep15 adopts a globular structure that is distinct from other reported Rab15, Rab3 and Rab34 effectors. Structure-based mutagenesis experiments explain the Rep15:Rab interaction specificity. Rep15 depletion in U138MG glioblastoma cells impairs cell proliferation, cell migration and receptor recycling, underscoring the need for further clarification of the role of Rep15 in cancer.

Episodic memory binds the diverse elements of an event into a coherent representation. This coherence allows for the reconstruction of different aspects of an experience when triggered by a cue related to a past event—a process of pattern completion. Previous work has shown that such holistic recollection is evident in young adults, as revealed by dependency in retrieval success for various associations from the same event. In addition, episodic memory shows clear quantitative increases during early childhood. However, the ontogeny of holistic recollection is uncharted. Using dependency analyses, we found here that 4-year-olds ( n = 32), 6-year-olds ( n = 30), and young adults ( n = 31) all retrieved complex events in a holistic manner; specifically, retrieval accuracy for one aspect of an event predicted accuracy for other aspects of the same event. However, the degree of holistic retrieval increased from the age 4 to adulthood. Thus, extended refinement of multiway binding may be one aspect of episodic memory development.

Episodic memory relies on discriminating among similar elements of episodes. Mnemonic discrimination is relatively poor at age 4, and then improves markedly. We investigated whether motivation to encode items with fine-grain resolution would change this picture of development, using an engaging computer-administered memory task in which a bird ate items that made her healthier (gain frame), sicker (loss frame), or led to no change (control condition). Using gain-loss framing led to enhanced mnemonic discrimination in 4- and 5-year-olds, but did not affect older children or adults. Despite this differential improvement, age-related differences persisted. An additional finding was that loss-framing led to greater mnemonic discrimination than gain-framing across age groups. Motivation only partially accounts for the improvement in mnemonic discrimination.

Autophagy mediates the degradation of damaged proteins, organelles and pathogens, and plays a key role in health and disease. Thus, the identification of new mechanisms involved in the regulation of autophagy is of major interest. In particular, little is known about the role of lipids and lipid-binding proteins in the early steps of autophagosome biogenesis. Using target-agnostic, high-content, image-based identification of indicative phenotypic changes induced by small molecules, we have identified autogramins as a new class of autophagy inhibitor. Autogramins selectively target the recently discovered cholesterol transfer protein GRAM domain-containing protein 1A (GRAMD1A, which had not previously been implicated in autophagy), and directly compete with cholesterol binding to the GRAMD1A StART domain. GRAMD1A accumulates at sites of autophagosome initiation, affects cholesterol distribution in response to starvation and is required for autophagosome biogenesis. These findings identify a new biological function of GRAMD1A and a new role for cholesterol in autophagy.

The ability to detect differences among similar events in our lives is a crucial aspect of successful episodic memory performance, which develops across early childhood. The neural substrate of this ability is supported by operations in the medial temporal lobe (MTL). Here, we used representational similarity analysis (RSA) to measure neural pattern similarity in hippocampus, perirhinal cortex, and parahippocampal cortex for 4- to 10-year-old children and adults during naturalistic viewing of clips from the same compared to different movies. Further, we assessed the role of prior exposure to individual movie clips on pattern similarity in the MTL. In both age groups, neural pattern similarity in hippocampus was lower for clips drawn from the same movies compared to those drawn from different movies, suggesting that related content activates processes focused on keeping representations with shared content distinct. However, children showed this only for movies with which they had prior exposures, whereas adults showed the effect regardless of any prior exposures to the movies. These findings suggest that children require repeated exposure to stimuli to show adult-like MTL functioning in distinguishing among similar events.

We report the first record of Siphonops paulensis predation by Burrowing Owl occurred in a Cerrado fragment. In addition to describing the predation event, we discuss the owl's ability to hunt for fossorial species and the presence of poison glands on the amphibian's skin, which can act as a defense against predators.

The goal of this study was to develop a method for ultrasound-guided percutaneous intraovarian injection in Wistar rats. Intraovarian administration of chemicals or needle aspiration of the ovary has been undertaken in some species, including humans, equines, and bovines. In rodents, which are widely used in scientific research, a technique for intraovarian injection without surgical exposure of the organ has not been described. The current study standardized the procedure of ovarian percutaneous injection of 0.9% sodium chloride guided by ultrasound in rats. The ovaries were measured by ultrasound imaging before and immediately after injection and showed a significant increase in ovarian length but not width. No clinical abnormalities were detected within 15 d after injection. These findings indicate that the steps of ultrasound localization of the organ, digital restraint, and correct needle insertion achieved successful intraovarian administration of saline without invasive surgery. These results document the feasibility of ultrasound-guided intraovarian percutaneous injection in rats and may be useful for future research on female reproduction and chemical sterilization.

Biochemical reconstitution of human kinetochore delivers complexes with all subunits in the expected stoichiometry., Centromeres are epigenetically determined chromosomal loci that seed kinetochore assembly to promote chromosome segregation during cell division. CENP-A, a centromere-specific histone H3 variant, establishes the foundations for centromere epigenetic memory and kinetochore assembly. It recruits the constitutive centromere-associated network (CCAN), which in turn assembles the microtubule-binding interface. How the specific organization of centromeric chromatin relates to kinetochore assembly and to centromere identity through cell division remains conjectural. Here, we break new ground by reconstituting a functional full-length version of CENP-C, the largest human CCAN subunit and a blueprint of kinetochore assembly. We show that full-length CENP-C, a dimer, binds stably to two nucleosomes and permits further assembly of all other kinetochore subunits in vitro with relative ratios closely matching those of endogenous human kinetochores. Our results imply that human kinetochores emerge from clustering multiple copies of a fundamental module and may have important implications for transgenerational inheritance of centromeric chromatin.

Humans have a remarkable ability to infer the mind of others. This mentalizing skill relies on a distributed network of brain regions but how these regions connect and interact is not well understood. Here we leveraged large-scale multimodal neuroimaging data to elucidate the brain-wide organization and mechanisms of mentalizing processing. Key connectomic features of the mentalizing network (MTN) have been delineated in exquisite detail. We found the structural architecture of MTN is organized by two parallel subsystems and constructed redundantly by local and long-range white matter fibers. We uncovered an intrinsic functional architecture that is synchronized according to the degree of mentalizing, and its hierarchy reflects the inherent information integration order. We also examined the correspondence between the structural and functional connectivity in the network and revealed their differences in network topology, individual variance, spatial specificity, and functional specificity. Finally, we scrutinized the connectome resemblance between the default mode network and MTN and elaborated their inherent differences in dynamic patterns, laterality, and homogeneity. Overall, our study demonstrates that mentalizing processing unfolds across functionally heterogeneous regions with highly structured fiber tracts and unique hierarchical functional architecture, which make it distinguishable from the default mode network and other vicinity brain networks supporting autobiographical memory, semantic memory, self-referential, moral reasoning, and mental time travel.

Centromeres are epigenetically determined chromosomal loci that seed kinetochore assembly to promote chromosome segregation during cell division. CENP-A, a centromere-specific histone H3 variant, establishes the foundations for centromere epigenetic memory and kinetochore assembly. It recruits the constitutive centromere-associated network (CCAN), which in turn assembles the microtubule-binding interface. How the specific organization of centromeric chromatin relates to kinetochore assembly and to centromere identity through cell division remains conjectural. Here, we break new ground by reconstituting a functional full-length version of CENP-C, the largest human CCAN subunit and a blueprint of kinetochore assembly. We show that full-length CENP-C, a dimer, binds stably to two nucleosomes, and permits further assembly of all other kinetochore subunits in vitro with relative ratios that closely match those of endogenous human kinetochores. Our results imply that human kinetochores emerge from clustering multiple copies of a fundamental module, and may have important implications for trans-generational inheritance of centromeric chromatin.

Background In a recent study we showed that blue light inactivates methicillin-resistant Staphylococcus aureus (MRSA) by perturbing, depolarizing, and disrupting its cell membrane. Purpose The current study presents visual evidence that the observed biochemical changes also result in cell metabolic changes and structural alteration of the cell membrane. Methods Cultures of MRSA were treated with 450 nm pulsed blue light (PBL) at 3 mW/cm2 irradiance, using a sub lethal dose of 2.7 J/cm2 radiant exposure three times at 30-min intervals. Following 24 h incubation at 37 °C, irradiated colonies and control non-irradiated colonies were processed for light and transmission electron microscopy. Results The images obtained revealed three major effects of PBL; (1) disruption of MRSA cell membrane, (2) alteration of membrane structure, and (3) disruption of cell replication. Conclusion These signs of bacterial inactivation at a dose deliberately selected to be sub-lethal supports our previous finding that rapid depolarization of bacterial cell membrane and disruption of cellular function comprise another mechanism underlying photo-inactivation of bacteria. Further, it affirms the potency of PBL.

Episodic memory consists of distinctive experiences, with specific spatiotemporal information about what happened maintained over time. These memories typically share overlapping elements in distinctive combinations. In this study, we evaluated: (1) whether overlapping elements pose a differential challenge for younger children; and (2) whether a sleep-filled delay stabilizes or even improves children’s episodic memories, and if so, whether effects vary by age. We compared memory for unique and overlapping pairs of visual stimuli, presented once to 4- and 6-year-old children, tested immediately and after a 24-hour delay. As expected, older children outperformed younger children, and both age groups performed worse on overlapping pairs. However, overlapping elements were not differentially problematic for young children, and a sleep-filled delay in testing resulted in decrements in memory performance, for both age groups on both pair types. Despite overall differences in accuracy, important aspects of episodic memory are similar across this key developmental period.

Siamese cats are a notable example of a temperature-sensitive partial albinism phenotype. The signature color-pointing pattern is the result of an amino acid substitution – G302R – in the cysteine-rich domain of feline tyrosinase. The precise mechanism for the loss of tyrosinase enzyme activity due to this mutation is unknown.ObjectiveWe have used a cellular biology approach to begin unravel relationships between feline coloration, behavior and increased risk for feline cognitive dysfunction syndrome. GFP-fusion constructs of wild type domestic short hair tyrosinase and Siamese (G302R) tyrosinase generated to study cellular trafficking, degradation and the propensity for cellular aggregation.Data DescriptionC-terminal GFP G302R expression has reduced Golgi localization, increased cytosolic fractions with reduced calnexin co-localization. N-terminal GFP constructs were retained in the ER, with little to no Golgi associated forms. C-terminal and N-terminal GFP G302R TYR is observed to have increased high molecular weight aggregation following proteasome inhibition.

Neotropical snakes form one of the most biodiverse groups of herpetofauna, making up an important part of their ecosystems (Guedes et al., 2018). Information about their dietary niche and trophic level provides important knowledge to our understanding of these complex systems. Such data can be collected through field observations (e.g. Zobel et al., 2018; Sellmeijer and van den Burg, 2020), stomach, faeces or intestine contents (Marques et al., 2006; Bellini et al., 2015; Unger et al., 2020), and also through the assessment of camera trap footage (Akcali et al., 2019). Direct field observations of predator-prey as well as other intra- and interspecies interactions are important to help to improve our knowledge about species niches, as well as their conservation., We thank Coordenação de Aperfeiçoamento de pessoal de Nível Superior (CAPES) and Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) for financial support.

The consistent finding of knowledge management practices with women’s entrepreneurial performance is one of the gaps intended to fill in this paper. Several previous research studies on knowledge management practices (KMPs) with sustainable women’s entrepreneurial performance (SWEP) have been drawing the attention of many researchers, and this study includes the mediating role of opportunity recognition (OR) and moderating role of family interference (FI). Smart-PLS software was used to test the proposed hypotheses with gathered data of 450 women-entrepreneur respondents. The findings show a positive and significant impact of KMPs on women’s entrepreneurship and partial mediation of opportunity recognition between sustainable women’s entrepreneurial performance and KMPs. Moreover, family interference strengthens the relationship between opportunity recognition and women’s entrepreneurial performance. The study results proposed that in Ivory Coast, entrepreneurial women face several challenges in running their businesses. Therefore, it is suggested that a combined effort of women entrepreneurs, family interference, society, market opportunities, and researchers can overcome their challenges. Discussion is based on the study findings, and suggestions have been made for researchers and practitioners.

Statins, which reduce LDL-cholesterol by inhibition of 3-hydroxy-3-methylglutaryl–coenzyme A reductase, are among the most widely prescribed drugs. Skeletal myopathy is a known statin-induced adverse effect associated with mitochondrial changes. We hypothesized that similar effects would occur in cardiac myocytes in a lipophilicity-dependent manner between 2 common statins: atorvastatin (lipophilic) and pravastatin (hydrophilic). Neonatal cardiac ventricular myocytes were treated with atorvastatin and pravastatin for 48 h. Both statins induced endoplasmic reticular (ER) stress, but only atorvastatin inhibited ERK1/2(T202/Y204), Akt(Ser473), and mammalian target of rapamycin signaling; reduced protein abundance of caveolin-1, dystrophin, epidermal growth factor receptor, and insulin receptor-β; decreased Ras homolog gene family member A activation; and induced apoptosis. In cardiomyocyte-equivalent HL-1 cells, atorvastatin, but not pravastatin, reduced mitochondrial oxygen consumption. When male mice underwent atorvastatin and pravastatin administration per os for up to 7 mo, only long-term atorvastatin, but not pravastatin, induced elevated serum creatine kinase; swollen, misaligned, size-variable, and disconnected cardiac mitochondria; alteration of ER structure; repression of mitochondria- and endoplasmic reticulum–related genes; and a 21% increase in mortality in cardiac-specific vinculin-knockout mice during the first 2 months of administration. To our knowledge, we are the first to demonstrate in vivo that long-term atorvastatin administration alters cardiac ultrastructure, a finding with important clinical implications.—Godoy, J. C., Niesman, I. R., Busija, A. R., Kassan, A., Schilling, J. M., Schwarz, A., Alvarez, E. A., Dalton, N. D., Drummond, J. C., Roth, D. M., Kararigas, G., Patel, H. H., Zemljic-Harpf, A. E. Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes.

Social neuroscience has traditionally focused on the functionality of gray matter regions, ignoring the critical role played by axonal fiber pathways in supporting complex social processes. In this paper, we argue that research on white matter is essential for understanding a range of topics in social neuroscience, such as face processing, theory of mind, empathy, and imitation, as well as clinical disorders defined by aberrant social behavior, such as prosopagnosia, autism, and schizophrenia. We provide practical advice on how best to carry out these studies, which ultimately will substantially deepen our understanding of the neurobiological basis of social behavior.

The study evaluated the impact of a multidimensional child cash grant (CCG) programme on safe water, sanitation and hygiene (WASH) outcomes. The intervention district received a CCG providing 200 Nepalese Rupee per month for up to two children for poor families with children under five, a capacity building component for effective child sensitive social protection, and behaviour change activities in addition to existing standard social welfare services in the form of targeted resource transfers (TRTs) for eligible families. The control district received only TRTs for eligible families. Propensity scores were used in difference-in-differences models to compare the changes over time between the intervention and control groups. The intervention resulted in a 5.5% (p < 0.01), 46.6% (p < 0.001) and 42.2% (p < 0.001) percentage points reduction in the proportion of households reporting drinking water from unimproved sources, having unimproved sanitation facilities, and practising unsanitary disposal of children's faeces, respectively. However, the prevalence of households practising inadequate water treatment methods did not differ between the intervention and comparison districts. In order to achieve WASH coverage in Nepal, strategies to scale up the intervention need to consider a social protection programme embedding different financial incentive and integrated capacity mechanisms.

Tree hollows are complex microhabitats in which a variety of abiotic and biotic factors shape the community assembly of saproxylic insects. Detecting non-random species co-occurrence patterns is a fundamental goal in ecology in order to understand the assembly mechanisms of communities. We study association patterns of species of Coleoptera and Diptera (Syrphidae), belonging to different trophic guilds, on 72 tree hollows at a local and regional scale in three protected areas in Mediterranean forests using a fixed–fixed null model. Our matrix-level analysis shows a tendency for segregation in species association (species exclusion) at the regional and site levels. However, the high complexity of tree-hollow habitats, offering different resources for a more or less specialized fauna, makes it difficult to prove competition interactions. Indeed, pairwise analysis shows a dominance of non-random aggregation patterns (species coexistence) at the local and regional levels. Both aggregation and segregation of non-random patterns were more common among species from different trophic guilds than within the same guilds, with predators being a common denominator for a high percentage of the inter-guild pairs. Our results suggest that predation and facilitation interactions, together with habitat segregation, are the main factors shaping tree-hollow assemblages, while competition seems to be less important. We conclude that species interactions take an important part of the process of assemblage structuration and special attention should be paid to ‘ecosystem engineers’ and threatened species in the conservation of tree hollow assemblages. We are very grateful to the financial support provided by ‘Ministerio de Economía y Competitividad (CGL2011-23658, CGL2012-31669),’ and also by European Feder Funder and by ‘Generalitat Valenciana’ (PROMETEO/2013/03412 Project). This research is part of the I.R. Sánchez-Galván Ph.D. studies, financed by Grisolía fellowship of the Generalitat Valenciana (2011/30).

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children’s performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory. Keywords: White matter, Memory development, Episodic memory, Diffusion weighted imaging

Social status is a salient cue that shapes our perceptions of other people and ultimately guides our social interactions. Despite the pervasive influence of status on social behavior, how information about the status of others is represented in the brain remains unclear. Here, we tested the hypothesis that social status information is embedded in our neural representations of other individuals. Participants learned to associate faces with names, job titles that varied in associated status, and explicit markers of reputational status (star ratings). Trained stimuli were presented in an functional magnetic resonance imaging experiment where participants performed a target detection task orthogonal to the variable of interest. A network of face-selective brain regions extending from the occipital lobe to the orbitofrontal cortex was localized and served as regions of interest. Using multivoxel pattern analysis, we found that face-selective voxels in the lateral orbitofrontal cortex - a region involved in social and nonsocial valuation, could decode faces based on their status. Similar effects were observed with two different status manipulations - one based on stored semantic knowledge (e.g., different careers) and one based on learned reputation (e.g., star ranking). These data suggest that a face-selective region of the lateral orbitofrontal cortex may contribute to the perception of social status, potentially underlying the preferential attention and favorable biases humans display toward high-status individuals.

imuABC (imuAB dnaE2) genes are responsible for SOS-mutagenesis in Caulobacter crescentus and other bacterial species devoid of umuDC. In this work, we have constructed operator-constitutive mutants of the imuABC operon. We used this genetic tool to investigate the effect of SOS-induced levels of these genes upon both spontaneous and damage-induced mutagenesis. We showed that constitutive expression of imuABC does not increase spontaneous or damage-induced mutagenesis, nor increases cellular resistance to DNA-damaging agents. Nevertheless, the presence of the operator-constitutive mutation rescues mutagenesis in a recA background, indicating that imuABC are the only genes required at SOS-induced levels for translesion synthesis (TLS) in C. crescentus. Furthermore, these data also show that TLS mediated by ImuABC does not require RecA, unlike umuDC-dependent mutagenesis in E. coli.

Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity can is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry.

Arginine-rich motifs (ARMs) bind RNA structures with high affinity and specificity, and the human immunodeficiency virus (HIV) exploits ARM-RNA interactions to regulate its lifecycle. The expression of HIV structural genes relies on recognition between the ARM of its Rev protein and its primary binding site, an internal loop in the viral RNA, the Rev-response element region IIB (IIB). Many functional variants of the Rev ARM-IIB interaction have been discovered, yet how easily it can evolve new specificities is poorly explored. A double mutant of Rev ARM, R35G-N40 V, uses an unknown strategy to recognize IIB. Here, isothermal titration calorimetry and gel shift assays show that the R35G-N40V-IIB interaction has high affinity and specificity in vitro and a larger unfavorable entropy change upon binding than that of wild-type Rev ARM-IIB. In stark contrast with the critical dependence of wild-type Rev on Arg35, Arg39, Asn40, and Arg44, mutational profiling shows R35G-N40V is highly mutable at positions 40 and 44 and dependent on Gly35, Arg38, Arg39, Arg42, and Arg43. Affinity measurements in vitro and reporter assay measurements in vivo are consistent with the wild-type Rev ARM and R35G-N40V maintaining their recognition strategies when binding IIB mutants specific to wild-type Rev ARM and R35G-N40V, respectively. Some single amino acid mutants of wild-type Rev ARM and R35G-N40V have enhanced specificity, recognizing mutant IIBs yet not wild-type IIB. These results provide another example of viral ARM-RNA interactions evolving new specificities with few mutations, consistent with neutral theories of evolution.