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Schizophrenia may represent a trade-off in the evolution of human-specific ontogenetic mechanisms that guide neurodevelopment. Human Accelerated Regions (HARs) are evolutionary markers functioning as neurodevelopmental transcription enhancers that have been associated with brain configuration, neural information processing, and schizophrenia risk. Here, we have investigated the influence of HARs' polygenic load on neuroanatomical measures through a case-control approach (128 patients with schizophrenia and 115 controls). To this end, we have calculated the global schizophrenia Polygenic Risk Score (Global PRSSZ) and that specific to HARs (HARs PRSSZ). We have also estimated the polygenic burden restricted to the HARs linked to transcriptional regulatory elements active in the foetal brain (FB-HARs PRSSZ) and the adult brain (AB-HARs PRSSZ). We have explored the main effects of the PRSs and the PRSs x diagnosis interactions on brain regional cortical thickness (CT) and surface area (SA). The results indicate that a higher FB-HARs PRSSZ is associated with patients' lower SA in the lateral orbitofrontal cortex, the superior temporal cortex, the pars triangularis and the paracentral lobule. While noHARs-derived PRSs show an effect on the risk, our neuroanatomical findings suggest that the human-specific transcriptional regulation during the prenatal period underlies SA variability, highlighting the role of these evolutionary markers in the schizophrenia genomic architecture. The analysis of the schizophrenia polygenic load along the genomic Human Accelerated Regions (HARs) provides insight into the influence of early brain development regulation on the neuroanatomical changes associated with schizophrenia. [ABSTRACT FROM AUTHOR]

Geographic variation in the vocal behavior of manatees has been reported but is largely unexplored. Vocalizations of wild West Indian manatees (Trichechus manatus) were recorded with hydrophones in Florida from Florida manatees (Trichechus manatus latirostris), and in Belize and Panama from Antillean manatees (Trichechus manatus manatus) to determine if calls varied between subspecies and geographic regions. Calls were visually classified into five categories: squeaks, high squeaks, squeals, squeak-squeals, and chirps. From these five categories, only three call types (squeaks, high squeaks and squeals) were observed in all three populations. Six parameters from the temporal and frequency domains were measured from the fundamental frequency of 2878 manatee vocalizations. A repeated measures PERMANOVA found significant differences for squeaks and high squeaks between each geographic location and for squeals between Belize and Florida. Almost all measured frequency and temporal parameters of manatee vocalizations differed between and within subspecies. Variables that may have influenced the variation observed may be related to sex, body size, habitat and/or other factors. Our findings provide critical information of manatee calls for wildlife monitoring and highlight the need for further study of the vocal behavior of manatees throughout their range. [ABSTRACT FROM AUTHOR]

Introduction: Candida auris (C. auris) is an emerging nosocomial pathogen, and a sharp rise in cases of colonization and infection has been registered in intensive care units (ICUs) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The unfavorable resistance profile of C. auris and the potential high mortality of C. auris infections represent an important challenge for physicians. Methods: We conducted a single-center retrospective study including all patients admitted to ICUs with isolation of C. auris in any non-sterile body site between February 20, 2020, and May 31, 2021. The primary aim of the study was to assess the cumulative incidence of C. auris candidemia in colonized patients. The secondary aim was to identify predictors of C. auris candidemia in the study population. Results: During the study period, 157 patients admitted to ICUs in our hospital became colonized with C. auris; 59% of them were affected by COVID-19. Overall, 27 patients (17%) developed C. auris candidemia. The cumulative risk of developing C. auris candidemia was > 25% at 60 days after first detection of C. auris colonization. Seven patients with C. auris candidemia (26%) also developed a late recurrent episode. All C. auris blood isolates during the first occurring episode were resistant to fluconazole and susceptible to echinocandins, while 15 (56%) were resistant to amphotericin B. During late recurrent episodes, emergent resistance to caspofungin and amphotericin B occurred in one case each. In the final multivariable model, only multisite colonization retained an independent association with the development of C. auris candidemia. Conclusion: Candida auris candidemia may occur in up to one fourth of colonized critically ill patients, and multisite colonization is an independent risk factor for the development of candidemia. Implementing adequate infection control measures remains crucial to prevent colonization with C. auris and indirectly the subsequent development of infection. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, the scientific community developed predictive models to evaluate potential governmental interventions. However, the analysis of the effects these interventions had is less advanced. Here, we propose a data-driven framework to assess these effects retrospectively. We use a regularized regression to find a parsimonious model that fits the data with the least changes in the R t parameter. Then, we postulate each jump in R t as the effect of an intervention. Following the do-operator prescriptions, we simulate the counterfactual case by forcing R t to stay at the pre-jump value. We then attribute a value to the intervention from the difference between true evolution and simulated counterfactual. We show that the recommendation to use facemasks for all activities would reduce the number of cases by 200,000 ( 95 % CI 190,000–210,000) in Connecticut, Massachusetts, and New York State. The framework presented here might be used in any case where cause and effects are sparse in time. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to investigate the prevalence and factors associated with persistent viral shedding (PVS) in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: This was a prospective observational study including all consecutive adults hospitalized with SARS-CoV-2 infection. When the first nasopharyngeal swab was positive for SARS-CoV-2 RNA (day 0), additional samples were obtained on days + 3, + 5, + 7 and then once every 7 days until virus detection was negative. PVS was defined as the duration of shedding of at least 21 days after diagnosis. The primary endpoint of this study was the prevalence of PVS. Results: Data were obtained regarding 121 consecutive hospitalized patients with SARS-CoV-2 infection (median age 66 years, male sex 65.3%). Overall, the prevalence of PVS was 38% (46/121 patients). According to univariate analysis, factors associated with PVS were immunosuppression (6.7% vs 21.7%, p = 0.02), increased interleukin-6 (IL-6) levels (≥ 35 ng/ml) at the time of diagnosis (43.4% vs 67.3%, p = 0.02), time from onset of symptoms to diagnosis (median days 7.0 vs 3.5, p = 0.001), intensive care unit admission (22.7% vs 43.5%, p = 0.02), and need for invasive mechanical ventilation (20.0% vs 41.3%, p = 0.01). The multivariate analysis indicated that immunosuppression, increased IL-6 levels at the time of diagnosis, time from onset of symptoms to diagnosis, and need for mechanical ventilation were independent factors associated with PVS. Conclusions: PVS was detected in up to 38% of hospitalized patients with SARS-CoV-2 infection and was strongly associated with immunosuppression, increased IL-6 levels, and the need for mechanical ventilation. [ABSTRACT FROM AUTHOR]

Reports on the adaptation by physicist Marcelo O. Magnasco of a muscle contraction model originally introduced by Kramers. Problem in classical mechanics; `Brownian domain' principle used by Magnasco.

Studies the mechanism for the sensing and reduction of DNA entanglements in cells by type II topoisomerases. Proposed two-collision reaction for disentangling; Similarity to `kinetic proofreading' models of molecular recognition.

Advances in theoretical understanding are frequently unlocked by access to large, diverse experimental datasets. Our understanding of olfactory neuroscience and psychophysics remain years behind the other senses, in part because rich datasets linking olfactory stimuli with their corresponding percepts, behaviors, and neural pathways remain scarce. Here we present a concerted effort to unlock and unify dozens of stimulus-linked olfactory datasets across species and modalities under a unified framework called Pyrfume. We present examples of how researchers might use Pyrfume to conduct novel analyses uncovering new principles, introduce trainees to the field, or construct benchmarks for machine olfaction. [ABSTRACT FROM AUTHOR]

Designing and optimizing the structure of urban transportation networks is a challenging task. In this study, we propose a method inspired by optimal transport theory and the principle of economy of scale that uses little information in input to generate structures that are similar to those of public transportation networks. Contrarily to standard approaches, it does not assume any initial backbone network infrastructure but rather extracts this directly from a continuous space using only a few origin and destination points, generating networks from scratch. Analyzing a set of urban train, tram and subway networks, we find a noteworthy degree of similarity in several of the studied cases between simulated and real infrastructures. By tuning one parameter, our method can simulate a range of different subway, tram and train networks that can be further used to suggest possible improvements in terms of relevant transportation properties. Outputs of our algorithm provide naturally a principled quantitative measure of similarity between two networks that can be used to automatize the selection of similar simulated networks. Planning effective urban network infrastructure often involves optimization principles that use a backbone network as a starting point. The authors propose an approach based on optimal transport theory to simulate real urban rail networks structure without need of initial backbone knowledge. [ABSTRACT FROM AUTHOR]

The problem of solving the equivalent resistance between two points for resistor networks has important significance in physics. This paper mainly changes and rewrites the formula for calculating the resistance between two points of an unconventional m × n cylindrical resistor network with a zero resistor axis and any two left and right boundaries. To enhance the efficiency of calculating the equivalent resistance between two points, Chebyshev polynomials and hyperbolic cosine functions are employed to represent the new formula. And in the inference process, the famous discrete cosine transform of the third kind (DCT-III) is used to process the matrix. We give the equivalent resistance formula for several special cases, and display them by a three-dimensional graph. Subsequently, the calculation efficiency of the original formula and the rewritten formula are compared. At the end of the paper, a heuristic algorithm suitable for robot path planning on cylindrical environment is proposed. [ABSTRACT FROM AUTHOR]

In daily life, in the operating room and in the laboratory, the operational way to assess wakefulness and consciousness is through responsiveness. A number of studies suggest that the awake, conscious state is not the default behavior of an assembly of neurons, but rather a very special state of activity that has to be actively maintained and curated to support its functional properties. Thus responsiveness is a feature that requires active maintenance, such as a homeostatic mechanism to balance excitation and inhibition. In this work we developed a method for monitoring such maintenance processes, focusing on a specific signature of their behavior derived from the theory of dynamical systems: stability analysis of dynamical modes. When such mechanisms are at work, their modes of activity are at marginal stability, neither damped (stable) nor exponentially growing (unstable) but rather hovering in between. We have previously shown that, conversely, under induction of anesthesia those modes become more stable and thus less responsive, then reversed upon emergence to wakefulness. We take advantage of this effect to build a single-trial classifier which detects whether a subject is awake or unconscious achieving high performance. We show that our approach can be developed into a means for intra-operative monitoring of the depth of anesthesia, an application of fundamental importance to modern clinical practice. [ABSTRACT FROM AUTHOR]

Highlights: The types, working principles, advantages and limitations of pattern recognition methods based on chemiresistive gas sensor array are reviewed and discussed comprehensively. Outstanding and novel advancements in the application of machine learning methods for gas recognition in different important areas are compared, summarized and evaluated. The current challenges and future prospects of machine learning methods in artificial olfactory systems are discussed and justified. As information acquisition terminals for artificial olfaction, chemiresistive gas sensors are often troubled by their cross-sensitivity, and reducing their cross-response to ambient gases has always been a difficult and important point in the gas sensing area. Pattern recognition based on sensor array is the most conspicuous way to overcome the cross-sensitivity of gas sensors. It is crucial to choose an appropriate pattern recognition method for enhancing data analysis, reducing errors and improving system reliability, obtaining better classification or gas concentration prediction results. In this review, we analyze the sensing mechanism of cross-sensitivity for chemiresistive gas sensors. We further examine the types, working principles, characteristics, and applicable gas detection range of pattern recognition algorithms utilized in gas-sensing arrays. Additionally, we report, summarize, and evaluate the outstanding and novel advancements in pattern recognition methods for gas identification. At the same time, this work showcases the recent advancements in utilizing these methods for gas identification, particularly within three crucial domains: ensuring food safety, monitoring the environment, and aiding in medical diagnosis. In conclusion, this study anticipates future research prospects by considering the existing landscape and challenges. It is hoped that this work will make a positive contribution towards mitigating cross-sensitivity in gas-sensitive devices and offer valuable insights for algorithm selection in gas recognition applications. [ABSTRACT FROM AUTHOR]

A geometrically symmetric gear with asymmetric surface wettability exhibits one-way spin on a vibrating water bed. On the side face of the gear, a parafilm was coated to create asymmetry in the surface energy. The gear shows fluctuations in both directions within a shorter timescale; however, for a longer timescale, the gear exhibits a one-way spin. This unique motion is generated by a stochastic process with a biased driving force produced by the interaction between the vibrating water surface and the side face of the gear. This new model resembles an active Brownian ratchet. Until now, most ratchet motors, which obtain regular motion from nonthermal fluctuations, utilize a geometrical ratchet structure. However, in this study, the surface energy forms a ratchet that rectifies the noisy motion. [ABSTRACT FROM AUTHOR]

Spatio-temporal activity patterns have been observed in a variety of brain areas in spontaneous activity, prior to or during action, or in response to stimuli. Biological mechanisms endowing neurons with the ability to distinguish between different sequences remain largely unknown. Learning sequences of spikes raises multiple challenges, such as maintaining in memory spike history and discriminating partially overlapping sequences. Here, we show that anti-Hebbian spike-timing dependent plasticity (STDP), as observed at cortico-striatal synapses, can naturally lead to learning spike sequences. We design a spiking model of the striatal output neuron receiving spike patterns defined as sequential input from a fixed set of cortical neurons. We use a simple synaptic plasticity rule that combines anti-Hebbian STDP and non-associative potentiation for a subset of the presented patterns called rewarded patterns. We study the ability of striatal output neurons to discriminate rewarded from non-rewarded patterns by firing only after the presentation of a rewarded pattern. In particular, we show that two biological properties of striatal networks, spiking latency and collateral inhibition, contribute to an increase in accuracy, by allowing a better discrimination of partially overlapping sequences. These results suggest that anti-Hebbian STDP may serve as a biological substrate for learning sequences of spikes. Mathematical models and computer simulations suggest that anti-Hebbian STDP, the type of plasticity observed between cortex and striatum, could support the learning of sequences in the brain. [ABSTRACT FROM AUTHOR]

Engineering multilayer networks that efficiently connect sets of points in space is a crucial task in all practical applications that concern the transport of people or the delivery of goods. Unfortunately, our current theoretical understanding of the shape of such optimal transport networks is quite limited. Not much is known about how the topology of the optimal network changes as a function of its size, the relative efficiency of its layers, and the cost of switching between layers. Here, we show that optimal networks undergo sharp transitions from symmetric to asymmetric shapes, indicating that it is sometimes better to avoid serving a whole area to save on switching costs. Also, we analyze the real transportation networks of the cities of Atlanta, Boston, and Toronto using our theoretical framework and find that they are farther away from their optimal shapes as traffic congestion increases. Finding an optimal shape for transport networks, represented as multilayer structures, is a challenging problem. The authors propose analytical and computational frameworks to analyze sharp transitions from symmetric to asymmetric shapes in optimal networks, that can be applied for planning and development of improved multimodal transportation systems within a city. [ABSTRACT FROM AUTHOR]

Expanded intronic G4C2 repeats in the C9ORF72 gene cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These intronic repeats are translated through a non-AUG-dependent mechanism into five different dipeptide repeat proteins (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and neurotoxic. Here, we report that Kapβ2 and GR interact, co-aggregating, in cultured neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction significantly decreased the risk of death of cultured GR-expressing neurons. Downregulation of Kapβ2 is detrimental to their survival, whereas increased Kapβ2 levels mitigated GR-mediated neurotoxicity. As expected, GR-expressing neurons displayed TDP-43 nuclear loss. Raising Kapβ2 levels did not restore TDP-43 into the nucleus, nor did alter the dynamic properties of GR aggregates. Overall, our findings support the design of therapeutic strategies aimed at up-regulating Kapβ2 expression levels as a potential new avenue for contrasting neurodegeneration in C9orf72-ALS/FTD. Expanded intronic G4C2 repeats in C9orf72 cause ALS/FTD. GR dipeptide repeats produced in C9orf72 ALS/FTD co-aggregate with Kap2 in neurons, affecting survival. Upregulating Kapβ2 may mitigate neurotoxicity, a potential therapy for C9orf72-ALS/FTD. [ABSTRACT FROM AUTHOR]

To interact successfully with objects, it is crucial to accurately perceive their spatial extent, an enclosed region they occupy in space. Although the topographic representation of space in the early visual cortex (EVC) has been favored as a neural correlate of spatial extent perception, its exact nature and contribution to perception remain unclear. Here, we inspect the topographic representations of human individuals' EVC and perception in terms of how much their anisotropy is influenced by the orientation (co-axiality) and radial position (radiality) of stimuli. We report that while the anisotropy is influenced by both factors, its direction is primarily determined by radiality in EVC but by co-axiality in perception. Despite this mismatch, the individual differences in both radial and co-axial anisotropy are substantially shared between EVC and perception. Our findings suggest that spatial extent perception builds on EVC's spatial representation but requires an additional mechanism to transform its topographic bias. FMRI and behavioral experiments on humans suggest that the early visual cortex makes a limited contribution to spatial extent perception, implying the need for a downstream mechanism to transform its topographic anisotropy to match perception. [ABSTRACT FROM AUTHOR]

We study the computation of the zero set of the Bargmann transform of a signal contaminated with complex white noise, or, equivalently, the computation of the zeros of its short-time Fourier transform with Gaussian window. We introduce the adaptive minimal grid neighbors algorithm (AMN), a variant of a method that has recently appeared in the signal processing literature, and prove that with high probability it computes the desired zero set. More precisely, given samples of the Bargmann transform of a signal on a finite grid with spacing δ , AMN is shown to compute the desired zero set up to a factor of δ in the Wasserstein error metric, with failure probability O (δ 4 log 2 (1 / δ)) . We also provide numerical tests and comparison with other algorithms. [ABSTRACT FROM AUTHOR]

The implications of the existence of different actins expressed in epithelial cells for network mechanics and dynamics is investigated by microrheology and confocal imaging. γ-actin predominately found in the apical cortex forms stiffer networks compared to β-actin, which is preferentially organized in stress fibers. We attribute this to selective interactions with Mg2+-ions interconnecting the filaments' N-termini. Bundling propensity of the isoforms is different in the presence of Mg2+-ions, while crosslinkers such as α-actinin, fascin, and heavy meromyosin alter the mechanical response independent of the isoform. In the presence of myosin, β-actin networks show a large number of small contraction foci, while γ-actin displays larger but fewer foci indicative of a stronger interaction with myosin motors. We infer that subtle changes in the amino acid sequence of actin isoforms lead to alterations of the mechanical properties on the network level with potential implications for specific biological functions. β-actin and γ-actin are nearly identical, and yet incorporate into different cytoskeletal structures. Here, the authors create isoform-pure reconstituted networks and study their structural and mechanical differences, underscoring the significance of the isoforms in diverse cellular functions. [ABSTRACT FROM AUTHOR]

Vertebrate color vision is predominantly mediated by the presence of multiple cone photoreceptor subtypes that are each maximally sensitive to different wavelengths of light. Thyroid hormone (TH) has been shown to be essential in the spatiotemporal patterning of cone subtypes in many species, including cone subtypes that express opsins that are encoded by tandemly replicated genes. TH has been shown to differentially regulate the tandemly replicated lws opsin genes in zebrafish, and exogenous treatments alter the expression levels of these genes in larvae and juveniles. In this study, we sought to determine whether gene expression in cone photoreceptors remains plastic to TH treatment in adults. We used a transgenic lws reporter line, multiplexed fluorescence hybridization chain reaction in situ hybridization, and qPCR to examine the extent to which cone gene expression can be altered by TH in adults. Our studies revealed that opsin gene expression, and the expression of other photoreceptor genes, remains plastic to TH treatment in adult zebrafish. In addition to retinal plasticity, exogenous TH treatment alters skin pigmentation patterns in adult zebrafish after 5 days. Taken together, our results show a remarkable level of TH-sensitive plasticity in the adult zebrafish. [ABSTRACT FROM AUTHOR]

Topological protection ensures stability of information and particle transport against perturbations. We explore experimentally and computationally the topologically protected transport of magnetic colloids above spatially inhomogeneous magnetic patterns, revealing that transport complexity can be encoded in both the driving loop and the pattern. Complex patterns support intricate transport modes when the microparticles are subjected to simple time-periodic loops of a uniform magnetic field. We design a pattern featuring a topological defect that functions as an attractor or a repeller of microparticles, as well as a pattern that directs microparticles along a prescribed complex trajectory. Using simple patterns and complex loops, we simultaneously and independently control the motion of several identical microparticles differing only in their positions above the pattern. Combining complex patterns and complex loops we transport microparticles from unknown locations to predefined positions and then force them to follow arbitrarily complex trajectories concurrently. Our findings pave the way for new avenues in transport control and dynamic self-assembly in colloidal science. External fields can control the motion of colloidal particles inducing different trajectories depending on for instance the particle size. The authors here use nonperiodic energy landscapes and topological protection to transport a collection of identical colloidal particles simultaneously and independently. [ABSTRACT FROM AUTHOR]

Context: With the advent of fast computing facilities, combined with rapid emerges of many new and intricate quantum mechanical functionals, computations with pure Hartree–Fock (HF) theory are now-a-days regarded as trivial or obsolete, or even considered as not reliable by many researchers. Consequently, current trends in computational chemistry show extensive use of post-HF theories for smaller molecular systems and various DFT methods for organic and inorganic chemistry related problems (larger molecules/systems). In this contribution, I have tried to show that sometimes, HF might be more suitable over DFT methodologies in addressing structure–property correlations. Molecules studied here were previously synthesized by Boyd in 1966 and important experimental data were produced by Alcalde and co-workers in 1987. Comparison of computed and experimental results clearly shows that HF method was more effective in reproducing the experimental data compared to especially the DFT methodologies. Reliability of HF method was further assured from the very similar results shown by the CCSD, CASSCF, CISD and QCISD methods. Current study also indicates that the localization issue associated with HF proved to be advantageous over delocalization issue of DFT based methodologies, in correctly describing the structure–property correlation for zwitterion systems. Methods: All computations were performed with Gaussian 09. A wide-range of quantum mechanical methodologies, HF, B3LYP, CAM-B3LYP, BMK, B3PW91, TPSSh, LC-ωPBE, M06-2X, M06-HF, ωB97xD, MP2, CASSCF, CCSD, QCISD, CISD and semi-empirical methods like, Huckel, CNDO, AM1, PM3MM and PM6, were used for investigations. [ABSTRACT FROM AUTHOR]

Odor perception affects physiological and psychological states. Pupillary light reflex (PLR) parameters can be affected by olfactory stimulation and psychological states, although it remains unclear whether the olfactory stimulation-induced psychological changes can associate with PLR parameter changes. This study aimed to investigate effects of olfactory stimulation-induced psychological changes on PLR parameter changes with repeated measurements. We collected data on six mood subscales of the profile of mood states, and on five PLR parameter measurements from 28 healthy participants. Participants underwent a 10-min olfactory stimulation on different days with six odorants available with the T&T olfactometer. As obtained data were clustered, we used linear mixed-effects models for statistical analyses. The olfactory stimulation using the no-odor liquid did not affect mood states and the initial pupil size (INIT). The sweat odorant worsened all mood subscales including fatigue–inertia (Fatigue)/Vigor–Activity (Vigor), and decreased INIT compared to the no-odor liquid. When comparing INIT responses related to changes in mood subscales between the no-odor liquid and the sweat odorant, worsened states of Fatigue/Vigor were associated with decreased INIT in the sweat odorant. Fatigue/Vigor can be used as mental fatigue indicators. Thus, mental fatigue can be associated with decreased INIT in the olfactory stimulation. [ABSTRACT FROM AUTHOR]

Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization. The lymphatic system is a transport network that controls immune response and tissue fluid circulation in the body. Here the authors combine experiment and theory to reveal that developing lymphatic capillary networks exploit complementary branching strategies to optimize tissue coverage. [ABSTRACT FROM AUTHOR]

Hydrological disasters, such as floods, can have dire consequences for human societies. Historical information plays a key role in detecting whether particular types of hydrological disasters have increased in frequency and/or magnitude and, if so, they are more likely attributable to natural or human-induced climatic and other environmental changes. The identification of regions with similar flood conditions is essential for the analysis of regional flooding regimes. To this end, we here present the longest existing flood reconstruction for the Eastern Liguria Area (ELA) in northwestern Italy, covering 1582 to 2022 CE, which offers a case study representative of the central Mediterranean region. An Annual Flood Intensification Index was developed to transform the historical data into a continuous annual hydrological time-series contained by a homogeneous data structure for the study-area. We found two change-points (trend breaks) in the reconstructed time-series, in 1787 and 1967, with only occasional heavy floods comparable to present-day disasters occurring before the first change-point, and an increasing intensification of floods after the second change-point up to the present day. The recent intensification of flooding in the ELA, associated with changes in land use and land cover, also appears to coincide with phases in which hydrological hazards have become more changeable and extreme in disaster-affected areas. This is evidenced by river basin responses to human-induced disturbances. [ABSTRACT FROM AUTHOR]

The song control nucleus HVC of songbirds has emerged as a widespread model system to study adult neurogenesis and the factors that modulate the incorporation of new neurons, including seasonal state, sex differences or sex steroid hormone concentrations. However, the specific function of these new neurons born in adulthood remains poorly understood. We implemented a new procedure based on focal X-ray irradiation to deplete neural progenitors in the ventricular zone adjacent to HVC and study the functional consequences. A 23 Gy dose depleted by more than 50 percent the incorporation of BrdU in neural progenitors, a depletion that was confirmed by a significant decrease in doublecortin positive neurons. This depletion of neurogenesis significantly increased the variability of testosterone-induced songs in females and decreased their bandwidth. Expression of the immediate early gene ZENK in secondary auditory areas of the telencephalon that respond to song was also inhibited. These data provide evidence that new neurons in HVC play a role in both song production and perception and that X-ray focal irradiation represents an excellent tool to advance our understanding of adult neurogenesis. [ABSTRACT FROM AUTHOR]

The approximately 120 MDa mammalian nuclear pore complex (NPC) acts as a gatekeeper for the transport between the nucleus and cytosol1. The central channel of the NPC is filled with hundreds of intrinsically disordered proteins (IDPs) called FG-nucleoporins (FG-NUPs)2,3. Although the structure of the NPC scaffold has been resolved in remarkable detail, the actual transport machinery built up by FG-NUPs—about 50 MDa—is depicted as an approximately 60-nm hole in even highly resolved tomograms and/or structures computed with artificial intelligence4–11. Here we directly probed conformations of the vital FG-NUP98 inside NPCs in live cells and in permeabilized cells with an intact transport machinery by using a synthetic biology-enabled site-specific small-molecule labelling approach paired with highly time-resolved fluorescence microscopy. Single permeabilized cell measurements of the distance distribution of FG-NUP98 segments combined with coarse-grained molecular simulations of the NPC allowed us to map the uncharted molecular environment inside the nanosized transport channel. We determined that the channel provides—in the terminology of the Flory polymer theory12—a ‘good solvent’ environment. This enables the FG domain to adopt expanded conformations and thus control transport between the nucleus and cytoplasm. With more than 30% of the proteome being formed from IDPs, our study opens a window into resolving disorder–function relationships of IDPs in situ, which are important in various processes, such as cellular signalling, phase separation, ageing and viral entry.Previously shown as a 60-nm hole in the nuclear pore complex, the transport machinery by FG-nucleoporins is mapped. [ABSTRACT FROM AUTHOR]

The ability to adopt novel tools continues to become more important for governments and environmental managers tasked with balancing economic development, social needs and environmental protection. An example of an emerging technology that can enable flexible, cost-effective data collection for conservation and environmental management is Unmanned Aerial Vehicles (UAVs). It is clear that UAVs are beginning to be adopted for a diversity of purposes, identification of barriers to their use is the first step in increasing their uptake amongst the environmental management community. Identifying the barriers to UAV usage will enable research and management communities to confidently utilise these powerful pieces of technology. However, the implementation of this technology for environmental research has received little overall assessment attention. This systematic literature review has identified 9 barrier categories (namely Technological, Analytical and Processing, Regulatory, Cost, Safety, Social, Wildlife impact, work suitability and others) inhibiting the uptake of UAV technologies. Technological barriers were referenced in the literature most often, with the inability of UAVs to perform in poor weather (such as rain or windy conditions) commonly mentioned. Analytical and Processing and Regulatory barriers were also consistently reported. It is likely that some barriers identified will lessen with time (e.g. technological and analytical barriers) as this technology continues to evolve. [ABSTRACT FROM AUTHOR]

Migratory storks could be vectors of transmission of bacteria of public health concern mediated by the colonization, persistence and excretion of such bacteria. This study aims to determine genera/species diversity, prevalence, and co-colonization indices of bacteria obtained from tracheal (T) and nasal (N) samples from storks in relation to exposure to point sources through foraging. One-hundred and thirty-six samples from 87 nestlings of colonies of parent white storks with different foraging habits (natural habitat and landfills) were obtained (84 T-samples and 52 N-samples) and processed. Morphologically distinct colonies (up to 12/sample) were randomly selected and identified by MALDI-TOF-MS. About 87.2% of the total 806 isolates recovered were identified: 398 from T-samples (56.6%) and 305 from N-samples (43.4%). Among identified isolates, 17 genera and 46 species of Gram-positive and Gram-negative bacteria were detected, Staphylococcus (58.0%) and Enterococcus (20.5%) being the most prevalent genera. S. sciuri was the most prevalent species from T (36.7%) and N (34.4%) cavities of total isolates, followed by E. faecalis (11.1% each from T and N), and S. aureus [T (6.5%), N (13.4%)]. Of N-samples, E. faecium was significantly associated with nestlings of parent storks foraging in landfills (p = 0.018). S. sciuri (p = 0.0034) and M. caseolyticus (p = 0.032) from T-samples were significantly higher among nestlings of parent storks foraging in natural habitats. More than 80% of bacterial species in the T and N cavities showed 1–10% co-colonization indices with one another, but few had ≥ 40% indices. S. sciuri and E. faecalis were the most frequent species identified in the stork nestlings. Moreover, they were highly colonized by other diverse and potentially pathogenic bacteria. Thus, storks could be sentinels of point sources and vehicles of bacterial transmission across the "One Health" ecosystems. [ABSTRACT FROM AUTHOR]

Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings. Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures. [ABSTRACT FROM AUTHOR]

Both human-made and natural supply systems, such as power grids and leaf venation networks, are built to operate reliably under changing external conditions. Many of these spatial networks exhibit community structures. Here, we show that a relatively strong connectivity between the parts of a network can be used to define a different class of communities: dual communities. We demonstrate that traditional and dual communities emerge naturally as two different phases of optimized network structures that are shaped by fluctuations and that they both suppress failure spreading, which underlines their importance in understanding the shape of real-world supply networks. Here the authors introduce dual communities, characterized by strong connections at their boundaries, and show that they are formed as a trade-off between efficiency and resilience in supply networks. [ABSTRACT FROM AUTHOR]

Neurons are connected by complex branching processes—axons and dendrites—that process information for organisms to respond to their environment. Classifying neurons according to differences in structure or function is a fundamental part of neuroscience. Here, by constructing biophysical theory and testing against empirical measures of branching structure, we develop a general model that establishes a correspondence between neuron structure and function as mediated by principles such as time or power minimization for information processing as well as spatial constraints for forming connections. We test our predictions for radius scale factors against those extracted from neuronal images, measured for species that range from insects to whales, including data from light and electron microscopy studies. Notably, our findings reveal that the branching of axons and peripheral nervous system neurons is mainly determined by time minimization, while dendritic branching is determined by power minimization. Our model also predicts a quarter-power scaling relationship between conduction time delay and body size. [ABSTRACT FROM AUTHOR]

Deciphering the relationship between molecules, olfactory receptors (ORs) and corresponding odors remains a challenging task. It requires a comprehensive identification of ORs responding to a given odorant. With the recent advances in artificial intelligence and the growing research in decoding the human olfactory perception from chemical features of odorant molecules, the applications of advanced machine learning have been revived. In this study, Convolutional Neural Network (CNN) and Graphical Convolutional Network (GCN) models have been developed on odorant molecules-odors and odorant molecules-olfactory receptors using a large set of 5955 molecules, 160 odors and 106 olfactory receptors. The performance of such models is promising with a Precision/Recall Area Under Curve of 0.66 for the odorant-odor and 0.91 for the odorant-olfactory receptor GCN models respectively. Furthermore, based on the correspondence of odors and ORs associated for a set of 389 compounds, an odor-olfactory receptor pairwise score was computed for each odor-OR combination allowing to suggest a combinatorial relationship between olfactory receptors and odors. Overall, this analysis demonstrate that artificial intelligence may pave the way in the identification of the smell perception and the full repertoire of receptors for a given odorant molecule. [ABSTRACT FROM AUTHOR]

Topological signals defined on nodes, links and higher dimensional simplices define the dynamical state of a network or of a simplicial complex. As such, topological signals are attracting increasing attention in network theory, dynamical systems, signal processing and machine learning. Topological signals defined on the nodes are typically studied in network dynamics, while topological signals defined on links are much less explored. Here we investigate Dirac synchronization, describing locally coupled topological signals defined on the nodes and on the links of a network, and treated using the topological Dirac operator. The dynamics of signals defined on the nodes is affected by a phase lag depending on the dynamical state of nearby links and vice versa. We show that Dirac synchronization on a fully connected network is explosive with a hysteresis loop characterized by a discontinuous forward transition and a continuous backward transition. The analytical investigation of the phase diagram provides a theoretical understanding of this topological explosive synchronization. The model also displays an exotic coherent synchronized phase, also called rhythmic phase, characterized by non-stationary order parameters which can shed light on topological mechanisms for the emergence of brain rhythms. Topological signals are dynamical variables that can be associated to nodes, links, triangles, etc. Here, the authors formulate Dirac synchronization that uses the Dirac operator to couple locally topological signals defined on nodes and links and show, numerically and analytically, that this gives rise to an explosive synchronization transition and to a coherent rhythmic phase. [ABSTRACT FROM AUTHOR]

Since the very beginning of the COVID-19 pandemic, control policies and restrictions have been the hope for containing the rapid spread of the virus. However, the psychological and economic toll they take on society entails the necessity to develop an optimal control strategy. Assessment of the effectiveness of these interventions aided with mathematical modelling remains a non-trivial issue in terms of numerical conditioning due to the high number of parameters to estimate from a highly noisy dataset and significant correlations between policy timings. We propose a solution to the problem of parameter non-estimability utilizing data from a set of European countries. Treating a subset of parameters as common for all countries and the rest as country-specific, we construct a set of individualized models incorporating 13 different pandemic control measures, and estimate their parameters without prior assumptions. We demonstrate high predictive abilities of these models on an independent validation set and rank the policies by their effectiveness in reducing transmission rates. We show that raising awareness through information campaigns, providing income support, closing schools and workplaces, cancelling public events, and maintaining an open testing policy have the highest potential to mitigate the pandemic. [ABSTRACT FROM AUTHOR]

Understanding and controlling transport through complex media is central for a plethora of processes ranging from technical to biological applications. Yet, the effect of micro-scale manipulations on macroscopic transport dynamics still poses conceptual conundrums. Here, we demonstrate the predictive power of a conceptual shift in describing complex media by local micro-scale correlations instead of an assembly of uncorrelated minimal units. Specifically, we show that the non-linear dependency between microscopic morphological properties and macroscopic transport characteristics in porous media is captured by transport statistics on the level of pore junctions instead of single pores. Probing experimentally and numerically transport through two-dimensional porous media while gradually increasing flow heterogeneity, we find a non-monotonic change in transport efficiency. Using analytic arguments, we built physical intuition on how this non-monotonic dependency emerges from junction statistics. The shift in paradigm presented here broadly affects our understanding of transport within the diversity of complex media. Dispersive transport through complex media, relevant for semiconductors, liquid crystals, and biological soft matter, is influenced by their microscopic, porous structure. The authors consider the statistics of pore-junction units, in contrast to individual pores, to link morphology and macroscopic transport characteristics. [ABSTRACT FROM AUTHOR]

Systemic or pulmonary reactivations of herpes simplex virus 1 (HSV-1) have been reported in critically ill patients with COVID-19, posing a dilemma for clinicians in terms of their diagnostic and clinical relevance. Prevalence of HSV-1 reactivation may be as high as > 40% in this population, but with large heterogeneity across studies, likely reflecting the different samples and/or cut-offs for defining reactivation. There is frequently agreement on the clinical significance of HSV-1 reactivation in the presence of severe manifestations clearly attributable to the virus. However, the clinical implications of HSV-1 reactivations in the absence of manifest signs and symptoms remain controversial. Our review aims at providing immunological background and at reviewing clinical findings on HSV-1 reactivations in critically ill patients with COVID-19. [ABSTRACT FROM AUTHOR]

Retina ganglion cells extract specific features from natural scenes and send this information to the brain. In particular, they respond to local light increase (ON responses), and/or decrease (OFF). However, it is unclear if this ON-OFF selectivity, characterized with synthetic stimuli, is maintained under natural scene stimulation. Here we recorded ganglion cell responses to natural images slightly perturbed by random noise patterns to determine their selectivity during natural stimulation. The ON-OFF selectivity strongly depended on the specific image. A single ganglion cell can signal luminance increase for one image, and luminance decrease for another. Modeling and experiments showed that this resulted from the non-linear combination of different retinal pathways. Despite the versatility of the ON-OFF selectivity, a systematic analysis demonstrated that contrast was reliably encoded in these responses. Our perturbative approach uncovered the selectivity of retinal ganglion cells to more complex features than initially thought. Ganglion cells classically respond to either light increase (ON) or decrease (OFF). Here, the authors show that during natural scene stimulation, a single ganglion cell can switch between ON and OFF depending on the visual context. [ABSTRACT FROM AUTHOR]

Sensory processing is distributed among many brain regions that interact via feedforward and feedback signaling. Neuronal oscillations have been shown to mediate intercortical feedforward and feedback interactions. Yet, the macroscopic structure of the multitude of such oscillations remains unclear. Here, we show that simple visual stimuli reliably evoke two traveling waves with spatial wavelengths that cover much of the cerebral hemisphere in awake mice. 30-50 Hz feedforward waves arise in primary visual cortex (V1) and propagate rostrally, while 3-6 Hz feedback waves originate in the association cortex and flow caudally. The phase of the feedback wave modulates the amplitude of the feedforward wave and synchronizes firing between V1 and parietal cortex. Altogether, these results provide direct experimental evidence that visual evoked traveling waves percolate through the cerebral cortex and coordinate neuronal activity across broadly distributed networks mediating visual processing. Processing sensory stimuli requires coordinated activation of neurons broadly distributed across many distant cortical sites, yet it is not clear how this coordination is accomplished in the brain. Here, the authors show that visual stimuli reliably evoke traveling waves of activity that percolate through the cortex and orchestrate neuronal firing across primary visual and association cortices. [ABSTRACT FROM AUTHOR]

Food quality control is essential in industry and daily life. In this work, we developed a novel colorimetric sensor array composed of several pH-sensitive dyes for monitoring meat freshness. A color change in the sensor array was seen after exposure to volatile organic compounds (VOCs), and the images were captured for precise quantification of the VOCs. In conjunction with pattern recognition, meat freshness at different storage periods was readily discerned, revealing that the as-fabricated colorimetric sensor array possessed excellent discrimination ability. The linear range for quantitative analysis of volatiles related to meat spoilage was from 5 ppm to 100 ppm, with a limit of detection at the ppb level (S/N = 3). Furthermore, the testing results obtained by the sensor in assessing meat freshness were validated by a standard method for measuring the total volatile basic nitrogen (TVB-N). The sensing signals showed good agreement with the results obtained in TVB-N when measuring real food samples. The sensor also displayed good reproducibility (RSD < 5%) and long-term stability. The sensor was successfully used for on-site and real-time determination of volatiles emitted from rotting meat, demonstrating its potential application in monitoring the quality and safety of meat products. [ABSTRACT FROM AUTHOR]

The transport behavior of potassium ions through carbon nanotubes (CNTs) under the effect of moving surface charges is studied by using non-equilibrium molecular dynamics and the Monte Carlo method. Two motion patterns of the surface charges, axial translation and radial vibration, are investigated. We found that when the surface charge is translated in the axial direction, there is an optimal translation velocity to maximize the particle flow density (PFD ), and the specific value of this optimal translation velocity is related to the surface charge period and the charge amount. When the surface charge vibrates in the radial direction, the PFD under the negative charge presents a step-type-decrease trend with an increase of the vibration frequency, and the trend is independent from the charge amount and the vibrating period. Our results provide new ideas for nanoscale transport devices and also provide possible insights into the transport mechanisms of biological ion channels. [ABSTRACT FROM AUTHOR]

We draw current efforts towards proposing a wing-type micro UAV with characteristics of being a basic operation risk self handled (Micro-Brosh) platform. Its micro-sized wingspan and weight, which are less than 0.30 m and 0.150 kg, respectively, guarantee the low risk to the operator and installations in case of crashing. It can be launched manually without using an appropriate runway, besides using a soft grass field for landing is recommended. Its associated costs for construction and maintenance are very low (below US$ 500) if compared to traditional aircraft. The main contribution here is the architectural design, besides we provide detailed documentation including techniques for determining lift, thrust, drag, minimum flight velocity, maximum time of flight and distance (autonomy), and other issues that we have solved related to the aircraft development. We validate our prototype with experiments including several tests done with the UAV with results that have proven its flight ability. To the end, we understand that this work provides a nice starting document to researchers that intend to develop a UAV or enter this field. [ABSTRACT FROM AUTHOR]

Binding interactions of the spike proteins of the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) to a peptide fragment derived from the human angiotensin converting enzyme 2 (hACE2) receptor are investigated. The peptide is employed as capture moiety in enzyme linked immunosorbent assays (ELISA) and quantitative binding interaction measurements that are based on fluorescence proximity sensing (switchSENSE). In both techniques, the peptide is presented on an oligovalent DNA nanostructure, in order to assess the impact of mono- versus trivalent binding modes. As the analyte, the spike protein and several of its subunits are tested as well as inactivated SARS-CoV-2 and pseudo viruses. While binding of the peptide to the full-length spike protein can be observed, the subunits RBD and S1 do not exhibit binding in the employed concentrations. Variations of the amino acid sequence of the recombinant full-length spike proteins furthermore influence binding behavior. The peptide was coupled to DNA nanostructures that form a geometric complement to the trimeric structure of the spike protein binding sites. An increase in binding strength for trimeric peptide presentation compared to single peptide presentation could be generally observed in ELISA and was quantified in switchSENSE measurements. Binding to inactivated wild type viruses could be shown as well as qualitatively different binding behavior of the Alpha and Beta variants compared to the wild type virus strain in pseudo virus models. [ABSTRACT FROM AUTHOR]

Podocytes are highly specialized cells playing a key role in the filtration function of the kidney. A damaged podocyte ultrastructure is associated with a reorganization of the actin cytoskeleton and accompanied with a loss of adhesion to the glomerular basement membrane leading to proteinuria in many forms of glomerular diseases, e.g. nephrotic syndrome. If the first-line therapy with glucocorticoids fails, alternative immunosuppressive agents are used, which are known to have the potential to stabilize the actin cytoskeleton. A new option for preventing relapses in steroid dependent nephrotic syndrome is the monoclonal antibody rituximab, which, in addition to its B-cell depleting effect, is assumed to have direct effects on podocytes. We here provide data on the non-immunological off-target effects of the immunosuppressant rituximab on podocyte structure and dynamics in an in vitro puromycin aminonucleoside model of podocyte injury. A conditionally immortalized human podocyte cell line was used. Differentiated podocytes were treated with puromycin aminonucleoside and rituximab. Our studies focussed on analyzing the structure of the actin cytoskeleton, cellular adhesion and apoptosis using immunofluorescence staining and protein biochemistry methods. Treatment with rituximab resulted in a stabilization of podocyte actin stress fibers in the puromycin aminonucleoside model, leading to an improvement in cell adhesion. A lower apoptosis rate was observed after parallel treatment with puromycin aminonucleoside and rituximab visualized by reduced nuclear fragmentation. Consistent with this data, Western-blot analyses demonstrated that rituximab directly affects the caspase pathways by inhibiting the activation of Caspases-8, -9 and -3, suggesting that rituximab may inhibit apoptosis. In conclusion, our results indicate an important role of the immunosuppressant rituximab in terms of stability and morphogenesis of podocytes, involving apoptosis pathways. This could help to improve therapeutical concepts for patients with proteinuria mediated by diseased podocytes. [ABSTRACT FROM AUTHOR]