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Recent studies show that, even in constant environments, the tuning of single neurons changes over time in a variety of brain regions. This representational drift has been suggested to be a consequence of continuous learning under noise, but its properties are still not fully understood. To investigate the underlying mechanism, we trained an artificial network on a simplified navigational task. The network quickly reached a state of high performance, and many units exhibited spatial tuning. We then continued training the network and noticed that the activity became sparser with time. Initial learning was orders of magnitude faster than ensuing sparsification. This sparsification is consistent with recent results in machine learning, in which networks slowly move within their solution space until they reach a flat area of the loss function. We analyzed four datasets from different labs, all demonstrating that CA1 neurons become sparser and more spatially informative with exposure to the same environment. We conclude that learning is divided into three overlapping phases: (i) Fast familiarity with the environment; (ii) slow implicit regularization; and (iii) a steady state of null drift. The variability in drift dynamics opens the possibility of inferring learning algorithms from observations of drift statistics.

ObjectiveAutomated surgical step recognition (SSR) using AI has been a catalyst in the “digitization” of surgery. However, progress has been limited to laparoscopy, with relatively few SSR tools in endoscopic surgery. This study aimed to create a SSR model for transurethral resection of bladder tumors (TURBT), leveraging a novel application of transfer learning to reduce video dataset requirements.Materials and methodsRetrospective surgical videos of TURBT were manually annotated with the following steps of surgery: primary endoscopic evaluation, resection of bladder tumor, and surface coagulation. Manually annotated videos were then utilized to train a novel AI computer vision algorithm to perform automated video annotation of TURBT surgical video, utilizing a transfer-learning technique to pre-train on laparoscopic procedures. Accuracy of AI SSR was determined by comparison to human annotations as the reference standard.ResultsA total of 300 full-length TURBT videos (median 23.96 min; IQR 14.13–41.31 min) were manually annotated with sequential steps of surgery. One hundred and seventy-nine videos served as a training dataset for algorithm development, 44 for internal validation, and 77 as a separate test cohort for evaluating algorithm accuracy. Overall accuracy of AI video analysis was 89.6%. Model accuracy was highest for the primary endoscopic evaluation step (98.2%) and lowest for the surface coagulation step (82.7%).ConclusionWe developed a fully automated computer vision algorithm for high-accuracy annotation of TURBT surgical videos. This represents the first application of transfer-learning from laparoscopy-based computer vision models into surgical endoscopy, demonstrating the promise of this approach in adapting to new procedure types.

Neural oscillations are ubiquitously observed in many brain areas. One proposed functional role of these oscillations is that they serve as an internal clock, or 'frame of reference'. Information can be encoded by the timing of neural activity relative to the phase of such oscillations. In line with this hypothesis, there have been multiple empirical observations of such phase codes in the brain. Here we ask: What kind of neural dynamics support phase coding of information with neural oscillations? We tackled this question by analyzing recurrent neural networks (RNNs) that were trained on a working memory task. The networks were given access to an external reference oscillation and tasked to produce an oscillation, such that the phase difference between the reference and output oscillation maintains the identity of transient stimuli. We found that networks converged to stable oscillatory dynamics. Reverse engineering these networks revealed that each phase-coded memory corresponds to a separate limit cycle attractor. We characterized how the stability of the attractor dynamics depends on both reference oscillation amplitude and frequency, properties that can be experimentally observed. To understand the connectivity structures that underlie these dynamics, we showed that trained networks can be described as two phase-coupled oscillators. Using this insight, we condensed our trained networks to a reduced model consisting of two functional modules: One that generates an oscillation and one that implements a coupling function between the internal oscillation and external reference. In summary, by reverse engineering the dynamics and connectivity of trained RNNs, we propose a mechanism by which neural networks can harness reference oscillations for working memory. Specifically, we propose that a phase-coding network generates autonomous oscillations which it couples to an external reference oscillation in a multi-stable fashion.

Abstract Classification of the Class Echinoidea is under significant revision in light of emerging molecular phylogenetic evidence. In particular, the sister-group relationships within the superorder Luminacea (Echinoidea: Irregularia) have been considerably updated. However, the placement of many families remains largely unresolved due to a series of incongruent evidence obtained from morphological, paleontological, and genetic data for the majority of extant representatives. In this study, we investigated the phylogenetic relationships of 25 taxa, belonging to eleven luminacean families. We proposed three new superfamilies: Astriclypeoidea, Mellitoidea, and Taiwanasteroidea (including Dendrasteridae, Taiwanasteridae, Scutellidae, and Echinarachniidae), instead of the currently recognized superfamily Scutelloidea Gray, 1825. In light of the new data obtained from ten additional species, the historical biogeography reconstructed shows that the tropical western Pacific and eastern Indian Oceans are the cradle for early sand dollar diversification. Hothouse conditions during the late Cretaceous and early Paleogene were coupled with diversification events of major clades of sand dollars. We also demonstrate that Taiwan fauna can play a key role in terms of understanding the major Cenozoic migration and dispersal events in the evolutionary history of Luminacea.

Attractors play a key role in a wide range of processes including learning and memory. Due to recent innovations in recording methods, there is increasing evidence for the existence of attractor dynamics in the brain. Yet, our understanding of how these attractors emerge or disappear in a biological system is lacking. By following the spontaneous network bursts of cultured cortical networks, we are able to define a vocabulary of spatiotemporal patterns and show that they function as discrete attractors in the network dynamics. We show that electrically stimulating specific attractors eliminates them from the spontaneous vocabulary, while they are still robustly evoked by the electrical stimulation. This seemingly paradoxical finding can be explained by a Hebbian-like strengthening of specific pathways into the attractors, at the expense of weakening non-evoked pathways into the same attractors. We verify this hypothesis and provide a mechanistic explanation for the underlying changes supporting this effect.

Objectives This study aimed to perform a meta-analysis of the short-term impact of ischaemic postconditioning (IPoC) on myocardial injury in ST elevation myocardial infarction (STEMI) using surrogate cardiac biomarkers.Methods Eligible studies were identified using several article databases. Randomised controlled trials published between 1 January 2000 and 1 December 2021 comparing IPoC to standard of therapy in STEMI patients were included in the search. Outcomes included surrogates of myocardial injury, specifically peak troponin, creatine-kinase (CK) and CK myoglobin binding (CK-MB) enzyme levels.Results 11 articles involving 1273 patients reported on CK-MB and 8 studies involving 505 patients reported on CK. Few studies used troponin as an outcome, thus, a subanalysis of troponin dynamics was not performed. Meta-regression analysis demonstrated no significant effect of IPoC on peak CK-MB (effect size −0.41, 95% CI −1.15 to 0.34) or peak CK (effect size −0.42, 95% CI −1.20 to 0.36). Linear regression analysis demonstrated a significant correlation between a history of smoking and CK-MB in the IPoC group (p=0.038).Conclusions IPoC does not seem to protect against myocardial injury in STEMI, except possibly in smokers. These results resonate with some studies using imaging techniques to ascertain myocardial damage. More research using troponin and cardiac imaging should be pursued to better assess the effects of IPoC on cardiovascular outcomes in STEMI.

Patient data from the Israeli Ministry of Health demonstrates that a 3rd dose of BNT162b2 is effective in reducing Omicron BA.1/BA.2 severe disease and does not wane over the seven month study period as well as that a fourth dose further improves the protective features of vaccination.

Abstract Background With increasing life expectancy, the prevalence of nonagenarians with cardiovascular disease is steadily growing. However, this population is underrepresented in randomized trials and thus poorly defined, with little quality evidence to support and guide optimal management. The aim of the present study was to evaluate the clinical management, therapeutic approach, and outcomes of nonagenarians admitted to a tertiary care center intensive coronary care unit (ICCU). Methods We prospectively collected all patients admitted to a tertiary care center ICCU between July 2019 – July 2022 and compared nonagenarians to all other patients. The primary outcome was in-hospital mortality. Results A total of 3807 patients were included in the study. Of them 178 (4.7%) were nonagenarians and 93 (52%) females. Each year the prevalence of nonagenarians has increased from 4.0% to 2019, to 4.2% in 2020, 4.6% in 2021 and 5.3% in 2022. Admission causes differed between groups, including a lower rate of acute coronary syndromes (27% vs. 48.6%, p

Due to the numerous challenges of providing for autistic children on a daily basis, parental cluelessness of how to care for autistic children, and lack of parental support for the therapy process that has been taught by the Autism Service Center, parents with autistic children are more likely to experience stress. As a result, employing the PAR methodology, Christian psychology study programs engage in community service projects that teach parenting techniques for raising autistic children. The PKM team engages in mentoring and psychoeducational activities, which are divided into two primary sessions (i.e, Session 1 included lecturing, relaxation, and question and answer; Session 2 including simulation, roleplaying, and question-and-answer). The PKM activity process was examined both quantitatively and qualitatively. With the highest scores in the very good category (74.07%, 59.25%, and 55.55% respectively), participants gave the elements of a comfortable setting or facility, handouts or teaching materials that are very helpful in learning and comprehending the content, and a willingness to join once more if the Christian Psychology Study Program offers another activity. Based on the qualitative data, the participants explicitly expressed their opinion that this activity was very good, useful, could transfer new knowledge in regards to caring for ASD children, could address their needs and difficulties, and it was hoped that this activity would be sustained in the future. Thus, resources and a number of delivery modalities can be used to provide support and psychoeducation about parenting styles for kids with autism, which can address the needs, aspirations, and issues of PLA Naimata Staff and Assisted Parents.

The Eastern Mediterranean Sea is an exceptional habitat. Its relative isolation and distinct characteristics create a unique ecosystem recognized as a marine biodiversity hot spot, where one-fifth of the species are endemic. Yet, native Mediterranean biodiversity is under increasing threat, mainly due to massive alien species invasions of Indo-Pacific origin. To date, more than 800 non-indigenous species have been reported in the Eastern Mediterranean Sea, justifying its reputation as one of the most severely affected habitats in the world in terms of marine biological invasions. Here we summarized the Mediterranean invasion dynamics of the long-spined echinoid Diadema setosum (Leske, 1778), one of the most ubiquitous Indo-Pacific sea urchin species. We show an alarming exponential population growth of D. setosum throughout the Eastern Mediterranean since 2018, following more than a decade of ‘invasion lag’ since its first detection in 2006. Molecular analyses illustrate the presence of a single genetic D. setosum clade in the Mediterranean Sea – corresponding to the Arabian Peninsula clade of this species, reinforcing the notion of a Red Sea origin. Our data support the current working hypothesis that the initial introduction of D. setosum occurred in the Northern Levantine Basin from which it gradually expanded in both north-west and south-east trajectories – in contrast to a stepping-stone hypothesis of gradual advancement from the opening of the Suez Canal. Demographic data of D. setosum along the Israeli Mediterranean coastline reveals a well-established population of broad size distributions, from juveniles to adult individuals of remarkably large size. Additionally, we provide evidence of the reproductive capacity of D. setosum in its new environment. Due to the magnitude of Diadema’s ecological footprint, it poses a severe threat to the entire Eastern Mediterranean Sea, including the Levantine Basin and South Aegean Sea, calling for rapid and coordinated action at both national and regional scales.

The sea urchin Diadema setosum is an ecological key species across its range, particularly on coral reefs. In 2006 D. setosum was first observed in the Mediterranean Sea, and since, it has proliferated to occupy the entire Levantine Basin. Here we report the mass mortality of the invasive D. setosum in the Mediterranean Sea. This is the first report of D. setosum mass mortality. The mortality spans over 1000 km along the Levantine coast of Greece and Turkey. The current mortality shows similar pathologies to previously reported Diadema mass mortality events, suggesting pathogenic infection as the cause of mortalities. Maritime transport, local currents, and fish predation of infected individuals may distribute pathogens at varying geographical scales. Due to the proximity of the Levantine Basin to the Red Sea, the risk of pathogen transport to the native Red Sea D. setosum population is imminent—with potentially catastrophic consequences.

Personalization — a paradigm that has been widely and successfully embraced in other areas of human activity, and primarily on social media — may be ready for the law. Social media as a data source to support personalized law is only suitable for a few areas if life. In those areas, however, personalized standards bear enormous potential.

ObjectiveTo utilize whole exome or genome sequencing and the scientific literature for identifying candidate genes for cyclic vomiting syndrome (CVS), an idiopathic migraine variant with paroxysmal nausea and vomiting.MethodsA retrospective chart review of 80 unrelated participants, ascertained by a quaternary care CVS specialist, was conducted. Genes associated with paroxysmal symptoms were identified querying the literature for genes associated with dominant cases of intermittent vomiting or both discomfort and disability; among which the raw genetic sequence was reviewed. “Qualifying” variants were defined as coding, rare, and conserved. Additionally, “Key Qualifying” variants were Pathogenic/Likely Pathogenic, or “Clinical” based upon the presence of a corresponding diagnosis. Candidate association to CVS was based on a point system.ResultsThirty-five paroxysmal genes were identified per the literature review. Among these, 12 genes were scored as “Highly likely” (SCN4A, CACNA1A, CACNA1S, RYR2, TRAP1, MEFV) or “Likely” (SCN9A, TNFRSF1A, POLG, SCN10A, POGZ, TRPA1) CVS related. Nine additional genes (OTC, ATP1A3, ATP1A2, GFAP, SLC2A1, TUBB3, PPM1D, CHAMP1, HMBS) had sufficient evidence in the literature but not from our study participants. Candidate status for mitochondrial DNA was confirmed by the literature and our study data. Among the above-listed 22 CVS candidate genes, a Key Qualifying variant was identified in 31/80 (34%), and any Qualifying variant was present in 61/80 (76%) of participants. These findings were highly statistically significant (p

Summary: Constraints on organisms possessing a unitary body plan appear almost absent from colonial organisms. Like unitary organisms, however, coral colonies seemingly delay reproduction until reaching a critical size. Elucidating ontogenetic processes, such as puberty and aging are complicated by corals' modular design, where partial mortality and fragmentation lead to distortions in colony size-age relationships. We explored these enigmatic relations and their influence on reproduction by fragmenting sexually mature colonies of five coral species into sizes below the known size at first reproduction, nurturing them for prolonged periods, and examining their reproductive capacity and trade-offs between growth rates and reproductive investment. Most fragments were reproductive regardless of their size, and growth rates hardly affected reproduction. Our findings suggest that once the ontogenetic milestone of puberty is reached, corals retain reproductive capacity irrespective of colony size, highlighting the key role that aging may have in colonial animals, which are commonly considered non-aging.

Autism spectrum disorder (ASD) is a common condition with lifelong implications. The last decade has seen dramatic improvements in DNA sequencing and related bioinformatics and databases. We analyzed the raw DNA sequencing files on the Variantyx® bioinformatics platform for the last 50 ASD patients evaluated with trio whole-genome sequencing (trio-WGS). “Qualified” variants were defined as coding, rare, and evolutionarily conserved. Primary Diagnostic Variants (PDV), additionally, were present in genes directly linked to ASD and matched clinical correlation. A PDV was identified in 34/50 (68%) of cases, including 25 (50%) cases with heterozygous de novo and 10 (20%) with inherited variants. De novo variants in genes directly associated with ASD were far more likely to be Qualifying than non-Qualifying versus a control group of genes (p = 0.0002), validating that most are indeed disease related. Sequence reanalysis increased diagnostic yield from 28% to 68%, mostly through inclusion of de novo PDVs in genes not yet reported as ASD associated. Thirty-three subjects (66%) had treatment recommendation(s) based on DNA analyses. Our results demonstrate a high yield of trio-WGS for revealing molecular diagnoses in ASD, which is greatly enhanced by reanalyzing DNA sequencing files. In contrast to previous reports, de novo variants dominate the findings, mostly representing novel conditions. This has implications to the cause and rising prevalence of autism.

This study compares SARS-CoV-2 infection rates following a recent second or third dose of the BNT162b2 (Pfizer/BioNTech) vaccine. They use data from Israel for 12–14 year olds (second dose) and 16–18 year olds (third dose), and find a 3.7-fold higher risk in the second-dose group.

Abstract Background Atrial fibrillation (AF) is associated with increased risk of sudden cardiac death (SCD) in humans, independent of secondary risk factors such as thrombogenic disorders. In dogs, SCD is described in a number of heart diseases, but an association between AF and SCD is unreported. Hypothesis (a) A higher proportion of dogs with AF will experience SCD, and (b) SCD will be associated with complex ventricular arrhythmias. Animals One‐hundred forty‐two dogs with AF, and 127 dogs without AF. Methods Retrospective, multicenter, case‐control study. Dogs included in the AF group were compared to a control group of dogs in sinus rhythm, matched for echocardiographic diagnosis. Descriptive statistics were used to identify proportions of each group suffering SCD, compared using chi‐squared testing. Risk factors for SCD in dogs with AF were evaluated at the univariable and multivariable level using binary logistic regression. Significance was P

SARSNTdb offers a curated, nucleotide-centric database for users of varying levels of SARS-CoV-2 knowledge. Its user-friendly interface enables querying coding regions and coordinate intervals to find out the various functional and selective constraints that act upon the corresponding nucleotides and amino acids. Users can easily obtain information about viral genes and proteins, functional domains, repeats, secondary structure formation, intragenomic interactions, and mutation prevalence. Currently, many databases are focused on the phylogeny and amino acid substitutions, mainly in the spike protein. We took a novel, more nucleotide-focused approach as RNA does more than just code for proteins and many insights can be gleaned from its study. For example, RNA-targeted drug therapies for SARS-CoV-2 are currently being developed and it is essential to understand the features only visible at that level. This database enables the user to identify regions that are more prone to forming secondary structures that drugs can target. SARSNTdb also provides illustrative mutation data from a subset of ~25,000 patient samples with a reliable read coverage across the whole genome (from different locations and time points in the pandemic. Finally, the database allows for comparing SARS-CoV-2 and SARS-CoV domains and sequences. SARSNTdb can serve the research community by being a curated repository for information that gives a jump start to analyze a mutation’s effect far beyond just determining synonymous/non-synonymous substitutions in protein sequences.

ObjectivesAnkle-brachial index (ABI) is an independent prognostic marker of cardiovascular events among patients with coronary artery disease (CAD). We aimed to investigate the outcome of patients hospitalized with acute coronary syndrome (ACS) and abnormal ABI.Approach and resultsABI was prospectively measured in 1,047 patients hospitalized due to ACS, who were stratified into three groups, namely, those with clinical peripheral artery disease (PAD) (N = 132), those without clinical PAD but with abnormal (< 0.9) ABI (subclinical PAD; N = 148), and those without clinical PAD with normal ABI (no PAD; N = 767). Patients were prospectively followed for 30-day major adverse cardiovascular event (MACE) and 1-year all-cause mortality. The mean age was 64 years. There was a significant gradual increase throughout the three groups in age, i.e., the incidence of prior stroke, diabetes mellitus, and hypertension (p for trend = 0.001 for all). The in-hospital course showed a gradual rise in the incidence of complications with an increase in heart failure [2.5, 6.1, and 9.2%, (p for trend = 0.001)] and acute kidney injury [2, 4.1, and 11.5%, (p for trend = 0.001)]. At day 30, there was a stepwise increase in MACE, such that patients without PAD had the lowest rate, followed by subclinical and clinical PADs (3.5, 6.8, and 8.1%, respectively, p for trend = 0.009). Similarly, there was a significant increase in 1-year mortality from 3.4% in patients without PAD, through 6.8% in those with subclinical PAD, to 15.2% in those with clinical PAD (p for trend = 0.001).ConclusionSubclinical PAD is associated with poor outcomes in patients with ACS, suggesting that routine ABI screening could carry important prognostic significance in these patients regardless of PAD symptoms.

Finding dipole orientation of nanostructures is a challenge. Here the authors report a method to determine the sign of the polarity of a single nanowire using electric-field-modulated second-harmonic generation from surface-guided ZnO nanowire.

Abstract AI is becoming ubiquitous, revolutionizing many aspects of our lives. In surgery, it is still a promise. AI has the potential to improve surgeon performance and impact patient care, from post-operative debrief to real-time decision support. But, how much data is needed by an AI-based system to learn surgical context with high fidelity? To answer this question, we leveraged a large-scale, diverse, cholecystectomy video dataset. We assessed surgical workflow recognition and report a deep learning system, that not only detects surgical phases, but does so with high accuracy and is able to generalize to new settings and unseen medical centers. Our findings provide a solid foundation for translating AI applications from research to practice, ushering in a new era of surgical intelligence.

Summary: Drug resistance and metastasis—the major complications in cancer—both entail adaptation of cancer cells to stress, whether a drug or a lethal new environment. Intriguingly, these adaptive processes share similar features that cannot be explained by a pure Darwinian scheme, including dormancy, increased heterogeneity, and stress-induced plasticity. Here, we propose that learning theory offers a framework to explain these features and may shed light on these two intricate processes. In this framework, learning is performed at the single-cell level, by stress-driven exploratory trial-and-error. Such a process is not contingent on pre-existing pathways but on a random search for a state that diminishes the stress. We review underlying mechanisms that may support this search, and show by using a learning model that such exploratory learning is feasible in a high-dimensional system as the cell. At the population level, we view the tissue as a network of exploring agents that communicate, restraining cancer formation in health. In this view, disease results from the breakdown of homeostasis between cellular exploratory drive and tissue homeostasis.

Echinoids are key components of modern marine ecosystems. Despite a remarkable fossil record, the emergence of their crown group is documented by few specimens of unclear affinities, rendering their early history uncertain. The origin of sand dollars, one of its most distinctive clades, is also unclear due to an unstable phylogenetic context. We employ 18 novel genomes and transcriptomes to build a phylogenomic dataset with a near-complete sampling of major lineages. With it, we revise the phylogeny and divergence times of echinoids, and place their history within the broader context of echinoderm evolution. We also introduce the concept of a chronospace – a multidimensional representation of node ages – and use it to explore methodological decisions involved in time calibrating phylogenies. We find the choice of clock model to have the strongest impact on divergence times, while the use of site-heterogeneous models and alternative node prior distributions show minimal effects. The choice of loci has an intermediate impact, affecting mostly deep Paleozoic nodes, for which clock-like genes recover dates more congruent with fossil evidence. Our results reveal that crown group echinoids originated in the Permian and diversified rapidly in the Triassic, despite the relative lack of fossil evidence for this early diversification. We also clarify the relationships between sand dollars and their close relatives and confidently date their origins to the Cretaceous, implying ghost ranges spanning approximately 50 million years, a remarkable discrepancy with their rich fossil record.

Abstract Background Population outbreaks of the crown-of-thorns starfish (Acanthaster planci sensu lato; COTS), a primary predator of reef-building corals in the Indo-Pacific Ocean, are a major threat to coral reefs. While biological and ecological knowledge of COTS has been accumulating since the 1960s, little is known about its associated bacteria. The aim of this study was to provide fundamental information on the dominant COTS-associated bacteria through a multifaceted molecular approach. Methods A total of 205 COTS individuals from 17 locations throughout the Indo-Pacific Ocean were examined for the presence of COTS-associated bacteria. We conducted 16S rRNA metabarcoding of COTS to determine the bacterial profiles of different parts of the body and generated a full-length 16S rRNA gene sequence from a single dominant bacterium, which we designated COTS27. We performed phylogenetic analysis to determine the taxonomy, screening of COTS27 across the Indo-Pacific, FISH to visualize it within the COTS tissues, and reconstruction of the bacterial genome from the hologenome sequence data. Results We discovered that a single bacterium exists at high densities in the subcuticular space in COTS forming a biofilm-like structure between the cuticle and the epidermis. COTS27 belongs to a clade that presumably represents a distinct order (so-called marine spirochetes) in the phylum Spirochaetes and is universally present in COTS throughout the Indo-Pacific Ocean. The reconstructed genome of COTS27 includes some genetic traits that are probably linked to adaptation to marine environments and evolution as an extracellular endosymbiont in subcuticular spaces. Conclusions COTS27 can be found in three allopatric COTS species, ranging from the northern Red Sea to the Pacific, implying that the symbiotic relationship arose before the speciation events (approximately 2 million years ago). The universal association of COTS27 with COTS and nearly mono-specific association at least with the Indo-Pacific COTS provides a useful model system for studying symbiont-host interactions in marine invertebrates and may have applications for coral reef conservation. Video Abstract

The Haifa Bay area (HBA) is a major metropolitan area in Israel, which consists of high volume transportation routes, major industrial complexes, and the largest international seaport in Israel. These, which lie relatively near densely populated residential areas, result in a multitude of air pollution sources, many of whose emissions are in the form of particulate matter (PM). Previous studies have associated exposure to such PM with adverse health effects. This potential consequence serves as the motivation for this study whose aim is to provide a realistic and detailed three-dimensional concentration field of PM, originating simultaneously from multiple sources. The IIBR in-house Lagrangian stochastic pollutant dispersion model (LSM) is suitable for this endeavor, as it describes the dispersion of a scalar by solving the velocity fluctuations in high Reynolds number flows. Moreover, the LSM was validated in urban field experiments, including in the HBA. However, due to the fact that the multiple urban sources reside within the canopy layer, it was necessary to integrate into the LSM a realistic canopy layer model that depicts the actual effect of the roughness elements’ drag on the flow and turbulent exchange of the urban morphology. This was achieved by an approach which treats the canopy as patches of porous media. The LSM was used to calculate the three-dimensional fields of PM10 and PM2.5 concentrations during the typical conditions of the two workday rush-hour periods. These were compared to three air quality monitoring stations located downstream of the PM sources in the HBA. The LSM predictions for PM2.5 satisfy all acceptance criteria. Regarding the PM10 predictions, the LSM results comply with three out of four acceptance criteria. The analysis of the calculated concentration fields has shown that the PM concentrations up to 105 m AGL exhibit a spatial pattern similar to the ground level. However, it decreases by a factor of two at 45 m AGL, while, at 105 m, the concentration values are close to the background concentrations.

Lockdown policies have been implemented worldwide to limit the spread of COVID-19. “Lockdown fatigue” is a state of exhaustion related to the accumulating effects of repeated lockdowns. The aim of the current study was to examine the effects of repeated lockdowns on children with respiratory disorders. Data on children aged 0–18 years old with respiratory disorders were collected by an electronic survey during the third lockdown in Israel. The retrieved information included demographics and baseline medical status, respiratory clinical status during the third lockdown compared to pre-lockdown periods, lockdown adherence, lifestyle modifications and caregiver emotional status. The results were compared to those of a similar questionnaire distributed during the first lockdown. A total of 234 patients (62% males, 37% females, mean age 6.8 years (confidence interval 6.1–7.5)) were enrolled. Respiratory symptoms and exacerbation frequency were reduced in 76 (35.5%) and 58 (27.4%) patients, respectively, compared to the pre-lockdown period and similar to the first lockdown (p = 0.840 and p = 0.063, respectively). However, compared to the first lockdown, the third lockdown was associated with greater use of reliever medications (p = 0.006), less use of inhaled corticosteroids as routine treatment (p = 0.027), and more pediatric emergency room visits and hospitalizations (p = 0.001 and p < 0.001, respectively). The results also showed an increase in sedentary lifestyle (e.g., reduced physical activity (p = 0.025), less healthy eating habits (p = 0.001)) and reduced adherence to lockdown policies (p < 0.001). These data show that the continuing stability of clinical improvement during lockdown was accompanied by deleterious sequelae that potentially indicate “lockdown fatigue” among children with respiratory disorders.

Insect flight is a complex interdisciplinary phenomenon. Understanding its multiple aspects, such as flight control, sensory integration, physiology and genetics, often requires the analysis of large amounts of free flight kinematic data. Yet, one of the main bottlenecks in this field is automatically and accurately extracting such data from multi-view videos. Here, we present a model-based method for the pose estimation of free-flying fruit flies from multi-view high-speed videos. To obtain a faithful representation of the fly with minimum free parameters, our method uses a 3D model that includes two new aspects of wing deformation: A non-fixed wing hinge and a twisting wing surface. The method is demonstrated for free and perturbed flight. Our method does not use prior assumptions on the kinematics apart from the continuity of the wing pitch angle. Hence, this method can be readily adjusted for other insect species.

How are stable memories maintained in the brain despite significant ongoing fluctuations in synaptic strengths? Here, the authors show that a model consistent with fluctuations, homeostasis and biologically plausible learning rules, naturally leads to memories implemented as dynamic attractors.

Mesophotic coral ecosystems (MCEs) are light-dependent coral-associated communities found at 30–150 m depth. Corals inhabiting these deeper reefs are often acclimatized to a limited and blue-shifted light environment, enabling them to maintain the relationship with their photosynthetic algal symbionts (family Symbiodiniaceae) despite the seemingly suboptimal light conditions. Among others, fluorescent proteins produced by the coral host may play a role in the modulation of the quality and spectral distribution of irradiance within the coral tissue through wavelength transformation. Here we examined the bio-optical properties and photosynthetic performances of different fluorescence morphs of two mesophotic coral species Goniopora minor and Alveopora ocellata, in order to test the photosynthesis enhancement hypothesis proposed for coral fluorescence. The green morph of G. minor and the low fluorescence morph of A. ocellata exhibit, in their natural habitats, higher abundance. The morphs also presented different spectral reflectance and light attenuation within the tissue. Nevertheless, chlorophyll a fluorescence-based, and O2 evolution measurements, revealed only minor differences between the photosynthetic abilities of three fluorescence morphs of the coral G. minor and two fluorescence morphs of A. ocellata. The fluorescence morphs did not differ in their algal densities or chlorophyll concentrations and all corals harbored Symbiodiniaceae from the genus Cladocopium. Thus, despite the change in the internal light quantity and quality that corals and their symbionts experience, we found no evidence for the facilitation or enhancement of photosynthesis by wavelength transformation.

Biological networks are often heterogeneous in their connectivity pattern, with degree distributions featuring a heavy tail of highly connected hubs. The implications of this heterogeneity on dynamical properties are a topic of much interest. Here we show that interpreting topology as a feedback circuit can provide novel insights on dynamics. Based on the observation that in finite networks a small number of hubs have a disproportionate effect on the entire system, we construct an approximation by lumping these nodes into a single effective hub, which acts as a feedback loop with the rest of the nodes. We use this approximation to study dynamics of networks with scale-free degree distributions, focusing on their probability of convergence to fixed points. We find that the approximation preserves convergence statistics over a wide range of settings. Our mapping provides a parametrization of scale free topology which is predictive at the ensemble level and also retains properties of individual realizations. Specifically, outgoing hubs have an organizing role that can drive the network to convergence, in analogy to suppression of chaos by an external drive. In contrast, incoming hubs have no such property, resulting in a marked difference between the behavior of networks with outgoing vs. incoming scale free degree distribution. Combining feedback analysis with mean field theory predicts a transition between convergent and divergent dynamics which is corroborated by numerical simulations. Furthermore, they highlight the effect of a handful of outlying hubs, rather than of the connectivity distribution law as a whole, on network dynamics.

Phenotypic switches are associated with alterations in the cell's gene expression profile and are vital to many aspects of biology. Previous studies have identified local motifs of the genetic regulatory network that could underlie such switches. Recent advancements allowed the study of networks at the global, many-gene, level; however, the relationship between the local and global scales in giving rise to phenotypic switches remains elusive. In this work, we studied the epithelial-mesenchymal transition (EMT) using a gene regulatory network model. This model supports two clusters of stable steady-states identified with the epithelial and mesenchymal phenotypes, and a range of intermediate less stable hybrid states, whose importance in cancer has been recently highlighted. Using an array of network perturbations and quantifying the resulting landscape, we investigated how features of the network at different levels give rise to these landscape properties. We found that local connectivity patterns affect the landscape in a mostly incremental manner; in particular, a specific previously identified double-negative feedback motif is not required when embedded in the full network, because the landscape is maintained at a global level. Nevertheless, despite the distributed nature of the switch, it is possible to find combinations of a few local changes that disrupt it. At the level of network architecture, we identified a crucial role for peripheral genes that act as incoming signals to the network in creating clusters of states. Such incoming signals are a signature of modularity and are expected to appear also in other biological networks. Hybrid states between epithelial and mesenchymal arise in the model due to barriers in the interaction between genes, causing hysteresis at all connections. Our results suggest emergent switches can neither be pinpointed to local motifs, nor do they arise as typical properties of random network ensembles. Rather, they arise through an interplay between the nature of local interactions, and the core-periphery structure induced by the modularity of the cell.

Abstract Background In Metazoa, mitochondrial markers are the most commonly used targets for inferring species-level molecular phylogenies due to their extremely low rate of recombination, maternal inheritance, ease of use and fast substitution rate in comparison to nuclear DNA. The mitochondrial control region (CR) is the main non-coding area of the mitochondrial genome and contains the mitochondrial origin of replication and transcription. While sequences of the cytochrome oxidase subunit 1 (COI) and 16S rRNA genes are the prime mitochondrial markers in phylogenetic studies, the highly variable CR is typically ignored and not targeted in such analyses. However, the higher substitution rate of the CR can be harnessed to infer the phylogeny of closely related species, and the use of a non-coding region alleviates biases resulting from both directional and purifying selection. Additionally, complete mitochondrial genome assemblies utilizing next generation sequencing (NGS) data often show exceptionally low coverage at specific regions, including the CR. This can only be resolved by targeted sequencing of this region. Results Here we provide novel sequence data for the echinoid mitochondrial control region in over 40 species across the echinoid phylogenetic tree. We demonstrate the advantages of directly targeting the CR and adjacent tRNAs to facilitate complementing low coverage NGS data from complete mitochondrial genome assemblies. Finally, we test the performance of this region as a phylogenetic marker both in the lab and in phylogenetic analyses, and demonstrate its superior performance over the other available mitochondrial markers in echinoids. Conclusions Our target region of the mitochondrial CR (1) facilitates the first thorough investigation of this region across a wide range of echinoid taxa, (2) provides a tool for complementing missing data in NGS experiments, and (3) identifies the CR as a powerful, novel marker for phylogenetic inference in echinoids due to its high variability, lack of selection, and high compatibility across the entire class, outperforming conventional mitochondrial markers.

The genus Halodiplosis includes 99 species restricted to host-plants of the Amaranthaceae, virtually all of which are from Central Asia. The discovery of numerous undescribed species putatively belonging to this genus in Israel instigated an exhaustive review of the original descriptions of all known species in this genus. This study revealed that the generic concept of Halodiplosis and some of the genera synonymized under it should be redefined based on morphological and life-history attributes, such that Halodiplosis is limited to only 13 species developing in plant tissues without obvious gall formation or as inquilines in galls of other cecidomyiids. Revised status were proposed for Asiodiplosis, Onodiplosis, and Desertomyia, all species of which are gall inducers. A detailed morphological study of the Israeli species combined with data on their life history and an analysis of mitochondrial COI and 16S gene sequences revealed nine gall-inducing species belonging to Asiodiplosis and one inquilinous species belonging to Halodiplosis. All ten species (Asiodiplosis admirabilis n.sp., A. bimoda n.sp., A. delicatula n.sp., A. largifica n.sp., A. mohicana n.sp., A. mucronata n.sp., A. paradoxa n.sp., A. pillosaeconspicua n.sp., A. stellata n.sp., and Halodiplosis fugax n.sp.) are described here as new to science, including the first descriptions of larvae and pupae for these genera.