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Over the past decades, there has been significant controversy regarding the role of exogenous electromagnetic (EM) fields on the dynamics of molecules in living cells. Here we present a model of electromagnetic forces in the synaptic cleft using the bidomain theory as a framework and the averaged field theory as the theoretical basis, suggesting that the exogenously induced magnetic field may modify the neurotransmitter dynamics. Our model is based on a voltage cell membrane amplification due to the Hall effect principle and the hypothesis that synaptic cleft electric conductivity is represented by tensors with non-zero off-diagonal terms. The physical interpretation of the off-diagonal components is explained, and analytical expressions for the induced magnetic field and conductivity tensor are derived.

To generate gametes, sexually reproducing organisms need to achieve a reduction in ploidy, via meiosis. Several mechanisms are set in place to ensure proper reductional chromosome segregation at the first meiotic division (MI), including chromosome remodeling during late prophase I. Chromosome remodeling after crossover formation involves changes in chromosome condensation and restructuring, resulting in a compact bivalent, with sister kinetochores oriented to opposite poles, whose structure is crucial for localized loss of cohesion and accurate chromosome segregation. Here, we review the general processes involved in late prophase I chromosome remodeling, their regulation, and the strategies devised by different organisms to produce bivalents with configurations that promote accurate segregation.

Since March of 2020, billions of people worldwide have been asked to limit their social contacts in an effort to contain the spread of the SARS-CoV-2 virus. However, little research has been carried out to date on the impact of such social distancing measures on the social isolation levels of the population. In this paper, we study the impact of the pandemic on the social isolation of the Spanish population, by means of 32,359 answers to a citizen survey collected over a period of 7 months. We uncover (1) a significant increase in the prevalence of social isolation in the population, reaching almost 26%; (2) gender and age differences, with the largest prevalence of isolation among middle-aged individuals; (3) a strong relationship between economic impact and social isolation; and (4) differences in social isolation, depending on the number of COVID-19 protection measures and on the perception of coronavirus infection risk by our participants. Our research sheds quantitative light on the sociological impact of the pandemic, and enables us to identify key factors in the interplay between the deployment of non-pharmaceutical interventions to contain the spread of an infectious disease and a population’s levels of social isolation.

Population confinements have been one of the most widely adopted non-pharmaceutical interventions (NPIs) implemented by governments across the globe to help contain the spread of the SARS-CoV-2 virus. While confinement measures have been proven to be effective to reduce the number of infections, they entail significant economic and social costs. Thus, different policy makers and social groups have exhibited varying levels of acceptance of this type of measures. In this context, understanding the factors that determine the willingness of individuals to be confined during a pandemic is of paramount importance, particularly, to policy and decision-makers. In this paper, we study the factors that influence the unwillingness to be confined during the COVID-19 pandemic by the means of a large-scale, online population survey deployed in Spain. We perform two types of analyses (logistic regression and automatic pattern discovery) and consider socio-demographic, economic and psychological factors, together with the 14-day cumulative incidence per 100,000 inhabitants. Our analysis of 109,515 answers to the survey covers data spanning over a 5-month time period to shed light on the impact of the passage of time. We find evidence of pandemic fatigue as the percentage of those who report an unwillingness to be in confinement increases over time; we identify significant gender differences, with women being generally less likely than men to be able to sustain long-term confinement of at least 6 months; we uncover that the psychological impact was the most important factor to determine the willingness to be in confinement at the beginning of the pandemic, to be replaced by the economic impact as the most important variable towards the end of our period of study. Our results highlight the need to design gender and age specific public policies, to implement psychological and economic support programs and to address the evident pandemic fatigue as the success of potential future confinements will depend on the population’s willingness to comply with them.

DNA double-strand breaks (DSBs) are deleterious lesions, which must be repaired precisely to maintain genomic stability. During meiosis, programmed DSBs are repaired via homologous recombination (HR) while repair using the nonhomologous end joining (NHEJ) pathway is inhibited, thereby ensuring crossover formation and accurate chromosome segregation.

Spatio-temporal models for count data are required in a wide range of scientific fields and they have become particularly crucial nowadays because of their ability to analyse COVID-19-related data. Models for count data are needed when the variable of interest take only non-negative integer values and these integers arise from counting occurrences. Several R-packages are currently available to deal with spatiotemporal areal count data. Each package focuses on different models and/or statistical methodologies. Unfortunately, the results generated by these models are rarely comparable due to differences in notation and methods. The main objective of this paper is to present a review describing the most important approaches that can be used to model and analyse count data when questions of scientific interest concern both their spatial and their temporal behaviour and we monitor their performance under the same data set. For this review, we focus on the three R-packages that can be used for this purpose and the different models assessed are representative of the two most widespread methodologies used to analyse spatiotemporal count data: the classical approach (based on Penalised Likelihood or Estimating Equations) and the Bayesian point of view. A case study is analysed as an illustration of these different methodologies. In this case study, these packages are used to model and predict daily hospitalisations from COVID-19 in 24 health regions within the Valencian Community (Spain), with data corresponding to the period from 28 June to 13 December 2020. Because of the current urgent need for monitoring and predicting data in the COVID-19 pandemic, this case study is, in itself, of particular importance and can be considered the secondary objective of this work. Satisfactory and promising results have been obtained in this second goal.

Population confinements have been one of the most widely adopted non-pharmaceutical interventions (NPIs) implemented by governments across the globe to help contain the spread of the SARS-CoV-2 virus. While confinement measures have been proven to be effective to reduce the number of infections, they entail significant economic and social costs. Thus, different policy makers and social groups have exhibited varying levels of acceptance of this type of measures. In this context, understanding the factors that determine the willingness of individuals to be confined during a pandemic is of paramount importance, particularly, to policy and decision-makers. In this paper, we study the factors that influence the unwillingness to be confined during the COVID-19 pandemic by means of a large-scale, online population survey deployed in Spain. We apply both quantitative (logistic regression) and qualitative (automatic pattern discovery) methods and consider socio-demographic, economic and psychological factors, together with the 14-day cumulative incidence per 100,000 inhabitants. Our analysis of 109,515 answers to the survey covers data spanning over a 5-month time period to shed light on the impact of the passage of time. We find evidence of pandemic fatigue as the percentage of those who report an unwillingness to be in confinement increases over time; we identify significant gender differences, with women being generally less likely than men to be able to sustain long-term confinement of at least 6 months; we uncover that the psychological impact was the most important factor to determine the willingness to be in confinement at the beginning of the pandemic, to be replaced by the economic impact as the most important variable towards the end of our period of study. Our results highlight the need to design gender and age specific public policies, to implement psychological and economic support programs and to address the evident pandemic fatigue as the success of potential future confinements will depend on the population’s willingness to comply with them.

The position of recombination events established along chromosomes in early prophase I and the chromosome remodeling that takes place in late prophase I are intrinsically linked steps of meiosis that need to be tightly regulated to ensure accurate chromosome segregation and haploid gamete formation. Here, we show that RAD-51 foci, which form at the sites of programmed meiotic DNA double-strand breaks (DSBs), exhibit a biased distribution toward off-centered positions along the chromosomes in wild-type Caenorhabditis elegans, and we identify two meiotic roles for chromatin-associated protein HIM-17 that ensure normal chromosome remodeling in late prophase I. During early prophase I, HIM-17 regulates the distribution of DSB-dependent RAD-51 foci and crossovers on chromosomes, which is critical for the formation of distinct chromosome subdomains (short and long arms of the bivalents) later during chromosome remodeling. During late prophase I, HIM-17 promotes the normal expression and localization of protein phosphatases GSP-1/2 to the surface of the bivalent chromosomes and may promote GSP-1 phosphorylation, thereby antagonizing Aurora B kinase AIR-2 loading on the long arms and preventing premature loss of sister chromatid cohesion. We propose that HIM-17 plays distinct roles at different stages during meiotic progression that converge to promote normal chromosome remodeling and accurate chromosome segregation.

Meiosis is the specialized cell division that generates haploid gametes and is therefore essential for sexual reproduction. This SnapShot encompasses key events taking place during prophase I of meiosis that are required for achieving proper chromosome segregation and highlights how these are both conserved and diverged throughout five different species. To view this SnapShot, open or download the PDF.

Rubylation is a conserved regulatory pathway similar to ubiquitination and essential in the response to the plant hormone auxin. In Arabidopsis thaliana, AUXIN RESISTANT1 (AXR1) functions as the E1-ligase in the rubylation pathway. The gene AXR1-LIKE (AXL), generated by a relatively recent duplication event, can partially replace AXR1 in this pathway. We have analysed mutants deficient for both proteins and complementation lines (with the AXR1 promoter and either AXR1 or AXL coding sequences) to further study the extent of functional redundancy between both genes regarding two processes: meiosis and DNA repair. Here we report that whereas AXR1 is essential to ensure the obligatory chiasma, AXL seems to be dispensable during meiosis, although its absence slightly alters chiasma distribution. In addition, expression of key DNA repair and meiotic genes is altered when either AXR1 or AXL are absent. Furthermore, our results support a significant role for both genes in DNA repair that was not previously described. These findings highlight that AXR1 and AXL show a functional divergence in relation to their involvement in homologous recombination, exemplifying a duplicate retention model in which one copy tends to have more sub-functions than its paralog.

Exposure to diethylhexyl phthalate (DEHP), the most abundant plasticizer used in the production of polyvinyl-containing plastics, has been associated to adverse reproductive health outcomes in both males and females. While the effects of DEHP on reproductive health have been widely investigated, the molecular mechanisms by which exposure to environmentally-relevant levels of DEHP and its metabolites impact the female germline in the context of a multicellular organism have remained elusive. Using the Caenorhabditis elegans germline as a model for studying reprotoxicity, we show that exposure to environmentally-relevant levels of DEHP and its metabolites results in increased meiotic double-strand breaks (DSBs), altered DSB repair progression, activation of p53/CEP-1-dependent germ cell apoptosis, defects in chromosome remodeling at late prophase I, aberrant chromosome morphology in diakinesis oocytes, increased chromosome non-disjunction and defects during early embryogenesis. Exposure to DEHP results in a subset of nuclei held in a DSB permissive state in mid to late pachytene that exhibit defects in crossover (CO) designation/formation. In addition, these nuclei show reduced Polo-like kinase-1/2 (PLK-1/2)-dependent phosphorylation of SYP-4, a synaptonemal complex (SC) protein. Moreover, DEHP exposure leads to germline-specific change in the expression of prmt-5, which encodes for an arginine methyltransferase, and both increased SC length and altered CO designation levels on the X chromosome. Taken together, our data suggest a model by which impairment of a PLK-1/2-dependent negative feedback loop set in place to shut down meiotic DSBs, together with alterations in chromosome structure, contribute to the formation of an excess number of DSBs and altered CO designation levels, leading to genomic instability., Author summary Faithful chromosome segregation during meiosis, the specialized cell division program that produces haploid gametes (i.e. eggs and sperm) from a diploid organism, is key for successful sexual reproduction. Diethylhexyl phthalate (DEHP), a commonly used plasticizer found in personal care and household products, has emerged as an endocrine disruptor that exerts reprotoxicity in mammals. In this study, we provide mechanistic insight into the modes of action by which environmentally-relevant levels of DEHP and its metabolites impair female meiosis in the C. elegans germline. Exposure to DEHP leads to defects in late prophase I chromosome remodeling, altered chromosome morphology in oocytes at diakinesis, errors in chromosome segregation, and impaired embryogenesis. Underlying these defects are higher levels of DSBs, altered DSB repair, defects in crossover (CO) designation/formation, germline-specific change in prmt-5 gene expression and altered chromosome structure. We propose that DEHP exposure induces an excess number of DSBs by interfering with mechanisms set in place to turn off DSBs once CO designation is accomplished and by altering chromosome structure resulting in increased chromatin accessibility to the DSB machinery.

In vision science, cascades of Linear+Nonlinear transforms are very successful in modeling a number of perceptual experiences. However, the conventional literature is usually too focused on only describing the forward input-output transform. Instead, in this work we present the mathematics of such cascades beyond the forward transform, namely the Jacobian matrices and the inverse. The fundamental reason for this analytical treatment is that it offers useful analytical insight into the psychophysics, the physiology, and the function of the visual system. For instance, we show how the trends of the sensitivity (volume of the discrimination regions) and the adaptation of the receptive fields can be identified in the expression of the Jacobian w.r.t. the stimulus. This matrix also tells us which regions of the stimulus space are encoded more efficiently in multi-information terms. The Jacobian w.r.t. the parameters shows which aspects of the model have bigger impact in the response, and hence their relative relevance. The analytic inverse implies conditions for the response and model parameters to ensure appropriate decoding. From the experimental and applied perspective, (a) the Jacobian w.r.t. the stimulus is necessary in new experimental methods based on the synthesis of visual stimuli with interesting geometrical properties, (b) the Jacobian matrices w.r.t. the parameters are convenient to learn the model from classical experiments or alternative goal optimization, and (c) the inverse is a promising model-based alternative to blind machine-learning methods for neural decoding that do not include meaningful biological information. The theory is checked by building and testing a vision model that actually follows a modular Linear+Nonlinear program. Our illustrative derivable and invertible model consists of a cascade of modules that account for brightness, contrast, energy masking, and wavelet masking. To stress the generality of this modular setting we show examples where some of the canonical Divisive Normalization modules are substituted by equivalent modules such as the Wilson-Cowan interaction model (at the V1 cortex) or a tone-mapping model (at the retina)., This work was partially funded by the Spanish Ministerio de Economia y Competitividad projects CICYT TEC2013-50520-EXP and CICYT BFU2014-59776-R, by the European Research Council, Starting Grant ref. 306337, by the Spanish government and FEDER Fund, grant ref. TIN2015-71537-P(MINECO/FEDER,UE), 1021, and by the ICREA Academia Award.

Neurons at primary visual cortex (V1) in humans and other species are edge filters organized in orientation maps. In these maps, neurons with similar orientation preference are clustered together in iso-orientation domains. These maps have two fundamental properties: (1) retinotopy, i.e. correspondence between displacements at the image space and displacements at the cortical surface, and (2) a trade-off between good coverage of the visual field with all orientations and continuity of iso-orientation domains in the cortical space. There is an active debate on the origin of these locally continuous maps. While most of the existing descriptions take purely geometric/mechanistic approaches which disregard the network function, a clear exception to this trend in the literature is the original approach of Hyvärinen and Hoyer based on infomax and Topographic Independent Component Analysis (TICA). Although TICA successfully addresses a number of other properties of V1 simple and complex cells, in this work we question the validity of the orientation maps obtained from TICA. We argue that the maps predicted by TICA can be analyzed in the retinal space, and when doing so, it is apparent that they lack the required continuity and retinotopy. Here we show that in the orientation maps reported in the TICA literature it is easy to find examples of violation of the continuity between similarly tuned mechanisms in the retinal space, which suggest a random scrambling incompatible with the maps in primates. The new experiments in the retinal space presented here confirm this guess: TICA basis vectors actually follow a random salt-and-pepper organization back in the image space. Therefore, the interesting clusters found in the TICA topology cannot be interpreted as the actual cortical orientation maps found in cats, primates or humans. In conclusion, Topographic ICA does not reproduce cortical orientation maps.

Specifically, during the passive stimulation task there is an abrupt decrease in the number of causal correlations after the first stimulation, which is shown to be independent of the spike-train variability of each area. Conclusions Neuronal causal correlation paths that are specific to the discriminations task are ubiquitous, bidirectional and remain approximately constant along the task in both sensory and motor areas. These findings are robust to the stimulation pair under study and the spike-train variability of each area.

Neural correlations during a cognitive task are central to study brain information processing and computation. However, they have been poorly analyzed due to the difficulty of recording simultaneous single neurons during task performance. In the present work, we quantified neural directional correlations using spike trains that were simultaneously recorded in sensory, premotor, and motor cortical areas of two monkeys during a somatosensory discrimination task. Upon modeling spike trains as binary time series, we used a nonparametric Bayesian method to estimate pairwise directional correlations between many pairs of neurons throughout different stages of the task, namely, perception, working memory, decision making, and motor report. We find that solving the task involves feedforward and feedback correlation paths linking sensory and motor areas during certain task intervals. Specifically, information is communicated by task-driven neural correlations that are significantly delayed across secondary somatosensory cortex, premotor, and motor areas when decision making takes place. Crucially, when sensory comparison is no longer requested for task performance, a major proportion of directional correlations consistently vanish across all cortical areas., Comment: Article and Supplementary Information

Processing of temporal information is key in auditory processing. In this study, we recorded single-unit activity from rat auditory cortex while they performed an interval-discrimination task. The animals had to decide whether two auditory stimuli were separated by either 150 or 300 ms and nose-poke to the left or to the right accordingly. The spike firing of single neurons in the auditory cortex was then compared in engaged vs. idle brain states. We found that spike firing variability measured with the Fano factor was markedly reduced, not only during stimulation, but also in between stimuli in engaged trials. We next explored if this decrease in variability was associated with an increased information encoding. Our information theory analysis revealed increased information content in auditory responses during engagement compared with idle states, in particular in the responses to task-relevant stimuli. Altogether, we demonstrate that task-engagement significantly modulates coding properties of auditory cortical neurons during an interval-discrimination task.

During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations. We mapped rQTL1 to semidominant polymorphisms in HEI10, which encodes a conserved ubiquitin E3 ligase that regulates crossovers. Null hei10 mutants are haploinsufficient, and, using genome-wide mapping and immunocytology, we show that transformation of additional HEI10 copies is sufficient to more than double euchromatic crossovers. However, heterochromatic centromeres remained recombination-suppressed. The strongest HEI10-mediated crossover increases occur in subtelomeric euchromatin, which is reminiscent of sex differences in Arabidopsis recombination. Our work reveals that HEI10 naturally limits Arabidopsis crossovers and has the potential to influence the response to selection.

Estimating the difficulty of a decision is a fundamental process to elaborate complex and adaptive behaviour. In this paper, we show that the movement time of behaving monkeys performing a decision-making task is correlated with decision difficulty and that the activity of a population of neurons in ventral Premotor cortex correlates with the movement time. Moreover, we found another population of neurons that encodes the discriminability of the stimulus, thereby supplying another source of information about the difficulty of the decision. The activity of neurons encoding the difficulty can be produced by very different computations. Therefore, we show that decision difficulty can be encoded through three different mechanisms: 1. Switch time coding, 2. rate coding and 3. binary coding. This rich representation reflects the basis of different functional aspects of difficulty in the making of a decision and the possible role of difficulty estimation in complex decision scenarios., Author Summary Understanding how the brain produces complex cognitive functions has been a crucial question since ancient philosophical inquiries. The encoding of decision difficulty in the brain is fundamental for complex and adaptive behaviour, and can provide valuable information in uncertain environments where the future outcome of a choice must be evaluated beforehand. Here we show that neurons in premotor cortex represent the difficulty of a decision using at least three different variables: 1) the time of the neuronal response, 2) the intensity of the neuronal response, 3) the probability of switching from a low activity to a high activity profile. Moreover, we show that, by encoding the time elapsed from the end of the stimulus and commitment to a choice, another set of premotor neurons is able to provide information about the difficulty of the decision. These results show that the brain is implementing heterogeneous neural mechanisms to fulfill a complex cognitive function.

The perceptual decision making process may involve a comparison between several stimuli occurring either simultaneously or successively. Depending on environmental demands, the response is given immediately or is delayed. A well-known paradigm for research in decision making is the comparison of two vibrotactile stimuli (f1, f2) applied to the fingertips with a fixed delay period between them. To complete this cognitive task the subject needs to store the information about the first stimulus, f1, in working memory and to compare it with the second one, f2, to make a decision of whether f1 f2. Further he needs to store in working memory its appropriate response. Along those lines, Lemus et al. (2) introduced an additional delay between the second stimulus and the subject's response. This new operation requires that the subject stores the somatosensory information, the decision and/or the response in working memory during this second delay period. We analysed neurons recorded from the Medial Premotor Cortex in monkeys during the above task. We found some neurons encoded the response just in two periods: after the second stimulus (f2) and when the answer is required, 3 s later. Moreover, those neurons only show relevant activity in these periods. In the present work we investigated the mechanisms that allow the neurons to encode the response information. For this purpose we use Mutual Information (MI) analysis in order to decode the information carried by the firing rates. We measured the MI between the following two variables: the firing rates and the behavioral response (f1 f2) made at the end of the trial. We found that for 157 neurons (18.1% of 867), the MI becomes significant during the second stimulus (f2), it disappears during the post-f2 period, and becomes significant again at the time of the response. Our hypothesis is that this particular pattern is due to a combination of signal-to-noise ratio in the rates, which makes it impossible to decode the information contained in the rates in the postponed response delay period after f2. We hypothesize that the neurons can use synaptic facilitation to allows them to hold the information during the delayed response memory period. Here, we present a biophysically realistic model for decision making with synaptic facilitation (3) extended to account for the activity in the delayed response period. We use integrate-and-fire neurons with three types of receptors mediating the synaptic currents: the excitatory recurrent postsynaptic currents are mediated by AMPA (fast) and NMDA (slow) receptors and the inhibitory recurrent postsynaptic currents to both excitatory and inhibitory neurons are mediated by GABA receptors. The external excitatory recurrent postsynaptic currents injected onto the network are driven only by AMPA receptors. The results show that the network is able to model this neuronal activity using a synaptic facilitation mechanism. After a decision making period the network is able to remember the response despite a low firing level in the delayed response period and to retrieve the memory evident in a high firing rate when a non-specific stimulus is provided just before the response is required. Thus a synaptic facilitation mechanism can implement a mechanism for postponed decisions which can be correct even when there is little neuronal firing during the delay period before the postponed decision.