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Spatiotemporal patterns of Rift Valley fever virus in Africa: a retrospective genomic epidemiology and phylodynamic modelling study.

BACKGROUND: Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen causing outbreaks in humans and ruminants across Africa and the Arabian Peninsula. Originally restricted to the Great Rift Valley, RVFV has expanded geographically, prompting its classification by WHO as a pathogen of pandemic potential. We investigated the evolutionary and spatial dynamics of RVFV across Africa. METHODS: We used genomic data generated at the International Livestock Research Institute Nairobi genomic laboratory (BioProject PRJNA1106221) and combined with publicly available datasets retrieved from the National Center for Biotechnology (NCBI) GenBank nucleotide database. In retrieving RVFV genome sequences from the NCBI GenBank, we applied the search terms "Rift Valley fever virus segment L AND 6404[SLEN]", "Rift Valley fever virus segment M AND 3885[SLEN]", and "Rift Valley fever virus segment S AND 1520:1690[SLEN]" for L (Large), M (Medium), and S (Small) segments, respectively. For sequences without additional spatiotemporal information, we searched PubMed to extract the associated sequence metadata. We performed molecular clock analysis, phylogenetic inference, phylodynamic modelling (continuous phylogeographic reconstruction), and landscape phylogeography on the three RVFV genome segments (L, M, and S). We aimed to assess evolutionary rates, dispersal patterns, and environmental drivers. Focus was placed on lineage C, the most widely distributed variant. FINDINGS: The global dataset used in this study consisted of large (n=236), medium (n=237), and small (n=247), which were further filtered to exclude potential reassortants and vaccine strains. Genome sequences retrieved from NCBI GenBank database comprised large (n=180), medium (n=184), and small (n=202). The genome sequences from retrospective human and livestock isolates comprised large (n=56), medium (n=53), and small (n=45) collected in Burundi (2018), Kenya (2007, 2018, 2019, 2021, and 2022), and Rwanda (2018 and 2022). Our dataset revealed that RVFV exhibited low overall genetic diversity. Lineage C, however, showed evidence of active evolution, with substitution rates ranging from 3·58 × 10-4 to 9·76 × 10-4 substitutions per site per year. This lineage probably originated in Zimbabwe in the mid-1970s and has since expanded across eastern and southern Africa. Phylogeographic reconstructions revealed rapid spread, with diffusion coefficients exceeding 50 000 km2 per year. INTERPRETATION: Lineage C appears capable of establishing endemic transmission in new regions, with ongoing diversification observed during interepidemic periods. These observations reinforce the value of continuous genomic surveillance, particularly during cryptic transmission phases when adaptive mutations might emerge. Although further evidence is needed, observed trends in climate variability and land-use change point to the potential benefit of targeted surveillance in settings that could be at increased risk, including urban centres and wetlands. FUNDING: This work was supported by the German Federal Ministry for Economic Cooperation and Development, the Rockefeller Foundation, and the Africa Centres for Disease Control and Prevention.

Rift Valley fever virus↗

The selective impairment of the perception of first-order motion by unilateral cortical brain damage.

First-order (Fourier) motion consists of stable spatiotemporal luminance variations. Second-order (non-Fourier) motion consists instead of spatiotemporal modulation of contrast, flicker, or spatial frequency. In spite of extensive psychophysical and computational analysis of the nature and relationship of these two types of motion, it remains unclear whether they are detected by the same mechanism or whether separate mechanisms are involved. Here we report the selective impairment of first-order motion, on a range of local and global motion tasks, in the contralateral visual hemifield of a patient with unilateral brain damage centered on putative visual areas V2 and V3 in the medial part of the occipital lobe. His perception of second-order motion was unimpaired. As his disorder is the obverse of that reported after damage in the vicinity of human visual area MT (V5), the results support models of motion processing in which first- and second-order motion are, at least in part, computed separately at the extrastriate cortical level.

Aged↗

Spatiotemporal dynamics of networks of excitable nodes.

A network of excitable nodes based on the photosensitive Belousov-Zhabotinsky reaction is studied in experiments and simulations. The addressable medium allows both local and nonlocal links between the nodes. The initial spread of excitation across the network as well as the asymptotic oscillatory behavior are described. Synchronization of the spatiotemporal dynamics occurs by entrainment to high-frequency network pacemakers formed by excitation loops. Analysis of the asymptotic behavior reveals that the dynamics of the network is governed by a subnetwork selected during the initial transient period.

Action Potentials↗

Executive and social behaviors under nicotinic receptor regulation.

Nicotine enhances several cognitive and psychomotor behaviors, and nicotinic antagonists cause impairments in tasks requiring cognitive effort. To explore the contribution of nicotinic receptors to complex cognitive functions, we developed an automated method to investigate sequential locomotor behavior in the mouse and an analysis of social behavior. We show that, in the beta2-/- mutant, the high-order spatiotemporal organization of locomotor behavior, together with conflict resolution and social interaction, is selectively dissociated from low-level, more automatic motor behaviors. Such deficits in executive functions resemble the rigid and asocial behavior found in some psychopathological disorders such as autism and attention deficit hyperactivity disorder.

Animals↗

Turbo-charging crop improvement: harnessing multiplex editing for polygenic trait engineering and beyond.

Multiplex CRISPR editing has emerged as a transformative platform for plant genome engineering, enabling the simultaneous targeting of multiple genes, regulatory elements, or chromosomal regions. This approach is effective for dissecting gene family functions, addressing genetic redundancy, engineering polygenic traits, and accelerating trait stacking and de novo domestication. Its applications now extend beyond standard gene knockouts to include epigenetic and transcriptional regulation, chromosomal engineering, and transgene-free editing. These capabilities are advancing crop improvement not only in annual species but also in more complex systems such as polyploids, undomesticated wild relatives, and species with long generation times. At the same time, multiplex editing presents technical challenges, including complex construct design and the need for robust, scalable mutation detection. We discuss current toolkits and recent innovations in vector architecture, such as promoter and scaffold engineering, that streamline workflows and enhance editing efficiency. High-throughput sequencing technologies, including long-read platforms, are improving the resolution of complex editing outcomes such as structural rearrangements-often missed by standard genotyping-when targeting repetitive or tandemly spaced loci. To fully realize the potential of multiplex genome engineering, there is growing demand for user-friendly, synthetic biology-compatible, and scalable computational workflows for gRNA design, construct assembly, and mutation analysis. Experimentally validated inducible or tissue-specific promoters are also highly desirable for achieving spatiotemporal control. As these tools continue to evolve, multiplex CRISPR editing is poised to become a foundational technology of next-generation crop improvement to address challenges in agriculture, sustainability, and climate resilience.

Gene Editing↗

Segment polarity and DV patterning gene expression reveals segmental organization of the Drosophila brain.

The insect brain is traditionally subdivided into the trito-, deuto- and protocerebrum. However, both the neuromeric status and the course of the borders between these regions are unclear. The Drosophila embryonic brain develops from the procephalic neurogenic region of the ectoderm, which gives rise to a bilaterally symmetrical array of about 100 neuronal precursor cells, called neuroblasts. Based on a detailed description of the spatiotemporal development of the entire population of embryonic brain neuroblasts, we carried out a comprehensive analysis of the expression of segment polarity genes (engrailed, wingless, hedgehog, gooseberry distal, mirror) and DV patterning genes (muscle segment homeobox, intermediate neuroblast defective, ventral nervous system defective) in the procephalic neuroectoderm and the neuroblast layer (until stage 11, when all neuroblasts are formed). The data provide new insight into the segmental organization of the procephalic neuroectodem and evolving brain. The expression patterns allow the drawing of clear demarcations between trito-, deuto- and protocerebrum at the level of identified neuroblasts. Furthermore, we provide evidence indicating that the protocerebrum (most anterior part of the brain) is composed of two neuromeres that belong to the ocular and labral segment, respectively. These protocerebral neuromeres are much more derived compared with the trito- and deutocerebrum. The labral neuromere is confined to the posterior segmental compartment. Finally, similarities in the expression of DV patterning genes between the Drosophila and vertebrate brains are discussed.

Animals↗

Live cell imaging to study signaling molecules in allergic reactions.

Mast cells are widely distributed throughout the body, predominantly near blood vessels and nerves, and express effector functions in allergic reactions, inflammatory diseases, and host defense. The activation of mast cells results in secretion of the preformed chemical mediators in their granules by a regulated process of exocytosis and leads to synthesis and secretion of lipid mediators and cytokines. Their soluble factors contribute to allergic inflammation. Mast cells are associated with hypersensitivity reactions, not only in the classical immunoglobulin E (IgE)-dependent mechanism but also in an IgE-independent manner. In particular, investigations of potential anatomical and functional interactions between mast cells and the nervous system have recently attracted great interest. To understand these molecular mechanisms in mast cell activation, the ability to visualize, track, and quantify molecules and events in living mast cells is an essential and powerful tool. Recent dramatic advances in imaging technology and labeling techniques have enabled us to carry out these tasks with high spatiotemporal resolution using confocal laser scanning microscopes, green fluorescent protein and its derivatives, and image analysis systems. Here we review our investigations of the dynamic processes of intracellular signaling molecules, cellular structure, and interactions with neurons in mast cells to provide basic and valuable information for allergy and clinical immunology using these new imaging methods.

Animals↗

Separate spatial scales determine neural activity-dependent changes in tissue oxygen within central visual pathways.

The relationship between oxygen levels and neural activity in the brain is fundamental to functional neuroimaging techniques. We have examined this relationship on a fine spatial scale in the lateral geniculate nucleus (LGN) and visual cortex of the cat using a microelectrode sensor that provides simultaneous colocalized measurements of oxygen partial pressure in tissue (tissue oxygen) and multiunit neural activity. In previous work with this sensor, we found that changes in tissue oxygen depend strongly on the location and spatial extent of neural activation. Specifically, focal neural activity near the microelectrode elicited decreases in tissue oxygen, whereas spatially extended activation, outside the field of view of our sensor, yielded mainly increases. In the current study, we report an expanded set of measurements to quantify the spatiotemporal relationship between neural responses and changes in tissue oxygen. For the purpose of data analysis, we develop a quantitative model that assumes that changes in tissue oxygen are composed of two response components (one positive and one negative) with magnitudes determined by neural activity on separate spatial scales. Our measurements from visual cortex and the LGN are consistent with this model and suggest that the positive response spreads over a distance of 1-2 mm, whereas the negative component is confined to a few hundred micrometers. These results are directly relevant to the mechanisms that generate functional brain imaging signals and place limits on their spatial properties.

Animals↗

Spatial deficits in ideomotor limb apraxia. A kinematic analysis of aiming movements.

Ideomotor limb apraxia is a classic neurological disorder manifesting as a breakdown in co-ordinated limb control with spatiotemporal deficits. We employed kinematic analyses of simple aiming movements in left hemisphere-damaged patients with and without limb apraxia and a normal control group to examine preprogramming and response implementation deficits in apraxia. Damage to the frontal and parietal lobes was more common in apraxics, but neither frontal nor parietal damage was associated with different arm movement deficits. Limb apraxia was associated with intact preprogramming but impaired response implementation. The response implementation deficits were characterized by spatial but not temporal deficits, consistent with decoupling of spatial and temporal features of movement in limb apraxia. While the apraxics' accuracy was normal when visual feedback was available, it was impaired when visual feedback of either target location or hand position was unavailable. This finding suggests that ideomotor limb apraxia is associated with disruption of the neural representations for the extrapersonal (spatial location) and intrapersonal (hand position) features of movement. The non-apraxic group's normal kinematic performance demonstrates that the deficits demonstrated in the apraxic group are not simply a reflection of left hemisphere damage per se.

Analysis of Variance↗

Analysis of a "phase transition" from tumor growth to latency.

A mathematical model, based on the local interaction simulation approach, is developed in order to allow simulations of the spatiotemporal evolution of neoplasies. The model consists of a set of rules, which govern the interaction of cancerous cells among themselves and in competition with other cell populations for the acquisition of essential nutrients. As a result of small variations in the basic parameters, it leads to four different outcomes: indefinite growth, metastasis, latency, and complete regression. In the present contribution a detailed analysis of the dormant phase is carried on and the critical parameters for the transition to other phases are computed. Interesting chaotic behaviors can also be observed, with different attractors in the parameters space. Interest in the latency phase has been aroused by therapeutical strategies aiming to reduce a growing tumor to dormancy. The effect of such strategies may be simulated with our approach.

Cell Division↗

Spatiotemporal anisotropic diffusion filtering to improve signal-to-noise ratios and object restoration in fluorescence microscopic image sequences.

We present an approach for significantly improving the quantitative analysis of motion in noisy fluorescence microscopic image sequences. The new partial differential equation based method is a general extension of a 2-D nonlinear anisotropic diffusion filtering scheme to a specially adapted 3-D nonlinear anisotropic diffusion filtering scheme, with two spatial image dimensions and the time t in the image sequence as the third dimension. Motion in image sequences is considered as oriented, line-like structures in the spatiotemporal x,y,t domain, which are determined by the structure tensor method. Image enhancement is achieved by a structure adopted smoothing kernel in three dimensions, thereby using the full 3-D information inherent in spatiotemporal image sequences. As an example for low signal-to-noise ratio (SNR) microscopic image sequences we have applied this method to noisy in vitro motility assay data, where fluorescently labeled actin filaments move over a surface of immobilized myosin. With the 3-D anisotropic diffusion filtering the SNR is significantly improved (by a factor of 3.8) and closed object structures are reliably restored, which were originally degraded by noise. Generally, this approach is very valuable for all applications where motion has to be measured quantitatively in low light level fluorescence microscopic image sequences of cellular, subcellular, and molecular processes.

Actins↗

delta-Protocadherins: unique structures and functions.

delta-Protocadherins constitute a group of cadherins characterized by several conserved motifs in their cytoplasmic domains. We present a phylogenetic analysis that further divides this group into delta1-protocadherins (comprising protocadherin-1, -7, -9 and -11 or -X/Y) and delta2-protocadherins (comprising protocadherin-8, -10, -17, -18 and -19). The delta-protocadherin genes, which are located on different chromosomes in man and mouse, have a similar gene structure. They are expressed as multiple splice forms, differing mostly in their cytoplasmic domains. Some delta-protocadherins were reported to mediate weak cell-cell adhesion in vitro and cell sorting in vivo. In addition, individual delta-protocadherins might play important roles in signaling pathways, as they bind to proteins such as TAF1/Set, protein phosphatase-1alpha and the Frizzled 7 receptor. The spatiotemporally restricted expression of delta-protocadherins in different tissues and species and the results of their functional analysis, mainly in Xenopus, suggest that they play multiple, tightly regulated roles in vertebrate development.

Alternative Splicing↗

Direct and spillover hospitalisation patterns during climate hazards across regions of different health-system resilience levels in China: a nationwide retrospective analysis.

BACKGROUND: Health-system resilience serves as a key contributor in mitigating adverse health impacts during climate hazards. However, quantitative insights into resilience-associated health-care utilisation patterns and targeted adaptation policies remain scarce. We aimed to capture the spatiotemporal health impacts in disaster-exposed counties and their neighbouring counties in China during storms, floods, tropical cyclones, and blizzards or winter storms; understand the association between health-system resilience metrics and hazard-attributable hospitalisations; and develop evidence-based adaptation policies towards climate extremes. METHODS: In this retrospective, observational analysis of county-level aggregated hospitalisation data, we used a propensity score matching-difference-in-differences framework to assess the spatiotemporal changes of nine types of disease-specific hospitalisations in both disaster-exposed and neighbouring regions during storms, floods, tropical cyclones, and blizzards in China. We quantified the relative importance and health gains of health-system metrics during such hazards through random forest approach with interpretable partial dependence plots to derive evidence-based adaptation recommendations. FINDINGS: We included hospitalisation data from Jan 1, 2016 to Dec 31, 2023. In this period, 3241 county-hazard event combinations and 41 747 482 hospitalisations were recorded across 955 Chinese counties. The disaster-exposed regions experienced an initial decline in hospitalisation rates, followed by admission surges after disasters. For example, infectious disease admissions decreased by 11·92% (95% CI -10·53 to -13·31) during the flood-active period but increased by 7·68% (6·46-8·91) after 1-2 weeks of floods. Neighbouring zones were also affected through spillover effects, with infectious disease admissions increasing by 3·18% (1·76-4·61) after 1-2 weeks of the floods. Cardiovascular disease, injuries, infectious, respiratory, and mental disorders were more sensitive across all regions. Particularly for disaster-exposed counties, cardiovascular hospitalisations increased by 14·31% (7·34-21·29) during the tropical cyclone-active period. Notably, compared with low-resilience counties, high-resilience counties were associated with 19·48-30·03% smaller hazard-related relative changes in hospitalisation rates during the hazard-active period and 27·07-31·08% smaller hazard-related relative changes in hospitalisation rates in post-hazard periods. For instance, during the storm-active period, the increase in respiratory hospitalisations was 7·21% (0·67-13·75) in high-resilience counties versus 12·13% (5·20-19·05) in low-resilience counties. Health workforce (relative importance 14·58% during the hazard-active period and 13·80% during the post-hazard period) and service delivery (14·10% during the hazard-active period and 14·17% during the post-hazard period) were identified as key contributors of health-system resilience. Empirical synergistic effects were observed when combining interventions during the post-hazard period, with the combined effect of service delivery (individual contribution 8%) and workforce (individual contribution 4%) exceeding the sum of their individual contributions (16% reduction in cumulative excess admissions) by 33%. INTERPRETATION: Climate hazards are associated with substantial changes in hospitalisation rates in both disaster-exposed and neighbouring regions. Health-system resilience is essential in addressing disaster-health challenges. Targeted adaptation interventions should be context-appropriate and threshold-aware, thereby maximising the public health benefits relative to resilience-oriented investments in health systems. FUNDING: Gates Foundation and the National Natural Science Foundation of China.

Journal Article↗

Bathymetric patterns of morphological disparity in deep-sea gastropods from the western North Atlantic basin.

Understanding patterns of species richness requires knowledge of the individual roles species play in community structure. Here, I use gastropod shells as a source of information about both their ecological and their evolutionary functions in generating bathymetric gradients of diversity. Specifically, morphological disparity of shell architecture in deep-sea gastropods is evaluated over a depth gradient in the western North Atlantic by constructing an empirical morphospace based on an eigenshape analysis. Morphological disparity is quantified by calculating the centroid, total range, and dispersion of the morphospace at each station along the depth gradient. The results indicate that local faunas are drawn from a regional pool with the same variance but that average dissimilarity in forms reflects the number of species in the sample. The range of the morphospace at local scales is also less than at regional scales, resulting from the variability of the morphospace centroid over depth. Although the position of the morphospace changes with depth, morphological disparity remains unaffected. Despite the lack of bathymetric patterns in variance, patterns in nearest neighbor distance persist. The findings suggest the importance of interacting ecological and evolutionary processes at varying spatiotemporal scales for both morphological disparity and species richness.

Analysis of Variance↗

Regulation of Ncx1 expression. Identification of regulatory elements mediating cardiac-specific expression and up-regulation.

The Na+-Ca2+ exchanger (NCX1) is up-regulated in hypertrophy and is often found up-regulated in end-stage heart failure. Studies have shown that the change in its expression contributes to contractile dysfunction. We have previously shown that the 1831-bp Ncx1 H1 (1831Ncx1) promoter directs cardiac-specific expression of the exchanger in both development and in the adult, and is sufficient for the up-regulation of Ncx1 in response to pressure overload. Here, we utilized adenoviral mediated gene transfer and transgenics to identify minimal regions and response elements that mediate Ncx1 expression in the heart. We demonstrate that the proximal 184 bp of the Ncx1 H1 (184Ncx1) promoter is sufficient for expression of reporter genes in adult cardiomyocytes and for the correct spatiotemporal pattern of Ncx1 expression in development but not for up-regulation in response to pressure overload. Mutational analysis revealed that both the -80 CArG and the -50 GATA elements were required for expression in isolated adult cardiomyocytes. Chromatin immunoprecipitation assays in adult cardiocytes demonstrate that SRF and GATA4 are associated with the proximal region of the endogenous Ncx1 promoter. Transgenic lines were established for the 1831Ncx1 promoter-luciferase containing mutations in the -80 CArG or -50 GATA element. No luciferase activity was detected during development, in the adult, or after pressure overload in any of the -80 CArG transgenic lines. The Ncx1 -50 GATA mutant promoter was sufficient for driving the normal spatiotemporal pattern of Ncx1 expression in development and for up-regulation in response to pressure overload but importantly, expression was no longer cardiac restricted. This work is the first in vivo study that demonstrates which cis elements are important for Ncx1 regulation.

Adenoviridae↗

Symptom perception in gastroesophageal reflux disease is dependent on spatiotemporal reflux characteristics.

BACKGROUND/AIMS: The mechanisms responsible for the development of symptoms in gastroesophageal reflux disease (GERD) are poorly understood. The aims of this study were to identify differences in spatiotemporal reflux characteristics (proximal extent and duration of reflux episodes, ascending velocity of the refluxate) between symptomatic and asymptomatic reflux episodes and to assess the influence of different pH sensor positions on the yield of symptom analysis. METHODS: Esophageal pH was measured for 24 hours at 3, 6, 9, 12, and 15 cm above the lower esophageal sphincter (LES) in 18 symptomatic patients with GERD, and spatiotemporal reflux characteristics were assessed for symptomatic and asymptomatic reflux episodes. Additionally, the symptom-association probability (SAP) was calculated for each esophageal level. RESULTS: The median episode duration (at 3 cm above the LES) was longer and the proximal extent was higher in symptomatic than in asymptomatic reflux episodes (P = 0.006 and P = 0.01). The ascending velocity of the refluxate was not significantly different. The SAP decreased significantly (P < 0.05) from distal to proximal, but no significant differences were found between distal and proximal esophageal levels for the proportion of patients with positive (> 95%) SAP values. CONCLUSIONS: The perception of reflux symptoms depends on the duration of acid-exposure episodes and on the proximal extent of the refluxate. Small changes in pH-sensor position do not significantly influence the yield of symptom analysis.

Adult↗

Repeatability of kinematic, kinetic, and electromyographic data in normal adult gait.

The repeatability of gait variables is an important consideration in the clinical use of results of quantitative gait analysis. Statistical measures were used to evaluate repeatability of kinematic, kinetic, and electromyographic data waveforms and spatiotemporal parameters of 40 normal subjects. Subjects were evaluated three times on each test day and on three different test days while walking at their preferred or natural speed. Intrasubject repeatability was excellent for kinematic data in the sagittal plane both within a test day as well as between test days. For joint angle motion in the frontal and transverse planes, the repeatability was good within a test day and poor between test days. Poor between-day repeatability of joint angle motion in the frontal and transverse planes was noted to be partly due to variabilities in the alignment of markers. Vertical reaction and fore-aft shear forces were more repeatable than the mediolateral shear force. Sagittal plane joint moments were more repeatable than frontal or transverse plane moments. For electromyographic data, repeatability within a day was slightly better than between test days. In general, the results demonstrate that with the subjects walking at their natural or preferred speed, the gait variables are quite repeatable. These observations suggest that it may be reasonable to base significant clinical decisions on the results of a single gait evaluation.

Ankle↗

Identification of neuromuscular synergies in natural upper-arm movements.

In this paper we study a natural upper-arm movement composed of sequential phases of reaching, grasping, and retrieval in the horizontal plane; in the present context, natural means that the spatiotemporal constraints active in the execution of the movement are low. The proposed method of quantitative analysis, which is applied to data obtained from healthy subjects, combines quantification of arm kinematics and kinesiologic electromyography assessment of neuromuscular control for each subject; to this aim, we propose using factor analysis. Despite the existence of a time-profile invariance of velocity traces, the identified factors may differ in the muscles that load on them; the interpretation is that different neuromuscular synergies are involved in the execution of the movement, which leads to cluster the subjects into two distinct groups. Compared with group-2 subjects, group-1 subjects present a more lateral hand path direction and a less smooth hand trajectory in their approach to the grasped object. To explain the identified factors and the kinematic findings, it is hypothesized that the feedforward motor commands involved in trajectory planning are different.

Adult↗