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Sickle cell disease (SCD) is a prevalent inherited blood disorder, particularly affecting populations in Africa. This review examined the disease's burden, its diverse clinical presentations, and the challenges associated with its management in African settings. Africa bears a significant burden of SCD, with prevalence varying across countries and age groups. Newborn screening programs have highlighted the high prevalence of SCD at birth, emphasizing the need for early diagnosis and intervention. The clinical manifestations of SCD in Africa are multifaceted, encompassing acute complications like vaso-occlusive crises, acute chest syndrome, and stroke, as well as chronic complications such as organ damage and leg ulcers. Biological factors, including fetal hemoglobin levels, and demographic factors, like age and sex, influence disease severity and outcomes. The management of SCD in Africa faces numerous challenges. Limited access to resources, including diagnostic tools, medications, and trained healthcare professionals, hinders optimal care. The high cost of advanced therapies further restricts patient access. Cultural stigma and a lack of awareness create additional barriers to effective management. To address these challenges, early diagnosis through newborn screening programs and point-of-care testing is crucial. Comprehensive care models, including hydroxyurea therapy, pain management, and patient education, are essential for improving outcomes. Collaboration with international networks and leveraging local resources can enhance the sustainability of SCD programs. In conclusion, SCD significantly impacts African populations. Overcoming the challenges associated with its management requires addressing resource limitations, affordability issues, and cultural barriers. Early diagnosis, comprehensive care models, and ongoing research focused on affordability and accessibility are crucial for improving the lives of individuals living with SCD in Africa.

Locomotor movements cause visual images to be displaced across the eye, a retinal slip that is counteracted by stabilizing reflexes in many animals. In insects, optomotor turning causes the animal to turn in the direction of rotating visual stimuli, thereby reducing retinal slip and stabilizing trajectories through the world. This behavior has formed the basis for extensive dissections of motion vision. Here, we report that under certain stimulus conditions, two Drosophila species, including the widely studied Drosophila melanogaster , can suppress and even reverse the optomotor turning response over several seconds. Such 'anti-directional turning' is most strongly evoked by long-lasting, high-contrast, slow-moving visual stimuli that are distinct from those that promote syn-directional optomotor turning. Anti-directional turning, like the syn-directional optomotor response, requires the local motion detecting neurons T4 and T5. A subset of lobula plate tangential cells, CH cells, show involvement in these responses. Imaging from a variety of direction-selective cells in the lobula plate shows no evidence of dynamics that match the behavior, suggesting that the observed inversion in turning direction emerges downstream of the lobula plate. Further, anti-directional turning declines with age and exposure to light. These results show that Drosophila optomotor turning behaviors contain rich, stimulus-dependent dynamics that are inconsistent with simple reflexive stabilization responses., Competing Interests: OM, MC, RT, MC, NM, JS, BB, TC No competing interests declared, DC Reviewing editor, eLife, (© 2023, Mano et al.)

Artificial neural networks trained to solve sensory tasks can develop statistical representations that match those in biological circuits. However, it remains unclear whether they can reproduce properties of individual neurons. Here, we investigated how artificial networks predict individual neuron properties in the visual motion circuits of the fruit fly Drosophila. We trained anatomically constrained networks to predict movement in natural scenes, solving the same inference problem as fly motion detectors. Units in the artificial networks adopted many properties of analogous individual neurons, even though they were not explicitly trained to match these properties. Among these properties was the split into ON and OFF motion detectors, which is not predicted by classical motion detection models. The match between model and neurons was closest when models were trained to be robust to noise. These results demonstrate how anatomical, task, and noise constraints can explain properties of individual neurons in a small neural network., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin. Genetic mouse studies revealed that dermal adipocytes are necessary to initiate inflammation after injury and promote subsequent repair. We find through histological, ultrastructural, lipidomic, and genetic experiments in mice that adipocytes adjacent to skin injury initiate lipid release necessary for macrophage inflammation. Tamoxifen-inducible genetic lineage tracing of mature adipocytes and single-cell RNA sequencing revealed that dermal adipocytes alter their fate and generate ECM-producing myofibroblasts within wounds. Thus, adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes., Competing Interests: Declaration of Interests The authors have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In functional imaging, large numbers of neurons are measured during sensory stimulation or behavior. This data can be used to map receptive fields that describe neural associations with stimuli or with behavior. The temporal resolution of these receptive fields has traditionally been limited by image acquisition rates. However, even when acquisitions scan slowly across a population of neurons, individual neurons may be measured at precisely known times. Here, we apply a method that leverages the timing of neural measurements to find receptive fields with temporal resolutions higher than the image acquisition rate. We use this temporal super-resolution method to resolve fast voltage and glutamate responses in visual neurons in Drosophila and to extract calcium receptive fields from cortical neurons in mammals. We provide code to easily apply this method to existing datasets. This method requires no specialized hardware and can be used with any optical indicator of neural activity.

Background: To study visual processing, it is necessary to precisely control visual stimuli while recording neural and behavioral responses. It can be important to present stimuli over a broad area of the visual field, which can be technically difficult., New Method: We present a simple geometry that can be used to display panoramic stimuli. A single digital light projector generates images that are reflected by mirrors onto flat screens that surround an animal. It can be used for behavioral and neurophysiological measurements, so virtually identical stimuli can be presented. Moreover, this geometry permits light from the projector to be used to activate optogenetic tools., Results: Using this geometry, we presented panoramic visual stimulation to Drosophila in three paradigms. We presented drifting contrast gratings while recording walking and turning speed. We used the same projector to activate optogenetic channels during visual stimulation. Finally, we used two-photon microscopy to record responses in direction-selective cells to drifting gratings., Comparison With Existing Method(s): Existing methods have typically required custom hardware or curved screens, while this method requires only flat back projection screens and a digital light projector. The projector generates images in real time and does not require pre-generated images. Finally, while many setups are large, this geometry occupies a 30 × 20 cm footprint with a 25 cm height., Conclusions: This flexible geometry enables measurements of behavioral and neural responses to panoramic stimuli. This allows moderate throughput behavioral experiments with simultaneous optogenetic manipulation, with easy comparisons between behavior and neural activity using virtually identical stimuli., (Copyright © 2019 Elsevier B.V. All rights reserved.)

An animal's self-motion generates optic flow across its retina, and it can use this visual signal to regulate its orientation and speed through the world. While orientation control has been studied extensively in Drosophila and other insects, much less is known about the visual cues and circuits that regulate translational speed. Here, we show that flies regulate walking speed with an algorithm that is tuned to the speed of visual motion, causing them to slow when visual objects are nearby. This regulation does not depend strongly on the spatial structure or the direction of visual stimuli, making it algorithmically distinct from the classic computation that controls orientation. Despite the different algorithms, the visual circuits that regulate walking speed overlap with those that regulate orientation. Taken together, our findings suggest that walking speed is controlled by a hierarchical computation that combines multiple motion detectors with distinct tunings. VIDEO ABSTRACT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The assembly of functional neuronal circuits requires growth cones to extend in defined directions and recognize the correct synaptic partners. Homophilic adhesion between vertebrate Sidekick proteins promotes synapse formation between retinal neurons involved in visual motion detection. We show here that Drosophila Sidekick accumulates in specific synaptic layers of the developing motion detection circuit and is necessary for normal optomotor behavior. Sidekick is required in photoreceptors, but not in their target lamina neurons, to promote the alignment of lamina neurons into columns and subsequent sorting of photoreceptor axons into synaptic modules based on their precise spatial orientation. Sidekick is also localized to the dendrites of the direction-selective T4 and T5 cells, and is expressed in some of their presynaptic partners. In contrast to its vertebrate homologs, Sidekick is not essential for T4 and T5 to direct their dendrites to the appropriate layers or to receive synaptic contacts. These results illustrate a conserved requirement for Sidekick proteins in establishing visual motion detection circuits that is achieved through distinct cellular mechanisms in Drosophila and vertebrates., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Sensory neuroscience seeks to understand and predict how sensory neurons respond to stimuli. Nonlinear components of neural responses are frequently characterized by the second-order Wiener kernel and the closely-related spike-triggered covariance (STC). Recent advances in data acquisition have made it increasingly common and computationally intensive to compute second-order Wiener kernels/STC matrices. In order to speed up this sort of analysis, we developed a graphics processing unit (GPU)-accelerated module that computes the second-order Wiener kernel of a system's response to a stimulus. The generated kernel can be easily transformed for use in standard STC analyses. Our code speeds up such analyses by factors of over 100 relative to current methods that utilize central processing units (CPUs). It works on any modern GPU and may be integrated into many data analysis workflows. This module accelerates data analysis so that more time can be spent exploring parameter space and interpreting data., Competing Interests: The authors have declared that no competing interests exist.

Animals estimate visual motion by integrating light intensity information over time and space. The integration requires nonlinear processing, which makes motion estimation circuitry sensitive to specific spatiotemporal correlations that signify visual motion. Classical models of motion estimation weight these correlations to produce direction-selective signals. However, the correlational algorithms they describe have not been directly measured in elementary motion-detecting neurons (EMDs). Here, we employed stimuli to directly measure responses to pairwise correlations in Drosophila's EMD neurons, T4 and T5. Activity in these neurons was required for behavioral responses to pairwise correlations and was predictive of those responses. The pattern of neural responses in the EMDs was inconsistent with one classical model of motion detection, and the timescale and selectivity of correlation responses constrained the temporal filtering properties in potential models. These results reveal how neural responses to pairwise correlations drive visual behavior in this canonical motion-detecting circuit., (Copyright © 2016 Elsevier Inc. All rights reserved.)