Notes

Spatial and also temporal attack mechanics from the 2014-2017 Zika and chikungunya epidemics within Colombia.
Our previous methodology in local sound speed estimation utilized time delays measured by the cross-correlation of delayed full synthetic aperture channel data to estimate the average speed of sound. However, focal distortions in this methodology lead to biased estimates of the average speed of sound, which, in turn, leads to biased estimates of the local speed of sound. Here, we demonstrate the bias in the previous methodology and introduce a coherence-based average sound speed estimator that eliminates this bias and is computationally much cheaper in practice. Because this coherence-based approach estimates the average sound speed in the medium over an equally-spaced grid in depth rather than time, we derive a refined model that relates the local and average speeds of sound as a function of depth in layered media. A fast, closed-form inversion of this model yields highly accurate local sound speed estimates. The root mean-square (RMS) error of local sound speed reconstruction in simulations of two-layer media is 4.6, and 2.5 m/s at 4 and 8 MHz, respectively. This work examines the impact of frequency, f-number, aberration, and reverberation on sound speed estimation. Phantom and in-vivo experiments in rats further validate the coherence-based sound speed estimator.Ataxia Telangiectasia (A-T) and Ataxia with Ocular Apraxia Type 1 (AOA1) are devastating neurological disorders caused by null mutations in the genome stability genes, A-T mutated (ATM) and Aprataxin (APTX), respectively. Our mechanistic understanding and therapeutic repertoire for treating these disorders are severely lacking, in large part due to the failure of prior animal models with similar null mutations to recapitulate the characteristic loss of motor coordination (i.e., ataxia) and associated cerebellar defects. By increasing genotoxic stress through the insertion of null mutations in both the Atm (nonsense) and Aptx (knockout) genes in the same animal, we have generated a novel mouse model that for the first time develops a progressively severe ataxic phenotype associated with atrophy of the cerebellar molecular layer. We find biophysical properties of cerebellar Purkinje neurons (PNs) are significantly perturbed (e.g., reduced membrane capacitance, lower action potential [AP] thresholds, etc.), while properties of synaptic inputs remain largely unchanged. These perturbations significantly alter PN neural activity, including a progressive reduction in spontaneous AP firing frequency that correlates with both cerebellar atrophy and ataxia over the animal's first year of life. Double mutant mice also exhibit a high predisposition to developing cancer (thymomas) and immune abnormalities (impaired early thymocyte development and T-cell maturation), symptoms characteristic of A-T. Finally, by inserting a clinically relevant nonsense-type null mutation in Atm, we demonstrate that Small Molecule Read-Through (SMRT) compounds can restore ATM production, indicating their potential as a future A-T therapeutic.Three-methyl cytosine (3meC) are toxic DNA lesions, blocking base pairing. Bacteria and humans, express members of the AlkB enzymes family, which directly remove 3meC. However, other organisms, including budding yeast, lack this class of enzymes. It remains an unanswered evolutionary question as to how yeast repairs 3meC, particularly in single-stranded DNA. The yeast Shu complex, a conserved homologous recombination factor, aids in preventing replication-associated mutagenesis from DNA base damaging agents such as methyl methanesulfonate (MMS). We found that MMS-treated Shu complex-deficient cells, exhibit a genome-wide increase in AT and GC substitutions mutations. The GC substitutions displayed transcriptional and replicational asymmetries consistent with mutations resulting from 3meC. Ectopic expression of a human AlkB homolog in Shu-deficient yeast rescues MMS-induced growth defects and increased mutagenesis. Thus, our work identifies a novel homologous recombination-based mechanism mediated by the Shu complex for coping with alkylation adducts.Plants develop new organs to adjust their bodies to dynamic changes in the environment. How independent organs achieve anisotropic shapes and polarities is poorly understood. To address this question, we constructed a mechano-biochemical model for Arabidopsis root meristem growth that integrates biologically plausible principles. Computer model simulations demonstrate how differential growth of neighboring tissues results in the initial symmetry-breaking leading to anisotropic root growth. Furthermore, the root growth feeds back on a polar transport network of the growth regulator auxin. Model, predictions are in close agreement with in vivo patterns of anisotropic growth, auxin distribution, and cell polarity, as well as several root phenotypes caused by chemical, mechanical, or genetic perturbations. Our study demonstrates that the combination of tissue mechanics and polar auxin transport organizes anisotropic root growth and cell polarities during organ outgrowth. Therefore, a mobile auxin signal transported through immobile cells drives polarity and growth mechanics to coordinate complex organ development.Bacteria must balance the different needs for substrate assimilation, growth functions, and resilience in order to thrive in their environment. Of all cellular macromolecules, the bacterial proteome is by far the most important resource and its size is limited. Here, we investigated how the highly versatile 'knallgas' bacterium Cupriavidus necator reallocates protein resources when grown on different limiting substrates and with different growth rates. We determined protein quantity by mass spectrometry and estimated enzyme utilization by resource balance analysis modeling. We found that C. necator invests a large fraction of its proteome in functions that are hardly utilized. Of the enzymes that are utilized, many are present in excess abundance. One prominent example is the strong expression of CBB cycle genes such as Rubisco during growth on fructose. Modeling and mutant competition experiments suggest that CO2-reassimilation through Rubisco does not provide a fitness benefit for heterotrophic growth, but is rather an investment in readiness for autotrophy.How cortical circuits build representations of complex objects is poorly understood. Individual neurons must integrate broadly over space, yet simultaneously obtain sharp tuning to specific global stimulus features. Groups of neurons identifying different global features must then assemble into a population that forms a comprehensive code for these global stimulus properties. Although the logic for how single neurons summate over their spatial inputs has been well explored in anesthetized animals, how large groups of neurons compose a flexible population code of higher-order features in awake animals is not known. To address this question, we probed the integration and population coding of higher-order stimuli in the somatosensory and visual cortices of awake mice using two-photon calcium imaging across cortical layers. We developed a novel tactile stimulator that allowed the precise measurement of spatial summation even in actively whisking mice. Using this system, we found a sparse but comprehensive population code for higher-order tactile features that depends on a heterogeneous and neuron-specific logic of spatial summation beyond the receptive field. Different somatosensory cortical neurons summed specific combinations of sensory inputs supra-linearly, but integrated other inputs sub-linearly, leading to selective responses to higher-order features. Visual cortical populations employed a nearly identical scheme to generate a comprehensive population code for contextual stimuli. These results suggest that a heterogeneous logic of input-specific supra-linear summation may represent a widespread cortical mechanism for the synthesis of sparse higher-order feature codes in neural populations. This may explain how the brain exploits the thalamocortical expansion of dimensionality to encode arbitrary complex features of sensory stimuli.Previously we showed that the vitamin A metabolite all-trans retinoic acid (atRA) induces synaptic plasticity in acute brain slices prepared from the mouse and human neocortex (Lenz et al., 2021). Depending on the brain region studied, distinct effects of atRA on excitatory and inhibitory neurotransmission have been reported. Here, we used intraperitoneal injections of atRA (10 mg/kg) in adult C57BL/6J mice to study the effects of atRA on excitatory and inhibitory neurotransmission in the mouse fascia dentata-a brain region implicated in memory acquisition. No major changes in synaptic transmission were observed in the ventral hippocampus while a significant increase in both spontaneous excitatory postsynaptic current frequencies and synapse numbers were evident in the dorsal hippocampus 6 hr after atRA administration. this website The intrinsic properties of hippocampal dentate granule cells were not significantly different and hippocampal transcriptome analysis revealed no essential neuronal changes upon atRA treatment. In light of these findings, we tested for the metaplastic effects of atRA, that is, for its ability to modulate synaptic plasticity expression in the absence of major changes in baseline synaptic strength. Indeed, in vivo long-term potentiation (LTP) experiments demonstrated that systemic atRA treatment improves the ability of dentate granule cells to express LTP. The plasticity-promoting effects of atRA were not observed in synaptopodin-deficient mice, therefore, extending our previous results regarding the relevance of synaptopodin in atRA-mediated synaptic strengthening in the mouse prefrontal cortex. Taken together, our data show that atRA mediates synaptopodin-dependent metaplasticity in mouse dentate granule cells.Acoustic signals serve communication within and across species throughout the animal kingdom. Studying the genetics, evolution, and neurobiology of acoustic communication requires annotating acoustic signals segmenting and identifying individual acoustic elements like syllables or sound pulses. To be useful, annotations need to be accurate, robust to noise, and fast.We here introduce DeepAudioSegmenter (DAS), a method that annotates acoustic signals across species based on a deep-learning derived hierarchical presentation of sound. We demonstrate the accuracy, robustness, and speed of DAS using acoustic signals with diverse characteristics from insects, birds, and mammals. DAS comes with a graphical user interface for annotating song, training the network, and for generating and proofreading annotations. The method can be trained to annotate signals from new species with little manual annotation and can be combined with unsupervised methods to discover novel signal types. DAS annotates song with high throughput and low latency for experimental interventions in realtime. Overall, DAS is a universal, versatile, and accessible tool for annotating acoustic communication signals.Absence of the astrocyte-specific membrane protein MLC1 is responsible for megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare type of leukodystrophy characterized by early-onset macrocephaly and progressive white matter vacuolation that lead to ataxia, spasticity, and cognitive decline. During postnatal development (from P5 to P15 in the mouse), MLC1 forms a membrane complex with GlialCAM (another astrocytic transmembrane protein) at the junctions between perivascular astrocytic processes. Perivascular astrocytic processes along with blood vessels form the gliovascular unit. It was not previously known how MLC1 influences the physiology of the gliovascular unit. Here, using the Mlc1 knock-out mouse model of MLC, we demonstrated that MLC1 controls the postnatal development and organization of perivascular astrocytic processes, vascular smooth muscle cell contractility, neurovascular coupling, and intraparenchymal interstitial fluid clearance. Our data suggest that MLC is a developmental disorder of the gliovascular unit, and perivascular astrocytic processes and vascular smooth muscle cell maturation defects are primary events in the pathogenesis of MLC and therapeutic targets for this disease.
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