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Guy Horton posted an update 6 months, 3 weeks ago
In contrast, individuals who tended to look at only one of the target choices as visual uncertainty increased preferred to step on the target that minimized motor cost. Overall, we demonstrate that how a person explores the environment with their eyes dictates where they step. These gaze and step decisions may relate to the value a person assigns to information gain, being certain of their actions, and conserving energy.Despite the outsized role of mangrove forests in sustaining biodiversity, ecosystem function, and local livelihoods, the protection of these vital habitats through blue carbon financing has been limited.1,2 Here, we quantify the extent of this missed conservation and financial opportunity, showing that the protection of ∼20% of the world’s mangrove forests (2.6 Mha) can be funded through carbon financing. Of these investible areas, 1.1-1.3 Mha can be financially sustainable over a 30-year time frame based on carbon prices of US$5-9.4 t-1CO2e. This contributes up to 29.8 MtCO2e year-1 and yields a return on investment of ∼US$3.7 billion per year. Our results point toward a disproportionately large potential of blue carbon finance that can be leveraged to meet national-level climate mitigation goals, particularly if combined with other conservation interventions that further safeguard carbon stocks and biodiversity in these irreplaceable forests. Robust information on return on investment highlights the potential for currently underutilized tropical coastal carbon credit projects.The term menstrual migraine refers to migraine that is associated with menstruation by more than chance, but it does not define pathophysiology. Menstrual migraine affects about 20-25% of female migraineurs in the general population, and 22-70% of patients presenting to headache clinics. In women diagnosed with menstrual migraine, perimenstrual migraine attacks are associated with substantially greater disability than their non-menstrual attacks. Loose interpretation of diagnostic criteria has led to conflicting results in studies on prevalence figures, clinical characteristics, and response to treatment. Importantly, clinical trials often do not distinguish between perimenstrual attacks in women diagnosed with menstrual migraine and attacks associated with menstruation by chance. Two pathophysiological mechanisms have been identified oestrogen withdrawal and prostaglandin release. Although management strategies targeting these mechanisms might be effective, the evidence is not robust. Given how common and debilitating this distinct condition is, more research investment is needed to expand understanding of its pathophysiology and to develop more effective treatment strategies.In some free-living and pathogenic bacteria, problems in the synthesis and assembly of early flagellar components can cause cell-division defects. However, the mechanism that couples cell division with the flagellar biogenesis has remained elusive. Herein, we discover the regulator MadA that controls transcription of flagellar and cell-division genes in Caulobacter crescentus. We demonstrate that MadA, a small soluble protein, binds the type III export component FlhA to promote activation of FliX, which in turn is required to license the conserved σ54-dependent transcriptional activator FlbD. BMS-935177 nmr While in the absence of MadA, FliX and FlbD activation is crippled, bypass mutations in FlhA restore flagellar biogenesis and cell division. Furthermore, we demonstrate that MadA safeguards the divisome stoichiometry to license cell division. We propose that MadA has a sentinel-type function that senses an early flagellar biogenesis event and, through cell-division control, ensures that a flagellated offspring emerges.Organelles are responsible for biochemical and cellular processes that sustain life and their dysfunction causes diseases from cancer to neurodegeneration. While researchers are continuing to appreciate new roles of organelles in disease, the rapid development of specifically targeted fluorescent probes that report on the structure and function of organelles will be critical to accelerate drug discovery. Here, we highlight four organelles that collectively exemplify the progression of phenotypic discovery, starting with mitochondria, where many functional probes have been described, then continuing with lysosomes and Golgi and concluding with nascently described membraneless organelles. We introduce emerging probe designs to explore organelle-specific morphology and dynamics and highlight recent case studies using high-content analysis to stimulate further development of probes and approaches for organellar high-throughput screening.The hypothalamus plays crucial roles in regulating endocrine, autonomic, and behavioral functions via its diverse nuclei and neuronal subtypes. The developmental mechanisms underlying ontogenetic establishment of different hypothalamic nuclei and generation of neuronal diversity remain largely unknown. Here, we show that combinatorial T-box 3 (TBX3), orthopedia homeobox (OTP), and distal-less homeobox (DLX) expression delineates all arcuate nucleus (Arc) neurons and defines four distinct subpopulations, whereas combinatorial NKX2.1/SF1 and OTP/DLX expression identifies ventromedial hypothalamus (VMH) and tuberal nucleus (TuN) neuronal subpopulations, respectively. Developmental analysis indicates that all four Arc subpopulations are mosaically and simultaneously generated from embryonic Arc progenitors, whereas glutamatergic VMH neurons and GABAergic TuN neurons are sequentially generated from common embryonic VMH progenitors. Moreover, clonal lineage-tracing analysis reveals that diverse lineages from multipotent radial glia progenitors orchestrate Arc and VMH-TuN establishment. Together, our study reveals cellular mechanisms underlying generation and organization of diverse neuronal subtypes and ontogenetic establishment of individual nuclei in the mammalian hypothalamus.Progressive loss of dopamine inputs in Parkinson’s disease leads to imbalances in coordinated signaling of dopamine and acetylcholine (ACh) in the striatum, which is thought to contribute to parkinsonian motor symptoms. As reciprocal interactions between dopamine inputs and cholinergic interneurons (ChIs) control striatal dopamine and ACh transmission, we examined how partial dopamine depletion in an early-stage mouse model for Parkinson’s disease alters nigral regulation of cholinergic activity. We found region-specific alterations in how remaining dopamine inputs regulate cholinergic excitability that differ between the dorsomedial (DMS) and dorsolateral (DLS) striatum. Specifically, we found that dopamine depletion downregulates metabotropic glutamate receptors (mGluR1) on DLS ChIs at synapses where dopamine inputs co-release glutamate, abolishing the ability of dopamine inputs to drive burst firing. This loss underlies parkinsonian motor impairments, as viral rescue of mGluR1 signaling in DLS ChIs was sufficient to restore circuit function and attenuate motor deficits in early-stage parkinsonian mice.
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