School in the time of Covid.

This article argues that extended school closures during the Covid-19 pandemic were a moral catastrophe. It focuses on closures in the United States of America and discusses their effect on the pandemic (or lack thereof), their harmful effects on children, and other morally relevant factors. It concludes by discussing how these closures came to pass and suggests that the root cause was structural, not individual: the relevant decision-makers were working in an institutional setting that stacked the deck heavily in favor of extended closures.

Geology, environment, and life in the deepest part of the world's oceans.

The hadal zone, mostly comprising of deep trenches and constituting of the deepest part of the world's oceans, represents the least explored habitat but one of the last frontiers on our planet. The present scientific understanding of the hadal environment is still relatively rudimentary, particularly in comparison with that of shallower marine environments. In the last 30 years, continuous efforts have been launched in deepening our knowledge regarding the ecology of the hadal trench. However, the geological and environmental processes that potentially affect the sedimentary, geochemical and biological processes in hadal trenches have received less attention. Here, we review recent advances in the geology, biology, and environment of hadal trenches and offer a perspective of the hadal science involved therein. For the first time, we release high-definition images taken by a new full-ocean-depth manned submersible Fendouzhe that reveal novel species with an unexpectedly high density, outcrops of mantle and basaltic rocks, and anthropogenic pollutants at the deepest point of the world's ocean. We advocate that the hydration of the hadal lithosphere is a driving force that influences a variety of sedimentary, geochemical, and biological processes in the hadal trench. Hadal lithosphere might host the Earth's deepest subsurface microbial ecosystem. Future research, combined with technological advances and international cooperation, should focus on establishing the intrinsic linkage of the geology, biology, and environment of the hadal trenches.

Deep seafloor plastics as the source and sink of organic pollutants in the northern South China Sea.

Large plastic litter (as opposed to microplastics and plastic pellets) could adsorb organic pollutants and thus pose a serious threat to the marine environment. We report high levels of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) adsorbed to plastic litter sampled from depths of 1800-3100 m in the Xisha Trough region of the northern South China Sea (NSCS). ∑PCBs on plastics ranged from 126.9-142.1 ng/g, with tri-PCBs accounting for 92-97% of the total PCB concentrations in all samples. Levels of ∑OCPs varied from 4280 to 5351 ng/g (average 4690 ng/g), with a total of 19 compounds detected in the seven samples. While no parent DDT (dichlorodiphenyltrichloroethane) was detected, op'-DDE (metabolite of DDT) was most abundant, with concentrations ranging from 947.5-1551.7 ng/g. ∑CHLs (heptachlor + heptachlor epoxide A + heptachlor epoxide B + cis-chlordane + trans-chlordane) ranged from 1083.1-1263.7 ng/g (mean 1153 ng/g) and accounted for 24% of ∑OCPs. Various compositional ratios of HCH (hexachlorocyclohexane) and DDT metabolites improved our understanding of the sources and transport pathways of OCPs. The total absence of DDT may be a "ghost indicator" of no recent DDT inputs into the oceans. There could well be inputs of DDT, but only as the degraded metabolites DDE and DDD when they are adsorbed to seafloor plastic litter. A comparison of HCH isomer ratios in seafloor plastics with technical HCH ratios revealed that HCHs were possibly not from early residues but from later inputs. An ecological risk assessment of the contaminants indicated a high risk from ∑DDTs, p,p-DDE, and γ-HCH in all the sampled locations. Finally, we propose a descriptive model depicting the movements and transportation of PCBs and OCPs from the ocean surface to seafloor plastics in the NSCS.

Dendritic Integration of Sensory Evidence in Perceptual Decision-Making.

Perceptual decisions require the accumulation of sensory information to a response criterion. Most accounts of how the brain performs this process of temporal integration have focused on evolving patterns of spiking activity. We report that subthreshold changes in membrane voltage can represent accumulating evidence before a choice. αß core Kenyon cells (αßc KCs) in the mushroom bodies of fruit flies integrate odor-evoked synaptic inputs to action potential threshold at timescales matching the speed of olfactory discrimination. The forkhead box P transcription factor (FoxP) sets neuronal integration and behavioral decision times by controlling the abundance of the voltage-gated potassium channel Shal (KV4) in αßc KC dendrites. αßc KCs thus tailor, through a particular constellation of biophysical properties, the generic process of synaptic integration to the demands of sequential sampling.

Cell-Specific Targeting of Genetically Encoded Tools for Neuroscience.

Genetically encoded tools for visualizing and manipulating neurons in vivo have led to significant advances in neuroscience, in large part because of the ability to target expression to specific cell populations of interest. Current methods enable targeting based on marker gene expression, development, anatomical projection pattern, synaptic connectivity, and recent activity as well as combinations of these factors. Here, we review these methods, focusing on issues of practical implementation as well as areas for future improvement.

FoxP influences the speed and accuracy of a perceptual decision in Drosophila.

Decisions take time if information gradually accumulates to a response threshold, but the neural mechanisms of integration and thresholding are unknown. We characterized a decision process in Drosophila that bears the behavioral signature of evidence accumulation. As stimulus contrast in trained odor discriminations decreased, reaction times increased and perceptual accuracy declined, in quantitative agreement with a drift-diffusion model. FoxP mutants took longer than wild-type flies to form decisions of similar or reduced accuracy, especially in difficult, low-contrast tasks. RNA interference with FoxP expression in αß core Kenyon cells, or the overexpression of a potassium conductance in these neurons, recapitulated the FoxP mutant phenotype. A mushroom body subdomain whose development or function require the transcription factor FoxP thus supports the progression of a decision toward commitment.

Alterations in membrane phospholipid fatty acids of Gram-positive piezotolerant bacterium Sporosarcina sp. DSK25 in response to growth pressure.

Pressure is an important thermodynamic property of the ocean and the deep biosphere that affects microbial physiology and biochemistry. Here, we report on our investigation of the response of Gram-positive piezotolerant bacterium Sporosarcina sp. DSK25 to hydrostatic pressure. Strain DSK25 responded in an adaptive manner to upshifts of growth pressure and showed systematic changes in phospholipid fatty acids. As the pressure increased from 0.1 to 10 MPa (Megapascal), unsaturated fatty acids in DSK25 increased from 21.7 to 31.1% of total fatty acids, while the level of iso- and anteiso-branched fatty acids remained unchanged. At higher pressures (30, 50, and 60 MPa), the amount of unsaturated fatty acids decreased, and that of anteiso-branched fatty acids increased from 34.4 to 49.9% at the expense of iso-branched fatty acids. For the first time, two polyunsaturated fatty acids (PUFA), 18:2n-6 and 18:2n-x, with the latter having much higher abundance than the former, were identified in DSK25. The concentration of the PUFA increased with growth pressure. These results indicate the involvement of unsaturated and methyl-branched fatty acids in the modulation of bacteria membrane fluidity and function over environmentally relevant parameter (pressure). Piezotolerant bacterium Sporosarcina sp. DSK25 appears to utilize two regulatory mechanisms for adaptation to high pressure, a rapid-responding mechanism on transient scale, expressed as increased biosynthesis of monounsaturated fatty acids, and a long-term adaptation mechanism in increased synthesis of anteiso-branched and polyunsaturated fatty acids. Our results further suggest that Gram-positive piezophilic bacteria respond differently than Gram-negative bacteria in adaptation to high pressure.

Transposition-driven genomic heterogeneity in the Drosophila brain.

Recent studies in mammals have documented the neural expression and mobility of retrotransposons and have suggested that neural genomes are diverse mosaics. We found that transposition occurs among memory-relevant neurons in the Drosophila brain. Cell type-specific gene expression profiling revealed that transposon expression is more abundant in mushroom body (MB) αß neurons than in neighboring MB neurons. The Piwi-interacting RNA (piRNA) proteins Aubergine and Argonaute 3, known to suppress transposons in the fly germline, are expressed in the brain and appear less abundant in αß MB neurons. Loss of piRNA proteins correlates with elevated transposon expression in the brain. Paired-end deep sequencing identified more than 200 de novo transposon insertions in αß neurons, including insertions into memory-relevant loci. Our observations indicate that genomic heterogeneity is a conserved feature of the brain.

Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling.

Adrenergic signaling has important roles in synaptic plasticity and metaplasticity. However, the underlying mechanisms of these functions remain poorly understood. We investigated the role of octopamine, the invertebrate counterpart of adrenaline and noradrenaline, in synaptic and behavioral plasticity in Drosophila. We found that an increase in locomotor speed induced by food deprivation was accompanied by an activity- and octopamine-dependent extension of octopaminergic arbors and that the formation and maintenance of these arbors required electrical activity. Growth of octopaminergic arbors was controlled by a cAMP- and CREB-dependent positive-feedback mechanism that required Octß2R octopamine autoreceptors. Notably, this autoregulation was necessary for the locomotor response. In addition, octopamine neurons regulated the expansion of excitatory glutamatergic neuromuscular arbors through Octß2Rs on glutamatergic motor neurons. Our results provide a mechanism for global regulation of excitatory synapses, presumably to maintain synaptic and behavioral plasticity in a dynamic range.

A neural circuit mechanism integrating motivational state with memory expression in Drosophila.

Behavioral expression of food-associated memory in fruit flies is constrained by satiety and promoted by hunger, suggesting an influence of motivational state. Here, we identify a neural mechanism that integrates the internal state of hunger and appetitive memory. We show that stimulation of neurons that express neuropeptide F (dNPF), an ortholog of mammalian NPY, mimics food deprivation and promotes memory performance in satiated flies. Robust appetitive memory performance requires the dNPF receptor in six dopaminergic neurons that innervate a distinct region of the mushroom bodies. Blocking these dopaminergic neurons releases memory performance in satiated flies, whereas stimulation suppresses memory performance in hungry flies. Therefore, dNPF and dopamine provide a motivational switch in the mushroom body that controls the output of appetitive memory.

There are many ways to train a fly.

A biological understanding of memory remains one of the great quests of neuroscience. For over 30 years the fruit fly Drosophila melanogaster has primarily been viewed as an excellent vehicle to find 'memory genes'. However, the recent advent of sophisticated genetic tools to manipulate neural activity has meant that these genes can now be viewed within the context of functioning neural circuits. A holistic understanding of memory in flies is therefore now a realistic goal. Larvae and adult flies exhibit remarkable behavioral complexity and they can both be trained in a number of ways. In this review, our intention is to summarize the many assays that have been developed to study plastic behaviors in flies. More specific and detailed reviews have been published by us and others, reviewed in references 1-6. While our bias for olfactory conditioning paradigms is obvious, our purpose here is not to pass judgment on each method. We would rather leave that to those readers who might be inspired to try each assay for themselves.

Learned odor discrimination in Drosophila without combinatorial odor maps in the antennal lobe.

A unifying feature of mammalian and insect olfactory systems is that olfactory sensory neurons (OSNs) expressing the same unique odorant-receptor gene converge onto the same glomeruli in the brain [1-7]. Most odorants activate a combination of receptors and thus distinct patterns of glomeruli, forming a proposed combinatorial spatial code that could support discrimination between a large number of odorants [8-11]. OSNs also exhibit odor-evoked responses with complex temporal dynamics [11], but the contribution of this activity to behavioral odor discrimination has received little attention [12]. Here, we investigated the importance of spatial encoding in the relatively simple Drosophila antennal lobe. We show that Drosophila can learn to discriminate between two odorants with one functional class of Or83b-expressing OSNs. Furthermore, these flies encode one odorant from a mixture and cross-adapt to odorants that activate the relevant OSN class, demonstrating that they discriminate odorants by using the same OSNs. Lastly, flies with a single class of Or83b-expressing OSNs recognize a specific odorant across a range of concentration, indicating that they encode odorant identity. Therefore, flies can distinguish odorants without discrete spatial codes in the antennal lobe, implying an important role for odorant-evoked temporal dynamics in behavioral odorant discrimination.

The Drosophila homolog of MCPH1, a human microcephaly gene, is required for genomic stability in the early embryo.

Mutation of human microcephalin (MCPH1) causes autosomal recessive primary microcephaly, a developmental disorder characterized by reduced brain size. We identified mcph1, the Drosophila homolog of MCPH1, in a genetic screen for regulators of S-M cycles in the early embryo. Embryos of null mcph1 female flies undergo mitotic arrest with barrel-shaped spindles lacking centrosomes. Mutation of Chk2 suppresses these defects, indicating that they occur secondary to a previously described Chk2-mediated response to mitotic entry with unreplicated or damaged DNA. mcph1 embryos exhibit genomic instability as evidenced by frequent chromatin bridging in anaphase. In contrast to studies of human MCPH1, the ATR/Chk1-mediated DNA checkpoint is intact in Drosophila mcph1 mutants. Components of this checkpoint, however, appear to cooperate with MCPH1 to regulate embryonic cell cycles in a manner independent of Cdk1 phosphorylation. We propose a model in which MCPH1 coordinates the S-M transition in fly embryos: in the absence of mcph1, premature chromosome condensation results in mitotic entry with unreplicated DNA, genomic instability, and Chk2-mediated mitotic arrest. Finally, brains of mcph1 adult male flies have defects in mushroom body structure, suggesting an evolutionarily conserved role for MCPH1 in brain development.