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Atypical sensory processing is common in autism, but how neural coding is disrupted in sensory cortex is unclear. We evaluate whisker touch coding in L2/3 of somatosensory cortex (S1) in Cntnap2-/- mice, which have reduced inhibition. This classically predicts excess pyramidal cell spiking, but this remains controversial, and other deficits may dominate. We find that c-fos expression is elevated in S1 of Cntnap2-/- mice under spontaneous activity conditions but is comparable to that of control mice after whisker stimulation, suggesting normal sensory-evoked spike rates. GCaMP8m imaging from L2/3 pyramidal cells shows no excess whisker responsiveness, but it does show multiple signs of degraded somatotopic coding. This includes broadened whisker-tuning curves, a blurred whisker map, and blunted whisker point representations. These disruptions are greater in noisy than in sparse sensory conditions. Tuning instability across days is also substantially elevated in Cntnap2-/-. Thus, Cntnap2-/- mice show no excess sensory-evoked activity, but a degraded and unstable tactile code in S1.

Mountains play an outsized role in water resource availability, and the amount and timing of water they provide depend strongly on temperature. To that end, we ask the question: How well are atmospheric models capturing mountain temperatures? We synthesize results showing that high-resolution, regionally relevant climate models produce 2-m air temperature (T2m) measurements colder than what is observed (a “cold bias”), particularly in snow-covered midlatitude mountain ranges during winter. We find common cold biases in 44 studies across global mountain ranges, including single-model and multimodel ensembles. We explore the factors driving these biases and examine the physical mechanisms, data limitations, and observational uncertainties behind T2m. Our analysis suggests that the biases are genuine and not due to observation sparsity or resolution mismatches. Cold biases occur primarily on mountain peaks and ridges, whereas valleys are often warm biased. Our literature review suggests that increasing model resolution does not clearly mitigate the bias. By analyzing data from the Surface Atmosphere Integrated Field Laboratory (SAIL) field campaign in the Colorado Rocky Mountains, we test various hypotheses related to cold biases and find that local wind circulations, longwave (LW) radiation, and surface-layer parameterizations contribute to the T2m biases in this particular location. We conclude by emphasizing the value of coordinated model evaluation and development efforts in heavily instrumented mountain locations for addressing the root cause(s) of T2m biases and improving predictive understanding of mountain climates. SIGNIFICANCE STATEMENT: Mountain climates are rapidly changing, and along with them are the temperature-sensitive components of the water budget that societies have relied on. Yet atmospheric models, from those that predict the weather to those that predict the future climate, are several degrees too cold on average in these same mountain regions. This cold bias has not been systematically identified in the published literature yet, so we discuss evidence of its pervasiveness across models, its potential causes, and pathways to eliminate it using targeted models and observations. With community support, this bias can be uprooted, thereby enabling model projections that better project the climatic and water resource changes in these vital regions.

Polarization surrounding bias correction (BC) in creating climate projections arises from its lack of physicality. Here, we perform and analyze 18 dynamical downscaling simulations (with and without BC) to better understand the physical impacts of BC, applied before downscaling, on regional climate output across the western United States. Without BC, downscaled precipitation is systematically and unrealistically wet biased compared to a hierarchy of observationally based datasets over the 1980–2014 period due to cascading mean-state Global Climate Model (GCM) biases: (a) overly strong lower-tropospheric lapse rates (5 K/km), (b) overly cold (2 K) tropospheric temperatures, and (c) anomalous mid-tropospheric cyclonic vorticity advection. With BC, downscaled precipitation (snow) biases are virtually eliminated (halved). Identified GCM biases are common to the broader Coupled Model Intercomparison Project ensemble. Physical effects of BC on the quality of the regionalized projections, pending an evaluation of BC's distortion of the downscaled climate response, may motivate its broader application by dynamical downscalers.

Vasoactive intestinal peptide (VIP) interneurons in sensory cortex modulate sensory responses based on global exploratory behavior and arousal state, but their function during non-exploratory, goal-directed behavior is not well understood. In particular, whether VIP cells are activated by sensory cues, reward-seeking actions, or directly by reinforcement is unclear. We trained mice on a Go/NoGo whisker touch detection task that included a delay period and other features designed to separate sensory-evoked, action-related, and reward-related neural activity. Mice had to lick in response to a whisker stimulus to receive a variable-sized reward. Using two-photon calcium imaging, we measured ΔF/F responses of L2/3 VIP neurons in whisker somatosensory cortex (S1) during behavior. In both expert and novice mice, VIP cells were strongly activated by whisker stimuli and goal-directed actions (licking), but not by reinforcement. VIP cells showed somatotopic whisker tuning that was spatially organized relative to anatomical columns in S1, unlike lick-related signals which were spatially widespread. In expert mice, lick-related VIP responses were suppressed, not enhanced, when a reward was delivered, and the amount of suppression increased with reward size. This reward-related suppression was not seen in novice mice, where reward delivery was not yoked to licking. These results indicate that besides arousal and global state variables, VIP cells are activated by local sensory features and goal-directed actions, but not directly by reinforcement. Instead, our results are consistent with a role for VIP cells in encoding the expectation of reward associated with motor actions.

Mountain hydrology is controlled by interacting processes extending from the atmosphere through the bedrock. Integrated process models (IPMs), one of the main tools needed to interpret observations and refine conceptual models of the mountainous water cycle, require meteorological forcing that simulates the atmospheric process to predict hydroclimate then subsequently impacts surface-subsurface hydrology. Complex terrain and extreme spatial heterogeneity in mountainous environments drive uncertainty in several key considerations in IPM configurations and require further quantification and sensitivity analyses. Here, we present an IPM using the Weather Research and Forecasting (WRF) model which forces an integrated hydrologic model, ParFlow-CLM, implemented over a domain centered over the East River watershed (ERW), located in the Upper Colorado River basin (UCRB). The ERW is a heavily instrumented 300g km2 region in the headwaters of the UCRB near Crested Butte, CO, with a growing atmosphere-Through-bedrock observation network. Through a series of experiments in the water year 2019 (WY19), we use four meteorological forcings derived from commonly used reanalysis datasets, three subgrid-scale physics scheme configurations in WRF, and two terrain shading options within WRF to test the relative importance of these experimental design choices for key hydrometeorological metrics including precipitation and snowpack, as well as evapotranspiration, groundwater storage, and discharge simulated by the ParFlow-CLM. Our hypothesis is that uncertainty from synoptic-scale forcings produces a much larger spread in surface-subsurface hydrologic fields than subgrid-scale physics scheme choice. Results reveal that the WRF subgrid-scale physics configuration leads to larger spatiotemporal variance in simulated hydrometeorological conditions, whereas variance across meteorological forcing with common subgrid-scale physics configurations is more spatiotemporally constrained. Despite reasonably simulating precipitation, a delay in simulated discharge peak is due to a systematic cold bias across WRF simulations, suggesting the need for bias correction. Discharge shows greater variance in response to the WRF simulations across subgrid-scale physics schemes (26g %) rather than meteorological forcing (6g %). The topographic radiation option has minor effects on the watershed-Average hydrometeorological processes but adds profound spatial heterogeneity to local energy budgets (±30g Wg m-2 in shortwave radiation and 1g K air temperature differences in late summer). This is the first presentation of sensitivity analyses that provide support to help guide the scientific community to develop observational constraints on atmosphere-Through-bedrock processes and their interactions.

Individuals with autism spectrum disorder (ASD) exhibit a diverse range of behavioral features and genetic backgrounds, but whether different genetic forms of autism involve convergent pathophysiology of brain function is unknown. Here, we analyze evidence for convergent deficits in neural circuit function across multiple transgenic mouse models of ASD. We focus on sensory areas of neocortex, where circuit differences may underlie atypical sensory processing, a central feature of autism. Many distinct circuit-level theories for ASD have been proposed, including increased excitation-inhibition (E-I) ratio and hyperexcitability, hypofunction of parvalbumin (PV) interneuron circuits, impaired homeostatic plasticity, degraded sensory coding, and others. We review these theories and assess the degree of convergence across ASD mouse models for each. Behaviorally, our analysis reveals that innate sensory detection behavior is heightened and sensory discrimination behavior is impaired across many ASD models. Neurophysiologically, PV hypofunction and increased E-I ratio are prevalent but only rarely generate hyperexcitability and excess spiking. Instead, sensory tuning and other aspects of neural coding are commonly degraded and may explain impaired discrimination behavior. Two distinct phenotypic clusters with opposing neural circuit signatures are evident across mouse models. Such clustering could suggest physiological subtypes of autism, which may facilitate the development of tailored therapeutic approaches.

Rodent sensory cortex contains salt-and-pepper maps of sensory features, whose structure is not fully known. Here we investigated the structure of the salt-and-pepper whisker somatotopic map among L2/3 pyramidal neurons in somatosensory cortex, in awake mice performing one-vs-all whisker discrimination. Neurons tuned for columnar (CW) and non-columnar (non-CW) whiskers were spatially intermixed, with co-tuned neurons forming local (20 µm) clusters. Whisker tuning was markedly unstable in expert mice, with 35-46% of pyramidal cells significantly shifting tuning over 5-18 days. Tuning instability was highly concentrated in non-CW tuned neurons, and thus was structured in the map. Instability of non-CW neurons was unchanged during chronic whisker paralysis and when mice discriminated individual whiskers, suggesting it is an inherent feature. Thus, L2/3 combines two distinct components: a stable columnar framework of CW-tuned cells that may promote spatial perceptual stability, plus an intermixed, non-columnar surround with highly unstable tuning.

Children's books of Nazi propaganda prove that a society can venerate science to the point of making biology the organizing principle of its educational system yet nevertheless produce children's literature shot through with fabrication and falsehood. Three children's books of Nazi propaganda that are frequently mentioned in accounts of anti-Semitism but seldom analyzed are discussed: Elvira Bauer's "Trau keinem Fuchs auf grüner Heid und keinem Jud auf seinem Eid" (1936), Ernst Hiemer's "Der Giftpilz" (1938), and Hiemer's "Der Pudelmopsdackelpinscher" (1940) illustrate the ways in which racist science and ideological narrative tautologically reinforce each other in an extreme version of how "narratives play a key role in communicating science" (Pauwels, 2019, p. 434) in children's nonfiction. These texts of lurid racism, all issued by the book publishing arm of Julius Streicher's virulently anti-Semitic newspaper "Der Stürmer," offer a monitory case study of how bad science and toxic narrative can coalesce into a literary poison intended to indoctrinate young readers. This analysis of Nazi nonfiction for children demonstrates how science and story can be exploited to promote a racist agenda.

Anthropogenic climate change is decreasing seasonal snowpacks globally, with potentially catastrophic consequences on water resources, given the long-held reliance on snowpack in water management. In this Review, we examine the changes and trickle-down impacts of snow loss in the western United States (WUS). Across the WUS, snow water equivalent declines of ~25% are expected by 2050, with losses comparable with contemporary historical trends. There is less consensus on the time horizon of snow disappearance, but model projections combined with a new low-to-no snow definition suggest ~35–60 years before low-to-no snow becomes persistent if greenhouse gas emissions continue unabated. Diminished and more ephemeral snowpacks that melt earlier will alter groundwater and streamflow dynamics. The direction of these changes are difficult to constrain given competing factors such as higher evapotranspiration, altered vegetation composition and changes in wildfire behaviour in a warmer world. These changes undermine conventional WUS water management practices, but through proactive implementation of soft and hard adaptation strategies, there is potential to build resilience to extreme, episodic and, eventually, persistent low-to-no snow conditions. Federal investments offer a timely opportunity to address these vulnerabilities, but they require a concerted portfolio of activities that cross historically siloed physical and disciplinary boundaries.

In the decade before the U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) facility was established in 1992, early modern climate models exhibited large differences in the climate response [...]

Lidocaine hydrochloride (HCl) 2% with 1:100,000 epinephrine (LW/E) is widely used to prevent pain during dental procedures and has been associated with injection sting, jittering effects, slow onset, and a bitter aftertaste. Since LW/E's introduction in 1948, no significant modifications have been proposed. This study aims to design and characterize an improved dental lidocaine HCl injectable formulation without epinephrine (LW/O/E) via buffers, sweeteners, and amino acids. LW/O/E injections were prepared with pH and osmolality values of 6.5–7.0 and 590–610 mOsm/kg. Using the electronic tongue (ETongue), the LW/O/E injectable formulations were characterized for viscosity, injectability, and taste analysis. The results were compared with the LW/E control. In vivo efficacy and anesthetic duration of the samples were measured through radiant heat tail-flick latency (RHTFL) and hot plate (HP) tests and local toxicity was assessed after a single intra-oral injection in Sprague Dawley rats (SDR). The viscosity and injectability values of the LW/O/E samples were found to be comparable to the LW/E injection. ETongue taste analysis showed an improvement in bitterness reduction of the LW/O/E samples compared to the LW/E formulation. Toxicity studies of samples in SDR showed minor and transient signs of erythema/eschar and edema. Anesthetic duration via RHTFL and HP paw withdrawal latency time in SDR were found to be comparable for the LW/O/E Sample 3A and the LW/E injection (p < 0.05). In conclusion, the buffered, higher osmolality and reduced bitterness developed LW/O/E formulation (Sample 3A) could be considered a promising alternative to the LW/E formulation for dental use. [ABSTRACT FROM AUTHOR]

Olomeinu was a children's magazine published by Torah Umesorah, an Orthodox American Jewish educational organization, from 1945 to 2011. Founded when the American Orthodox community was in its infancy, Olomeinu tracks the renaissance of Orthodox Judaism in America and reflects the movement's search for an interpretation of the past reflecting its values. Of particular importance to the intellectual development of American Orthodox historiography was the movement's relationship with the Holocaust. From the magazine's founding in the immediate aftermath of World War II until the publication was discontinued, depiction of the Holocaust for the child readers of Olomeinu evolved from the magazine's historical backdrop to its ideological foreground. Over time, consecration of prewar European Jewry increasingly justified the religious and educational purposes of American Orthodox pedagogy. Highlighting representation of the Holocaust in Olomeinu throughout the publication's history demonstrates how the Holocaust moved from the periphery of Orthodox American Jewish pedagogy to its center. [ABSTRACT FROM AUTHOR]