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Palladium-catalyzed enantioselective β-hydride elimination for the construction of remote stereocenters
A robust crystal structure prediction method to support small molecule drug development with large scale validation and blind study
Neural Correlates of Perceptual Plasticity in the Auditory Midbrain and Thalamus
Hearing is an active process in which listeners must detect and identify sounds, segregate and discriminate stimulus features, and extract their behavioral relevance. Adaptive changes in sound detection can emerge rapidly, during sudden shifts in acoustic or environmental context, or more slowly as a result of practice. Although we know that context- and learning-dependent changes in the sensitivity of auditory cortical (ACX) neurons support many aspects of perceptual plasticity, the contribution of subcortical auditory regions to this process is less understood. Here, we recorded single- and multiunit activity from the central nucleus of the inferior colliculus (ICC) and the ventral subdivision of the medial geniculate nucleus (MGV) of male and female Mongolian gerbils under two different behavioral contexts: as animals performed an amplitude modulation (AM) detection task and as they were passively exposed to AM sounds. Using a signal detection framework to estimate neurometric sensitivity, we found that neural thresholds in both regions improve during task performance, and this improvement is largely driven by changes in the firing rate rather than phase locking. We also found that ICC and MGV neurometric thresholds improve as animals learn to detect small AM depths during a multiday perceptual training paradigm. Finally, we revealed that in the MGV, but not the ICC, context-dependent enhancements in AM sensitivity grow stronger during perceptual training, mirroring prior observations in the ACX. Together, our results suggest that the auditory midbrain and thalamus contribute to changes in sound processing and perception over rapid and slow timescales.
Host ecology and phylogeny shape the temporal dynamics of social bee viromes
Abstract The composition of viral communities (i.e. viromes) can be dynamic and complex. Co-evolution may lead to virome host-specificity. However, eco-evolutionary factors may influence virome dynamics in wild host communities, potentially leading to disease emergence. Social bees are relevant models to address the drivers of virome composition: these important pollinators form multi-species assemblages, with high niche overlap and strong seasonality in their biotic interactions. We applied a microbial community approach to disentangle the role of host phylogeny and host ecology in shaping bee viromes, combining plant-pollinator networks with meta-transcriptomics, and small interfering RNAs as proxies for viral replication in pollinators and pollen. We identified over a hundred insect and plant viral sequences from ca. 4500 insect pollinator samples across three time points in one year. While host genetic distance drives the distribution of bee viruses, we find that plant-pollinator interactions and phenology drive plant virus communities collected by bees. This reveals the opportunities for virus spread in the bee assemblage. However, we show that transmission to multiple hosts is only realized for a fraction of insect viruses, with even fewer found to be actively replicating in multiple species, including the particularly virulent multi-host acute bee paralysis virus.
Pressure-induced charge amorphisation in BiNiO3
Abstract The order or disorder of electrons is fundamental to materials properties and also provides simple analogues to the different states of matter. A charge ordered (CO) insulating state, analogous to a crystalline solid, is observed in many mixed valence materials. On heating, this melts to a charge liquid (metallic) phase, often with interesting associated physics and functions such as the Verwey transition of Fe 3 O 4 , colossal magnetoresistances in manganites (e.g., La 0.5 Ca 0.5 MnO 3 ), and superconductivity in K-doped BaBiO 3 . Here we report the observation of pressure induced charge amorphisation in a crystalline material. BiNiO 3 has charge distribution Bi 3+ 0.5 Bi 5+ 0.5 Ni 2+ O 3 with long range order of the Bi 3+ and Bi 5+ states at ambient pressure, but adopts another, structurally crystalline, but charge glassy, insulating phase at pressures of 4–5 GPa and temperatures below 200 K, before metallization above 6 GPa. This is analogous to the much-studied pressure induced amorphisations of many crystalline materials and melting is even observed at accessible pressure/temperature. BiNiO 3 provides fundamental insights to the study of amorphisation using charge states rather than atoms or molecules.
Analysis of human urinary extracellular vesicles reveals disordered renal metabolism in myotonic dystrophy type 1
Dimensional evolution of charge mobility and porosity in covalent organic frameworks
Abstract Covalent organic frameworks are an emerging class of covalently linked polymers with programmable lattices and well-defined nanopores. Developing covalent organic frameworks with both high porosity and excellent charge transport properties is crucial for widespread applications, including sensing, catalysis, and organic electronics. However, achieving the combination of both features remains challenging due to the lack of overarching structure-property correlations. Here, we report a strategy toward covalent organic frameworks with tunable dimensionality. The concept relies on splicing one-dimensional charge-conducting channels to form extended networks with tailorable substitution patterns. Such dimensional evolution and substitution control enable fine-tuning of electronic band structure, charge mobility, and porosity. According to surface-area characterization, high-frequency terahertz photoconductivity measurements, and theoretical calculations, the transition from one-dimensional to para-linked two-dimensional networks furnishes a substantial increase in surface area and a decrease in local charge mobility. The latter feature is assigned to substitution-induced electronic band flattening. A subtle balance of surface area (947 m2·g−1) and local charge mobility (49 ± 10 cm2·V−1·s−1) is achieved through the rational design of meta-linked analogs with mixed one-dimensional and two-dimensional superior nature. This work provides fundamental insights and new structural knobs for the design of conductive covalent organic frameworks.
Author Correction: Bioprinting of bespoke islet-specific niches to promote maturation of stem cell-derived islets
Structural basis for the allosteric activation of Lon by the heat shock protein LarA
Weakly Bound but Strongly Interacting: The Structures, Stabilities, and Dynamics of Osmium(II) Ethane, Propane, and Butane Complexes
Marine ecosystem role in setting up preindustrial and future climate
Abstract The ocean ecosystem is a vital component of the global carbon cycle, storing enough carbon to keep atmospheric CO2 considerably lower than it would otherwise be. However, this conception is based on simple models, neglecting the coupled land-ocean feedback. Using an interactive Earth system model, we show that the role ocean biology plays in controlling atmospheric CO2 is more complex than previously thought. Atmospheric CO2 in a new equilibrium state after the biological pump is shut down increases by more than 50% (163 ppm), lower than expected as approximately half the carbon lost from the ocean is adsorbed by the land. The abiotic ocean is less capable of taking up anthropogenic carbon due to the warmer climate, an absent biological surface pCO2 deficit and a higher Revelle factor. Prioritizing research on and preserving marine ecosystem functioning would be crucial to mitigate climate change and the risks associated with it.
Dynamic <i>In Vivo</i> Mapping of the Methylproteome Using a Chemoenzymatic Approach
Publisher Correction: Herpesviruses mimic zygotic genome activation to promote viral replication
Melanin-Concentrating Hormone Projections to the Nucleus Accumbens Enhance the Reward Value of Food Consumption and Do Not Induce Feeding or REM Sleep
Regulation of food intake and energy balance is critical to survival. Hunger develops as a response to energy deficit and drives food-seeking and consumption. However, motivations to eat are varied in nature and promoted by factors other than energy deficit. When dysregulated, nonhomeostatic drives to consume can contribute to disorders of food intake, adding to the increasing prevalence of restrictive eating disorders and obesity. Melanin-concentrating hormone (MCH) neurons have been implicated in the regulation of feeding behavior, in addition to a number of other fundamental behaviors including sleep, anxiety, and maternal behavior. Several studies suggest that MCH peptide increases food consumption, while studies of MCH neurons show effects only on cued feeding, and others show no effect of MCH neuron manipulation on feeding. MCH neurons have widespread projections to diverse downstream brain regions, yet few studies have investigated the function of specific projections or differentiated the behaviors they regulate. Here we use optogenetics, in combination with different behavioral paradigms, to elucidate the role of MCH projections to the nucleus accumbens (NAc) in sleep and feeding behavior. We show that MCH neurons projecting to the NAc do not induce changes in baseline feeding or REM sleep but do enhance the preference for a food paired with optogenetic stimulation. Furthermore, this effect is diminished in female mice relative to males, in line with previous results suggesting sex differences in the functional role of MCH neurons. These results suggest that MCH projections to the NAc can enhance the rewarding value of consumed food.
Assessing the role of children in the COVID-19 pandemic in Belgium using perturbation analysis
Abstract Understanding the evolving role of different age groups in virus transmission is essential for effective pandemic management. We investigated SARS-CoV-2 transmission in Belgium from November 2020 to February 2022, focusing on age-specific patterns. Using a next generation matrix approach integrating social contact data and simulating population susceptibility evolution, we performed a longitudinal perturbation analysis of the effective reproduction number to unravel age-specific transmission dynamics. From November to December 2020, adults in the [18, 60) age group were the main transmission drivers, while children contributed marginally. This pattern shifted between January and March 2021, when in-person education resumed, and the Alpha variant emerged: children aged under 12 years old were crucial in transmission. Stringent social distancing measures in March 2021 helped diminish the noticeable contribution of the [18, 30) age group. By June 2021, as the Delta variant became the predominant strain, adults aged [18, 40) years emerged as main contributors to transmission, with a resurgence in children’s contribution during September-October 2021. This study highlights the effectiveness of our methodology in identifying age-specific transmission patterns.
Ancient humans used bone tools one million years earlier than thought
p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells
Abstract Genomic instability and inflammation are distinct hallmarks of aging, but the connection between them is poorly understood. Here we report a mechanism directly linking genomic instability and inflammation in senescent cells through a mitochondria-regulated molecular circuit involving p53 and cytoplasmic chromatin fragments (CCF) that are enriched for DNA damage signaling marker γH2A.X. We show that p53 suppresses CCF accumulation and its downstream inflammatory phenotype. p53 activation suppresses CCF formation linked to enhanced DNA repair and genome integrity. Activation of p53 in aged mice by pharmacological inhibition of MDM2 reverses transcriptomic signatures of aging and age-associated accumulation of monocytes and macrophages in liver. Mitochondrial ablation in senescent cells suppresses CCF formation and activates p53 in an ATM-dependent manner, suggesting that mitochondria-dependent formation of γH2A.X + CCF dampens nuclear DNA damage signaling and p53 activity. These data provide evidence for a mitochondria-regulated p53 signaling circuit in senescent cells that controls DNA repair, genome integrity, and senescence- and age-associated inflammation, with relevance to therapeutic targeting of age-associated disease.