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  1. Free, publicly-accessible full text available October 23, 2024
  2. The nitrogen-interrupted Nazarov cyclization can be a powerful method for the stereocontrolled synthesis of sp 3 -rich N -heterocycles. However, due to the incompatibility between the basicity of nitrogen and the acidic reaction conditions, examples of this type of Nazarov cyclization are scarce. Herein, we report a one-pot nitrogen-interrupted halo -Prins/ halo -Nazarov coupling cascade that joins two simple building blocks, an enyne and a carbonyl partner, to furnish functionalized cyclopenta[ b ]indolines with up to four contiguous stereocenters. For the first time, we provide a general method for the alkynyl halo -Prins reaction of ketones, thus enabling the formation of quaternary stereocenters. Additionally, we describe the outcomes of secondary alcohol enyne couplings, which exhibit helical chirality transfer. Furthermore, we investigate the impact of aniline enyne substituents on the reaction and evaluate the tolerance of different functional groups. Finally, we discuss the reaction mechanism and demonstrate various transformations of the prepared indoline scaffolds, highlighting their applicability in drug discovery campaigns. 
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    Free, publicly-accessible full text available May 24, 2024
  3. R. Causse (Ed.)
    Here we present length-weight relationships (LWR) for 11 reef fish species from eight islands in French Polynesia. A total of 1,930 fish were collected from five islands in the Society Archipelago (Moorea, Tahiti, Raiatea, Huahine, Tetiaroa) and in three atolls of the Tuamotu Archipelago (Takapoto, Tikehau, and Rangiroa). These fishes span trophic levels, including planktivores, herbivores, and carnivores, and are among the most abundant species for the region. Estimates include LWRs for species never previously published or available in the literature or accessible databases. Measurements of total length (TL: 0.1 cm precision) and total weight (W: 0.01 g precision) were taken. These estimates increase the number of available and robust LWRs for coral reef fishes, providing a better understanding of patterns of growth for these species. With a particular focus on small-bodied species, among the most abundant observed in underwater visual censuses, these estimates will allow marine resource managers and local scientists to characterize fish biomass in French Polynesia with greater precision. 
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    Free, publicly-accessible full text available September 11, 2024
  4. Alternative polymer feedstocks are highly desirable to address environmental, social, and security concerns associated with petrochemical-based materials. Lignocellulosic biomass (LCB) has emerged as one critical feedstock in this regard because it is an abundant and ubiquitous renewable resource. LCB can be deconstructed to generate valuable fuels, chemicals, and small molecules/oligomers that are amenable to modification and polymerization. However, the diversity of LCB complicates the evaluation of biorefinery concepts in areas including process scale-up, production outputs, plant economics, and life-cycle management. We discuss aspects of current LCB biorefinery research with a focus on the major process stages, including feedstock selection, fractionation/deconstruction, and characterization, along with product purification, functionalization, and polymerization to manufacture valuable macromolecular materials. We highlight opportunities to valorize underutilized and complex feedstocks, leverage advanced characterization techniques to predict and manage biorefinery outputs, and increase the fraction of biomass converted into valuable products. 
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    Free, publicly-accessible full text available April 11, 2024
  5. We report a Brønsted acid-catalyzed carbocyclization cascade, featuring condensation of an alcohol/sulfonamide with an aldehyde followed by an intramolecular three-component coupling involving an alkyne, an oxocarbenium/iminium ion, and an arene. A formal cycloaddition is embedded in the cationic cascade, which enables the synthesis of a wide range of fused heterotricycles. The diastereoselectivity of the cascade is studied using secondary alcohols/sulfonamides with different carbonyl partners. The described method results in the preparation of synthetically versatile scaffolds with ample opportunity for further derivatization at the resulting tetrasubstituted olefin, or by inclusion of other functionalizable motifs from the starting materials. It is worth noting that this chemistry also facilitates the synthesis of piperidines and 1,4-oxazepanes, as well as the inclusion of indoles and benzofurans, which are privileged motifs for medicinal chemistry. Herein we present the generality of this approach and some chemical transformations that can be achieved with our substrates. 
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  6. Piezo1 is the stretch activated Ca2+channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells using a combination of super-resolution microscopy techniques and electron microscopy. Piezo1 adopts a non-uniform distribution on the red blood cell surface, with a bias toward the biconcave ‘dimple’. Trajectories of diffusing Piezo1 molecules, which exhibit confined Brownian diffusion on short timescales and hopping on long timescales, also reflect a bias toward the dimple. This bias can be explained by ‘curvature coupling’ between the intrinsic curvature of the Piezo dome and the curvature of the red blood cell membrane. Piezo1 does not form clusters with itself, nor does it colocalize with F-actin, Spectrin, or the Gardos channel. Thus, Piezo1 exhibits the properties of a force-through-membrane sensor of curvature and lateral tension in the red blood cell. 
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  7. Abstract During recent decades, pathogens that originated in bats have become an increasing public health concern. A major challenge is to identify how those pathogens spill over into human populations to generate a pandemic threat 1 . Many correlational studies associate spillover with changes in land use or other anthropogenic stressors 2,3 , although the mechanisms underlying the observed correlations have not been identified 4 . One limitation is the lack of spatially and temporally explicit data on multiple spillovers, and on the connections among spillovers, reservoir host ecology and behaviour and viral dynamics. We present 25 years of data on land-use change, bat behaviour and spillover of Hendra virus from Pteropodid bats to horses in subtropical Australia. These data show that bats are responding to environmental change by persistently adopting behaviours that were previously transient responses to nutritional stress. Interactions between land-use change and climate now lead to persistent bat residency in agricultural areas, where periodic food shortages drive clusters of spillovers. Pulses of winter flowering of trees in remnant forests appeared to prevent spillover. We developed integrative Bayesian network models based on these phenomena that accurately predicted the presence or absence of clusters of spillovers in each of the 25 years. Our long-term study identifies the mechanistic connections between habitat loss, climate and increased spillover risk. It provides a framework for examining causes of bat virus spillover and for developing ecological countermeasures to prevent pandemics. 
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  8. Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the viability of upper and lower motor neurons. Current options for treatment are limited, necessitating deeper understanding of the mechanisms underlying ALS pathogenesis. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a six-transmembrane protein that acts on the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers some proteins to the membrane. GDE2 is required for the survival of spinal motor neurons but whether GDE2 neuroprotective activity is disrupted in ALS is not known. We utilized a combination of mouse models and patient post-mortem samples to evaluate GDE2 functionality in ALS. Haplogenetic reduction of GDE2 exacerbated motor neuron degeneration and loss in SOD1 G93A mice but not in control SOD1 WT transgenic animals, indicating that GDE2 neuroprotective function is diminished in the context of SOD1 G93A . In tissue samples from patients with ALS, total levels of GDE2 protein were equivalent to healthy controls; however, membrane levels of GDE2 were substantially reduced. Indeed, GDE2 was found to aberrantly accumulate in intracellular compartments of ALS motor cortex, consistent with a disruption of GDE2 function at the cell surface. Supporting the impairment of GDE2 activity in ALS, tandem-mass-tag mass spectrometry revealed a pronounced reduction of GPI-anchored proteins released into the CSF of patients with ALS compared with control patients. Taken together, this study provides cellular and biochemical evidence that GDE2 distribution and activity is disrupted in ALS, supporting the notion that the failure of GDE2-dependent neuroprotective pathways contributes to neurodegeneration and motor neuron loss in disease. These observations highlight the dysregulation of GPI-anchored protein pathways as candidate mediators of disease onset and progression and accordingly, provide new insight into the mechanisms underlying ALS pathogenesis. 
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