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Nicotinamide adenine dinucleotide (NAD + ) has emerged as a critical co-substrate for enzymes involved in the beneficial effects of regular calorie restriction on healthspan. As such, the use of NAD + precursors to augment NAD + bioavailability has been proposed as a strategy for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence in a 2 × 6-week randomized, double-blind, placebo-controlled, crossover clinical trial that chronic supplementation with the NAD + precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD + metabolism in healthy middle-aged and older adults. Our results also provide initial insight into the effects of chronic NR supplementation on physiological function in humans, and suggest that, in particular, future clinical trials should further assess the potential benefits of NR for reducing blood pressure and arterial stiffness in this group. Declining NAD + levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD + levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.

Viral infection of the heart is a common but underappreciated cause of heart failure. Viruses can cause direct cardiac damage by lysing infected cardiomyocytes. Inflammatory immune responses that limit viral replication can also indirectly cause damage during infection, making regulatory factors that fine-tune these responses particularly important. Identifying and understanding these factors that regulate cardiac immune responses during infection will be essential for developing targeted treatments for virus-associated heart failure. Our laboratory has discovered Brain Expressed X-linked protein 1 (BEX1) as a novel stress-regulated pro-inflammatory factor in the heart. Here we report that BEX1 plays a cardioprotective role in the heart during viral infection. Specifically, we adopted genetic gain- and loss-of-function strategies to modulate BEX1 expression in the heart in the context of coxsackievirus B3 (CVB3)-induced cardiomyopathy and found that BEX1 limits viral replication in cardiomyocytes. Interestingly, despite the greater viral load observed in mice lacking BEX1, inflammatory immune cell recruitment in the mouse heart was profoundly impaired in the absence of BEX1. Overall, the absence of BEX1 accelerated CVB3-driven heart failure and pathologic heart remodeling. This result suggests that limiting inflammatory cell recruitment has detrimental consequences for the heart during viral infections. Conversely, transgenic mice overexpressing BEX1 in cardiomyocytes revealed the efficacy of BEX1 for counteracting viral replication in the heart in vivo . We also found that BEX1 retains its antiviral role in isolated cells. Indeed, BEX1 was necessary and sufficient to counteract viral replication in both isolated primary cardiomyocytes and mouse embryonic fibroblasts suggesting a broader applicability of BEX1 as antiviral agent that extended to viruses other than CVB3, including Influenza A and Sendai virus. Mechanistically, BEX1 regulated interferon beta (IFN-β) expression in infected cells. Overall, our study suggests a multifaceted role of BEX1 in the cardiac antiviral immune response.

High-entropy alloys (HEAs) are a class of alloys that are being considered for a number of applications. In the present study, the microstructures and 1050°C oxidation behaviors of two HEAs, Al 10 Cr 22.5 Co 22.5 Ni 22.5 Fe 22.5 (at.%) and Al 20 Cr 25 Co 25 Ni 25 Si 5 have been investigated along with Al 15 Cr 10 Co 35 Ni 35 Si 5 , which is a high-temperature shape-memory alloy. Oxide formation occurred via selective oxidation in a manner that was consistent with the oxide formation model devised by Giggins and Pettit for model Ni-Cr-Al alloys. The lower Al content alloy formed an external Cr 2 O 3 scale and an internal subscale consisting of Al 2 O 3 and AlN precipitates. The higher Al content alloys exhibited smaller mass gains and formed external Al 2 O 3 scales without any internal oxidation of the alloys.

A laser–plasma accelerator delivering 5-MeV electrons at kHz repetition rate is demonstrated. It is achieved in the laser-wakefield-acceleration regime by using a multi-mJ laser system delivering near-single-cycle laser pulses of 3.4-fs duration. Laser–plasma acceleration 1 , 2 is an emerging technique for accelerating electrons to high energies over very short distances. The accelerated electron bunches have femtosecond duration 3 , 4 , making them particularly relevant for applications such as ultrafast imaging 5 or femtosecond X-ray generation 6 , 7 . Current laser–plasma accelerators deliver 100 MeV (refs  8 – 10 ) to GeV (refs  11 , 12 ) electrons using Joule-class laser systems that are relatively large in scale and have low repetition rates, with a few shots per second at best. Nevertheless, extending laser–plasma acceleration to higher repetition rates would be extremely useful for applications requiring lower electron energy. Here, we use single-cycle laser pulses to drive high-quality MeV relativistic electron beams, thereby enabling kHz operation and dramatic downsizing of the laser system. Numerical simulations indicate that the electron bunches are only ∼1 fs long. We anticipate that the advent of these kHz femtosecond relativistic electron sources will pave the way to applications with wide impact, such as ultrafast electron diffraction in materials 13 , 14 with an unprecedented sub-10 fs resolution 15 .

Viruses are an underappreciated cause of heart failure. Indeed, several types of viral infections carry cardiovascular risks. Understanding shared and unique mechanisms by which each virus compromises heart function is critical to inform on therapeutic interventions. This review describes how the key viruses known to lead to cardiac dysfunction operate. Both direct host-damaging mechanisms and indirect actions on the immune systems are discussed. As viral myocarditis is a key pathologic driver of heart failure in infected individuals, this review also highlights the role of cytokine storms and inflammation in virus-induced cardiomyopathy.

Paludiculture, the productive use of wet or rewetted peatlands, offers an option for continued land use by farmers after rewetting formerly drained peatlands, while reducing the greenhouse gas emissions from peat soils. Biodiversity conservation may benefit, but research on how biodiversity responds to paludiculture is scarce. We conducted a multi-taxon study investigating vegetation, breeding bird and arthropod diversity at six rewetted fen sites dominated by Carex or Typha species. Sites were either unharvested, low- or high-intensity managed, and were located in Mecklenburg-Vorpommern in northeastern Germany. Biodiversity was estimated across the range of Hill numbers using the iNEXT package, and species were checked for Red List status. Here we show that paludiculture sites can provide biodiversity value even while not reflecting historic fen conditions; managed sites had high plant diversity, as well as Red Listed arthropods and breeding birds. Our study demonstrates that paludiculture has the potential to provide valuable habitat for species even while productive management of the land continues.

Drought intensity is commonly characterized using meteorologically‐based metrics that do not provide insight into water deficits within deeper hydrologic systems. In contrast, global positioning system (GPS) displacements are sensitive to both local and regional hydrologic‐storage fluctuations. While a few studies have leveraged this sensitivity to produce geodetic drought indices, hydrologic drought characterization using GPS is not commonly accounted for in drought assessment and management. To motivate this application, we produce a new geodetic drought index (GDI) and quantify its ability to characterize hydrologic drought conditions in key surface and sub‐surface hydrologic reservoirs/pools across California. In northern California, the GDI exhibits a strong regional association with surface‐reservoir storage at the 1‐month time scale (correlation coefficient: 0.83) and groundwater levels at the 3‐month time scale (correlation coefficient: 0.87), along with moderate associations with stream discharge at the daily (instantaneous) time scale (correlation coefficient: 0.50). Groundwater in southern California is best characterized with a 12‐month GDI (correlation coefficient: 0.77), and surface‐reservoir storage is optimized with the 3‐month GDI (correlation coefficient: 0.72). Two sigma uncertainties are ±0.03. Differences between northern and southern California reveal that the GDI is sensitive to unique aquifer and drainage basin characteristics. In addition to capturing long‐term hydrologic trends, rapid changes in the GDI initiate during clusters of large atmospheric river events that closely mirror fluctuations in traditional hydrologic and meteorological observations. We show that GPS‐based hydrologic drought indices provide a significant opportunity to improve drought assessment, in California and beyond, by improving our understanding of the hydrologic cycle. Plain Language Summary Although quantifying the total volume of water loss is of critical importance during periods of drought, drought intensity is often characterized using meteorologic observations, such as precipitation, rather than using more holistic hydrologic observations, such as reservoir levels and groundwater. While precipitation is a good measure of the amount of water entering a region, precipitation models do not determine the amount of water retained in a watershed or the amount lost due to runoff and evapotranspiration, which are important factors for drought management. We address this need by producing a hydrologically based drought index that captures changes in both surface and subsurface hydrologic reservoirs/pools using surface‐loading geodesy, which quantifies changes in water volume based on how the shape of the Earth changes under the weight of the water. In this study, we use three‐dimensional global positioning system data to develop a geodetic drought index (GDI). Comparison with independent hydrologic observations indicates strong regional and temporal correlations with reservoir storage, groundwater fluctuations, and stream discharge observations, suggesting the GDI can effectively characterize variations in total hydrologic storage. The GDI provides an opportunity to improve hydrologic models for drought management and to advance our understanding of the water cycle. Key Points Current drought assessment methods rely primarily on meteorologic drought indices that do not characterize total water storage The geodetic drought index quantifies hydrologic drought and is especially sensitive to groundwater and surface‐reservoir storage Drought metrics based on geodetic data improve characterization of total water storage, providing unique insight for drought management

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed. Clinical Trials.gov registration: NCT03743636. In peripheral artery disease (PAD), this randomized trial assessed whether nicotinamide riboside (NR), with and without resveratrol, improved walking, compared to placebo. Here, the authors show that NR meaningfully improves 6-min walk, and resveratrol did not add benefit to NR alone.

Cells generate diverse microtubule populations by polymerization of a common alpha/beta-tubulin building block. How microtubule associated proteins translate microtubule heterogeneity into specific cellular functions is not clear. We evaluated the ability of kinesin motors involved in vesicle transport to read microtubule heterogeneity by using single molecule imaging in live cells. We show that individual Kinesin-1 motors move preferentially on a subset of microtubules in COS cells, identified as the stable microtubules marked by post-translational modifications. In contrast, individual Kinesin-2 (KIF17) and Kinesin-3 (KIF1A) motors do not select subsets of microtubules. Surprisingly, KIF17 and KIF1A motors that overtake the plus ends of growing microtubules do not fall off but rather track with the growing tip. Selection of microtubule tracks restricts Kinesin-1 transport of VSVG vesicles to stable microtubules in COS cells whereas KIF17 transport of Kv1.5 vesicles is not restricted to specific microtubules in HL-1 myocytes. These results indicate that kinesin families can be distinguished by their ability to recognize microtubule heterogeneity. Furthermore, this property enables kinesin motors to segregate membrane trafficking events between stable and dynamic microtubule populations.

Cilia dysfunction underlies a class of human diseases with variable penetrance in different organ systems. Across eukaryotes, intraflagellar transport (IFT) facilitates cilia biogenesis and cargo trafficking, but our understanding of mammalian IFT is insufficient. Here we perform live analysis of cilia ultrastructure, composition and cargo transport in native mammalian tissue using olfactory sensory neurons. Proximal and distal axonemes of these neurons show no bias towards IFT kinesin-2 choice, and Kif17 homodimer is dispensable for distal segment IFT. We identify Bardet–Biedl syndrome proteins (BBSome) as bona fide constituents of IFT in olfactory sensory neurons, and show that they exist in 1:1 stoichiometry with IFT particles. Conversely, subpopulations of peripheral membrane proteins, as well as transmembrane olfactory signalling pathway components, are capable of IFT but with significantly less frequency and/or duration. Our results yield a model for IFT and cargo trafficking in native mammalian cilia and may explain the penetrance of specific ciliopathy phenotypes in olfactory neurons. Loss of olfactory function is one of the many symptoms of the ciliopathy Bardet–Biedl syndrome. Williams et al . show that Bardet–Biedl proteins are components of intraflagellar transport particles within cilia, and directly visualize their trafficking in native mammalian olfactory neurons.