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Cerebral strokes can disrupt descending commands from motor cortical areas to the spinal cord, which can result in permanent motor deficits of the arm and hand. However, below the lesion, the spinal circuits that control movement remain intact and could be targeted by neurotechnologies to restore movement. Here we report results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis ( NCT04512690 ). Participants were implanted for 29 d with two linear leads in the dorsolateral epidural space targeting spinal roots C3 to T1 to increase excitation of arm and hand motoneurons. We found that continuous stimulation through selected contacts improved strength (for example, grip force +40% SCS01; +108% SCS02), kinematics (for example, +30% to +40% speed) and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported. While we cannot conclusively evaluate safety and efficacy from two participants, our data provide promising, albeit preliminary, evidence that spinal cord stimulation could be an assistive as well as a restorative approach for upper-limb recovery after stroke. Electrical stimulation of cervical spinal circuits facilitates arm and hand movements in two participants with moderate and severe chronic post-stroke hemiparesis.

In the ProtecT trial, over 1600 men with PSA-detected localized prostate cancer were assigned to active monitoring, prostatectomy, or radiotherapy. Although more patients assigned to active monitoring had disease progression, overall survival was similar in the three groups. The management of clinically localized prostate cancer that is detected on the basis of prostate-specific antigen (PSA) levels remains controversial. In the United States alone, an estimated 180,890 cases will be diagnosed in 2016, and 26,120 men will die from the disease. 1 The widespread use of PSA testing has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer, but many men do not benefit from intervention because the disease is either indolent or disseminated at diagnosis. Prostate cancer often progresses slowly, and many men die of competing causes. In addition, interventions for prostate cancer can have . . .

In men with prostate cancer on PSA screening, radical treatments led to half the incidence of metastasis and local progression as active monitoring without affecting disease-specific or overall survival.

The blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal is commonly used to assess functional connectivity across brain regions, particularly in the resting state (rs-fMRI). However, the BOLD fMRI signal is not merely a representation of neural activity, but a combination of neural activity and vascular response. These aspects of the BOLD signal are easily influenced by systemic physiology, potentially biasing BOLD-based functional connectivity measurements. In this work, we focus on the following physiological modulators of the BOLD signal: cerebral blood flow (CBF), venous blood oxygenation, and cerebrovascular reactivity (CVR). We use simulations and experiments to examine the relationship between the physiological parameters and rs-fMRI functional connectivity measurements in three resting-state networks: default mode network, somatosensory network and visual network. By using the general linear model, we demonstrate that physiological modulators significantly impact functional connectivity measurements in these regions, but in a manner that depends on the interplay between signal- and noise-driven correlations. Moreover, we find that the physiological effects vary by brain region and depend on the range of physiological conditions probed; the associations are more complex than previously reported. The results confirm that it is important to account for the effect of physiological modulators when comparing resting-state fMRI metrics. We note that such modulatory effects may be amplified by disease conditions, which will warrant future investigations. •We characterize the effect of physiological metrics on resting-state fMRI.•Metrics include cerebral blood flow (CBF), venous blood oxygenation, and cerebrovascular reactivity (CVR).•Physiological variables significantly impact functional connectivity values.•This impact depends heavily on the interplay between signal- and noise-driven correlations.•The physiological effects vary by brain region and range of physiological conditions probed.

The origin of species diversity has challenged biologists for over two centuries. Allopatric speciation, the divergence of species resulting from geographical isolation, is well documented. However, sympatric speciation, divergence without geographical isolation, is highly controversial. Claims of sympatric speciation must demonstrate species sympatry, sister relationships, reproductive isolation, and that an earlier allopatric phase is highly unlikely. Here we provide clear support for sympatric speciation in a case study of two species of palm (Arecaceae) on an oceanic island. A large dated phylogenetic tree shows that the two species of Howea, endemic to the remote Lord Howe Island, are sister taxa and diverged from each other well after the island was formed 6.9 million years ago. During fieldwork, we found a substantial disjunction in flowering time that is correlated with soil preference. In addition, a genome scan indicates that few genetic loci are more divergent between the two species than expected under neutrality, a finding consistent with models of sympatric speciation involving disruptive/divergent selection. This case study of sympatric speciation in plants provides an opportunity for refining theoretical models on the origin of species, and new impetus for exploring putative plant and animal examples on oceanic islands.

Hierarchical multiple stellar systems with short outer periods comprise an important subgroup of multiple star systems. In this paper we present the discovery and spectro-photodynamical analysis of the most compact known 3+1 quadruple stellar system, TIC 120362137. Through investigations of the observations made with the TESS satellite and ground-based follow up measurements, we find that the system consists of an eclipsing binary with a few-day-period that in turn eclipses, and is eclipsed by, a third star on a P mid  = 51.3 d orbit. This inner subsystem, which contains three stars that are more massive and hotter than the Sun, is more spatially compact than Mercury’s orbit around our Sun, and is orbited by a fourth Sun-like star with a period P out  = 1046 d. We detect the spectral lines of all four stars, making this system the most thoroughly studied 3+1 type quadruple stellar system. The future evolution of TIC 120362137 is also modeled, and we conclude that this entire system will likely end up as a pair of white dwarfs. There are only a few 3+1-type stellar systems known. Here the authors show that TIC 120362137 is the most compact hierarchical quadruple star, with three stars revolving within an area smaller than Mercury’s orbit, while the fourth star orbits closer to them than Jupiter from our Sun.

Whole transcriptome amplification (WTA2) and sequence-independent single primer amplification (SISPA) are two widely used methods for combined metagenomic sequencing of RNA and DNA viruses. However, information on the reproducibility and bias of these methods on diverse viruses in faecal samples is currently lacking. A mock community (MC) of diverse viruses was developed and used to spike faecal samples at different concentrations. Virus-like particles (VLPs) were extracted, nucleic acid isolated, reverse-transcribed, and PCR amplified using either WTA2 or SISPA and sequenced for metagenomic analysis. A bioinformatics pipeline measured the recovery of MC viruses in replicates of faecal samples from three human donors, analysing the consistency of viral abundance measures and taxonomy. Viruses had different recovery levels with VLP extraction introducing variability between replicates, while WTA2 and SISPA produced comparable results. In comparing WTA2- and SISPA-generated libraries, WTA2 gave more uniform coverage depth profiles and improved assembly quality and virus identification. SISPA produced more consistent abundance, with a 50% difference between replicates occurring in ~20% and ~10% of sequences for WTA2 and SISPA, respectively. In conclusion, a bioinformatics pipeline has been developed to assess the methodological variability and bias of WTA2 and SISPA, demonstrating higher sensitivity with WTA2 and higher consistency with SISPA.

The availability of small, lightweight tracking devices enhances our ability to study birds during mobile phases of their lives. Tree Swallows Tachycineta bicolor, a model species of wild songbird, are well-studied during their breeding season; but our understanding of their biology at other times of the year, when they are not tied to the fixed location of a nest, is more limited. We developed a lightweight radio tag with no battery (solar nanotag) to study the movements of small animals, and we deployed it to explore the behavior of Tree Swallows after the end of their summer breeding season. We tagged 32 breeding adult swallows and 36 juveniles and monitored their presence and absence at the breeding site during the post-fledging period. Although our observations are based on very small sample sizes, the tags revealed previously unknown patterns in Tree Swallow behavior during the post-breeding season. Some Tree Swallow fledglings continued to visit the site repeatedly in the months following the nesting season, with the latest detection occurring on September 30th; by contrast, all adults had permanently departed by the end of July. These results inform future hypotheses about post-breeding movements in Tree Swallows. But, more generally, the detection of tagged swallows on their distant wintering grounds, seven months after tagging, indicates the potential of studying small passerine movements throughout their entire lifetimes, and suggests a rich array of applications for these \"Life Tags\" to study the movements of small animals world-wide.

ATG16L1, an autophagy mediator that specifies the site of LC3 lipidation, includes a C-terminal domain formed by 7 WD40-type repeats (WD40 domain, WDD), the function of which is unclear. Here we show that the WDD interacts with the intracellular domain of cytokine receptors to regulate their signaling output in response to ligand stimulation. Using a refined version of a previously described WDD-binding amino acid motif, here we show that this element is present in the intracellular domain of cytokine receptors. Two of these receptors, IL-10RB and IL-2Rγ, recognize the WDD through the motif and exhibit WDD-dependent LC3 lipidation activity. IL-10 promotes IL-10RB/ATG16L1 interaction through the WDD, and IL-10 signaling is suboptimal in cells lacking the WDD owing to delayed endocytosis and inefficient early trafficking of IL10/IL-10R complexes. Our data reveal WDD-dependent roles of ATG16L1 in the regulation of cytokine receptor trafficking and signaling, and provide a WDD-binding motif that might be used to identify additional WDD activators. The WD40 domain of ATG16L1 is thought to be involved in non-canonical autophagy. Here the authors screen peptide libraries and identify interactions between this domain and the IL-2Rγ and IL-10RB receptors, indicating endosomal regulation of cytokine signalling by non-canonical autophagy.

Background Skeletal muscle mass and function are partly maintained by the supply of amino acids, altered amino acid transport is an important cause of frailty that can lead to decreased independence with increasing age and slow trauma recovery. The system‐A sodium coupled neutral amino acid transporter (SNAT)‐2 coded by gene family SLC38A2 generates a 506 amino acid 56 kDa protein that is an important transporter of amino acids in skeletal muscle. Ageing is associated with a decrease in expression of SNAT2 transporters. Methods In this study, we used the C2C12 cell line, using myoblast cells and cells differentiated into myotubes. We investigated if the expression of SNAT2 DNA would enhance intracellular amino acid levels and increase their availability for protein synthesis. Results In control myoblasts and myotubes, we found significantly decreased expression of SNAT2 (6.5× decrease, n = 4 per group, P < 0.05) in myotubes than found in myoblasts. After transfection with a SNAT2‐eGFP cDNA plasmid, C2C12 myoblasts significantly increased perinuclear punctate SNAT2‐eGFP expression that persisted and was more cytoplasmic after differentiation into myotubes. Interestingly, transfected cells were significantly more responsive to the hormone 5α‐dihydrotestosterone (DHT, 4.5 nM, by 1.6×, n = 3 per group, P < 0.04). Starvation significantly enhanced the amino acid C14‐MeAIB transport (1.7×, n = 3 per group, P < 0.05) indicating increased function of SNAT2. Inhibiting SNAT2 with high concentrations of MeAIB (3.3 or 5 mM) significantly reduced C14‐Isoleucine transport by L‐type amino acid transporter (LAT2, 52.8% and 77%, respectively, n = 3 per group, P < 0.05). However, there was no increase in the LAT2 transport of C14‐isoleucine detectable in SNAT2‐eGFP transfected cells after DHT (4.5 nM) exposure. This indicated that small amino acid availability was not rate limiting to LAT2 function in myoblasts. Conclusions Overall, these data show that transfection of SNAT2‐eGFP expression enhanced its function following starvation and treatment with physiological levels of DHT. Enhanced SNAT2 expression in muscle cells offers a viable epigenetic target in pathological conditions associated with altered amino acid transport.