Notes

The entire chloroplast genome of Eleutherococcus gracilistylus (Watts.M.Sm.) Utes.Y.Hu (Araliaceae).
A recent report found that rare predicted loss-of-function (pLOF) variants across 13 candidate genes in TLR3- and IRF7-dependent type I IFN pathways explain up to 3.5% of severe COVID-19 cases. We performed whole-exome or whole-genome sequencing of 1,864 COVID-19 cases (713 with severe and 1,151 with mild disease) and 15,033 ancestry-matched population controls across 4 independent COVID-19 biobanks. We tested whether rare pLOF variants in these 13 genes were associated with severe COVID-19. We identified only 1 rare pLOF mutation across these genes among 713 cases with severe COVID-19 and observed no enrichment of pLOFs in severe cases compared to population controls or mild COVID-19 cases. We found no evidence of association of rare LOF variants in the 13 candidate genes with severe COVID-19 outcomes.Cerebral cavernous malformations (CCMs) are common neurovascular lesions caused by loss-of-function mutations in 1 of 3 genes, including KRIT1 (CCM1), CCM2, and PDCD10 (CCM3), and generally regarded as an endothelial cell-autonomous disease. Here we reported that proliferative astrocytes played a critical role in CCM pathogenesis by serving as a major source of VEGF during CCM lesion formation. An increase in astrocyte VEGF synthesis is driven by endothelial nitric oxide (NO) generated as a consequence of KLF2- and KLF4-dependent elevation of eNOS in CCM endothelium. CX-5461 ic50 The increased brain endothelial production of NO stabilized HIF-1α in astrocytes, resulting in increased VEGF production and expression of a "hypoxic" program under normoxic conditions. We showed that the upregulation of cyclooxygenase-2 (COX-2), a direct HIF-1α target gene and a known component of the hypoxic program, contributed to the development of CCM lesions because the administration of a COX-2 inhibitor significantly prevented the progression of CCM lesions. Thus, non-cell-autonomous crosstalk between CCM endothelium and astrocytes propels vascular lesion development, and components of the hypoxic program represent potential therapeutic targets for CCMs.Peripheral T cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcomes. The T cell receptor (TCR) is emerging as a key driver of T lymphocyte transformation. However, the role of chronic TCR activation in lymphomagenesis and in lymphoma cell survival is still poorly understood. Using a mouse model, we report that chronic TCR stimulation drove T cell lymphomagenesis, whereas TCR signaling did not contribute to PTCL survival. The combination of kinome, transcriptome, and epigenome analyses of mouse PTCLs revealed a NK cell-like reprogramming of PTCL cells with expression of NK receptors (NKRs) and downstream signaling molecules such as Tyrobp and SYK. Activating NKRs were functional in PTCLs and dependent on SYK activity. In vivo blockade of NKR signaling prolonged mouse survival, demonstrating the addiction of PTCLs to NKRs and downstream SYK/mTOR activity for their survival. We studied a large collection of human primary samples and identified several PTCLs recapitulating the phenotype described in this model by their expression of SYK and the NKR, suggesting a similar mechanism of lymphomagenesis and establishing a rationale for clinical studies targeting such molecules.In a time of upheaval, robotics has an opportunity to offer long-term solutions and radical change.The predatory strike of dragonfly larvae can inspire the design of fast robotic movement with enhanced control and precision.Sampling genetic material from phytoplankton in open ocean eddies becomes more precise and efficient using a heterogeneous network of autonomous marine robots.A swarm of agile fish-robots uses vision-based implicit coordination to demonstrate self-organizing behaviors in a laboratory tank.A squid-like robot leverages resonance to match the swimming efficiency of biological animals.Miniaturized robotic laser steering opens new horizons for laser microsurgery.Many fish species gather by the thousands and swim in harmony with seemingly no effort. Large schools display a range of impressive collective behaviors, from simple shoaling to collective migration and from basic predator evasion to dynamic maneuvers such as bait balls and flash expansion. A wealth of experimental and theoretical work has shown that these complex three-dimensional (3D) behaviors can arise from visual observations of nearby neighbors, without explicit communication. By contrast, most underwater robot collectives rely on centralized, above-water, explicit communication and, as a result, exhibit limited coordination complexity. Here, we demonstrate 3D collective behaviors with a swarm of fish-inspired miniature underwater robots that use only implicit communication mediated through the production and sensing of blue light. We show that complex and dynamic 3D collective behaviors-synchrony, dispersion/aggregation, dynamic circle formation, and search-capture-can be achieved by sensing minimal, noisy impressions of neighbors, without any centralized intervention. Our results provide insights into the power of implicit coordination and are of interest for future underwater robots that display collective capabilities on par with fish schools for applications such as environmental monitoring and search in coral reefs and coastal environments.The creation of multiarticulated mechanisms for use with minimally invasive surgical tools is difficult because of fabrication, assembly, and actuation challenges on the millimeter scale of these devices. Nevertheless, such mechanisms are desirable for granting surgeons greater precision and dexterity to manipulate and visualize tissue at the surgical site. Here, we describe the construction of a complex optoelectromechanical device that can be integrated with existing surgical tools to control the position of a fiber-delivered laser. By using modular assembly and a laminate fabrication method, we are able to create a smaller and higher-bandwidth device than the current state of the art while achieving a range of motion similar to existing tools. The device we present is 6 millimeters in diameter and 16 millimeters in length and is capable of focusing and steering a fiber-delivered laser beam at high speed (1.2-kilohertz bandwidth) over a large range (over ±10 degrees in both of two axes) with excellent static repeatability (200 micrometers).
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