Notes

Competitors with abundance-dependent conditioning along with the character regarding heterogeneous communities in changing surroundings.
Genome-wide loss-of-function screens have revealed genes essential for cancer cell proliferation, called cancer dependencies. It remains challenging to link cancer dependencies to the molecular compositions of cancer cells or to unscreened cell lines and further to tumors. Here, we present DeepDEP, a deep learning model that predicts cancer dependencies using integrative genomic profiles. It uses a unique unsupervised pretraining that captures unlabeled tumor genomic representations to improve the learning of cancer dependencies. We demonstrated DeepDEP's improvement over conventional machine learning methods and validated the performance with three independent datasets. By systematic model interpretations, we extended the current dependency maps with functional characterizations of dependencies and a proof-of-concept in silico assay of synthetic essentiality. We applied DeepDEP to pan-cancer tumor genomics and built the first pan-cancer synthetic dependency map of 8000 tumors with clinical relevance. In summary, DeepDEP is a novel tool for investigating cancer dependency with rapidly growing genomic resources.Isopenicillin N synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNSFe(II)ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.Ecosystems provide multiple services to humans. However, agricultural systems are usually evaluated on their productivity and economic performance, and a systematic and quantitative assessment of the multifunctionality of agroecosystems including environmental services is missing. Using a long-term farming system experiment, we evaluated and compared the agronomic, economic, and ecological performance of the most widespread arable cropping systems in Europe organic, conservation, and conventional agriculture. We analyzed 43 agroecosystem properties and determined overall agroecosystem multifunctionality. We show that organic and conservation agriculture promoted ecosystem multifunctionality, especially by enhancing regulating and supporting services, including biodiversity preservation, soil and water quality, and climate mitigation. In contrast, conventional cropping showed reduced multifunctionality but delivered highest yield. Organic production resulted in higher economic performance, thanks to higher product prices and additional support payments. Our results demonstrate that different cropping systems provide opposing services, enforcing the productivity-environmental protection dilemma for agroecosystem functioning.Reef-building corals thriving in extreme thermal environments may provide genetic variation that can assist the evolution of populations to rapid climate warming. However, the feasibility and scale of genetic improvements remain untested despite ongoing population declines from recurrent thermal stress events. Here, we show that corals from the hottest reefs in the world transfer sufficient heat tolerance to a naïve population sufficient to withstand end-of-century warming projections. Heat survival increased up to 84% when naïve mothers were selectively bred with fathers from the hottest reefs because of strong heritable genetic effects. We identified genomic loci associated with tolerance variation that were enriched for heat shock proteins, oxidative stress, and immune functions. Unexpectedly, several coral families exhibited survival rates and genomic associations deviating from origin predictions, including a few naïve purebreds with exceptionally high heat tolerance. Our findings highlight previously uncharacterized enhanced and intrinsic potential of coral populations to adapt to climate warming.Tuberculosis-causing mycobacteria have thick cell-wall and capsule layers that are formed from complex structures. Protein secretion across these barriers depends on a specialized protein secretion system, but none has been reported. We show that Mycobacterium tuberculosis Rv3705c and its homologous MSMEG_6251 in Mycobacterium smegmatis are tube-forming proteins in the mycobacterial envelope (TiME). Crystallographic and cryo-EM structures of these two proteins show that both proteins form rotationally symmetric rings. Two layers of TiME rings pack together in a tail-to-tail manner into a ring-shaped complex, which, in turn, stacks together to form tubes. M. smegmatis TiME was detected mainly in the cell wall and capsule. Knocking out the TiME gene markedly decreased the amount of secreted protein in the M. smegmatis culture medium, and expression of this gene in knocked-out strain partially restored the level of secreted protein. Our structure and functional data thus suggest that TiME forms a protein transport tube across the mycobacterial outer envelope.Although single-source white emissive perovskite has emerged as a class of encouraging light-emitting material, the synthesis of lead-free halide perovskite materials with high luminous efficiency is still challenging. Here, we report a series of zero-dimensional indium-antimony (In/Sb) alloyed halide single crystals, BAPPIn2-2x Sb2x Cl10 (BAPP = C10H28N4, x = 0 to 1), with tunable emission. In BAPPIn1.996Sb0.004Cl10, bright yellow emission with near 100% photoluminescence quantum yield (PLQY) is yielded when it was excited at 320 nm, which turns into bright white-light emission with a PLQY of 44.0% when excited at 365 nm. Combined spectroscopy and theoretical studies reveal that the BAPP4+-associated blue emission and inorganic polyhedron-afforded orange emission function as a perfect pair of complementary colors affording white light in BAPPIn1.996Sb0.004Cl10 Moreover, the interesting afterglow behavior, together with excitation-dependent emission property, makes BAPPIn2-2x Sb2x Cl10 as high-performance anti-counterfeiting/information storage materials.Transition metal dichalcogenide (TMD)/graphene (Gr) heterostructures constitute a key component for two-dimensional devices. The operation of TMD/Gr devices relies on interfacial charge/energy transfer processes, which remains unclear and challenging to unravel. Fortunately, the coupled spin and valley index in TMDs adds a new degree of freedom to the charges and, thus, another dimension to spectroscopy. Here, by helicity-resolved ultrafast spectroscopy, we find that photoexcitation in TMDs transfers to graphene by asynchronous charge transfer, with one type of charge transferring in the order of femtoseconds and the other in picoseconds. The rate correlates well with energy offset between TMD and graphene, regardless of compositions and charge species. Spin-polarized hole injection or long-lived polarized hole can be achieved with deliberately designed heterostructures. This study shows helicity-resolved ultrafast spectroscopy as a powerful and facile approach to reveal the fundamental and complex charge/spin dynamics in TMD-based heterostructures, paving the way toward valleytronic and optoelectronic applications.A three-dimensional microengineered human coronary artery-on-a-chip was developed for investigation of the mechanism by which low and oscillatory shear stress (OSS) induces pro-atherogenic changes. Single-cell RNA sequencing revealed that OSS induced distinct changes in endothelial cells (ECs) including pro-inflammatory endothelial-to-mesenchymal transition (EndMT). OSS promoted pro-inflammatory EndMT through the Notch1/p38 MAPK-NF-κB signaling axis. Moreover, OSS-induced EC phenotypic changes resulted in proliferation and extracellular matrix (ECM) protein up-regulation in smooth muscle cells (SMCs) through the RANTES-mediated paracrine mechanism. IL-37 suppressed OSS-induced pro-inflammatory EndMT and thereby abrogated SMC proliferation and ECM protein remodeling. Overall, this study provides insights into endothelial heterogeneity under atheroprone shear stress and identifies the mechanistic role of a novel EC subtype in promoting adverse vascular remodeling. Further, this study demonstrates that anti-inflammatory approach is capable of mitigating vascular pathobiology evoked by atheroprone shear stress.Intensive building energy efficiency improvements can reduce emissions from energy use, improving outdoor air quality and human health, but may also affect ventilation and indoor air quality. This study examines the effects of highly ambitious, yet feasible, building energy efficiency upgrades in the United States. Our energy efficiency scenarios, derived from the literature, lead to a 6 to 11% reduction in carbon dioxide emissions and 18 to 25% reductions in particulate matter (PM2.5) emissions in 2050. These reductions are complementary with a carbon pricing policy on electricity. However, our results also point to the importance of mitigating indoor PM2.5 emissions, improving PM2.5 filtration, and evaluating ventilation-related policies. Even with no further ventilation improvements, we estimate that intensive energy efficiency scenarios could prevent 1800 to 3600 premature deaths per year across the United States in 2050. MEK inhibitor side effects With further investments in indoor air quality, this can rise to 2900 to 5100.Mothers contribute cytoplasmic components to their progeny in a process called maternal provisioning. Provisioning is influenced by the parental environment, but the molecular pathways that transmit environmental cues between generations are not well understood. Here, we show that, in Caenorhabditis elegans, social cues modulate maternal provisioning to regulate gene silencing in offspring. Intergenerational signal transmission depends on a pheromone-sensing neuron and neuronal FMRFamide (Phe-Met-Arg-Phe)-like peptides. Parental FMRFamide-like peptide signaling dampens oxidative stress resistance and promotes the deposition of mRNAs for translational components in progeny, which, in turn, reduces gene silencing. This study identifies a previously unknown pathway for intergenerational communication that links neuronal responses to maternal provisioning. We suggest that loss of social cues in the parental environment represents an adverse environment that stimulates stress responses across generations.Soft robotics revolutionized human-robot interactions, yet there exist persistent challenges for developing high-performance soft actuators that are powerful, rapid, controllable, safe, and portable. Here, we introduce a class of self-contained soft electrofluidic actuators (SEFAs), which can directly convert electrical energy into the mechanical energy of the actuators through electrically responsive fluids that drive the outside elastomer deformation. The use of special dielectric liquid enhances fluid flow capabilities, improving the actuation performance of the SEFAs. SEFAs are easily manufactured by using widely available materials and common fabrication techniques, and display excellent comprehensive performances in portability, controllability, rapid response, versatility, safety, and actuation. An artificial muscle stretching a joint and a soft bionic ray swimming in a tank demonstrate their effective performance. Hence, SEFAs offer a platform for developing soft actuators with potential applications in wearable assistant devices and soft robots.
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