Braggcarstensen0150
Extending the toolbox from mono- to bimetallic catalysts is key in realizing efficient chemical processes1. Traditionally, the performance of bimetallic catalysts featuring one active and one selective metal is optimized by varying the metal composition1-3, often resulting in a compromise between the catalytic properties of the two metals4-6. Here we show that by designing the atomic distribution of bimetallic Au-Pd nanocatalysts, we obtain a synergistic catalytic performance in the industrially relevant selective hydrogenation of butadiene. Our single-crystalline Au-core Pd-shell nanorods were up to 50 times more active than their alloyed and monometallic counterparts, while retaining high selectivity. We find a shell-thickness-dependent catalytic activity, indicating that not only the nature of the surface but also several subsurface layers play a crucial role in the catalytic performance, and rationalize this finding using density functional theory calculations. Our results open up an alternative avenue for the structural design of bimetallic catalysts.Transcription initiates at promoters, DNA regions recognized by a DNA-dependent RNA polymerase. We previously identified horizontally acquired Escherichia coli promoters from which the direction of transcription was unclear. In the present study, we show that more than half of these promoters are bidirectional and drive divergent transcription. Using genome-scale approaches, we demonstrate that 19% of all transcription start sites detected in E. coli are associated with a bidirectional promoter. Bidirectional promoters are similarly common in diverse bacteria and archaea, and have inherent symmetry specific bases required for transcription initiation are reciprocally co-located on opposite DNA strands. Bidirectional promoters enable co-regulation of divergent genes and are enriched in both intergenic and horizontally acquired regions. Divergent transcription is conserved among bacteria, archaea and eukaryotes, but the underlying mechanisms for bidirectionality are different.The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field.Nanoparticulate albumin bound paclitaxel (nab-paclitaxel, nab-PTX) is among the most widely prescribed nanomedicines in clinical use, yet it remains unclear how nanoformulation affects nab-PTX behaviour in the tumour microenvironment. Here, we quantified the biodistribution of the albumin carrier and its chemotherapeutic payload in optically cleared tumours of genetically engineered mouse models, and compared the behaviour of nab-PTX with other clinically relevant nanoparticles. We found that nab-PTX uptake is profoundly and distinctly affected by cancer-cell autonomous RAS signalling, and RAS/RAF/MEK/ERK inhibition blocked its selective delivery and efficacy. In contrast, a targeted screen revealed that IGF1R kinase inhibitors enhance uptake and efficacy of nab-PTX by mimicking glucose deprivation and promoting macropinocytosis via AMPK, a nutrient sensor in cells. This study thus shows how nanoparticulate albumin bound drug efficacy can be therapeutically improved by reprogramming nutrient signalling and enhancing macropinocytosis in cancer cells.Ultracompact spintronic devices greatly benefit from the implementation of two-dimensional materials that provide large spin polarization of charge current together with long-distance transfer of spin information. Here spin-transport measurements in bilayer graphene evidence a strong spin-charge coupling due to a large induced exchange interaction by the proximity of an interlayer antiferromagnet (CrSBr). This results in the direct detection of the spin polarization of conductivity (up to 14%) and a spin-dependent Seebeck effect in the magnetic graphene. The efficient electrical and thermal spin-current generation is the most technologically relevant aspect of magnetism in graphene, controlled here by the antiferromagnetic dynamics of CrSBr. The high sensitivity of spin transport in graphene to the magnetization of the outermost layer of the adjacent antiferromagnet, furthermore, enables the read-out of a single magnetic sublattice. The combination of gate-tunable spin-dependent conductivity and Seebeck coefficient with long-distance spin transport in a single two-dimensional material promises ultrathin magnetic memory and sensory devices based on magnetic graphene.Light detection and ranging (LiDAR) technology, a laser-based imaging technique for accurate distance measurement, is considered one of the most crucial sensor technologies for autonomous vehicles, artificially intelligent robots and unmanned aerial vehicle reconnaissance. Until recently, LiDAR has relied on light sources and detectors mounted on multiple mechanically rotating optical transmitters and receivers to cover an entire scene. Such an architecture gives rise to limitations in terms of the imaging frame rate and resolution. In this Review, we examine how novel nanophotonic platforms could overcome the hardware restrictions of existing LiDAR technologies. After briefly introducing the basic principles of LiDAR, we present the device specifications required by the industrial sector. We then review a variety of LiDAR-relevant nanophotonic approaches such as integrated photonic circuits, optical phased antenna arrays and flat optical devices based on metasurfaces. The latter have already demonstrated exceptional functional beam manipulation properties, such as active beam deflection, point-cloud generation and device integration using scalable manufacturing methods, and are expected to disrupt modern optical technologies. In the outlook, we address the upcoming physics and engineering challenges that must be overcome from the viewpoint of incorporating nanophotonic technologies into commercially viable, fast, ultrathin and lightweight LiDAR systems.Major histocompatibility complex-I (MHC-I) presents tumour antigens to CD8+ T cells and triggers anti-tumour immunity. Humans may have 30,000-60,000 long noncoding RNAs (lncRNAs). However, it remains poorly understood whether lncRNAs affect tumour immunity. Here, we identify a lncRNA, lncRNA inducing MHC-I and immunogenicity of tumour (LIMIT), in humans and mice. We found that IFNγ stimulated LIMIT, LIMIT cis-activated the guanylate-binding protein (GBP) gene cluster and GBPs disrupted the association between HSP90 and heat shock factor-1 (HSF1), thereby resulting in HSF1 activation and transcription of MHC-I machinery, but not PD-L1. RNA-guided CRISPR activation of LIMIT boosted GBPs and MHC-I, and potentiated tumour immunogenicity and checkpoint therapy. Silencing LIMIT, GBPs and/or HSF1 diminished MHC-I, impaired antitumour immunity and blunted immunotherapy efficacy. Clinically, LIMIT, GBP- and HSF1-signalling transcripts and proteins correlated with MHC-I, tumour-infiltrating T cells and checkpoint blockade response in patients with cancer. Together, we demonstrate that LIMIT is a cancer immunogenic lncRNA and the LIMIT-GBP-HSF1 axis may be targetable for cancer immunotherapy.Organs consist of multiple cell types that ensure proper architecture and function. GC7 purchase How different cell types coexist and interact to maintain their homeostasis in vivo remains elusive. The skin epidermis comprises mostly epithelial cells, but also harbours Langerhans cells (LCs) and dendritic epidermal T cells (DETCs). Whether and how distributions of LCs and DETCs are regulated during homeostasis is unclear. Here, by tracking individual cells in the skin of live adult mice over time, we show that LCs and DETCs actively maintain a non-random spatial distribution despite continuous turnover of neighbouring basal epithelial cells. Moreover, the density of epithelial cells regulates the composition of LCs and DETCs in the epidermis. Finally, LCs require the GTPase Rac1 to maintain their positional stability, density and tiling pattern reminiscent of neuronal self-avoidance. We propose that these cellular mechanisms provide the epidermis with an optimal response to environmental insults.Chondrichthyan dentitions are conventionally interpreted to reflect the ancestral gnathostome condition but interpretations of osteichthyan dental evolution in this light have proved unsuccessful, perhaps because chondrichthyan dentitions are equally specialized, or else evolved independently. Ischnacanthid acanthodians are stem-Chondrichthyes; as phylogenetic intermediates of osteichthyans and crown-chondrichthyans, the nature of their enigmatic dentition may inform homology and the ancestral gnathostome condition. Here we show that ischnacanthid marginal dentitions were statodont, composed of multicuspidate teeth added in distally diverging rows and through proximal superpositional replacement, while their symphyseal tooth whorls are comparable to chondrichthyan and osteichthyan counterparts. Ancestral state estimation indicates the presence of oral tubercles on the jaws of the gnathostome crown-ancestor; tooth whorls or tooth rows evolved independently in placoderms, osteichthyans, ischnacanthids, other acanthodians and crown-chondrichthyans. Crown-chondrichthyan dentitions are derived relative to the gnathostome crown-ancestor, which possessed a simple dentition and lacked a permanent dental lamina, which evolved independently in Chondrichthyes and Osteichthyes.Loss of recombination between sex chromosomes often depletes Y chromosomes of functional content and genetic variation, which might limit their potential to generate adaptive diversity. Males of the freshwater fish Poecilia parae occur as one of five discrete morphs, all of which shoal together in natural populations where morph frequency has been stable for over 50 years. Each morph uses a different complex reproductive strategy and morphs differ dramatically in colour, body size and mating behaviour. Morph phenotype is passed perfectly from father to son, indicating there are five Y haplotypes segregating in the species, which encode the complex male morph characteristics. Here, we examine Y diversity in natural populations of P. parae. Using linked-read sequencing on multiple P. parae females and males of all five morphs, we find that the genetic architecture of the male morphs evolved on the Y chromosome after recombination suppression had occurred with the X. Comparing Y chromosomes between each of the morphs, we show that, although the Ys of the three minor morphs that differ in colour are highly similar, there are substantial amounts of unique genetic material and divergence between the Ys of the three major morphs that differ in reproductive strategy, body size and mating behaviour.