•Low temperature (450K) hydrogen production from ammonia to unlock its potential as energy vector.•Highly conductive supports (graphitized CNT’s) allows distance electronic modification by ...promoter.•Synergetic effect of promoter and support enhances low temperature activity.
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Low temperature hydrogen production via ammonia decomposition is achieved by the synergetic combination of a highly conductive support and an electron donating promoter in a ruthenium-based system, with activity at temperatures as low as 450K. The high conductivity of graphitized carbon nanotubes allows for greater electronic modification of the ruthenium nanoparticles by cesium located in close proximity but without direct contact, avoiding the blockage of the active sites. This development of low temperature catalytic activity represents a breakthrough toward the use of ammonia as chemical storage for in-situ hydrogen production in fuel cells.
In many areas of oncology, we lack sensitive tools to track low-burden disease. Although cell-free DNA (cfDNA) shows promise in detecting cancer mutations, we found that the combination of low tumor ...fraction (TF) and limited number of DNA fragments restricts low-disease-burden monitoring through the prevailing deep targeted sequencing paradigm. We reasoned that breadth may supplant depth of sequencing to overcome the barrier of cfDNA abundance. Whole-genome sequencing (WGS) of cfDNA allowed ultra-sensitive detection, capitalizing on the cumulative signal of thousands of somatic mutations observed in solid malignancies, with TF detection sensitivity as low as 10
. The WGS approach enabled dynamic tumor burden tracking and postoperative residual disease detection, associated with adverse outcome. Thus, we present an orthogonal framework for cfDNA cancer monitoring via genome-wide mutational integration, enabling ultra-sensitive detection, overcoming the limitation of cfDNA abundance and empowering treatment optimization in low-disease-burden oncology care.
Immune responses to cancer are highly variable, with mismatch repair-deficient (MMRd) tumors exhibiting more anti-tumor immunity than mismatch repair-proficient (MMRp) tumors. To understand the rules ...governing these varied responses, we transcriptionally profiled 371,223 cells from colorectal tumors and adjacent normal tissues of 28 MMRp and 34 MMRd individuals. Analysis of 88 cell subsets and their 204 associated gene expression programs revealed extensive transcriptional and spatial remodeling across tumors. To discover hubs of interacting malignant and immune cells, we identified expression programs in different cell types that co-varied across tumors from affected individuals and used spatial profiling to localize coordinated programs. We discovered a myeloid cell-attracting hub at the tumor-luminal interface associated with tissue damage and an MMRd-enriched immune hub within the tumor, with activated T cells together with malignant and myeloid cells expressing T cell-attracting chemokines. By identifying interacting cellular programs, we reveal the logic underlying spatially organized immune-malignant cell networks.
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•A scRNA-seq study reveals shared and distinct features of human MMRd and MMRp CRC•Co-variation of single-cell transcriptional programs across specimens predicts immune hubs•A myeloid-rich inflammatory hub is identified below the colonic lumen in human CRC•CXCR3-ligand+ cells form foci with activated T cells in human MMRd CRC
Single-cell transcriptomics-based co-variation analysis of human colorectal cancer identifies a spatially resolved myeloid-rich inflammatory hub that is shared by mismatch repair-deficient (MMRd) and mismatch repair-proficient (MMRp) tumors and CXCR3-ligand+ multicellular foci distinct for MMRd tumors.
Dysregulated pH is a common characteristic of cancer cells, as they have an increased intracellular pH (pH
) and a decreased extracellular pH (pH
) compared with normal cells. Recent work has ...expanded our knowledge of how dysregulated pH dynamics influences cancer cell behaviors, including proliferation, metastasis, metabolic adaptation and tumorigenesis. Emerging data suggest that the dysregulated pH of cancers enables these specific cell behaviors by altering the structure and function of selective pH-sensitive proteins, termed pH sensors. Recent findings also show that, by blocking pH
increases, cancer cell behaviors can be attenuated. This suggests ion transporter inhibition as an effective therapeutic approach, either singly or in combination with targeted therapies. In this Cell Science at a Glance article and accompanying poster, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression and adaptation.
Polyoxygenated hydrocarbons that bear one or more hydroxyl groups comprise a large set of natural and synthetic compounds, often with potent biological activity. In synthetic chemistry, alcohols are ...important precursors to carbonyl groups, which then can be converted into a wide range of oxygen- or nitrogen-based functionality. Therefore, the selective conversion of a single hydroxyl group in natural products into a ketone would enable the selective introduction of unnatural functionality. However, the methods known to convert a simple alcohol, or even an alcohol in a molecule that contains multiple protected functional groups, are not suitable for selective reactions of complex polyol structures. We present a new ruthenium catalyst with a unique efficacy for the selective oxidation of a single hydroxyl group among many in unprotected polyol natural products. This oxidation enables the introduction of nitrogen-based functional groups into such structures that lack nitrogen atoms and enables a selective alcohol epimerization by stepwise or reversible oxidation and reduction.
We sequenced the 2 botulinum toxin gene clusters of Clostridium botulinum strain IBCA10-7060 type Bh. The sequence of bont/H differed substantially from the sequences of the 7 known bont genes for ...toxin types A-G. The 5' one-third terminus of bont/H that codes for the botulinum toxin light chain differed markedly from the light chain coding sequences of toxin types A-G. The 3' two-thirds terminus of bont/H that codes for the botulinum toxin heavy chain contained a novel Hn translocation domain coding sequence and a nonneutralizing type A-like Hc binding domain coding sequence. bont/H was part of an orfX toxin gene cluster that was located at a unique chromosomal site distant from those used by other botulinum toxin gene clusters. The bont/B sequence was similar to that of subtype bont/B2 and was located within its ha toxin gene cluster at the oppA/brnQ site. Our findings further establish that C. botulinum IBCA10-7060 produces novel BoNT/H.
Most multicellular terrestrial organisms experience climate at scales of millimetres to metres, yet most species-climate associations are analysed at resolutions of kilometres or more. Because ...individuals experience heterogeneous microclimates in the landscape, species sometimes survive where the average background climate appears unsuitable, and equally may be eliminated from sites within apparently suitable grid cells where microclimatic extremes are intolerable. Local vegetation structure and topography can be important determinants of fine-resolution microclimate, but a literature search revealed that the vast majority of bioclimate studies do not include fine-scale habitat information, let alone a representation of how habitat affects microclimate. In this paper, we show that habitat type (grassland, heathland, deciduous woodland) is a major modifier of the temperature extremes experienced by organisms. We recorded differences among these habitats of more than 5°C in monthly temperature maxima and minima, and of 10°C in thermal range, on a par with the level of warming expected for extreme future climate change scenarios. Comparable differences were found in relation to variation in local topography (slope and aspect). Hence, we argue that the microclimatic effects of habitat and topography must be included in studies if we are to obtain sufficiently detailed projections of the ecological impacts of climate change to develop detailed adaptation strategies for the conservation of biodiversity.
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