W boson mass is worth the wait
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Impact of low muscle mass and myosteatosis on treatment toxicity and survival outcomes in non-resectable pancreatic cancer patients treated with chemoradiotherapy
Low skeletal muscle mass and impaired muscle quality (myosteatosis) have been associated with poor outcomes in cancer patients. This study aimed to evaluate the impact of pre-therapeutic low muscle mass and myosteatosis on chemoradiotherapy (CRT)-induced toxicity and survival outcomes in patients with non-resectable pancreatic cancer (PC).
High-throughput multiplexed serology via the mass-spectrometric analysis of isotopically barcoded beads
In serology, each sample is typically tested individually, one antigen at a time. This is costly and time consuming. Serology techniques should ideally allow recurrent measurements in parallel in small sample volumes and be inexpensive and fast. Here we show that mass cytometry can be used to scale up multiplexed serology testing by leveraging polystyrene beads uniformly loaded with combinations of stable isotopes. We generated 18,480 unique isotopically barcoded beads to simultaneously detect, in a single tube with 924 serum samples, the levels of immunoglobulins G and M against 19 proteins from SARS-CoV-2 (a total of 36,960 tests in 400 nl of sample volume and 30 μl of reaction volume). As a rapid, high-throughput and cost-effective technique, serology by mass cytometry may contribute to the effective management of public health emergencies originating from infectious diseases.
Beclin 1 of megakaryocytic lineage cells is locally dispensable for platelet hemostasis but functions distally in bone homeostasis
The crosstalk between megakaryocytic lineage cells and the skeletal system has just begun to be explored but remains largely elusive. Using conditional gene knockout mouse models, we demonstrated that loss of Beclin 1 (Becn1), a major regulator of mammalian autophagy, exclusively in the megakaryocytic lineage disrupted autophagy in platelets but did not compromise megakaryopoiesis or the formation and function of platelets. Unexpectedly, conditional Becn1 deletion in male mice led to a remarkable increase in bone mass with improved bone quality, in association with a decrease in sex hormone binding globulin (SHBG) and an increase in free testosterone (FT). In vivo Becn1 overexpression in megakaryocytic lineage-specific cells reduced bone mass and quality, along with an increase in SHBG and a decrease in FT. Transplantation of wild-type bone marrow cells into megakaryocytic lineage Becn1-deficient male mice restored bone mass and normalized SHBG and FT. Furthermore, bilateral orchiectomy of Becn1f/f;Pf4-iCre mice, which are crippled with the production of testosterone, resulted in a reduction in bone mass and quality, whereas in vivo overexpression of SHBG, specifically in the liver of Becn1f/f;Pf4-iCre mice, decreased FT and reduced bone mass and quality. In addition, metformin treatment, which induces SHBG expression, reduced FT and normalized bone mass in Becn1f/f;Pf4-iCre mice. We thus concluded that Becn1 of the megakaryocytic lineage is dispensable locally for platelet hemostasis but limits bone mass by increasing SHBG, which in turn reduces the FT of male mice. Our findings highlight a mechanism by which Becn1 from megakaryocytic lineage cells distally balances bone growth.
Dynamic social interactions and keystone species shape the diversity and stability of mixed-species biofilms – an example from dairy isolates
Identifying interspecies interactions in mixed-species biofilms is a key challenge in microbial ecology and is of paramount importance given that interactions govern community functionality and stability. We previously reported a bacterial four-species biofilm model comprising Stenotrophomonas rhizophila, Bacillus licheniformis, Microbacterium lacticum, and Calidifontibacter indicus that were isolated from the surface of a dairy pasteuriser after cleaning and disinfection. These bacteria produced 3.13-fold more biofilm mass compared to the sum of biofilm masses in monoculture. The present study confirms that the observed community synergy results from dynamic social interactions, encompassing commensalism, exploitation, and amensalism. M. lacticum appears to be the keystone species as it increased the growth of all other species that led to the synergy in biofilm mass. Interactions among the other three species (in the absence of M. lacticum) also contributed towards the synergy in biofilm mass. Biofilm inducing effects of bacterial cell-free-supernatants were observed for some combinations, revealing the nature of the observed synergy, and addition of additional species to dual-species combinations confirmed the presence of higher-order interactions within the biofilm community. Our findings provide understanding of bacterial interactions in biofilms which can be used as an interaction–mediated approach for cultivating, engineering, and designing synthetic bacterial communities.
Abundant ammonia and nitrogen-rich soluble organic matter in samples from asteroid (101955) Bennu
Organic matter in meteorites reveals clues about early Solar System chemistry and the origin of molecules important to life, but terrestrial exposure complicates interpretation. Samples returned from the B-type asteroid Bennu by the Origins, Spectral Interpretation, Resource Identification, and Security–Regolith Explorer mission enabled us to study pristine carbonaceous astromaterial without uncontrolled exposure to Earth’s biosphere. Here we show that Bennu samples are volatile rich, with more carbon, nitrogen and ammonia than samples from asteroid Ryugu and most meteorites. Nitrogen-15 isotopic enrichments indicate that ammonia and other N-containing soluble molecules formed in a cold molecular cloud or the outer protoplanetary disk. We detected amino acids (including 14 of the 20 used in terrestrial biology), amines, formaldehyde, carboxylic acids, polycyclic aromatic hydrocarbons and N-heterocycles (including all five nucleobases found in DNA and RNA), along with ~10,000 N-bearing chemical species. All chiral non-protein amino acids were racemic or nearly so, implying that terrestrial life’s left-handed chirality may not be due to bias in prebiotic molecules delivered by impacts. The relative abundances of amino acids and other soluble organics suggest formation and alteration by low-temperature reactions, possibly in NH3-rich fluids. Bennu’s parent asteroid developed in or accreted ices from a reservoir in the outer Solar System where ammonia ice was stable.
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