A new taeniolabidoid multituberculate (Mammalia) from the middle Puercan of the Nacimiento Formation, New Mexico, and a revision of taeniolabidoid systematics and phylogeny

Multituberculates were amongst the most abundant and taxonomically diverse mammals of the late Mesozoic and the Paleocene, reaching their zenith in diversity and body size in the Paleocene. Taeniolabidoidea, the topic of this paper, includes the largest known multituberculates, which possess highly complex cheek teeth adapted for herbivory. A new specimen from the early Paleocene (middle Puercan; biochron Pu2) of the Nacimiento Formation, New Mexico represents a new large-bodied taeniolabidoid genus and species, Kimbetopsalis simmonsae. A phylogenetic analysis to examine the relationships within Taeniolabidoidea that includes new information from Kimbetopsalis gen. et sp. nov. and gen. nov. and from new specimens of Catopsalis fissidens, first described here, and data from all other described North American and Asian taeniolabidoids. This analysis indicates that Catopsalis is nonmonophyletic and justifies our transfer of the basal-most taeniolabidoid ‘Catopsalis’ joyneri to a new genus, Valenopsalis. Kimbetopsalis and Taeniolabis form a clade (Taeniolabididae), as do the Asian Lambdopsalis, Sphenopsalis, and possibly also Prionessus (Lambdopsalidae). Taeniolabidoids underwent a modest taxonomic radiation during the early Paleocene of North America and underwent a dramatic increase in body size, with Taeniolabis taoensis possibly exceeding 100 kg. Taeniolabidoids appear to have gone extinct in North America by the late Paleocene but the appearance of lambdopsalids in the late Paleocene of Asia suggests that they dispersed from North America in the early to middle Paleocene

Gaps in Safe Food Handling Practices of Older Adults

We identified gaps in safe food handling practices that may be placing older adults at increased risk of food-borne illness. A convenience sample of 1,019 older adults completed the Food Safety Behavior Questionnaire. Majority groups among participants were those who were female, those who were White, and those who were widowed. Participants had lower adherences to safe practices related to temperature control, attention to sell-by/use-by dates on food packages, and cross-contamination. Adherences were significantly (p \u3c .05) influenced by gender, race/ethnicity, age, marital status, and education. Our findings suggest the need for older adult–focused safe food handling education related to temperature control, product selection practices, and cross-contamination

Cytoplasmic chromatin triggers inflammation in senescence and cancer

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders

Black carbon in the Southern Andean snowpack

The Andean snowpack is an important source of water for many communities. As other snow-covered regions around the world, the Andes are sensitive to black carbon (BC) deposition from fossil fuel and biomass combustion. BC darkens the snow surface, reduces the albedo, and accelerates melting. Here, we report on measurements of the BC content conducted by using the meltwater filtration (MF) technique in snow samples collected across a transect of more than 2500 km from the mid-latitude Andes to the southern tip of South America. Addressing some of the key knowledge gaps regarding the effects of the BC deposition on the Andean snow, we identified BC-impacted areas, assessed the BC-related albedo reduction, and estimated the resulting snow losses. We found that BC concentrations in our samples generally ranged from 2 to 15 ng g-1, except for the nearly BC-free Patagonian Icefields and for the BC-impacted sites nearby Santiago (a metropolis of 6 million inhabitants). We estimate that the seasonal snowpack shrinking attributable to the BC deposition ranges from 4 mm water equivalent (w.e.) at relatively clean sites in Patagonia to 241 mm w.e. at heavily impacted sites close to Santiago. © 2022 The Author(s). Published by IOP Publishing Ltd

Black carbon in the Southern Andean snowpack

The Andean snowpack is an important source of water for many communities. As other snow-covered regions around the world, the Andes are sensitive to black carbon (BC) deposition from fossil fuel and biomass combustion. BC darkens the snow surface, reduces the albedo, and accelerates melting. Here, we report on measurements of the BC content conducted by using the meltwater filtration (MF) technique in snow samples collected across a transect of more than 2500 km from the mid-latitude Andes to the southern tip of South America. Addressing some of the key knowledge gaps regarding the effects of the BC deposition on the Andean snow, we identified BC-impacted areas, assessed the BC-related albedo reduction, and estimated the resulting snow losses. We found that BC concentrations in our samples generally ranged from 2 to 15 ng g-1, except for the nearly BC-free Patagonian Icefields and for the BC-impacted sites nearby Santiago (a metropolis of 6 million inhabitants). We estimate that the seasonal snowpack shrinking attributable to the BC deposition ranges from 4 mm water equivalent (w.e.) at relatively clean sites in Patagonia to 241 mm w.e. at heavily impacted sites close to Santiago. © 2022 The Author(s). Published by IOP Publishing Ltd

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Expression profiling of familial breast cancers demonstrates higher expression of FGFR2 in BRCA2-associated tumors

BackgroundBRCA1- and BRCA2-associated tumors appear to have distinct molecular signatures. BRCA1-associated tumors are predominantly basal-like cancers, whereas BRCA2-associated tumors have a predominant luminal-like phenotype. These two molecular signatures reflect in part the two cell types found in the terminal duct lobular unit of the breast. To elucidate novel genes involved in these two spectra of breast tumorigenesis we performed global gene expression analysis on breast tumors from germline BRCA1 and BRCA2 mutation carriers. Methodology Breast tumor RNAs from 7 BRCA1 and 6 BRCA2 mutation carriers were profiled using UHN human 19K cDNA microarrays. Supervised univariate analyses were conducted to identify genes differentially expressed between BRCA1 and BRCA2-associated tumors. Selected discriminatory genes were validated using real time reverse transcription polymerase chain reaction in the tumor RNAs, and/or by immunohistochemistry (IHC) or by in situ hybridization (ISH) on tissue microarrays (TMAs) containing an independent set of 58 BRCA1 and 64 BRCA2-associated tumors. Results Genes more highly expressed in BRCA1-associated tumors included stathmin, osteopontin, TGFβ2 and Jagged 1 in addition to genes previously identified as characteristic of basal-like breast cancers. BRCA2-associated cancers were characterized by the higher relative expression of FGF1 and FGFR2. FGFR2 protein was also more highly expressed in BRCA2-associated cancers (P = 0.004). SignificanceBRCA1-associated tumours demonstrated increased expression of component genes of the Notch and TGFβ pathways whereas the higher expression of FGFR2 and FGF1 in BRCA2-associated cancers suggests the existence of an autocrine stimulatory loop

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology