The role of aerodynamic drag in propagation of interplanetary coronal mass ejections

Context. The propagation of interplanetary coronal mass ejections (ICMEs) and the forecast of their arrival on Earth is one of the central issues of space weather studies. Aims. We investigate to which degree various ICME parameters (mass, size, take-off speed) and the ambient solar-wind parameters (density and velocity) affect the ICME Sun-Earth transit time. Methods. We study solutions of a drag-based equation of motion by systematically varying the input parameters. The analysis is focused on ICME transit times and 1 AU velocities. Results. The model results reveal that wide ICMEs of low masses adjust to the solar-wind speed already close to the sun, so the transit time is determined primarily by the solar-wind speed. The shortest transit times and accordingly the highest 1 AU velocities are related to narrow and massive ICMEs (i.e. high-density eruptions) propagating in high-speed solar wind streams. We apply the model to the Sun-Earth event associated with the CME of 25 July 2004 and compare the results with the outcome of the numerical MHD modeling

Sperm competition intensity affects sperm precedence patterns in a polyandrous gift-giving spider

Abstract Sperm competition drives traits that enhance fertilization success. The amount of sperm transferred relative to competitors is key for attaining paternity. Female reproductive morphology and male mating order may also influence fertilization, however the outcome for sperm precedence under intense sperm competition remains poorly understood. In the polyandrous spider Pisaura mirabilis, males offer nuptial gifts which prolong copulation and increase sperm transfer, factors proposed to alter sperm precedence patterns under strong sperm competition. First, we assessed the degree of female polyandry by genotyping wild broods. A conservative analysis identified up to four sires, with a mean of two sires per brood, consistent with an optimal mating female rate. Then we asked whether intense sperm competition shifts sperm precedence patterns from first male priority, as expected from female morphology, to last male advantage. We varied sexual selection intensity experimentally and determined competitive fertilization outcome by genotyping broods. In double matings, one male monopolised paternity regardless of mating order. A mating order effect with first male priority was revealed when females were mated to four males, however this effect disappeared when females were mated to six males, probably due to increased sperm mixing. The proportion of males that successfully sired offspring drastically decreased with the number of competitors. Longer copulations translated into higher paternity shares independently of mating order, reinforcing the advantage of traits that prolong copulation duration under intense competition, such as the nuptial gift. Sperm competition intensity enhances the impact of competitive sexual traits and imposes multiple effects on paternity

Cognitive dysfunction in early experimental metabolic dysfunction-associated steatotic liver disease is associated with systemic inflammation and neuroinflammation

Background & Aims: Cognitive dysfunction is an increasingly recognised manifestation of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanistic link remains unclear. The aim of this study was to investigate the hypothesis that experimental MASLD leads to cognitive dysfunction via systemic inflammation and neuroinflammation. Methods: Twenty male Sprague Dawley rats were randomised to a high-fat high-cholesterol (HFHC) diet to induce MASLD, or a standard diet (n = 10/group), for 16 weeks. Assessments included: MASLD severity (histology), neurobehaviour, inflammation (liver, plasma and cerebrospinal fluid), brain microglia and astrocyte activation, and synaptic density. Results: The HFHC diet induced MASLD with extensive steatosis and lobular inflammation without fibrosis. Several plasma cytokines were elevated (CXCL1, IL-6, IL-17, MIP-1α, MCP-1, IL-10; all p <0.05) and correlated with increases in hepatic chemokine gene expression. Cerebrospinal fluid concentrations of CXCL1 were elevated (p = 0.04). In the prefrontal brain cortex, we observed a 19% increase in microglial activation confirmed by Iba1 immunohistochemistry (p = 0.03) and 3H-PK11195 autoradiography (p <0.01). In parallel, synaptic density was reduced to 92%, assessed by 3H-UCB-J autoradiography (p <0.01). MASLD animals exhibited impaired memory to previously encountered objects in the novel object recognition test (p = 0.047) and showed depression-like behaviour evidenced by increased immobility time (p <0.01) and reduced swimming time (p = 0.03) in the forced swim test. Conclusions: Experimental non-fibrotic MASLD, as a model to reflect the early stage of human disease, results in cognitive impairment and depression-like behaviour. This is associated with an inflammatory phenotype not only in the liver but also in the plasma and brain, which together with diminished synaptic density, provides a pathophysiological link between liver disease and cognitive dysfunction in MASLD. Impact and implications: Cognitive dysfunction is an increasingly recognised comorbidity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), yet the underlying mechanisms remain unclear. This study provides evidence of impaired memory and depression-like symptoms in early experimental MASLD and indicates that hepatic inflammation may drive a systemic inflammatory response, resulting in neuroinflammation and reduced brain synaptic density. The evidence of impaired memory in MASLD and establishing its underlying pathophysiological link provides insights that could guide the development of potential new treatments for this increasingly common condition in people of working age. The study also emphasises the need to develop better tools for clinical cognitive testing, which will enable physicians to assess and manage brain dysfunction early in MASLD

Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects

Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion with hydrocortisone or saline. Glucose effectiveness was assessed by a combined somatostatin and insulin infusion protocol to maintain insulin concentration at basal level in the presence of prandial glucose infusions. Despite elevated insulin concentrations (P < 0.05), hypercortisolemia resulted in higher glucose (P < 0.05) and free fatty acid concentrations (P < 0.05). Furthermore, basal insulin concentrations were higher during hydrocortisone than during saline infusion (P < 0.01), indicating the presence of steroid-induced insulin resistance. Postabsorptive glucose production (P = 0.64) and the fractional contribution of gluconeogenesis to EGR (P = 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P < 0.05), implying a decrease in net glucose effectiveness (4.42 +/- 0.52 vs. 6.65 +/- 0.83 ml.kg-1.min-1; P < 0.05). To determine whether this defect is attributable to an impaired ability of glucose to suppress glucose production, to stimulate its own uptake, or both, glucose turnover and "hot" (labeled) indexes of glucose effectiveness (GE) were calculated. Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P < 0.05), indicating a defect in the ability of glucose to restrain its own production. In addition, in the presence of excess cortisol, glucose disappearance was inappropriate for the prevailing glucose concentration, implying a decrease in glucose clearance (P < 0.05). The decrease in glucose clearance was confirmed by the higher increment in [3-3H]glucose during hydrocortisone than during saline infusion (P < 0.05), despite the administration of identical tracer infusion rates. In conclusion, short-term hypercortisolemia in healthy individuals with normal beta-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose space results in impaired peripheral glucose clearance. These results suggest that cortisol excess impairs glucose tolerance by decreasing both insulin action and glucose effectiveness

Risk Assessment for Supply Chain Meat Inspection of Danish Finisher Pigs

The food safety value of routine incision into the major mandibular lymph nodes and the heart was assessed in finisher pigs from integrated production systems in Denmark. A risk assessment was conducted following international guidelines as a joint effort between university, industry and veterinary services. It was concluded that omission of routine incisions into the mandibular lymph nodes and the heart was not associated with a significant increase in the risk for human health. The main reason is that Denmark is officially free from bovine tuberculosis since 29 years, and the pathogens causing granulomatous lymphadenitis and endocarditis are not likely to be food-borne. The new way of conducting meat inspection is called supply chain meat inspection - the Danish way. The system will gradually be implemented on all slaughterhouses in Denmark during 2009

Synergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation.

The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region. We identify a narrow megafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts

Original Article

Objective: Glucagon is well known to regulate blood glucose but may be equally important for amino acid metabolism. Plasma levels of amino acids are regulated by glucagon-dependent mechanism(s), while amino acids stimulate glucagon secretion from alpha cells, completing the recently described liver-alpha cell axis. The mechanisms underlying the cycle and the possible impact of hepatic steatosis are unclear. Methods: We assessed amino acid clearance in vivo in mice treated with a glucagon receptor antagonist (GRA), transgenic mice with 95% reduction in alpha cells, and mice with hepatic steatosis. In addition, we evaluated urea formation in primary hepatocytes from ob/ob mice and humans, and we studied acute metabolic effects of glucagon in perfused rat livers. We also performed RNA sequencing on livers from glucagon receptor knock-out mice and mice with hepatic steatosis. Finally, we measured individual plasma amino acids and glucagon in healthy controls and in two independent cohorts of patients with biopsy-verified non-alcoholic fatty liver disease (NAFLD). Results: Amino acid clearance was reduced in mice treated with GRA and mice lacking endogenous glucagon (loss of alpha cells) concomitantly with reduced production of urea. Glucagon administration markedly changed the secretion of rat liver metabolites and within minutes increased urea formation in mice, in perfused rat liver, and in primary human hepatocytes. Transcriptomic analyses revealed that three genes responsible for amino acid catabolism (Cps1, Slc7a2, and Slc38a2) were downregulated both in mice with hepatic steatosis and in mice with deletion of the glucagon receptor. Cultured ob/ob hepatocytes produced less urea upon stimulation with mixed amino acids, and amino acid clearance was lower in mice with hepatic steatosis. Glucagon-induced ureagenesis was impaired in perfused rat livers with hepatic steatosis. Patients with NAFLD had hyperglucagonemia and increased levels of glucagonotropic amino acids, including alanine in particular. Both glucagon and alanine levels were reduced after diet-induced reduction in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, a marker of hepatic steatosis). Conclusions: Glucagon regulates amino acid metabolism both non-transcriptionally and transcriptionally. Hepatic steatosis may impair glucagon-dependent enhancement of amino acid catabolism. (C) 2020 The Author(s). Published by Elsevier GmbH

Alcoholic cirrhosis in Denmark – population-based incidence, prevalence, and hospitalization rates between 1988 and 2005: A descriptive cohort study

<p>Abstract</p> <p>Background</p> <p>Denmark has one of the highest alcohol consumption rates in Northern Europe. The overall per capita alcohol consumption has been stable in recent decades, but surveys have indicated that consumption has decreased in the young and increased in the old. However, there is no recent information on the epidemiology of alcoholic cirrhosis. We examined time trends in incidence, prevalence, and hospitalization rates of alcoholic cirrhosis in Denmark between 1988 and 2005.</p> <p>Methods</p> <p>We used data from a nationwide population-based hospital registry to identify all Danish citizens with a hospital diagnosis of alcoholic cirrhosis. We computed standardized incidence rates, prevalence and hospitalization rates of alcoholic cirrhosis within the Danish population. We also computed the number of hospitalizations per alcoholic cirrhosis patient per year.</p> <p>Results</p> <p>From 1988 to 1993, incidence rates for men and women of any age showed no clear trend, and after a 32 percent increase in 1994, rates were stable throughout 2005. In 2001–2005, the incidence rates were 265 and 118 per 1,000,000 per year for men and women, respectively, and the prevalence rates were 1,326 and 701 per 1,000,000. From 1994, incidence, prevalence, and hospitalization rates decreased for men and women younger than 45 years and increased in the older population, although the latter finding might be partly explained by changes in coding practice. Men and women born around 1960 or later had progressively lower age-specific alcoholic cirrhosis incidence rates than the generations before them. From 1996 to 2005, the number of hospitalizations per alcoholic cirrhosis patient per year increased from 1.3 to 1.5 for men and from 1.1 to 1.2 for women.</p> <p>Conclusion</p> <p>From 1988 to 2005, alcoholic cirrhosis put an increasing burden on the Danish healthcare system. However, the decreasing incidence rate in the population younger than 45 years from 1994 indicated that men and women born around 1960 or later had progressively lower incidence rates than the generations before them. Therefore, we expect the overall incidence and prevalence rates of alcoholic cirrhosis to decrease in the future.</p

PCSK9 deficiency alters brain lipid composition without affecting brain development and function

PCSK9 induces lysosomal degradation of the low-density lipoprotein (LDL) receptor (LDLR) in the liver, hereby preventing removal of LDL cholesterol from the circulation. Accordingly, PCSK9 inhibitory antibodies and siRNA potently reduce LDL cholesterol to unprecedented low levels and are approved for treatment of hypercholesterolemia. In addition, PCSK9 inactivation alters the levels of several other circulating lipid classes and species. Brain function is critically influenced by cholesterol and lipid composition. However, it remains unclear how the brain is affected long-term by the reduction in circulating lipids as achieved with potent lipid lowering therapeutics such as PCSK9 inhibitors. Furthermore, it is unknown if locally expressed PCSK9 affects neuronal circuits through regulation of receptor levels. We have studied the effect of lifelong low peripheral cholesterol levels on brain lipid composition and behavior in adult PCSK9 KO mice. In addition, we studied the effect of PCSK9 on neurons in culture and in vivo in the developing cerebral cortex. We found that PCSK9 reduced LDLR and neurite complexity in cultured neurons, but neither PCSK9 KO nor overexpression affected cortical development in vivo. Interestingly, PCSK9 deficiency resulted in changes of several lipid classes in the adult cortex and cerebellum. Despite the observed changes, PCSK9 KO mice had unchanged behavior compared to WT controls. In conclusion, our findings demonstrate that altered PCSK9 levels do not compromise brain development or function in mice, and are in line with clinical trials showing that PCSK9 inhibitors have no adverse effects on cognitive function

Synergistic roles of climate warming and human occupation in Patagonian megafaunal extinctions during the Last Deglaciation

The causes of Late Pleistocene megafaunal extinctions (60,000 to 11,650 years ago, hereafter 60 to 11.65 ka) remain contentious, with major phases coinciding with both human arrival and climate change around the world. The Americas provide a unique opportunity to disentangle these factors as human colonization took place over a narrow time frame (~15 to 14.6 ka) but during contrasting temperature trends across each continent. Unfortunately, limited data sets in South America have so far precluded detailed comparison. We analyze genetic and radiocarbon data from 89 and 71 Patagonian megafaunal bones, respectively, more than doubling the high-quality Pleistocene megafaunal radiocarbon data sets from the region.We identify a narrowmegafaunal extinction phase 12,280 ± 110 years ago, some 1 to 3 thousand years after initial human presence in the area. Although humans arrived immediately prior to a cold phase, the Antarctic Cold Reversal stadial, megafaunal extinctions did not occur until the stadial finished and the subsequent warming phase commenced some 1 to 3 thousand years later. The increased resolution provided by the Patagonian material reveals that the sequence of climate and extinction events in North and South America were temporally inverted, but in both cases, megafaunal extinctions did not occur until human presence and climate warming coincided. Overall, metapopulation processes involving subpopulation connectivity on a continental scale appear to have been critical for megafaunal species survival of both climate change and human impacts.Fil: Metcalf, Jessica L.. University of Adelaide; Australia. State University of Colorado Boulder; Estados UnidosFil: Turney, Chris. University of New South Wales; AustraliaFil: Barnett, Ross. University of Oxford; Reino Unido. Universidad de Copenhagen; DinamarcaFil: Martin, Fabiana. Universidad de Magallanes. Instituto de la Patagonia. Centro de Estudios del Hombre Austral; ChileFil: Bray, Sarah C.. University of Adelaide; Australia. University of South Australia; AustraliaFil: Vilstrup, Julia T.. Universidad de Copenhagen; DinamarcaFil: Orlando, Ludovic. Universidad de Copenhagen; DinamarcaFil: Salas-Gismondi, Rodolfo. Université de Montpellier. Institut des Sciences de l’Evolution; Francia. Universidad Nacional Mayor de San Marcos; PerúFil: Loponte, Daniel Marcelo. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Medina, Matias Eduardo. Centro de Estudios Históricos ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Nigris, Mariana Eleonor. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Civalero, Maria Teresa. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernández, Pablo Marcelo. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gasco, Alejandra Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología Humana; ArgentinaFil: Duran, Victor Alberto. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales. Laboratorio de Paleoecología Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seymour, Kevin L.. Royal Ontario Museum. Department of Natural History; CanadáFil: Otaola, Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Gil, Adolfo Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla | Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Museo de Historia Natural de San Rafael - Ianigla; ArgentinaFil: Paunero, Rafael. Universidad Nacional de La Plata; ArgentinaFil: Prevosti, Francisco Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; ArgentinaFil: Bradshaw, Corey J. A.. University of Adelaide; AustraliaFil: Wheeler, Jane C.. Instituto de Investigación y Desarrollo de Camélidos Sudamericanos; PerúFil: Borrero, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Austin, Jeremy J.. University of Adelaide; AustraliaFil: Cooper, Alan. University of Adelaide; Australia. University of Oxford; Reino Unid