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When a first order belief accurately reflects the evidence, how should this affect the epistemic justification of a higher order belief that this is the case? In an influential paper, Kelly argues that first order evidential accuracy tends to generate more justified higher order beliefs (Kelly 2010). Call this Bottom Up. I argue that neither general views about what justifies our higher order beliefs nor the specific arguments that Kelly offers support Bottom Up. Second, I suggest that while we can reject Bottom Up, we can still accept that justified higher order beliefs significantly affect the justification of first order beliefs. Third, I argue that the epistemic justification of higher order belief is fragile in the sense that it tends to dissipate when a subject is confronted with certain defeaters, including notably the sort of defeaters arising from disagreement, precisely when higher order justification depends on first order success in the ways that one may think support Bottom Up.
Objectives: In complex real life situations, memories for temporal and spatial information are naturally linked since sequential events coincide in time and space. Whether this connection is inseparable or instead whether these processes are functionally dissociable was investigated in this patient study. Methods: Spatial object-location and temporal order memory tasks were administered to 36 stroke patients and 44 healthy control participants. Results: On group level, patients with a stroke in the left hemisphere performed worse on temporal order memory, compared to the control participants. On individual level, using a multiple case-study approach, a clear pattern of dissociations was found between memory for temporal and for spatial features. Conclusions: These findings indicate that location and temporal order memory contain functionally separable processes. This adds to our understanding of how context information is processed in human memory. (JINS, 2017, 23, 421–430)
This review summarises current knowledge on camel milk proteins, with focus on significant peculiarities in protein composition and molecular properties. Camel milk is traditionally consumed as a fresh or naturally fermented product. Within the last couple of years, an increasing quantity is being processed in dairy plants, and a number of consumer products have been marketed. A better understanding of the technological and functional properties, as required for product improvement, has been gained in the past years. Absence of the whey protein β-LG and a low proportion of к-casein cause differences in relation to dairy processing. In addition to the technological properties, there are also implications for human nutrition and camel milk proteins are of interest for applications in infant foods, for food preservation and in functional foods. Proposed health benefits include inhibition of the angiotensin converting enzyme, antimicrobial and antioxidant properties as well as an antidiabetogenic effect. Detailed investigations on foaming, gelation and solubility as well as technological consequences of processing should be investigated further for the improvement of camel milk utilisation in the near future.
We examine the results of s-Processlng occurring in a low mass star of low metallicity during the pulsed He-instability in AGB phases by comparing them with the s-Classical analysis. Neutron exposures are provided by the C13(Alpha, N)016 reaction, according to the mechanism suggested by Iben and Renzini (1983) for the formation in the interpulse phase of a small zone rich of C13 and its subsequent ingestion in the next pulse.
The family Cheirogaleidae is arguably the most interesting group of primates alive today. Within this single clade, hypothesized to have originated approximately 25–30 Mya, we find the world's smallest living primate (genus Microcebus), one species that went “missing” for more than three decades (genus Allocebus), the only known obligate hibernator within the primates (genus Cheirogaleus), the only primate species that preys upon other members of its phylogenetic family (genus Mirza), and also, a taxonomic system that has exploded within the past two decades. This taxonomic explosion has been decidedly lopsided, however. Whereas the genus Allocebus has remained monotypic, containing the single species A. trichotis since its original description in 1875 (Günther 1875), the genus Microcebus (mouse lemurs) has gone from a two species system as recently as 1993 to one that that now contains more than 20 recognized species. This apparent skew in species-level diversity cries out for further exploration. Is it an artifact of organismal and geographic sampling bias, with certain species and ecosystems preferentially sampled, or is it based in biology, with some branches of the cheirogaleid tree (namely, the mouse lemurs) intrinsically more prone to evolutionary divergence? An exploration of these themes and questions is our goal in this chapter.
The first genus-level phylogeny of the cheirogaleid lemurs was published by Rumpler et al. (1994) and has remained virtually unchanged in the subsequent decades. Using karyotype data and restriction fragment analysis, the authors found strong support for the phylogeny illustrated in Figure 1.1. Notably, Rumpler and Albignac (1972) had long before discovered that the karyotype of Phaner (2n = 46) is quite distinct from that of the other four genera (2n = 66), leading those authors to propose a two-subfamily taxonomy of the Cheirogaleidae, the monotypic Phanerinae (including only the genus Phaner) and the Cheirogaleinae (comprising the four remaining genera). More recent molecular phylogenetic analyses have sampled more densely at the species level and have yielded fresh insights into interspecific relationships within the various genera, while leaving the “skeleton” of the phylogeny unchanged.
Plant lignans are diphenolic compounds ingested with whole grains and seeds and converted to enterolignans by the colonic microbiota. In the present study, we investigated absorption and metabolism of plant lignans and enterolignans in vivo after consumption of cereal-based diets. Six pigs fitted with catheters in the mesenteric artery and portal vein and with a flow probe attached to the portal vein along with twenty pigs for quantitative collection of urine were used for this study. The animals were fed bread based on wheat flour low in plant lignans and three lignan-rich breads based on whole-wheat grain, wheat aleurone flour or rye aleurone flour. Plant lignans and enterolignans in plasma were monitored daily at fast after 0–3 d of lignan-rich intake, and on the 4th day of lignan-rich intake a 10-h profile was completed. Urine samples were collected after 11 d of lignan-rich diet consumption. The concentrations of plant lignans were low at fast, and was 1·2–2·6 nmol/l after switching from the low-lignan diet to the lignan-rich diets. However, on the profile day, the concentration and quantitative absorption of plant lignans increased significantly from 33 nmol/h at fast to 310 nmol/h 0–2·5 h after ingestion with a gradual increase in the following periods. Quantitatively, the absorption of plant lignans across diets amounted to 7 % of ingested plant lignans, whereas the urinary excretion of plant lignans was 3 % across diets. In conclusion, there is a substantial postprandial uptake of plant lignans from cereals, suggesting that plant lignans are absorbed from the small intestine.
Elucidating the detailed process of ligand binding to a receptor is pharmaceutically important for identifying druggable binding sites. With the ability to provide atomistic detail, computational methods are well poised to study these processes. Here, accelerated molecular dynamics (aMD) is proposed to simulate processes of ligand binding to a G-protein-coupled receptor (GPCR), in this case the M3 muscarinic receptor, which is a target for treating many human diseases, including cancer, diabetes and obesity. Long-timescale aMD simulations were performed to observe the binding of three chemically diverse ligand molecules: antagonist tiotropium (TTP), partial agonist arecoline (ARc) and full agonist acetylcholine (ACh). In comparison with earlier microsecond-timescale conventional MD simulations, aMD greatly accelerated the binding of ACh to the receptor orthosteric ligand-binding site and the binding of TTP to an extracellular vestibule. Further aMD simulations also captured binding of ARc to the receptor orthosteric site. Additionally, all three ligands were observed to bind in the extracellular vestibule during their binding pathways, suggesting that it is a metastable binding site. This study demonstrates the applicability of aMD to protein–ligand binding, especially the drug recognition of GPCRs.
Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents.
Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography.
Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups.
High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.
The effects of increased colonic fermentation of dietary fibres (DF) on the net portal flux (NPF) of carbohydrate-derived metabolites (glucose, SCFA and, especially, butyrate), hormones (insulin, C-peptide, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide) and NEFA were studied in a healthy catheterised pig model. A total of six pigs weighing 59 (sem 1·6) kg were fitted with catheters in the mesenteric artery and in the portal and hepatic veins, and a flow probe around the portal vein, and included in a double 3 × 3 cross-over design with three daily feedings (at 09.00, 14.00 and 19.00 hours). Fasting and 5 h postprandial blood samples were collected after 7 d adaptation to each diet. The pigs were fed a low-DF Western-style control diet (WSD) and two high-DF diets (an arabinoxylan-enriched diet (AXD) and a resistant starch-enriched diet (RSD)). The NPF of insulin was lower (P= 0·04) in AXD-fed pigs (4·6 nmol/h) than in RSD-fed pigs (10·5 nmol/h), despite the lowest NPF of glucose being observed in RSD-fed pigs (203 mmol/h, P= 0·02). The NPF of total SCFA, acetate, propionate and butyrate were high, intermediate and low (P< 0·01) in AXD-, RSD- and WSD-fed pigs, respectively, with the largest relative increase being observed for butyrate in response to arabinoxylan supplementation. In conclusion, the RSD and AXD had different effects on the NPF of insulin and glucose, suggesting different impacts of arabinoxylan and resistant starch on human health.