The Affectionate Walrus

Many different species of very young seal and sea lion pups are extremely friendly to man after they overcome their initial fear upon being captured. Sometimes this will require a matter of days but in other species, such as a few-days-old Steller sea lion pup, they will have lost all sense of fear within the first fifteen minutes after their capture. ... the walrus which has been hunted by the Eskimos for many years is the most naturally affectionate of all marine mammals. They weigh about one hundred and twenty pounds at birth and show almost no fear of man even up to a year of age in the wild. Very young walrus can be easily trained to nurse a special formula from a bottle and they require about a gallon of formula per day. ... Whereas the Weddell seal pup may rest its head upon your knee, the walrus is not satisfied unless it can climb all over you even after he gets up to fifteen hundred pounds or more. It therefore soon becomes unsafe to get into a pool with them because of the danger of being drowned, and out of water one may be pinned down so as to require help to get up, particularly if there is more than one walrus. If anyone sits down where there are two or three young walrus being raised by hand, they will all try to climb upon you at the same time. In the case of most marine mammals if any object such as a hydrophone is placed in their pool they completely ignore it, but the walrus is there almost immediately and has it in his mouth or is playing with it in his flippers. It is therefore difficult to obtain underwater recordings of them unless the hydrophone is placed in some inaccessible place. Even placing dummy hydrophones in the tank for a week ahead of time helps very little if they see the new hydrophone go in. If one throws a half gallon nursing bottle half full of formula into their pool, they will occasionally pick it up in their flippers, lie on their back and nurse from the bottle while holding it up over them with their flippers. Their baby-like whimper and low-pitch woof! woof! and their apparent desire for physical contact with human beings make them one of the most attractive of the marine mammals

The Effect of Pressures up to 16000 Atmospheres Upon the E.M.F. of the Weston Standard Cell

A variety of types of Weston standard cells were constructed and the electromotive force was found to increase with the pressure. The shape of the curve being effected somewhat by the material of which the cell case was constructed

A Study of Phosphorescent Zinc Sulphide Screens and Radioactivity Under Extremely High Pressure

For a study of the effect of pressure on fluorescent zinc sulphide screens, an arrangement very similar to that used in the preceeding paper was employed. In this case the fluorescent zinc sulphide was mounted on the inner surface of the pressure window with a transparent cement

A Study of the Absorption of Hydrogen Bromide by Cinnamic Acid in the Presence of Ultra Violet Light

In the absorption of various reagents at the double bond of organic compounds it has been noted that in some cases a different product was obtained when the absorption was carried out in the presence of ultra-violet light. This difference has been frequently explained on the basis that the polarity of the reagent being absorbed was changed by the ultra-violet light. The question has been raised as to whether the difference was actually due to the change in polarity in the double bond

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study):a prospective, randomised, open-label, blinded-endpoint clinical trial

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension. Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600–1000 h) or in the evening (2000–0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete. Findings: Between Dec 17, 2011, and June 5, 2018, 24 610 individuals were screened and 21 104 were randomly assigned to evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%) were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African, Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%] participants); and 2725 (13·0%) had a previous cardiovascular disease. By the end of study follow-up (March 31, 2021), median follow-up was 5·2 years (IQR 4·9–5·7), and 529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%) of 10 601 assigned to morning treatment had withdrawn from all follow-up. A primary endpoint event occurred in 362 (3·4%) participants assigned to evening treatment (0·69 events [95% CI 0·62–0·76] per 100 patient-years) and 390 (3·7%) assigned to morning treatment (0·72 events [95% CI 0·65–0·79] per 100 patient-years; unadjusted hazard ratio 0·95 [95% CI 0·83–1·10]; p=0·53). No safety concerns were identified. Interpretation: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects. Funding: British Heart Foundation

Forest responses to last‐millennium hydroclimate variability are governed by spatial variations in ecosystem sensitivity

Forecasts of future forest change are governed by ecosystem sensitivity to climate change, but ecosystem model projections are under‐constrained by data at multidecadal and longer timescales. Here, we quantify ecosystem sensitivity to centennial‐scale hydroclimate variability, by comparing dendroclimatic and pollen‐inferred reconstructions of drought, forest composition and biomass for the last millennium with five ecosystem model simulations. In both observations and models, spatial patterns in ecosystem responses to hydroclimate variability are strongly governed by ecosystem sensitivity rather than climate exposure. Ecosystem sensitivity was higher in models than observations and highest in simpler models. Model‐data comparisons suggest that interactions among biodiversity, demography and ecophysiology processes dampen the sensitivity of forest composition and biomass to climate variability and change. Integrating ecosystem models with observations from timescales extending beyond the instrumental record can better understand and forecast the mechanisms regulating forest sensitivity to climate variability in a complex and changing world

Immunohistochemical, morphological and ultrastructural resemblance between dendritic cells and folliculo-stellate cells in normal human and rat anterior pituitaries

Immunolabeling of cryo-sections of human anterior pituitaries obtained at autopsy, and of cryo-sections of freshly prepared rat anterior pituitaries, with a panel of monoclonal antibodies against markers of the monocyte/dendritic cell/macrophage lineage, reveals in both species a characteristic pattern of immunopositive cells, among which many cells with dendritic phenotype are found. Cells characterized by marker expression of MHC-class II determinants and a dendritic morphology are present in both human and rat anterior pituitary. Markers characteristic of dendritic cells such as the L25 antigen and the OX62 antigen were present in anterior pituitaries from human and rat respectively. The population of MHC-class II expressing dendritic cells of the rat anterior pituitary is compared at the ultrastructural level with the folliculo-stellate cell population, which cell type has been previously characterized by its distinctive ultrastructure and immunopositivity for the S100 protein. Using immune-electron microscopy of rat anterior pituitaries fixed with periodate-lysine-paraformaldehyde, we were able to distinguish non-granulated cells expressing MHC-class II determinants, whereas no MHC-class II expression was found in the granulated endocrine cells. Using double immunolabeling of cryo-sections of these rat AP with 25 nm and 15 nm gold labels, we demonstrated an overlap between the populations of MHC-class II-expressing and S100 protein-expressing cells. Furthermore, MHC-class II-expressing and S100-positive cells showed ultrastructural characteristics that have been previously ascribed to folliculo-stellate cells. At the light microscopical level in the rat AP, a proportion of 10 to 20% of the S100-positive cells was found immunopositive for the MHC-class II marker OX6. In the hu

Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo

The predominantly pre-synaptic intrinsically disordered protein α-synuclein is prone to misfolding and aggregation in synucleinopathies, such as Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB). Molecular chaperones play important roles in protein misfolding diseases and members of the chaperone machinery are often deposited in Lewy bodies. Here, we show that the Hsp90 co-chaperone STI1 co-immunoprecipitated α-synuclein, and co-deposited with Hsp90 and Hsp70 in insoluble protein fractions in two mouse models of α-synuclein misfolding. STI1 and Hsp90 also co-localized extensively with filamentous S129 phosphorylated α-synuclein in ubiquitin-positive inclusions. In PD human brains, STI1 transcripts were increased, and in neurologically healthy brains, STI1 and α-synuclein transcripts correlated. Nuclear Magnetic Resonance (NMR) analyses revealed direct interaction of α-synuclein with STI1 and indicated that the STI1 TPR2A, but not TPR1 or TPR2B domains, interacted with the C-terminal domain of α-synuclein. In vitro, the STI1 TPR2A domain facilitated S129 phosphorylation by Polo-like kinase 3. Moreover, mice over-expressing STI1 and Hsp90ß presented elevated α-synuclein S129 phosphorylation accompanied by inclusions when injected with α-synuclein pre-formed fibrils. In contrast, reduced STI1 function decreased protein inclusion formation, S129 α-synuclein phosphorylation, while mitigating motor and cognitive deficits as well as mesoscopic brain atrophy in α-synuclein-over-expressing mice. Our findings reveal a vicious cycle in which STI1 facilitates the generation and accumulation of toxic α-synuclein conformers, while α-synuclein-induced proteostatic stress increased insoluble STI1 and Hsp90

The effect of starch-based biomaterials on leukocyte adhesion and activation in vitro

Leukocyte adhesion to biomaterials has long been recognised as a key element to determine their inflammatory potential. Results regarding leukocyte adhesion and activation are contradictory in some aspects of the material’s effect in determining these events. It is clear that together with the wettability or hydrophilicity/hydrophobicity, the roughness of a substrate has a major effect on leukocyte adhesion. Both the chemical and physical properties of a material influence the adsorbed proteins layer which in turn determines the adhesion of cells. In this work polymorphonuclear (PMN) cells and a mixed population of monocytes/macrophages and lymphocytes (mononuclear cells) were cultured separately with a range of starch-based materials and composites with hydroxyapatite (HA). A combination of both reflected light microscopy and scanning electron microscopy (SEM) was used in order to study the leukocyte morphology. The quantification of the enzyme lactate dehydrogenase (LDH) was used to determine the number of viable cells adhered to the polymers. Cell adhesion and activation was characterised by immunocytochemistry based on the expression of several adhesion molecules, crucial in the progress of an inflammatory response. This work supports previous in vitro studies with PMN and monocytes/macrophages, which demonstrated that there are several properties of the materials that can influence and determine their biological response. From our study, monocytes/macrophages and lymphocytes adhere in similar amounts to more hydrophobic (SPCL) and to moderately hydrophilic (SEVA-C) surfaces and do not preferentially adhere to rougher substrates (SCA). Contrarily, more hydrophilic surfaces (SCA) induced higher PMN adhesion and lower activation. In addition, the hydroxyapatite reinforcement induces changes in cell behaviour for some materials but not for others. The observed response to starch-based biodegradable polymers was not significantly different from the control materials. Thus, the results reported herein indicate the low potential of the starch-based biodegradable polymers to induce inflammation especially the HA reinforced composite materials