Modified wind chill temperatures determined by a whole body thermoregulation model and human-based facial convective coefficients

Wind chill equivalent temperatures (WCETs) were estimated by a modified Fiala’s whole body thermoregulation model of a clothed person. Facial convective heat exchange coefficients applied in the computations concurrently with environmental radiation effects were taken from a recently derived human-based correlation. Apart from these, the analysis followed the methodology used in the derivation of the currently used wind chill charts. WCET values are summarized by the following equation: $$ \mathrm{WCET}=12.87+0.5334\ast {T}_o-\left(12.66-0.4414\ast {T}_o\right)\ast {U}_{reported}{}^{0.1228} $$ Results indicate consistently lower estimated facial skin temperatures and consequently higher WCETs than those listed in the literature and used by the North American weather services. Calculated dynamic facial skin temperatures were additionally applied in the estimation of probabilities for the occurrence of risks of frostbite. Predicted weather combinations for probabilities of “Practically no risk of frostbite for most people,” for less than 5 % risk at wind speeds above 40 km h^?1, were shown to occur at air temperatures above ?10 °C compared to the currently published air temperature of ?15 °C. At air temperatures below ?35 °C, the presently calculated weather combination of 40 km h^?1/?35 °C, at which the transition for risks to incur a frostbite in less than 2 min, is less conservative than that published: 60 km h^?1/?40 °C. The present results introduce a fundamentally improved scientific basis for estimating facial skin temperatures, wind chill temperatures and risk probabilities for frostbites over those currently practiced.     

Live-Cell Imaging in Caenorhabditis elegans Reveals the Distinct Roles of Dynamin Self-Assembly and Guanosine Triphosphate Hydrolysis in the Removal of Apoptotic Cells

Dynamins are large GTPases that oligomerize along membranes. Dynamin''s membrane fission activity is believed to underlie many of its physiological functions in membrane trafficking. Previously, we reported that DYN-1 (Caenorhabditis elegans dynamin) drove the engulfment and degradation of apoptotic cells through promoting the recruitment and fusion of intracellular vesicles to phagocytic cups and phagosomes, an activity distinct from dynamin''s well-known membrane fission activity. Here, we have detected the oligomerization of DYN-1 in living C. elegans embryos and identified DYN-1 mutations that abolish DYN-1''s oligomerization or GTPase activities. Specifically, abolishing self-assembly destroys DYN-1''s association with the surfaces of extending pseudopods and maturing phagosomes, whereas inactivating guanosine triphosphate (GTP) binding blocks the dissociation of DYN-1 from these membranes. Abolishing the self-assembly or GTPase activities of DYN-1 leads to common as well as differential phagosomal maturation defects. Whereas both types of mutations cause delays in the transient enrichment of the RAB-5 GTPase to phagosomal surfaces, only the self-assembly mutation but not GTP binding mutation causes failure in recruiting the RAB-7 GTPase to phagosomal surfaces. We propose that during cell corpse removal, dynamin''s self-assembly and GTP hydrolysis activities establish a precise dynamic control of DYN-1''s transient association to its target membranes and that this control mechanism underlies the dynamic recruitment of downstream effectors to target membranes.     

A sensitive and selective liquid chromatography/tandem mass spectrometry method for determination of MLN8237 in human plasma

We describe a selective and a highly sensitive high-performance liquid chromatography–electron spray ionization-collision induced dissociation-tandem mass spectrometry (HPLC–ESI-CID-MS/MS) assay for the Aurora A kinase inhibitor MLN8237 in human plasma. The intra-day precision based on the standard deviation of replicates of quality control samples ranged from 0.2 to 4% and with accuracy ranging from 96 to 102%. The inter-day precision ranged from 0.5 to 7% and the accuracy ranged from 93 to 105%. Stability studies showed that MLN8237 was stable both during the expected conditions for sample preparation and storage. The lower limit of quantification for MLN8237 was 5 ng/mL. The analytical method showed excellent sensitivity, precision, and accuracy. This method is robust and is being successfully employed in a Children's Oncology Group Phase 1 Consortium study of MLN8237 in children with cancer.     

Living with p53, dying of p53

The p53 tumor suppressor protein acts as a major defense against cancer. Among its most distinctive features is the ability to elicit both apoptotic death and cell cycle arrest. In this issue of Cell, Das et al. (2007) and Tanaka et al. (2007) provide new insights into the mechanisms that dictate the life and death decisions of p53.     

Scavenger receptor C-type lectin binds to the leukocyte cell surface glycan Lewis(x) by a novel mechanism

The scavenger receptor C-type lectin (SRCL) is unique in the family of class A scavenger receptors, because in addition to binding sites for oxidized lipoproteins it also contains a C-type carbohydrate-recognition domain (CRD) that interacts with specific glycans. Both human and mouse SRCL are highly specific for the Lewis(x) trisaccharide, which is commonly found on the surfaces of leukocytes and some tumor cells. Structural analysis of the CRD of mouse SRCL in complex with Lewis(x) and mutagenesis show the basis for this specificity. The interaction between mouse SRCL and Lewis(x) is analogous to the way that selectins and DC-SIGN bind to related fucosylated glycans, but the mechanism of the interaction is novel, because it is based on a primary galactose-binding site similar to the binding site in the asialoglycoprotein receptor. Crystals of the human receptor lacking bound calcium ions reveal an alternative conformation in which a glycan ligand would be released during receptor-mediated endocytosis.     

Raised salivary testosterone in women is associated with increased attraction to masculine faces

Women's preferences for masculinity in men's faces, voices and behavioral displays change during the menstrual cycle and are strongest around ovulation. While previous findings suggest that change in progesterone level is an important hormonal mechanism for such variation, it is likely that changes in the levels of other hormones will also contribute to cyclic variation in masculinity preferences. Here we compared women's preferences for masculine faces at two points in the menstrual cycle where women differed in salivary testosterone, but not in salivary progesterone or estrogen. Preferences for masculinity were strongest when women's testosterone levels were relatively high. Our findings complement those from previous studies that show systematic variation in masculinity preferences during the menstrual cycle and suggest that change in testosterone level may play an important role in cyclic shifts in women's preferences for masculine traits.