Immunotherapeutic targeting of membrane Hsp70-expressing tumors using recombinant human granzyme B

Background: We have previously reported that human recombinant granzyme B (grB) mediates apoptosis in membrane heat shock protein 70 (Hsp70)-positive tumor cells in a perforin-independent manner

Cp2TiCl/D2O/Mn, a formidable reagent for the deuteration of organic compounds

Cp2TiCl/D2O/Mn is an efficient combination, sustainable and cheap reagent that mediates the D-atom transfer from D2O to different functional groups and can contribute to the synthesis of new deuterated organic compounds under friendly experimental conditions and with great economic advantages.The Spanish MICINN (Project CTQ2015-70724-R)University of Sevill

Chemically-Mediated quantum criticality in NbFe_2

Laves-phase Nb{1+c}Fe_{2-c} is a rare itinerant intermetallic compound exhibiting magnetic quantum criticality at c_{cr}=1.5%Nb excess; its origin, and how alloying mediates it, remains an enigma. For NbFe_2, we show that an unconventional band critical point (uBCP) above the Fermi level E_F explains most observations, and that chemical alloying mediates access to this uBCP by an increase in E_F with decreasing electrons (increasing %Nb), counter to rigid-band concepts. We calculate that E_F enters the uBCP region for c_{cr} > 1.5%Nb and by 1.74%Nb there is no Nb site-occupation preference between symmetry-distinct Fe sites, i.e., no electron-hopping disorder, making resistivity near constant as observed. At larger Nb (Fe) excess, the ferromagnetic Stoner criterion is satisfied.Comment: 4 pages, 5 figure

In situ generation of Mes2Mg as a non-nucleophilic carbon-centred base reagent for the efficient one-pot conversion of ketones to silyl enol ethers

Treatment of commercially available MesMgBr with 1,4-dioxane produces the key Mes2Mg reagent in situ which then mediates the deprotonation of ketones to deliver trimethylsilyl enol ethers, at readily accessible temperatures and without any nucleophilic addition, in an expedient and high yielding one-pot process

mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue

Activation of non-shivering thermogenesis (NST) in brown adipose tissue (BAT) has been proposed as an anti-obesity treatment. Moreover, cold-induced glucose uptake could normalize blood glucose levels in insulin-resistant patients. It is therefore important to identify novel regulators of NST and cold-induced glucose uptake. Mammalian target of rapamycin complex 2 (mTORC2) mediates insulin-stimulated glucose uptake in metabolic tissues, but its role in NST is unknown. We show that mTORC2 is activated in brown adipocytes upon β-adrenergic stimulation. Furthermore, mice lacking mTORC2 specifically in adipose tissue (AdRiKO mice) are hypothermic, display increased sensitivity to cold, and show impaired cold-induced glucose uptake and glycolysis. Restoration of glucose uptake in BAT by overexpression of hexokinase II or activated Akt2 was sufficient to increase body temperature and improve cold tolerance in AdRiKO mice. Thus, mTORC2 in BAT mediates temperature homeostasis via regulation of cold-induced glucose uptake. Our findings demonstrate the importance of glucose metabolism in temperature regulation

Long-term culture captures injury-repair cycles of colonic stem cells

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hop

A conserved metalloprotease mediates ecdysis in Caenorhabditis elegans

Molting is required for progression between larval stages in the life cycle of nematodes. We have identified four mutant alleles of a <i>Caenorhabditis elegans</i> metalloprotease gene, <i>nas-37</i>, that cause incomplete ecdysis. At each molt the cuticle fails to open sufficiently at the anterior end and the partially shed cuticle is dragged behind the animal. The gene is expressed in hypodermal cells 4 hours before ecdysis during all larval stages. The <i>NAS-37</i> protein accumulates in the anterior cuticle and is shed in the cuticle after ecdysis. This pattern of protein accumulation places NAS- 37 in the right place and at the right time to degrade the cuticle to facilitate ecdysis. The nas-37 gene has orthologs in other nematode species, including parasitic nematodes, and they undergo a similar shedding process. For example, <i>Haemonchus contortus</i> molts by digesting a ring of cuticle at the tip of the nose. Incubating <i>Haemonchus</i> larvae in extracted exsheathing fluids causes a refractile ring of digested cuticle to form at the tip of the nose. When <i>Haemonchus</i> cuticles are incubated with purified NAS-37, a similar refractile ring forms. NAS-37 degradation of the <i>Haemonchus</i> cuticle suggests that the metalloproteases and the cuticle substrates involved in exsheathment of parasitic nematodes are conserved in free-living nematodes

From social context and resilience to performance through job satisfaction: A multilevel study over time

Giving the crucial role of organizational context in shaping individual attitudes and behaviors at work, in this research we studied the effects of collective work-unit Perceptions of Social Context (PoSC) on individual work resilience and two key individual outcomes: job satisfaction and job performance as rated by the supervisor. We theorized that collective PoSC act as antecedents of individual variables, and that individual job satisfaction mediates the relationship between collective PoSC and job performance, and between work resilience and job performance over time. A sample of 305 white-collar employees, clustered in 67 work-units, participated in the study. Hierarchical linear modeling highlighted that collective PoSC are significant related to individual work resilience. Moreover, results showed that individual job satisfaction fully mediates the relationship between collective PoSC and individual job performance and the relationship between individual work resilience and individual job performance. At a practical level, results suggest that interventions on collective PoSC may increase work resilience, job satisfaction and job performance over time at the individual level