Replication confers β cell immaturity.

Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal β cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that β-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult β cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal β that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the β cell reverts to a less functional one in response to proliferative cues

Macropinocytosis confers resistance to therapies targeting cancer anabolism.

Macropinocytic cancer cells scavenge amino acids from extracellular proteins. Here, we show that consuming necrotic cell debris via macropinocytosis (necrocytosis) offers additional anabolic benefits. A click chemistry-based flux assay reveals that necrocytosis provides not only amino acids, but sugars, fatty acids and nucleotides for biosynthesis, conferring resistance to therapies targeting anabolic pathways. Indeed, necrotic cell debris allow macropinocytic breast and prostate cancer cells to proliferate, despite fatty acid synthase inhibition. Standard therapies such as gemcitabine, 5-fluorouracil (5-FU), doxorubicin and gamma-irradiation directly or indirectly target nucleotide biosynthesis, creating stress that is relieved by scavenged nucleotides. Strikingly, necrotic debris also render macropinocytic, but not non-macropinocytic, pancreas and breast cancer cells resistant to these treatments. Selective, genetic inhibition of macropinocytosis confirms that necrocytosis both supports tumor growth and limits the effectiveness of 5-FU in vivo. Therefore, this study establishes necrocytosis as a mechanism for drug resistance

Norms, Law and the Impeachment Power

[Excerpt] Most experts believe that, while a president can be criminally prosecuted after leaving office, he cannot be prosecuted while he is president. And while the president may be sued civilly while holding office, the office confers powerful immunities and other constitutional defenses that are unavailable to ordinary civilian defendants

AESTHETICS CONFERS VALUE TO THE FIRM

The aesthetics offers multiple, powerful, specific and tangible advantages to the firm such as: it creates fidelity; it expresses the personality of the firm and of its marks; it allows the establishment of superior prices; the aesthetics message penetrates the informational amalgam; it protects it from the competitional offensive; it induces the rising of productivity and the reduction of costs; it reduces the distances between the stages of the launch of a new product on the market and its maturity.transmitting messages, aesthetics in marketing

Ligand induced cleavage and nuclear localization of the rice XA21 immune receptor

The rice XA21 receptor confers immunity to the Gram-negative bacterial pathogen, _Xanthomonas oryzae_ pv. _oryzae_ (_Xoo_) upon recognition of the conserved microbial signature AxY^S^22. Here, we demonstrate that the intracellular kinase domain of XA21 translocates to the nucleus upon AxY^S^22-mediated perception and that this translocation event is required for XA21-mediated immunity

Whole-blood transcriptomic signatures induced during immunization by chloroquine prophylaxis and Plasmodium falciparum sporozoites

A highly effective vaccine that confers sterile protection to malaria is urgently needed. Immunization under chemoprophylaxis with sporozoites (CPS) consistently confers high levels of protection in the Controlled Human Malaria infection (CHMI) model. To provide a broad, unbiased assessment of the composition and kinetics of direct ex vivo human immune responses to CPS, we profiled whole-blood transcriptomes by RNA-seq before and during CPS immunization and following CHMI challenge. Differential expression of genes enriched in modules related to T cells, NK cells, protein synthesis, and mitochondrial processes were detected in fully protected individuals four weeks after the first immunization. Non-protected individuals demonstrated transcriptomic changes after the third immunization and the day of treatment, with upregulation of interferon and innate inflammatory genes and downregulation of B-cell signatures. Protected individuals demonstrated more significant interactions between blood transcription modules compared to non-protected individuals several weeks after the second and third immunizations. These data provide insight into the molecular and cellular basis of CPS-induced immune protection from P. falciparum infection

On the adaptive advantage of always being right (even when one is not)

We propose another positive illusion – overconfidence in the generalisability of one’s theory – that fits with McKay & Dennett’s (M&D’s) criteria for adaptive misbeliefs. This illusion is pervasive in adult reasoning but we focus on its prevalence in children’s developing theories. It is a strongly held conviction arising from normal functioning of the doxastic system that confers adaptive advantage on the individual

Phillip DeVito Honors and Awards: Confrere de la Chaine des Rotisseurs Framed Certificate

This framed certificate confirms Phillip DeVito as a member of the Confrerie de la Chaine des Rotisseurs, an international food and wine society dedicated to fine cuisine and table art. This confers upon DeVito the title of Chef de Table. DeVito was the maître d’hôtel and cellar master for the fine dining and wine program at Salishan Lodge in Gleneden Beach, Oregon from 1972 to 1994