Cas9+ conditionally-immortalized macrophages as a tool for bacterial pathogenesis and beyond.

Macrophages play critical roles in immunity, development, tissue repair, and cancer, but studies of their function have been hampered by poorly-differentiated tumor cell lines and genetically-intractable primary cells. Here we report a facile system for genome editing in non-transformed macrophages by differentiating ER-Hoxb8 myeloid progenitors from Cas9-expressing transgenic mice. These conditionally immortalized macrophages (CIMs) retain characteristics of primary macrophages derived from the bone marrow yet allow for easy genetic manipulation and a virtually unlimited supply of cells. We demonstrate the utility of this system for dissection of host genetics during intracellular bacterial infection using two important human pathogens: Listeria monocytogenes and Mycobacterium tuberculosis

Repartnering: the relevance of parenthood and gender to cohabitation and remarriage among the formerly married

This paper is an exploratory analysis of the impact of current and anticipated parenthood on cohabitation and remarriage among those formerly living in marriage-type relationships. The focus on children is embedded within a broader analysis of repartnering which takes account of other factors, including gender. Quantitative and qualitative analyses are used, with a multivariate analysis of repartnering patterns, using data from the General Household Survey, being complementedby in-depth interview data examining the attitudes of the formerly married to future relationships. The paper demonstrates that parenthood has a statistically significant effect on the likelihood of formerly married women repartnering, with a higher number of children being associated with a lower probability of repartnering. The presence of children can work against repartnering in a variety of ways. Children place demands on their parents and can deter or object to potential partners. Parents may see their parental role as more important than, and a barrier to, new relationships. However, mothers are typically looking for partners for themselves rather than fathers for their children. Among formerly married people without children, the desire to become a parent encourages repartnering. The paper concludes that parenthood should be a key consideration in analyses of repartnering

The relative impact of cloud condensation nuclei and ice nucleating particle concentrations on phase partitioning in Arctic mixed-phase stratocumulus clouds

This study investigates the interactions between cloud dynamics and aerosols in idealized large-eddy simulations (LES) of Arctic mixed-phase stratocumulus clouds (AMPS) observed at Oliktok Point, Alaska, in April 2015. This case was chosen because it allows the cloud to form in response to radiative cooling starting from a cloud-free state, rather than requiring the cloud ice and liquid to adjust to an initial cloudy state. Sensitivity studies are used to identify whether there are buffering feedbacks that limit the impact of aerosol perturbations. The results of this study indicate that perturbations in ice nucleating particles (INPs) dominate over cloud condensation nuclei (CCN) perturbations; i.e., an equivalent fractional decrease in CCN and INPs results in an increase in the cloud-top longwave cooling rate, even though the droplet effective radius increases and the cloud emissivity decreases. The dominant effect of ice in the simulated mixed-phase cloud is a thinning rather than a glaciation, causing the mixed-phase clouds to radiate as a grey body and the radiative properties of the cloud to be more sensitive to aerosol perturbations. It is demonstrated that allowing prognostic CCN and INPs causes a layering of the aerosols, with increased concentrations of CCN above cloud top and increased concentrations of INPs at the base of the cloud-driven mixed layer. This layering contributes to the maintenance of the cloud liquid, which drives the dynamics of the cloud system

Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis

Selenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LC-MS/MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels.National Cancer Institute (U.S.) (Grant R01 DK090311)National Cancer Institute (U.S.) (Grant R24OD017870

Signaling in Secret: Pay-for-Performance and the Incentive and Sorting Effects of Pay Secrecy

Key Findings: Pay secrecy adversely impacts individual task performance because it weakens the perception that an increase in performance will be accompanied by increase in pay; Pay secrecy is associated with a decrease in employee performance and retention in pay-for-performance systems, which measure performance using relative (i.e., peer-ranked) criteria rather than an absolute scale (see Figure 2 on page 5); High performing employees tend to be most sensitive to negative pay-for- performance perceptions; There are many signals embedded within HR policies and practices, which can influence employees’ perception of workplace uncertainty/inequity and impact their performance and turnover intentions; and When pay transparency is impractical, organizations may benefit from introducing partial pay openness to mitigate these effects on employee performance and retention

Calpain-5 Expression in the Retina Localizes to Photoreceptor Synapses

Purpose: We characterize calpain-5 (CAPN5) expression in retinal and neuronal subcellular compartments. Methods: CAPN5 gene variants were classified using the exome variant server, and RNA-sequencing was used to compare expression of CAPN5 mRNA in the mouse and human retina and in retinoblastoma cells. Expression of CAPN5 protein was ascertained in humans and mice in silico, in mouse retina by immunohistochemistry, and in neuronal cancer cell lines and fractionated central nervous system tissue extracts by Western analysis with eight antibodies targeting different CAPN5 regions. Results: Most CAPN5 genetic variation occurs outside its protease core; and searches of cancer and epilepsy/autism genetic databases found no variants similar to hyperactivating retinal disease alleles. The mouse retina expressed one transcript for CAPN5 plus those of nine other calpains, similar to the human retina. In Y79 retinoblastoma cells, the level of CAPN5 transcript was very low. Immunohistochemistry detected CAPN5 expression in the inner and outer nuclear layers and at synapses in the outer plexiform layer. Western analysis of fractionated retinal extracts confirmed CAPN5 synapse localization. Western blots of fractionated brain neuronal extracts revealed distinct subcellular patterns and the potential presence of autoproteolytic CAPN5 domains. Conclusions: CAPN5 is moderately expressed in the retina and, despite higher expression in other tissues, hyperactive disease mutants of CAPN5 only manifest as eye disease. At the cellular level, CAPN5 is expressed in several different functional compartments. CAPN5 localization at the photoreceptor synapse and with mitochondria explains the neural circuitry phenotype in human CAPN5 disease alleles