Comparing Infrared Star-Formation Rate Indicators with Optically-Derived Quantities

We examine the UV reprocessing efficiencies of warm dust and polycyclic aromatic hydrocarbons (PAHs) through an analysis of the mid- and far-infrared surface luminosity densities of 85 nearby H$\alpha$-selected star-forming galaxies detected by the volume-limited KPNO International Spectroscopic Survey (KISS). Because H$\alpha$ selection is not biased toward continuum-bright objects, the KISS sample spans a wide range in stellar masses ($10^8$-$10^{12}\rm{M}_\odot$), as well as H$\alpha$ luminosity ($10^{39}$-$10^{43}\rm{ergs/s}$), mid-infrared 8.0$\mu$m luminosity ($10^{41}$-$10^{44}\rm{ergs/s}$), and [Bw-R] color (-.1-2.2). We find that mid-infrared polycyclic aromatic hydrocarbon (PAH) emission in the Spitzer IRAC 8.0$\mu$m band correlates with star formation, and that the efficiency with which galaxies reprocess UV energy into PAH emission depends on metallicity. We also find that the relationship between far-infrared luminosity in the Spitzer MIPS 24$\mu$m band pass and H$\alpha$-measured star-formation rate varies from galaxy to galaxy within our sample; we do not observe a metallicity dependence in this relationship. We use optical colors and established mass-to-light relationships to determine stellar masses for the KISS galaxies; we compare these masses to those of nearby galaxies as a confirmation that the volume-limited nature of KISS avoids strong biases. We also examine the relationship between IRAC 3.6$\mu$m luminosity and galaxy stellar mass, and find a color-dependent correlation between the two.Comment: 15 pages, 10 figure

Genetic Dissection of T4 Lysis

t is the holin gene for coliphage T4, encoding a 218-amino-acid (aa) protein essential for the inner membrane hole formation that initiates lysis and terminates the phage infection cycle. T is predicted to be an integral membrane protein that adopts an N(in)-C(out) topology with a single transmembrane domain (TMD). This holin topology is different from those of the well-studied holins S105 (3 TMDs; N(out)-C(in)) of the coliphage lambda and S68 (2 TMDs; N(in)-C(in)) of the lambdoid phage 21. Here, we used random mutagenesis to construct a library of lysis-defective alleles of t to discern residues and domains important for holin function and for the inhibition of lysis by the T4 antiholin, RI. The results show that mutations in all 3 topological domains (N-terminal cytoplasmic, TMD, and C-terminal periplasmic) can abrogate holin function. Additionally, several lysis-defective alleles in the C-terminal domain are no longer competent in binding RI. Taken together, these results shed light on the roles of the previously uncharacterized N-terminal and C-terminal domains in lysis and its real-time regulation

Time for change: a new training programme for morpho-molecular pathologists?

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised

Inter-laboratory validation of the measurement of follicle stimulating hormone (FSH) after various lengths of frozen storage

<p>Abstract</p> <p>Background</p> <p>Serum follicle stimulating hormone (FSH) levels are used clinically to evaluate infertility, pituitary and gonadal disorders. With increased frequency of research collaborations across institutions, it is essential that inter-laboratory validation is addressed.</p> <p>Methods</p> <p>An inter-laboratory validation of three commercial FSH immunoassays was performed with human serum samples of varying frozen storage length (2 batches of 15 samples each) at -25 degree C. Percentage differences and Bland-Altman limits of agreement were calculated.</p> <p>Results</p> <p>The inter- and intra-laboratory consistency of FSH values with the same assay manufacturer was much higher after shorter-term storage (frozen for less than 11 months, mean percentage degradation less than 4%) than after long-term storage (2-3 years, mean percentage degradation = 23%). Comparing assay results from different manufacturers, there was similar overall long term degradation as seen with the same manufacturer (-25%), however the degradation was greater when the original FSH was greater than 20 mIU/mL relative to less than 10 mIU/mL (p < 0.001 trend test).</p> <p>Conclusion</p> <p>The findings suggest that degradation of serum samples stored between 11 months and 2-3 years at -25 degrees C can lead to unstable FSH measurements. Inter-laboratory variability due to frozen storage time and manufacturer differences in assay results should be accounted for when designing and implementing research or clinical quality control activities involving serum FSH at multiple study sites.</p

Racism and the Pinkerton syndrome in Singapore: effects of race on hiring decisions

The aim of the study was to examine racism and the Pinkerton syndrome in Singapore. Specifically, the study examined the effects of race on hiring decisions in a simulated hiring decision task. Participants were 171 (61% males) Singaporean Chinese undergraduates from a private university in Singapore. They were randomly assigned into one of nine groups and asked to review a resume of a job applicant. The study used a 3 (Academic qualifications: strong, moderate, or weak) × 3 (Race: White, Chinese, or Malay) between-subjects design with perceived warmth, competence, applicant suitability and recommended salary as the dependent variables. The results showed that while Chinese participants discriminated against Malay applicants (racism), they discriminated in favor of White applicants (the Pinkerton syndrome). The results provided a potential explanation to the economic disparities between Malays and the other races, and first experimental evidence for racism and the Pinkerton syndrome in Singapore

Considering Questions Before Methods in Dementia Research With Competing Events and Causal Goals

Studying causal exposure effects on dementia is challenging when death is a competing event. Researchers often interpret death as a potential source of bias, although bias cannot be defined or assessed if the causal question is not explicitly specified. Here we discuss 2 possible notions of a causal effect on dementia risk: the “controlled direct effect” and the “total effect.” We provide definitions and discuss the “censoring” assumptions needed for identification in either case and their link to familiar statistical methods. We illustrate concepts in a hypothetical randomized trial on smoking cessation in late midlife, and emulate such a trial using observational data from the Rotterdam Study, the Netherlands, 1990–2015. We estimated a total effect of smoking cessation (compared with continued smoking) on 20-year dementia risk of 2.1 (95% confidence interval: −0.1, 4.2) percentage points and a controlled direct effect of smoking cessation on 20-year dementia risk had death been prevented of −2.7 (95% confidence interval: −6.1, 0.8) percentage points. Our study highlights how analyses corresponding to different causal questions can have different results, here with point estimates on opposite sides of the null. Having a clear causal question in view of the competing event and transparent and explicit assumptions are essential to interpreting results and potential bias.</p

Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA.

Macroautophagy (hereafter autophagy) is a key pathway in neurodegeneration. Despite protective actions, autophagy may contribute to neuron demise when dysregulated. Here we consider X-linked spinal and bulbar muscular atrophy (SBMA), a repeat disorder caused by polyglutamine-expanded androgen receptor (polyQ-AR). We found that polyQ-AR reduced long-term protein turnover and impaired autophagic flux in motor neuron-like cells. Ultrastructural analysis of SBMA mice revealed a block in autophagy pathway progression. We examined the transcriptional regulation of autophagy and observed a functionally significant physical interaction between transcription factor EB (TFEB) and AR. Normal AR promoted, but polyQ-AR interfered with, TFEB transactivation. To evaluate physiological relevance, we reprogrammed patient fibroblasts to induced pluripotent stem cells and then to neuronal precursor cells (NPCs). We compared multiple SBMA NPC lines and documented the metabolic and autophagic flux defects that could be rescued by TFEB. Our results indicate that polyQ-AR diminishes TFEB function to impair autophagy and promote SBMA pathogenesis