Diabetes and kidney cancer: A direct or indirect association?

A positive association between diabetes and kidney cancer has been reported in several investigations, but it is unclear whether diabetes or its complications account for this association. Recent advances in estimating direct associations may be useful for elucidating the association between diabetes and kidney cancer. Therefore, we performed a case-control analysis to evaluate whether the direct association between diabetes and kidney cancer is the primary concern in this exposure-outcome relation. Discharge data (with International Classification of Diseases – 9 codes) from 2001 for hospitals throughout Florida were used to construct a case-control population of inpatients aged ≥45 years. Cases (n=1,909) were inpatients with malignant kidney cancer and controls (n=6,451) were inpatients with motor vehicle injuries. Diabetes status was ascertained for cases and controls. Covariates that required adjustment to estimate the total (age, gender, ethnicity, obesity, and smoking) and direct (age, gender, ethnicity, obesity, smoking, hypertension, and kidney disease) associations were identified in a directed acyclic graph. Binary logistic regression was used to estimate the adjusted total and direct odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of kidney cancer for diabetics. The odds of kidney cancer were higher for inpatients with diabetes than inpatients without diabetes when estimating the total association (OR=1.27, 95%CI: 1.10, 1.47) but attenuated when estimating the direct association (OR=1.08, 95%CI: 0.93, 1.25). Our findings provide preliminary insight that the direct association between diabetes and kidney cancer may not be the primary concern in this exposure-outcome relation; indirect pathways (i.e. diabetic complications) may have greater influence on this relation. A similar analysis using longitudinal data with appropriately measured covariates may provide more definitive conclusions and could have implications for kidney cancer prevention among diabetics

Baylisascaris procyonis in the Metropolitan Atlanta Area

Baylisascaris procyonis, the raccoon roundworm responsible for fatal larva migrans in humans, has long been thought to be absent from many regions in the southeastern United States. During spring 2002, 11 (22%) of 50 raccoons trapped in DeKalb County, Georgia, had B. procyonis infection. The increasing number of cases highlight this emerging zoonotic infection

The Evolution of Deep Ocean Chemistry and Respired Carbon in the Eastern Equatorial Pacific Over the Last Deglaciation

It has been shown that the deep Eastern Equatorial Pacific (EEP) region was poorly ventilated during the Last Glacial Maximum (LGM) relative to Holocene values. This finding suggests a more efficient biological pump, which indirectly supports the idea of increased carbon storage in the deep ocean contributing to lower atmospheric CO2 during the last glacial. However, proxies related to respired carbon are needed in order to directly test this proposition. Here we present Cibicides wuellerstorfi B/Ca ratios from Ocean Drilling Program Site 1240 measured by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) as a proxy for deep water carbonate saturation state ([CO32-], and therefore [CO32-]), along with C-13 measurements. In addition, the U/Ca ratio in foraminiferal coatings has been analyzed as an indicator of oxygenation changes. Our results show lower [CO32-], C-13, and [O-2] values during the LGM, which would be consistent with higher respired carbon levels in the deep EEP driven, at least in part, by reduced deep water ventilation. However, the difference between LGM and Holocene [CO32-] observed at our site is relatively small, in accordance with other records from across the Pacific, suggesting that a counteracting mechanism, such as seafloor carbonate dissolution, also played a role. If so, this mechanism would have increased average ocean alkalinity, allowing even more atmospheric CO2 to be sequestered by the ocean. Therefore, the deep Pacific Ocean very likely stored a significant amount of atmospheric CO2 during the LGM, specifically due to a more efficient biological carbon pump and also an increase in average ocean alkalinity

Retention and loss of PIT tags and surgically implanted devices in the Eurasian beaver

Background Passive integrated transponder devices (PIT tags) are a valuable tool for individual identification of animals. Similarly, the surgical implantation of transmitters and bio-loggers can provide useful data on animal location, physiology and behavior. However, to avoid unnecessary recapture and related stress of study animals, PIT tags and bio-loggers should function reliably for long periods of time. Here, we evaluated the retention of PIT tags, and of very high frequency (VHF) transmitters and bio-loggers that were either implanted subcutaneously or into the peritoneal cavity of Eurasian beavers (Castor fiber). Results Over a 21-year period, we implanted PIT tags in 456 individuals and failed to detect a PIT tag at recapture in 30 cases, consisting of 26 individuals (6% of individuals). In all instances, we were still able to identify the individual due to the presence of unique ear tag numbers and tail scars. Moreover, we implanted 6 VHFs, 36 body temperature loggers and 21 heart rate loggers in 28 individuals, and experienced frequent loss of temperature loggers (at least 6 of 23 recaptured beavers) and heart rate loggers (10 of 18 recaptured beavers). No VHFs were lost in 2 recaptured beavers. Conclusions Possible causes for PIT tag loss (or non-detection) were incorrect implantation, migration of the tag within the body, a foreign body reaction leading to ejection, or malfunctioning of the tag. We speculate that logger loss was related to a foreign body reaction, and that loggers were either rejected through the incision wound or, in the case of temperature loggers, possibly adhered and encapsulated to intestines, and then engulfed by the gastro-intestinal tract and ejected. We discuss animal welfare implications and give recommendations for future studies implanting bio-loggers into wildlife

Interferon-γ signaling in human iPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes.

Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-γ (IFN-γ), in offspring's brains play a central role. IFN-γ activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-γ is implicated in brain development. We tested the hypothesis that IFN-γ signaling contributes to molecular and cellular phenotypes associated with neurodevelopmental disorders. Transient IFN-γ treatment of neural progenitors derived from human induced pluripotent stem cells increased neurite outgrowth. RNA sequencing analysis revealed that major histocompatibility complex class I (MHCI) genes were persistently up-regulated through neuronal differentiation-an effect that was mediated by IFN-γ-induced promyelocytic leukemia protein (PML) nuclear bodies. Critically, IFN-γ-induced neurite outgrowth required both PML and MHCI. We also found evidence that IFN-γ disproportionately altered the expression of genes associated with schizophrenia and autism, suggesting convergence between genetic and environmental risk factors. Together, these data implicate IFN-γ signaling in neurodevelopmental disorder etiology

Complexity on Small Scales II: Metallicities and Ages in the Leo II Dwarf Spheroidal Galaxy

We present metallicities and ages for 52 red giants in the remote Galactic dwarf spheroidal (dSph) galaxy Leo II. These stars cover the entire surface area of Leo II and are radial velocity members. We obtained medium-resolution multi-fiber spectroscopy with ESO/VLT's FLAMES spectrograph. The metallicities were determined based on the near-infrared Ca II triplet. The resulting metallicity distribution (MD) is asymmetric and peaks at [Fe/H]=-1.74 dex on the Carretta & Gratton scale. The full range in metallicities extends from -2.4 to -1.1 dex. As in other dSphs, no extremely metal-poor red giants were found. We compare Leo II's observed MD with model predictions for several other Galactic dSphs from the literature. Leo II clearly exhibits a lack of more metal poor stars, in analogy to the classical G-dwarf problem, which may indicate a comparable `K-giant problem'. Moreover, its evolution appears to have been affected by galactic winds. We use our inferred metallicities as an input parameter for isochrone fits to SDSS photometry and derive approximate ages. The resulting age-metallicity distribution covers the full age range from 2-15 Gyr on our adopted isochrone scale. During the first 7 Gyr relative to the oldest stars [Fe/H] appears to have remained almost constant. The almost constant metallicity at higher ages and a slight drop by about 0.3 dex thereafter may be indicative of rejuvenation by low metallicity gas. Overall, the age-metallicity relation appears to support the formation of Leo II from pre-enriched gas. Evidence for enrichment is seen during the recent 2-4 Gyr. Our findings support earlier photometric findings of Leo II as a galaxy with a prominent old and a dominant intermediate-age population. We do not find a significant radial metallicity gradient nor age gradient in our data.(Abridged)Comment: 23 pages, 12 Figures, accepted for publication in the A

DUSP5-mediated inhibition of smooth muscle cell proliferation suppresses pulmonary hypertension and right ventricular hypertrophy

Pulmonary hypertension (PH) is associated with structural remodeling of pulmonary arteries (PAs) because of excessive proliferation of fibroblasts, endothelial cells, and smooth muscle cells (SMCs). The peptide hormone angiotensin II (ANG II) contributes to pulmonary vascular remodeling, in part, through its ability to trigger extracellular signal-regulated kinase (ERK1/2) activation. Here, we demonstrate that the ERK1/2 phosphatase, dual-specificity phosphatase 5 (DUSP5), functions as a negative regulator of ANG II-mediated SMC proliferation and PH. In contrast to wild-type controls, Dusp5 null mice infused with ANG II developed PH and right ventricular (RV) hypertrophy. PH in Dusp5 null mice was associated with thickening of the medial layer of small PAs, suggesting an in vivo role for DUSP5 as a negative regulator of ANG II-dependent SMC proliferation. Consistent with this, overexpression of DUSP5 blocked ANG II-mediated proliferation of cultured human pulmonary artery SMCs (hPASMCs) derived from patients with idiopathic PH or from failed donor controls. Collectively, the data support a role for DUSP5 as a feedback inhibitor of ANG II-mediated ERK signaling and PASMC proliferation and suggest that disruption of this circuit leads to adverse cardiopulmonary remodeling. NEW & NOTEWORTHY Dual-specificity phosphatases (DUSPs) serve critical roles in the regulation of mitogen-activated protein kinases, but their functions in the cardiovascular system remain poorly defined. Here, we provide evidence that DUSP5, which resides in the nucleus and specifically dephosphorylates extracellular signal-regulated kinase (ERK1/2), blocks pulmonary vascular smooth muscle cell proliferation. In response to angiotensin II infusion, mice lacking DUSP5 develop pulmonary hypertension and right ventricular cardiac hypertrophy. These findings illustrate DUSP5-mediated suppression of ERK signaling in the lungs as a protective mechanism

From absent to present pasts: civil society, democracy and the shifting place of memory in Brazil

This paper takes Alexis de Tocqueville’s concern with the emotional life of citizens as a cue for exploring the role of collective memory within ‘the self-organizing sphere’ and asking how the invocation of memory affects progress towards democracy. The paper hones in on the Brazilian experience, re-assessing Brazil’s amnesiac past as well as its much lauded ‘turn to memory’. Against common assertions that Brazil’s ‘turn to memory’ will enhance the country’s democratic credentials, this paper argues that the move from an ‘absent’ to a ‘present’ past in Brazil in fact bodes rather mixed prospects for the country’s democratic deepening