Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades

The mammalian visual system relies upon light detection by outer-retinal rod/cone photoreceptors and melanopsin-expressing retinal ganglion cells. Gnat1(-/-); Cnga3(-/-); Opn4(-/-) mice lack critical elements of each of these photoreceptive mechanisms via targeted disruption of genes encoding rod alpha transducin (Gnat1); the cone-specific alpha 3 cyclic nucleotide gated channel subunit (Cnga3); and melanopsin (Opn4). Although assumed blind, we show here that these mice retain sufficiently widespread retinal photoreception to drive a reproducible flash electroretinogram (ERG). The threshold sensitivity of this ERG is similar to that of cone-based responses, however it is lost under light adapted conditions. Its spectral efficiency is consistent with that of rod opsin, but not cone opsins or melanopsin, indicating that it originates with light absorption by the rod pigment. The TKO light response survives intravitreal injection of U73122 (a phospholipase C antagonist), but is inhibited by a missense mutation of cone alpha transducin (Gnat2(cpfl3)), suggesting Gnat2-dependence. Visual responses in TKO mice extend beyond the retina to encompass the lateral margins of the lateral geniculate nucleus and components of the visual cortex. Our data thus suggest that a Gnat1-independent phototransduction mechanism downstream of rod opsin can support relatively widespread responses in the mammalian visual system. This anomalous rod opsin-based vision should be considered in experiments relying upon Gnat1 knockout to silence rod phototransduction

Defining critical factors in multi-country studies of assisted reproductive technologies (ART): data from the US and UK health systems

As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each other’s limitations

Doppler velocimetry of spin propagation in a two-dimensional electron gas

Controlling the flow of electrons by manipulation of their spin is a key to the development of spin-based electronics. While recent demonstrations of electrical-gate control in spin-transistor configurations show great promise, operation at room temperature remains elusive. Further progress requires a deeper understanding of the propagation of spin polarization, particularly in the high mobility semiconductors used for devices. Here we report the application of Doppler velocimetry to resolve the motion of spin-polarized electrons in GaAs quantum wells driven by a drifting Fermi sea. We find that the spin mobility tracks the high electron mobility precisely as a function of T. However, we also observe that the coherent precession of spins driven by spin-orbit interaction, which is essential for the operation of a broad class of spin logic devices, breaks down at temperatures above 150 K for reasons that are not understood theoretically

Dietary antioxidant intake and the risk of developing Barrett’s oesophagus and oesophageal adenocarcinoma

Background: We investigated in a cohort study, for the first time using 7-day food diaries (7-DFDs), for age-dependent inverse associations with antioxidants, which have anti-carcinogenic properties, and development of Barrett’s oesophagus (BO) and oesophageal adenocarcinoma (OAC). Methods: A total of 24,068 well individuals completed 7-DFDs and donated blood. Vitamins C and E, carotenes, zinc and selenium intakes, and plasma vitamin C were measured. Participants were monitored for 15 years for BO and OAC. Hazard ratios (HRs) were estimated for: quintiles of intake and in participants younger and >=65 years at recruitment, the midpoint of BO peak prevalence. Results: A total of 197 participants developed BO and 74 OAC. There were no significant associations between antioxidants and BO or OAC in the whole cohort or if >65 years at recruitment. In participants <65 years, for BO, there was an inverse trend across plasma vitamin C quintiles (trend HR = 0.82; 95% CI = 0.71–0.96, P = 0.01), OAC for plasma vitamin C (trend HR = 0.58; 95% CI = 0.37–0.92, P = 0.02) and for dietary vitamins C and E (trend HR = 0.71 95% CI = 0.51–0.99, P = 0.04 and trend HR = 0.70; 95% CI = 0.51–0.96; P = 0.03). Conclusions: Data supports a role for dietary antioxidants prevent BO and OAC, perhaps at the earlier stages of carcinogenesis

Prosopanche: a remarkable genus of parasitic plants

Prosopanche is a poorly known genus of parasitic plants from South and Central America. Growing almost entirely underground with a complete lack of leaves, plants of Prosopanche bear more resemblance to fungi than plants and have many remarkable aspects to their life history and ecology that require further investigation. Here, we provide an up-to-date revision of the current state of understanding of Prosopanche, including taxonomy, biogeography, plant-pollinator ecology and host-parasite interactions. We discuss the untapped research potential of this group of plants and recommend the Prosopanche as an ideal candidate for exploring the evolutionary origins of parasitism among flowering plants

Should physical activity recommendations be ethnicity-specific? Evidence from a cross-sectional study of south Asian and European men

Background Expert bodies and health organisations recommend that adults undertake at least 150 min.week−1 of moderate-intensity physical activity (MPA). However, the underpinning data largely emanate from studies of populations of European descent. It is unclear whether this level of activity is appropriate for other ethnic groups, particularly South Asians, who have increased cardio-metabolic disease risk compared to Europeans. The aim of this study was to explore the level of MPA required in South Asians to confer a similar cardio-metabolic risk profile to that observed in Europeans undertaking the currently recommended MPA level of 150 min.week−1.&lt;p&gt;&lt;/p&gt; Methods Seventy-five South Asian and 83 European men, aged 40–70, without cardiovascular disease or diabetes had fasted blood taken, blood pressure measured, physical activity assessed objectively (using accelerometry), and anthropometric measures made. Factor analysis was used to summarise measured risk biomarkers into underlying latent ‘factors’ for glycaemia, insulin resistance, lipid metabolism, blood pressure, and overall cardio-metabolic risk. Age-adjusted regression models were used to determine the equivalent level of MPA (in bouts of ≥10 minutes) in South Asians needed to elicit the same value in each factor as Europeans undertaking 150 min.week−1 MPA.&lt;p&gt;&lt;/p&gt; Findings For all factors, except blood pressure, equivalent MPA values in South Asians were significantly higher than 150 min.week−1; the equivalent MPA value for the overall cardio-metabolic risk factor was 266 (95% CI 185-347) min.week−1.&lt;p&gt;&lt;/p&gt; Conclusions South Asian men may need to undertake greater levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile, suggesting that a conceptual case can be made for ethnicity-specific physical activity guidance. Further study is needed to extend these findings to women and to replicate them prospectively in a larger cohort.&lt;p&gt;&lt;/p&gt

Learning Interpretable Rules for Multi-label Classification

Multi-label classification (MLC) is a supervised learning problem in which, contrary to standard multiclass classification, an instance can be associated with several class labels simultaneously. In this chapter, we advocate a rule-based approach to multi-label classification. Rule learning algorithms are often employed when one is not only interested in accurate predictions, but also requires an interpretable theory that can be understood, analyzed, and qualitatively evaluated by domain experts. Ideally, by revealing patterns and regularities contained in the data, a rule-based theory yields new insights in the application domain. Recently, several authors have started to investigate how rule-based models can be used for modeling multi-label data. Discussing this task in detail, we highlight some of the problems that make rule learning considerably more challenging for MLC than for conventional classification. While mainly focusing on our own previous work, we also provide a short overview of related work in this area.Comment: Preprint version. To appear in: Explainable and Interpretable Models in Computer Vision and Machine Learning. The Springer Series on Challenges in Machine Learning. Springer (2018). See http://www.ke.tu-darmstadt.de/bibtex/publications/show/3077 for further informatio

Cooperation of p300 and PCAF in the Control of MicroRNA 200c/141 Transcription and Epithelial Characteristics

Epithelial to mesenchymal transition (EMT) not only occurs during embryonic development and in response to injury, but is an important element in cancer progression. EMT and its reverse process, mesenchymal to epithelial transition (MET) is controlled by a network of transcriptional regulators and can be influenced by posttranscriptional and posttranslational modifications. EMT/MET involves many effectors that can activate and repress these transitions, often yielding a spectrum of cell phenotypes. Recent studies have shown that the miR-200 family and the transcriptional suppressor ZEB1 are important contributors to EMT. Our previous data showed that forced expression of SPRR2a was a powerful inducer of EMT and supports the findings by others that SPRR gene members are highly upregulated during epithelial remodeling in a variety of organs. Here, using SPRR2a cells, we characterize the role of acetyltransferases on the microRNA-200c/141 promoter and their effect on the epithelial/mesenchymal status of the cells. We show that the deacetylase inhibitor TSA as well as P300 and PCAF can cause a shift towards epithelial characteristics in HUCCT-1-SPRR2a cells. We demonstrate that both P300 and PCAF act as cofactors for ZEB1, forming a P300/PCAF/ZEB1 complex on the miR200c/141 promoter. This binding results in lysine acetylation of ZEB1 and a release of ZEB1 suppression on miR-200c/141 transcription. Furthermore, disruption of P300 and PCAF interactions dramatically down regulates miR-200c/141 promoter activity, indicating a PCAF/P300 cooperative function in regulating the transcriptional suppressor/activator role of ZEB1. These data demonstrate a novel mechanism of miRNA regulation in mediating cell phenotype

Prices and availability of locally produced and imported medicines in Ethiopia and Tanzania

Background: To assess the effect of policies supporting local medicine production to improve access to medicines. Methods: We adapted the WHO/HAI instruments measuring medicines availability and prices to differentiate local from imported products, then pilot tested in Ethiopia and Tanzania. In each outlet, prices were recorded for all products in stock for medicines on a country-specific list. Government procurement prices were also collected. Prices were compared to an international reference and expressed as median price ratios (MPR). Results: The Ethiopian government paid more for local products (median MPR = 1.20) than for imports (median MPR = 0.84). Eight of nine medicines procured as both local and imported products were cheaper when imported. Availability was better for local products compared to imports, in the public (48% vs. 19%, respectively) and private (54% vs. 35%, respectively) sectors. Patient prices were lower for imports in the public sector (median MPR = 1.18[imported] vs. 1.44[local]) and higher in the private sector (median MPR = 5.42[imported] vs. 1.85[local]). In the public sector, patients paid 17% and 53% more than the government procurement price for local and imported products, respectively. The Tanzanian government paid less for local products (median MPR = 0.69) than imports (median MPR = 1.34). In the public sector, availability of local and imported products was 21% and 32% respectively, with patients paying slightly more for local products (median MPR = 1.35[imported] vs. 1.44[local]). In the private sector, local products were less available (21%) than imports (70%) but prices were similar (median MPR = 2.29[imported] vs. 2.27[local]). In the public sector, patients paid 135% and 65% more than the government procurement price for local and imported products, respectively. Conclusions: Our results show how local production can affect availability and prices, and how it can be influenced by preferential purchasing and mark-ups in the public sector. Governments need to evaluate the impact of local production policies, and adjust policies to protect patients from paying more for local products.Scopu