Ferredoxin 1b deficiency leads to testis disorganization, impaired spermatogenesis and feminization in zebrafish

The roles of steroids in zebrafish sex differentiation, gonadal development and function of the adult gonad are poorly understood. Herein, we have employed a ferredoxin 1b (fdx1b) mutant zebrafish to explore such processes. Fdx1b is an essential electron-providing cofactor to mitochondrial steroidogenic enzymes, which are crucial for glucocorticoid and androgen production in vertebrates. Fdx1b-/- zebrafish mutants develop into viable adults, in which concentrations of androgens and the glucocorticoid, cortisol, are significantly reduced. Adult fdx1b-/- mutant zebrafish display predominantly female secondary sex characteristics but may possess either ovaries or testes, confirming that androgen signaling is dispensable for testicular differentiation in this species, as previously demonstrated in androgen receptor mutant zebrafish. Adult male fdx1b-/- mutant zebrafish do not exhibit characteristic breeding behaviors, and sperm production is reduced, resulting in infertility in standard breeding scenarios. However, eggs collected from wild-type females can be fertilized by the sperm of fdx1b-/- mutant males by IVF. The testes of fdx1b-/- mutant males are disorganized and lack defined seminiferous tubule structure. Expression of several pro-male and spermatogenic genes is decreased in the testes of fdx1b-/- mutant males, including pro-male transcription factor SRY-box 9a (sox9a) and spermatogenic genes insulin-like growth factor 3 (igf3) and insulin-like 3 (insl3). This study establishes an androgen- and cortisol-deficient fdx1b zebrafish mutant as a model for understanding the impacts of steroid deficiency on sex development and reproductive function. This model will be particularly useful for further investigation of the roles of steroids in spermatogenesis, gonadal development and regulation of reproductive behavior, thus enabling further elucidation of the physiological consequences of endocrine disruption in vertebrates

11β-hydroxylase loss disrupts steroidogenesis and reproductive function in zebrafish

The roles of androgens in male reproductive development and function in zebrafish are poorly understood. To investigate this topic we employed CRISPR/Cas9 to generate cyp11c1 (11β-hydroxylase) mutant zebrafish lines. Our study confirms recently published findings from a different cyp11c1-/- mutant zebrafish line, and also reports novel aspects of the phenotype caused by loss of Cyp11c1 function. We report that Cyp11c1-deficient zebrafish display predominantly female secondary sex characteristics, but may possess either ovaries or testes. Moreover, we observed that cyp11c1-/- mutant male zebrafish are profoundly androgen- and cortisol-deficient. These results provide further evidence that androgens are dispensable for testis formation in zebrafish, as has been demonstrated previously in androgen-deficient and androgen-resistant zebrafish. Herein, we show that the testes of cyp11c1-/- mutant zebrafish exhibit a disorganised tubular structure; and for the first time demonstrate that the spermatic ducts, which connect the testes to the urogenital orifice, are severely hypoplastic in androgen-deficient zebrafish. Furthermore, we show that spermatogenesis and characteristic breeding behaviours are impaired in cyp11c1-/- mutant zebrafish. Expression of nanos2, a type A spermatogonia marker, was significantly increased in the testes of Cyp11c1-deficient zebrafish, whereas expression of markers for later stages of spermatogenesis was significantly decreased. These observations indicate that in zebrafish, production of type A spermatogonia is androgen-independent, but differentiation of type A spermatogonia is an androgen-dependent process. Overall, our results demonstrate that whilst androgens are not required for testis formation, they play important roles in determining secondary sexual characteristics, proper organisation of seminiferous tubules, and differentiation of male germ cells

Systemic problems hampering innovation in the New Zealand agricultural innovation system

This study identifies systemic problems in the New Zealand Agricultural Innovation System (AIS) that affect the ability of participants in the agricultural sectors to co-develop technologies. We integrate structural and functional streams of innovation system enquiry, gathering data through 30 semi-structured interviews with individuals in Government, industry and research. Interviews explored perceptions of the influence of actors, interactions, institutions, infrastructure, and market structure on the effectiveness of AIS functions. Examples of systemic problems were: (i) a lack of facilitative and transformational leadership and systemic intermediaries to support the formation of strategic innovation agendas in vertically and horizontally fragmented industries; (ii) a culture of hunting for funding within research organisations; hindering sustained involvement of researchers in innovation, (iii) a large number of actors in the R&D component of the AIS competing for public resources to pursue uncoordinated innovation agendas; and (iv) a lack of institutional support for interactions between actors and roles that support interactions, such as innovation platforms and innovation brokers. The existing New Zealand AIS limits innovation to a linear process; restricting opportunities for innovation to occur and fostering competition amongst organisations that collectively have much to contribute to innovation in the agricultural sectors through constructive collaboration and roles in all facets of the innovation process. These findings indicate an urgent need to create a policy and legislative framework, built on a systemic understanding of innovation that more pro-actively stimulates and fosters co-innovation. Such a framework would facilitate the formation and effectiveness of innovation-brokering organisations and multi-actor platforms, enabling coordinated innovation agenda setting and prioritisation of issues in which all actors in the value chain and innovation support system jointly articulate a shared agenda for change

A Low-Fat Vegan Diet Elicits Greater Macronutrient Changes, but Is Comparable in Adherence and Acceptability, Compared with a More Conventional Diabetes Diet among Individuals with Type 2 Diabetes

Although therapeutic diets are critical to diabetes management, their acceptability to patients is largely unstudied

A New Solution to the Relative Orientation Problem using only 3 Points and the Vertical Direction

This paper presents a new method to recover the relative pose between two images, using three points and the vertical direction information. The vertical direction can be determined in two ways: 1- using direct physical measurement like IMU (inertial measurement unit), 2- using vertical vanishing point. This knowledge of the vertical direction solves 2 unknowns among the 3 parameters of the relative rotation, so that only 3 homologous points are requested to position a couple of images. Rewriting the coplanarity equations leads to a simpler solution. The remaining unknowns resolution is performed by an algebraic method using Grobner bases. The elements necessary to build a specific algebraic solver are given in this paper, allowing for a real-time implementation. The results on real and synthetic data show the efficiency of this method

D2 dopamine receptor Taq1A polymorphism, body weight, and dietary intake in type 2 diabetes

Certain D2 dopamine receptor Taq 1A genotypes (A1A1, A1A2) have been associated with obesity and substance abuse. We hypothesized that their presence would be associated with reduced efficacy of dietary interventions in individuals with type 2 diabetes

The variation of geomagnetic storm duration with intensity

Variability in the near-Earth solar wind conditions can adversely affect a number of ground- and space-based technologies. Such space-weather impacts on ground infrastructure are expected to increase primarily with geomagnetic storm intensity, but also storm duration, through time-integrated effects. Forecasting storm duration is also necessary for scheduling the resumption of safe operating of affected infrastructure. It is therefore important to understand the degree to which storm intensity and duration are correlated. The long-running, global geomagnetic disturbance index, aa , has recently been recalibrated to account for the geographic distribution of the component stations. We use this aaH index to analyse the relationship between geomagnetic storm intensity and storm duration over the past 150 years, further adding to our understanding of the climatology of geomagnetic activity. Defining storms using a peak-above-threshold approach, we find that more intense storms have longer durations, as expected, though the relationship is nonlinear. The distribution of durations for a given intensity is found to be approximately log-normal. On this basis, we provide a method to probabilistically predict storm duration given peak intensity, and test this against the aaH dataset. By considering the average profile of storms with a superposed-epoch analysis, we show that activity becomes less recurrent on the 27-day timescale with increasing intensity. This change in the dominant physical driver, and hence average profile, of geomagnetic activity with increasing threshold is likely the reason for the nonlinear behaviour of storm duration

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer's disease

Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 μm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (shortand long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 μg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage

Gene-gene Interaction Analyses for Atrial Fibrillation

Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in a