Androgen action via testicular arteriole smooth muscle cells is important for leydig cell function, vasomotion and testicular fluid dynamics

Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis

Distribution of normalized water-leaving radiances at UV and visible wave bands in relation with chlorophyll a and colored detrital matter content in the southeast Pacific

International audience[1] In-water radiometric measurements were performed in the southeast Pacific (8°S-35°S, 141°W-72°W) from October to December 2004 during the Biogeochemistry and Optics South Pacific Experiment cruise. Normalized water-leaving radiances (nL w (l)) were determined at eight wave bands within the ultraviolet (UV) (305, 325, 340, and 380 nm) and visible (412, 443, 490, and 565 nm) spectral domains. The highest nL w (l) (mW cm À2 sr À1) were recorded in the hyperoligotrophic waters of the South Pacific Gyre, with values increasing with wavelength from 305 (nL w = 0.64) to 380 nm (nL w = 3.18) in the UV range and decreasing from 412 (nL w = 4.46) to 565 nm (nL w = 0.23) in the visible region. The intense nL w (l) observed in the violet-blue domains were attributed to very low absorptions of colored detrital matter (CDM), likely related to a strong photobleaching of colored dissolved organic matter in the surface waters. We evaluated the relationships between the UV, violet, or blue/green wave band ratios of nL w (l) and surface total chlorophyll a (TChl a) concentration and CDM absorption (a CDM (l)). For TChl a, the best correlation was found with the blue/green ratio at 443 nm: TChl a (mg m À3) = 2.37[nL w (443)/nL w (565)] À1.51 (r 2 = 0.86 and RMS error (RMSE) = 23%). By contrast, for a CDM (l), the best correlation was observed when using the UV/green ratio at 325 nm: a CDM (325) (m À1) = 0.16[nL w (325)/nL w (565)] À0.69 (r 2 = 0.82 and RMSE = 16%). These results show the potential role of nL w (l) at UV wave bands for the assessment, through empirical algorithms, of colored detrital matter in the surface oceanic waters. Citation: Tedetti, M., B. Charrière, A. Bricaud, J. Para, P. Raimbault, and R. Sempéré (2010), Distribution of normalized water-leaving radiances at UV and visible wave bands in relation with chlorophyll a and colored detrital matter content in the southeast Pacific

Etude de la Matière Organique Dissoute Chromophorique et du rayonnement solaire (UV-visible) dans les eaux de surfaces côtières méditerranéennes et articques

Afin de comprendre, caractériser et prédire l évolution des cycles biogéochimiques océaniques face au changement climatique global, il est nécessaire d appréhender au mieux la dynamique de la matière organique (MO) au niveau des interfaces terre/océan . Dans ce contexte, l objectif général de cette thèse était d améliorer les connaissances sur la dynamique de la fraction dissoute chromophorique de la MO (CDOM) des eaux de surface côtières méditerranéennes et arctiques, et d en déterminer l impact sur l atténuation du rayonnement UV (UVR) et visible (PAR) sous-marin. Pour cela, l étude des propriétés optiques d absorbance et de fluorescence de la CDOM, couplée à des mesures radiométriques atmosphériques et sous-marines, ont été réalisées lors d un cycle saisonnier en Baie de Marseille (station SOFCOM), et lors d une mission océanographique en Mer de Beaufort durant l été 2009. La Baie de Marseille est caractérisée par des quantités de CDOM faibles (aCDOM(350) = 0,10 +- 0,02 m-1), particulièrement à la fin de la période estivale de stratification, à cause de l intensité de l éclairement solaire, enrichi en UVR-B, qui dégrade et blanchie cette CDOM (SCDOM = 0,023 +- 0,003 nm-1). Dans cette zone côtière fortement urbanisée, la dynamique de la CDOM est pilotée par des processus biotiques (production biologique in situ et induite par les intrusions épisodiques du panache du Rhône) et abiotiques (photo-blanchiment et brassage). La CDOM est essentiellement d origine autochtone, même lors d événements d intrusion du panache du Rhône (photo-dégradation de la CDOM terrestre durant son transit). Lors des périodes d efflorescences algales, la CDOM se compose principalement de matériel récent, de type protéique (pic T), qui absorbe préférentiellement les courts UVR. Ces pulses de CDOM récente se superposent à un persistent signal de fond de CDOM composé majoritairement de matériel âgé, de type humique (pics M et C), qui absorbe les UVR et également le PAR. Au niveau du plateau Canadien de la Mer de Beaufort, la CDOM est très abondante (aCDOMmax(350) = 6,36 m-1), fortement influencée par les apports allochtones du Mackenzie (pics A-C et M) et décroit de manière conservatrice avec la salinité. Dans les eaux marines (salinité >25), la CDOM, qui présente de plus faibles concentrations (aCDOM(350) = 0,21 +- 0,13 m-1), provient d une production biologique in situ récente favorisée par des upwellings ainsi que d injections de CDOM (pics B-T et M) lors de la formation/fonte de la glace de mer. Etonnamment, la source principale du composé humique marin (pic M) n est pas autochtone. Elle est issue d apports allochtones provenant du Mackenzie. Celui-ci draine en effet de nombreux lacs qui sont le siège d une intense activité biologique, et il est proposé dans cette thèse que les macrophytes qui s y développent seraient à l origine du pic M. Cette source de CDOM biologique allochtone, couplée aux processus de photo-blanchiment et d absorption sur les particules de la CDOM terrestre, pourraient expliquer les valeurs élevées de SCDOM (≈ 0,020 nm-1) du Mackenzie en été.To understand, characterize, and predict the evolution of oceanic biogeochemical cycles in relation to the global climate change, it is necessary to better understand the dynamics of organic matter (OM). In this context, the overall objective of this thesis was to get more insights chromophoric dissolved fraction of OM (CDOM) dynamics in surface Mediterranean and Arctic coastal waters and to determine the impact on attenuation of ultraviolet (UVR) and visible (PAR) underwater radiation. For this, the study of optical properties of absorbance and fluorescence of CDOM, coupled with atmospheric and underwater radiometric measurements, were made during a seasonal cycle in the Bay of Marseille (SOFCOM station), and in the Beaufort Sea during summer 2009. The Bay of Marseilles is characterized by low amounts of CDOM (aCDOM(350) = 0.10 +- 0.02 m-1), particularly in end summer stratification period due to the intensity of the solar irradiance, enriched in UVR-B, which degrades and bleaches CDOM (SCDOM = 0.023 +- 0.003 nm-1). In this highly urbanized coastal area, the dynamics of CDOM are driven by biotic processes (in situ biological production and within the Rhône River plume) and abiotic (photo-bleaching and mixing). Our results showed that CDOM is mostly of autochthonous origin, even during Rhône plume intrusion events (photo-degradation of terrestrial CDOM during the transit). During bloom periods, the CDOM consists mainly of a recent type protein (peak T), which preferentially absorbs in the short UVR. These pulses of recent CDOM are superimposed on a persistent background of CDOM mainly composed of aged material, humic-type (peaks M and C), which absorbs UVR and PAR. Over the Canadian shelf of the Beaufort Sea, CDOM is highly abundant (aCDOMmax (350) = 6.36 m-1) and strongly influenced by allochthonous inputs from the Mackenzie (peaks A-C and M) decreasing conservatively with salinity. In marine waters (salinity> 25), CDOM had lower concentrations (aCDOM(350) = 0.21 +- 0.13 m-1) and originated from a recent in situ biological production favored by upwelling and brine injections (peaks B-T and M). Surprisingly, the main source of the marine humic-like component (peak M) was not autochthonous. This material originates from allochthonous inputs from the Mackenzie River, which traverses numerous lakes where intense biological activity occurs. We suggest that this activity is mainly due to the macrophytes development, which may in part explain the origin of the peak M. This source of organic allochthonous CDOM coupled to other processes such as photobleaching and absorption on the particles of terrestrial CDOM, could explain the high values of SCDOM (≈ 0.020 nm-1) recorded in the Mackenzie during summertime.AIX-MARSEILLE2-Bib.electronique (130559901) / SudocSudocFranceF

Fluorescence and absorption properties of chromophoric dissolved organic matter (CDOM) in coastal surface waters of the northwestern Mediterranean Sea, influence of the Rhône River

International audienceSeawater samples were collected monthly in surface waters (2 and 5 m depths) of the Bay of Marseilles (northwestern Mediterranean Sea; 5 • 17 30 E, 43 • 14 30 N) during one year from November 2007 to December 2008 and studied for total organic carbon (TOC) as well as chro-mophoric dissolved organic matter (CDOM) optical properties (absorbance and fluorescence). The annual mean value of surface CDOM absorption coefficient at 350 nm [a CDOM (350)] was very low (0.10 ± 0.02 m −1) in comparison to values usually found in coastal waters, and no significant seasonal trend in a CDOM (350) could be determined. By contrast, the spectral slope of CDOM absorption (S CDOM) was significantly higher (0.023 ± 0.003 nm −1) in summer than in fall and winter periods (0.017 ± 0.002 nm −1), reflecting either CDOM photobleaching or production in surface waters during stratified sunny periods. The CDOM fluorescence, assessed through excitation emission matrices (EEMs), was dominated by protein-like component (peak T; 1.30-21.94 QSU) and marine humic-like component (peak M; 0.55-5.82 QSU), while terrestrial humic-like fluores-cence (peak C; 0.34-2.99 QSU) remained very low. This reflected a dominance of relatively fresh material from biological origin within the CDOM fluorescent pool. At the end of summer, surface CDOM fluorescence was very low and strongly blue shifted, reinforcing the hypothesis of CDOM photobleaching. Our results suggested that unusual Rhône Correspondence to: R. Sempéré ([email protected]) River plume eastward intrusion events might reach Mar-seilles Bay within 2-3 days and induce local phytoplank-ton blooms and subsequent fluorescent CDOM production (peaks M and T) without adding terrestrial fluorescence signatures (peaks C and A). Besides Rhône River plumes, mixing events of the entire water column injected relative aged (peaks C and M) CDOM from the bottom into the surface and thus appeared also as an important source of CDOM in surface waters of the Marseilles Bay. Therefore, the assessment of CDOM optical properties, within the hydrological context, pointed out several biotic (in situ biological production , biological production within Rhône River plumes) and abiotic (photobleaching, mixing) factors controlling CDOM transport, production and removal in this highly urbanized coastal area

The Eastern Arm of M83 Revisited: High-Resolution Mapping of 12CO 1-0 Emission

We have used the Owens Valley Millimeter Array to map 12CO (J=1-0) along a 3.5 kpc segment of M83's eastern spiral arm at resolutions of 6.5"x3.5", 10", and 16". The CO emission in most of this segment lies along the sharp dust lane demarking the inner edge of the spiral arm, but beyond a certain point along the arm the emission shifts downstream from the dust lane to become better aligned with the young stars seen in blue and H-beta images. This morphology resembles that of the western arm of M100. Three possibilities, none of which is wholly satisfactory, are considered to explain the deviation of the CO arm from the dust lane: heating of the CO by UV radiation from young stars, heating by low-energy cosmic rays, and a molecular medium consisting of two (diffuse and dense) components which react differently to the density wave. Regardless, the question of what CO emission traces along this spiral arm is a complicated one. Strong tangential streaming is observed where the arm crosses the kinematic major axis of the galaxy, implying that the shear becomes locally prograde in the arms. Inferred from the streaming is a very high gas surface density of about 230 solar masses/pc**2 and an arm-interarm contrast greater than 2.3 in the part of the arm near the major axis. Using two different criteria, we find that the gas at this location is well above the threshold for gravitational instability -- much more clearly so than in either M51 or M100.Comment: Accepted for publication in ApJ. 25 pages, 5 figures. Manuscript in LaTeX, figures in pdf. Fig 3 in colo

microRNAs and the evolution of complex multicellularity:Identification of a large, diverse complement of microRNAs in the brown alga Ectocarpus

There is currently convincing evidence that microRNAs have evolved independently in at least six different eukaryotic lineages: animals, land plants, chlorophyte green algae, demosponges, slime molds and brown algae. MicroRNAs from different lineages are not homologous but some structural features are strongly conserved across the eukaryotic tree allowing the application of stringent criteria to identify novel microRNA loci. A large set of 63 microRNA families was identified in the brown alga Ectocarpus based on mapping of RNA-seq data and nine microRNAs were confirmed by northern blotting. The Ectocarpus microRNAs are highly diverse at the sequence level with few multi-gene families, and do not tend to occur in clusters but exhibit some highly conserved structural features such as the presence of a uracil at the first residue. No homologues of Ectocarpus microRNAs were found in other stramenopile genomes indicating that they emerged late in stramenopile evolution and are perhaps specific to the brown algae. The large number of microRNA loci in Ectocarpus is consistent with the developmental complexity of many brown algal species and supports a proposed link between the emergence and expansion of microRNA regulatory systems and the evolution of complex multicellularity

Defining a novel leptin–melanocortin–kisspeptin pathway involved in the metabolic control of puberty

Objective Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction. However, its role in the metabolic regulation of puberty and interplay with kisspeptin, an essential puberty-regulating neuropeptide encoded by Kiss1, remain largely unknown. We aim here to unveil the potential contribution of central α-MSH signaling in the metabolic control of puberty by addressing its role in mediating the pubertal effects of leptin and its potential interaction with kisspeptin. Methods Using wild type and genetically modified rodent models, we implemented pharmacological studies, expression analyses, electrophysiological recordings, and virogenetic approaches involving DREADD technology to selectively inhibit Kiss1 neurons, in order to interrogate the physiological role of a putative leptin→α-MSH→kisspeptin pathway in the metabolic control of puberty. Results Stimulation of central α-MSH signaling robustly activated the reproductive axis in pubertal rats, whereas chronic inhibition of melanocortin receptors MC3/4R, delayed puberty, and prevented the permissive effect of leptin on puberty onset. Central blockade of MC3/4R or genetic elimination of kisspeptin receptors from POMC neurons did not affect kisspeptin effects. Conversely, congenital ablation of kisspeptin receptors or inducible, DREADD-mediated inhibition of arcuate nucleus (ARC) Kiss1 neurons resulted in markedly attenuated gonadotropic responses to MC3/4R activation. Furthermore, close appositions were observed between POMC fibers and ARC Kiss1 neurons while blockade of α-MSH signaling suppressed Kiss1 expression in the ARC of pubertal rats. Conclusions Our physiological, virogenetic, and functional genomic studies document a novel α-MSH→kisspeptin→GnRH neuronal signaling pathway involved in transmitting the permissive effects of leptin on pubertal maturation, which is relevant for the metabolic (and, eventually, pharmacological) regulation of puberty onsetThis work was supported by grants BFU2011-025021 & BFU2014-57581-P (Ministerio de Economía y Competitividad, Spain; co-funded with EU funds from FEDER Program); project PIE-00005 (Flexi-Met, Instituto de Salud Carlos III, Ministerio de Sanidad, Spain); Projects P08-CVI-03788 and P12-FQM-01943 (Junta de Andalucía, Spain); EU research contract DEER FP7-ENV-2007-1 and the New Zealand Health Research Council. CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of Instituto de Salud Carlos III. Senior authors are indebted with Dr. R.A. Steiner (University of Washington, Seattle, USA) and Dr. U. Boehm (University of Saarland School of Medicine, Homburg, Germany) for provision of relevant mouse lines, essential for conduction of some of the experiments included in this studyS

Modeling factors influencing the demand for emergency department services in ontario: a comparison of methods

<p>Abstract</p> <p>Background</p> <p>Emergency departments are medical treatment facilities, designed to provide episodic care to patients suffering from acute injuries and illnesses as well as patients who are experiencing sporadic flare-ups of underlying chronic medical conditions which require immediate attention. Supply and demand for emergency department services varies across geographic regions and time. Some persons do not rely on the service at all whereas; others use the service on repeated occasions. Issues regarding increased wait times for services and crowding illustrate the need to investigate which factors are associated with increased frequency of emergency department utilization. The evidence from this study can help inform policy makers on the appropriate mix of supply and demand targeted health care policies necessary to ensure that patients receive appropriate health care delivery in an efficient and cost-effective manner. The purpose of this report is to assess those factors resulting in increased demand for emergency department services in Ontario. We assess how utilization rates vary according to the severity of patient presentation in the emergency department. We are specifically interested in the impact that access to primary care physicians has on the demand for emergency department services. Additionally, we wish to investigate these trends using a series of novel regression models for count outcomes which have yet to be employed in the domain of emergency medical research.</p> <p>Methods</p> <p>Data regarding the frequency of emergency department visits for the respondents of Canadian Community Health Survey (CCHS) during our study interval (2003-2005) are obtained from the National Ambulatory Care Reporting System (NACRS). Patients' emergency department utilizations were linked with information from the Canadian Community Health Survey (CCHS) which provides individual level medical, socio-demographic, psychological and behavioral information for investigating predictors of increased emergency department utilization. Six different multiple regression models for count data were fitted to assess the influence of predictors on demand for emergency department services, including: Poisson, Negative Binomial, Zero-Inflated Poisson, Zero-Inflated Negative Binomial, Hurdle Poisson, and Hurdle Negative Binomial. Comparison of competing models was assessed by the Vuong test statistic.</p> <p>Results</p> <p>The CCHS cycle 2.1 respondents were a roughly equal mix of males (50.4%) and females (49.6%). The majority (86.2%) were young-middle aged adults between the ages of 20-64, living in predominantly urban environments (85.9%), with mid-high household incomes (92.2%) and well-educated, receiving at least a high-school diploma (84.1%). Many participants reported no chronic disease (51.9%), fell into a small number (0-5) of ambulatory diagnostic groups (62.3%), and perceived their health status as good/excellent (88.1%); however, were projected to have high Resource Utilization Band levels of health resource utilization (68.2%). These factors were largely stable for CCHS cycle 3.1 respondents. Factors influencing demand for emergency department services varied according to the severity of triage scores at initial presentation. For example, although a non-significant predictor of the odds of emergency department utilization in high severity cases, access to a primary care physician was a statistically significant predictor of the likelihood of emergency department utilization (OR: 0.69; 95% CI OR: 0.63-0.75) and the rate of emergency department utilization (RR: 0.57; 95% CI RR: 0.50-0.66) in low severity cases.</p> <p>Conclusion</p> <p>Using a theoretically appropriate hurdle negative binomial regression model this unique study illustrates that access to a primary care physician is an important predictor of both the odds and rate of emergency department utilization in Ontario. Restructuring primary care services, with aims of increasing access to undersupplied populations may result in decreased emergency department utilization rates by approximately 43% for low severity triage level cases.</p

KLB , encoding β‐Klotho, is mutated in patients with congenital hypogonadotropic hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic form of isolated gonadotropin‐releasing hormone (GnRH) deficiency caused by mutations in > 30 genes. Fibroblast growth factor receptor 1 (FGFR1) is the most frequently mutated gene in CHH and is implicated in GnRH neuron development and maintenance. We note that a CHH FGFR1 mutation (p.L342S) decreases signaling of the metabolic regulator FGF21 by impairing the association of FGFR1 with β‐Klotho (KLB), the obligate co‐receptor for FGF21. We thus hypothesized that the metabolic FGF21/KLB/FGFR1 pathway is involved in CHH. Genetic screening of 334 CHH patients identified seven heterozygous loss‐of‐function KLB mutations in 13 patients (4%). Most patients with KLB mutations (9/13) exhibited metabolic defects. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Peripheral FGF21 administration could indeed reach GnRH neurons through circumventricular organs in the hypothalamus. We conclude that FGF21/KLB/FGFR1 signaling plays an essential role in GnRH biology, potentially linking metabolism with reproduction

Impact of gastro-oesophageal reflux on microRNA expression, location and function

We have shown that miRNA expression is altered in the oesophageal squamous mucosa from individuals with gastro-oesophageal reflux and ulcerative oesophagitis. These changes in miR-143, miR-145 and miR-205 expression appear to be most pronounced in the basal layer of the oesophageal epithelium. In the context of gastro-oesophageal reflux these expression changes might influence proliferation and apoptosis and thereby regulate epithelial restoration. It is reasonable to hypothesise that they could represent early molecular events preceding the development of Barrett’s oesophagus, although proving this will require further studies as described above. Future detailed analyses of the role of these miRNAs in progression from gastro-oesophageal reflux to Barrett’s oesophagus, and then to oesophageal adenocarcinoma will be valuable, and may help in efforts to control and treat these diseases.This study was funded by a Competing Project Grant from the National Health and Medical Research Council of Australia. Cameron Smith was supported by a PROBE-NET PhD scholarship funded by a Strategic research Partnerships Grant from the Cancer Council of New South Wales