Distribution of melanopsin positive neurons in pigmented and albino mice: evidence for melanopsin interneurons in the mouse retina.

Here we have studied the population of intrinsically photosensitive retinal ganglion cells (ipRGCs) in adult pigmented and albino mice. Our data show that although pigmented (C57Bl/6) and albino (Swiss) mice have a similar total number of ipRGCs, their distribution is slightly different: while in pigmented mice ipRGCs are more abundant in the temporal retina, in albinos the ipRGCs are more abundant in superior retina. In both strains, ipRGCs are located in the retinal periphery, in the areas of lower Brn3a(+)RGC density. Both strains also contain displaced ipRGCs (d-ipRGCs) in the inner nuclear layer (INL) that account for 14% of total ipRGCs in pigmented mice and 5% in albinos. Tracing from both superior colliculli shows that 98% (pigmented) and 97% (albino) of the total ipRGCs, become retrogradely labeled, while double immunodetection of melanopsin and Brn3a confirms that few ipRGCs express this transcription factor in mice. Rather surprisingly, application of a retrograde tracer to the optic nerve (ON) labels all ipRGCs, except for a sub-population of the d-ipRGCs (14% in pigmented and 28% in albino, respectively) and melanopsin positive cells residing in the ciliary marginal zone (CMZ) of the retina. In the CMZ, between 20% (pigmented) and 24% (albino) of the melanopsin positive cells are unlabeled by the tracer and we suggest that this may be because they fail to send an axon into the ON. As such, this study provides the first evidence for a population of melanopsin interneurons in the mammalian retina

Estimation of the XUV radiation onto close planets and their evaporation

Context: The current distribution of planet mass vs. incident stellar X-ray flux supports the idea that photoevaporation of the atmosphere may take place in close-in planets. Integrated effects have to be accounted for. A proper calculation of the mass loss rate due to photoevaporation requires to estimate the total irradiation from the whole XUV range. Aims: The purpose of this paper is to extend the analysis of the photoevaporation in planetary atmospheres from the accessible X-rays to the mostly unobserved EUV range by using the coronal models of stars to calculate the EUV contribution to the stellar spectra. The mass evolution of planets can be traced assuming that thermal losses dominate the mass loss of their atmospheres. Methods: We determine coronal models for 82 stars with exoplanets that have X-ray observations available. Then a synthetic spectrum is produced for the whole XUV range (~1-912 {\AA}). The determination of the EUV stellar flux, calibrated with real EUV data, allows us to calculate the accumulated effects of the XUV irradiation on the planet atmosphere with time, as well as the mass evolution for planets with known density. Results: We calibrate for the first time a relation of the EUV luminosity with stellar age valid for late-type stars. In a sample of 109 exoplanets, few planets with masses larger than ~1.5 Mj receive high XUV flux, suggesting that intense photoevaporation takes place in a short period of time, as previously found in X-rays. The scenario is also consistent with the observed distribution of planet masses with density. The accumulated effects of photoevaporation over time indicate that HD 209458b may have lost 0.2 Mj since an age of 20 Myr. Conclusions: Coronal radiation produces rapid photoevaporation of the atmospheres of planets close to young late-type stars. More complex models are needed to explain fully the observations.Comment: Accepted by A&A. 10 pages, 8 figures, 7 Tables (2 online). Additional online material includes 7 pages, 6 figures and 6 tables, all include

A role for the outer retina in development of the intrinsic pupillary light reflex in mice.

Mice do not require the brain in order to maintain constricted pupils. However, little is known about this intrinsic pupillary light reflex (iPLR) beyond a requirement for melanopsin in the iris and an intact retinal ciliary marginal zone (CMZ). Here, we study the mouse iPLR in vitro and examine a potential role for outer retina (rods and cones) in this response. In wild-type mice the iPLR was absent at postnatal day 17 (P17), developing progressively from P21-P49. However, the iPLR only achieved ∼ 30% of the wild-type constriction in adult mice with severe outer retinal degeneration (rd and rdcl). Paradoxically, the iPLR increased significantly in retinal degenerate mice >1.5 years of age. This was accompanied by an increase in baseline pupil tone in the dark to levels indistinguishable from those in adult wild types. This rejuvenated iPLR response was slowed by atropine application, suggesting the involvement of cholinergic neurotransmission. We could find no evidence of an increase in melanopsin expression by quantitative PCR in the iris and ciliary body of aged retinal degenerates and a detailed anatomical analysis revealed a significant decline in melanopsin-positive intrinsically photosensitive retinal ganglion cells (ipRGCs) in rdcl mice >1.5 years. Adult mice lacking rod function (Gnat1(-/-)) also had a weak iPLR, while mice lacking functional cones (Cpfl5) maintained a robust response. We also identify an important role for pigmentation in the development of the mouse iPLR, with only a weak and transient response present in albino animals. Our results show that the iPLR in mice develops unexpectedly late and are consistent with a role for rods and pigmentation in the development of this response in mice. The enhancement of the iPLR in aged degenerate mice was extremely surprising but may have relevance to behavioral observations in mice and patients with retinitis pigmentosa

Inherited photoreceptor degeneration causes the death of melanopsin-positive retinal ganglion cells and increases their coexpression of brn3a

Purpose: To study the population of intrinsically photosensitive retinal ganglion cells (melanopsin-expressing RGCs, m+RGCs) in P23H-1 rats, a rat model of inherited photoreceptor degeneration. Methods: At postnatal (P) times P30, P365, and P540, retinas from P23H dystrophic rats (line 1, rapid degeneration; and line 3, slow degeneration) and Sprague Dawley (SD) rats (control) were dissected as whole-mounts and immunodetected for melanopsin and/or Brn3a. The dendritic arborization of m+RGCs and the numbers of Brn3a+RGCs and m+RGCs were quantified and their retinal distribution and coexpression analyzed. Results: In SD rats, aging did not affect the population of Brn3a+RGCs or m+RGCs or the percentage that showed coexpression (0.27%). Young P23H-1 rats had a significantly lower number of Brn3a+RGCs and showed a further decline with age. The population of m+RGCs in young P23H-1 rats was similar to that found in SD rats and decreased by 22.6% and 28.2% at P365 and P540, respectively, similarly to the decrease of the Brn3a+RGCs. At these ages the m+RGCs showed a decrease of their dendritic arborization parameters, which was similar in both the P23H-1 and P23H-3 lines. The percentage of coexpression of Brn3a was, however, already significantly higher at P30 (3.31%) and increased significantly with age (10.65% at P540). Conclusions: Inherited photoreceptor degeneration was followed by secondary loss of Brn3a+RGCs and m+RGCs. Surviving m+RGCs showed decreased dendritic arborization parameters and increased coexpression of Brn3a and melanopsin, phenotypic and molecular changes that may represent an effort to resist degeneration and/or preferential survival of m+RGCs capable of synthesizing Brn3a

Aortic root remodelling in competitive athletes.

BACKGROUND: Controversy remains about the cut-off limits for detecting aortic dilatation in athletes, particularly in large-sized individuals. The allometric scaling model has been used to obtain size-independent measurements in cardiovascular structures in the general population. AIM: The purpose of this study was to validate the use of allometric scaling in the measurement of the aortic root for competitive athletes and to offer reference values. METHODS: This was a cross-sectional study that analyses the dimensions of aortic root found in the echocardiogram performed as part of pre-participation sports screening in competitive athletes between 2012-2015. Beta exponents were calculated for height and body surface area in the whole cohort. In order to establish whether a common exponent could be used in both genders the following model was assessed y = axb*exp(c*sex). If a common exponent could not be applied then sex-specific beta exponents were calculated. RESULTS: Two thousand and eighty-three athletes (64% men) were included, from a broad spectrum of 44 different sports disciplines, including basketball, volleyball and handball. The mean age was 18.2 ± 5.1 years (range 12-35 years) and all athletes were Caucasian, with a training load of 12.5 ± 5.4 h per week. Indexed aortic root dimension showed a correlation with ratiometric scaling by body surface area (r: -0.419) and generated size independence values with a very light correlation with height (r: -0.084); and with the allometric scaling by body surface area (r: -0.063) and height (r: -0.070). The absolute value of aortic root was higher in men than in women (p < 0.001). These differences were maintained with allometric scaling. CONCLUSION: Size-independent aortic root dimension values are provided using allometric scaling by body surface area and height in a large cohort of competitive athletes. Aortic root values were larger in men than in women, both in absolute values and after allometric scaling. The use of these indexed aortic reference ranges can be useful for the early detection of aortic pathologies

Temporal variations in the evaporating atmosphere of the exoplanet HD 189733b

Atmospheric escape has been detected from the exoplanet HD 209458b through transit observations of the hydrogen Lyman-alpha line. Here we present spectrally resolved Lyman-alpha transit observations of the exoplanet HD 189733b at two different epochs. These HST/STIS observations show for the first time, that there are significant temporal variations in the physical conditions of an evaporating planetary atmosphere. While atmospheric hydrogen is not detected in the first epoch observations, it is observed at the second epoch, producing a transit absorption depth of 14.4+/-3.6% between velocities of -230 to -140 km/s. Contrary to HD 209458b, these high velocities cannot arise from radiation pressure alone and require an additional acceleration mechanism, such as interactions with stellar wind protons. The observed absorption can be explained by an atmospheric escape rate of neutral hydrogen atoms of about 10^9 g/s, a stellar wind with a velocity of 190 km/s and a temperature of ~10^5K. An X-ray flare from the active star seen with Swift/XRT 8 hours before the second-epoch observation supports the idea that the observed changes within the upper atmosphere of the planet can be caused by variations in the stellar wind properties, or by variations in the stellar energy input to the planetary escaping gas (or a mix of the two effects). These observations provide the first indication of interaction between the exoplanet's atmosphere and stellar variations.Comment: To be published in A&A Letters, June 28, 201

Tracing the retina to analyze the integrity and phagocytic capacity of the retinal pigment epithelium

We have developed a new technique to study the integrity, morphology and functionality of the retinal neurons and the retinal pigment epithelium (RPE). Young and old control albino (Sprague-Dawley) and pigmented (Piebald Virol Glaxo) rats, and dystrophic albino (P23H-1) and pigmented (Royal College of Surgeons) rats received a single intravitreal injection of 3% Fluorogold (FG) and their retinas were analyzed from 5 minutes to 30 days later. Retinas were imaged in vivo with SD-OCT and ex vivo in flat-mounts and in cross-sections. Fifteen minutes and 24 hours after intravitreal administration of FG retinal neurons and the RPE, but no glial cells, were labeled with FG-filled vesicles. The tracer reached the RPE 15 minutes after FG administration, and this labeling remained up to 30 days. Tracing for 15 minutes or 24 hours did not cause oxidative stress. Intraretinal tracing delineated the pathological retinal remodelling occurring in the dystrophic strains. The RPE of the P23H-1 strain was highly altered in aged animals, while the RPE of the RCS strain, which is unable to phagocytose, did not accumulate the tracer even at young ages when the retinal neural circuit is still preserved. In both dystrophic strains, the RPE cells were pleomorphic and polymegathic

A giant comet-like cloud of hydrogen escaping the warm Neptune-mass exoplanet GJ 436b

Exoplanets orbiting close to their parent stars could lose some fraction of their atmospheres because of the extreme irradiation. Atmospheric mass loss primarily affects low-mass exoplanets, leading to suggest that hot rocky planets might have begun as Neptune-like, but subsequently lost all of their atmospheres; however, no confident measurements have hitherto been available. The signature of this loss could be observed in the ultraviolet spectrum, when the planet and its escaping atmosphere transit the star, giving rise to deeper and longer transit signatures than in the optical spectrum. Here we report that in the ultraviolet the Neptune-mass exoplanet GJ 436b (also known as Gliese 436b) has transit depths of 56.3 +/- 3.5% (1 sigma), far beyond the 0.69% optical transit depth. The ultraviolet transits repeatedly start ~2 h before, and end >3 h after the ~1 h optical transit, which is substantially different from one previous claim (based on an inaccurate ephemeris). We infer from this that the planet is surrounded and trailed by a large exospheric cloud composed mainly of hydrogen atoms. We estimate a mass-loss rate in the range of ~10^8-10^9 g/s, which today is far too small to deplete the atmosphere of a Neptune-like planet in the lifetime of the parent star, but would have been much greater in the past.Comment: Published in Nature on 25 June 2015. Preprint is 28 pages, 12 figures, 2 table

The Truncated Isoform of Somatostatin Receptor5 (sst5TMD4) Is Associated with Poorly Differentiated Thyroid Cancer

Somatostatin receptors (ssts) are expressed in thyroid cancer cells, but their biological significance is not well understood. The aim of this study was to assess ssts in well differentiated (WDTC) and poorly differentiated thyroid cancer (PDTC) by means of imaging and molecular tools and its relationship with the efficacy of somatostatin analog treatment. Thirty-nine cases of thyroid carcinoma were evaluated (20 PDTC and 19 WDTC). Depreotide scintigraphy and mRNA levels of sst-subtypes, including the truncated variant sst5TMD4, were carried out. Depreotide scans were positive in the recurrent tumor in the neck in 6 of 11 (54%) PDTC, and in those with lung metastases in 5/11 cases (45.4%); sst5TMD4 was present in 18/20 (90%) of PDTC, being the most densely expressed sst-subtype, with a 20-fold increase in relation to sst2. In WDTC, sst2 was the most represented, while sst5TMD4 was not found; sst2 was significantly increased in PDTC in comparison to WDTC. Five depreotide positive PDTC received octreotide for 3-6 months in a pilot study with no changes in the size of the lesions in 3 of them, and a significant increase in the pulmonary and cervical lesions in the other 2. All PDTC patients treated with octreotide showed high expression of sst5TMD4. ROC curve analysis demonstrated that only sst5TMD4 discriminates between PDTC and WDTC. We conclude that sst5TMD4 is overexpressed in PDTC and may be involved in the lack of response to somatostatin analogue treatment

Extrinsic and intrinsic determinants of nerve regeneration

After central nervous system (CNS) injury axons fail to regenerate often leading to persistent neurologic deficit although injured peripheral nervous system (PNS) axons mount a robust regenerative response that may lead to functional recovery. Some of the failures of CNS regeneration arise from the many glial-based inhibitory molecules found in the injured CNS, whereas the intrinsic regenerative potential of some CNS neurons is actively curtailed during CNS maturation and limited after injury. In this review, the molecular basis for extrinsic and intrinsic modulation of axon regeneration within the nervous system is evaluated. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which is used to develop improved treatments for nervous system injury