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

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

An international approach of the relationship between board attributes and the disclosure of corporate social responsibility issues

This is the pre-peer reviewed version of the following article: An international approach of the relationship between board attributes and the disclosure of corporate social responsibility issues. Corporate Social Responsibility and Environmental Management (2018), which has been published in final form at https://doi.org/10.1002/csr.1707. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Firms interested in being perceived by all stakeholders and society as drivers of corporate social responsibility (CSR) activities, especially regarding CSR reporting, should have boards of directors that defend not only shareholder interests but also all stakeholders' needs. Thus, we expect that efficient boards, particularly if well‐structured, will impact on CSR disclosure. As a result, in this paper, we examine the effect of board composition, particularly board size, board independence, board gender diversity, chief executive officer (CEO) duality, and CSR board committee, on CSR reporting. Using a sample of international firms, concretely 13,178 observations belonging to 39 countries, we hypothesize that all these attributes positively affect CSR disclosure, except board independence and CEO duality, which are expected to impact negatively. These hypotheses are theoretically supported by the agency and stakeholder perspectives. Our findings support all the hypotheses, except that of CEO duality, and therefore, we conclude that board characteristics such as board size, board gender diversity, and CSR board committees encourage the disclosure of CSR matters, whereas board independence discourages this reporting. Contrary to our predictions, CEO duality has a positive effect on CSR reporting

Recessive dystrophic epidermolysis bullosa: the origin of the c.6527insC mutation in the Spanish population

This work was supported by grants from the Spanish Ministry of Science and Innovation (MICINN) (SAF2007-61019 and SAF 2010-16976), INTRA ⁄08 ⁄714.1 and INTRA ⁄09 ⁄758 from the Biomedical Network Research Centre on Rare Diseases (CIBERER) and S2010 ⁄BMD-2420 (CELLCAM) from Comunidad de Madrid

Evaluation of parasite and host phenolic composition and bioactivities − The practical case of Cytinus hypocistis (L.) L. and Halimium lasianthum (Lam.) Greuter

Cytinus hypocistis (L.) L. is a comestible holoparasite with great potential for cosmeceutical application. Although its high tannin content has been associated with its bioactive and inhibitory enzyme properties, this is the first report establishing a relationship between parasite and host (Halimium lasianthum (Lam.) Greuter) phenolic profile and bioactive properties. Thus, five extracts (aerial and root extracts of non-parasited and parasited H. lasianthum and C. hypocistis) were evaluated. The tentative identification of both species comprises 39 phenolic compounds. Hydrolysable tannins and flavonoids were the main identified groups in C. hypocistis and H. lasianthum extracts, respectively. Regarding bioactivities, C. hypocistis exhibited excellent antioxidant results both in Oxidative Haemolysis (OxHLIA) and inhibition of Thiobarbituric Acid Reactive Substances Formation (TBARS). The tested extracts presented antimicrobial inhibition, anti-inflammatory activity, and effective cytotoxicity against tumour cells. C. hypocistis exhibited the lowest cytotoxicity on a non-tumour cell line. Principal Component Analysis (PCA) was a suitable approach to analyse differences among samples, explaining up to 67% of data variability and suggesting no similarities between parasite and host phenolic composition and bioactivities. Therefore, this comparative study emphasises the significance of both species as a source of biologically active compounds.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). A. R. Silva is grateful to FCT and FSE for her Doctoral Grant (SFRH/BD/145834/2019). L. Barros, C. Pereira, I. Dias, and R. C. Calhelha are grateful to F.C.T. and P.I. for their contracts through the institutional scientific employment programme. The authors are also thankful to the FEDER-Interreg Espa˜na-Portugal programme for financial support through the project TRANSCoLAB: 0612_TRANS_CO_LAB_2_P and to ERDF through the Regional Operational Program North 2020, within the scope of the Project GreenHealth - Norte-01–0145-FEDER-000042. This research was also funded by the Serbian Ministry of Education, Science and Technological Development (Contract No. 451–03-9/2021–14/200007).info:eu-repo/semantics/publishedVersio

Phenolic profiling and in vitro bioactivities of three medicinal Bryophyllum plants

Bryophyllum constitutes a subgenus within the genus Kalanchoe that contains several plant species used in traditional medicine worldwide for the treatment of several diseases. However, little is known about the phytoconstituents of Bryophyllum spp. and previous reports have pointed at their low in Planta concentrations of bioactive compounds. In this work, we take advantage of plant in vitro culture for the study of the phenolic compounds found in the aerial parts of Bryophyllum spp. and their associated bioactivities. Our results show that the induction of nutritional stress leads to an improved accumulation of phenolic compounds, mainly flavonols and anthocyanins, represented by myricetin and malvidin glycosides, respectively. This effect is mainly found for B. × houghtonii, whose hydroethanolic extracts promoted the highest antioxidant, cytotoxic and anti-inflammatory activities. In the case of cytotoxic activity, Bryophyllum extracts showed an enhanced activity against the MCF-7 human breast carcinoma cell line. Meanwhile, extracts from B. daigremontianum promoted a wide range of effectiveness against different bacterial and fungal strains. This study is committed to shed light about the phytochemical potential associated to this unexplored subgenus, with the aim of considering Bryophyllum spp. as a valuable source of bioactive compounds for their exploitation in food, cosmetic and pharmaceutical industries.The authors acknowledge the Spanish Ministry of Education for the FPU grant awarded to Pascual García-Pérez (FPU15/04849) and ADICAM research center for kindly providing the plant material.info:eu-repo/semantics/publishedVersio

A recurrent nonsense mutation occurring as a de novo event in a patient with recessive dystrophic epidermolysis bullosa

Publicad

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

Background Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. Methods We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. Results We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. Conclusions Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.post-print1360 K