Stable transgenesis in the marine annelid Platynereis dumerilii sheds new light on photoreceptor evolution

Research in eye evolution has mostly focused on eyes residing in the head. In contrast, noncephalic light sensors are far less understood and rather regarded as evolutionary innovations. We established stable transgenesis in the annelid Platynereis, a reference species for evolutionary and developmental comparisons. EGFP controlled by cis-regulatory elements of r-opsin, a characteristic marker for rhabdomeric photoreceptors, faithfully recapitulates known r-opsin expression in the adult eyes, and marks a pair of pigment-associated frontolateral eyelets in the brain. Unexpectedly, transgenic animals revealed an additional series of photoreceptors in the ventral nerve cord as well as photoreceptors that are located in each pair of the segmental dorsal appendages (notopodia) and project into the ventral nerve cord. Consistent with a photosensory function of these noncephalic cells, decapitated animals display a clear photoavoidance response. Molecular analysis of the receptors suggests that they differentiate independent of pax6, a gene involved in early eye development of many metazoans, and that the ventral cells may share origins with the Hesse organs in the amphioxus neural tube. Finally, expression analysis of opn4×-2 and opn4m-2, two zebrafish orthologs of Platynereis r-opsin, reveals that these genes share expression in the neuromasts, known mechanoreceptors of the lateral line peripheral nervous system. Together, this establishes that noncephalic photoreceptors are more widespread than assumed, and may even reflect more ancient aspects of sensory systems. Our study marks significant advance for the understanding of photoreceptor cell (PRC) evolution and development and for Platynereis as a functional lophotrochozoan model system.     

Testosterone, facial symmetry and cooperation in the prisoners' dilemma

Recent research has analyzed how individual characteristics, like the exposure to different hormones and symmetry, affect decision-making and strategic behaviour. The present article investigates the effect of symmetry, of exposure to testosterone (T) in utero and during puberty and of current T on cooperation in a Prisoners' Dilemma Game (PDG). T is a hormone with well known effect on males' behaviour, and that promotes activities that seek to increase reproductive success. Fluctuating Asymmetry (FA) reflects the ability of the organism to maintain a stable development and it is usually employed as a variable reflecting genetic quality (low FA values are thought to signal higher genetic quality). Our results show that subjects with intermediate levels of second to fourth digit ratio (a proxy of exposure to T in utero) and with high FA cooperate more often in the PDG. We also observe that the latter effect is due to the fact that FA has an impact on subjects' expectations about the behaviour of their counterpart in the game. These results reinforce the described link between markers related to genetic quality and cooperative behaviour. This possible linkage of individual condition and pro-social behaviour in humans clearly merits further attention.     

Acute intravenous injection and short‐term oral administration of NG‐nitro‐l‐arginine methyl ester to the rat provoke increased pressor responses to agonists and hypertension,but not inhibition of acetylcholine‐induced hypotensive responses

In experiments in vivo, we studied whether the endothelial dysfunction induced by nitric oxide (NO) synthesis inhibition is simultaneously or sequentially manifested as a reduced level of endothelium‐dependent agonist‐induced vasodilatation, an increased responsiveness to vasoconstrictors, and hypertension. Vascular responses to acetylcholine, phenylephrine, and angiotensin II were measured in pithed rats after acute intravenous injection (100 mg/kg) and short‐term oral administration of N^G‐nitro‐l ‐arginine methyl ester (l ‐NAME; 60 mg/kg per day) for 1 and 3 days (l ‐NAME_1d and l ‐NAME_3d, respectively). Pithed rats were chosen because drug‐induced cardiovascular responses reflect only peripheral effects. Parallel experiments examined mean arterial pressure (MAP) values in anesthetized rats. After short‐term l ‐NAME_1d and l ‐NAME_3d treatments, the MAP was significantly elevated in anesthetized but not pithed rats. Acute intravenous administration of l ‐NAME elevated MAP in pithed rats. Intravenous infusion of phenylephrine was used to compensate for the pressor response induced by l ‐NAME in pithed animals. The maximum decrease and duration of the hypotensive responses to acetylcholine were unaltered by the acute and both short‐term l ‐NAME treatments in pithed rats. These treatments, on the other hand, increased phenylephrine‐ and angiotensin II‐induced pressor responses in pithed animals. In isolated aortic rings prepared from pithed rats treated acutely and short‐term with l ‐NAME, acetylcholine‐induced relaxations were inhibited. Thus, the inhibition of NO‐dependent vasodilator tone after acute intravenous injection and short‐term oral l ‐NAME administration may be associated with vascular smooth muscle hyper‐responsiveness to pressor agonists and hypertension, whereas the hypotensive responses to acetylcholine could not be associated with the l ‐NAME‐induced endothelial dysfunction in pithed rats.     

Oxidative markers in children with severe obesity following low‐calorie diets supplemented with mandarin juice

Aim: To evaluate the effect of supplementing a hypocaloric diet with mandarin juice, a food with a high content of antioxidants (vitamin C, flavonoids and carotenoids), on biomarkers of oxidant/antioxidant status of severe obese children. Methods: Forty obese children were randomized into two groups pair‐wise in a 4‐week controlled intervention study. Both groups followed a hypocaloric diet. One group received additionally a supplementation of 500 mL of 100% mandarin juice daily. Clinical data, anthropometry, dietary intake and fasting blood samples were collected at baseline and after the intervention. Lipid peroxidation was assessed by circulating levels of malondialdehyde, and protein oxidation was determined by the concentration of plasma carbonyl groups. The antioxidant defence was evaluated by red cell‐reduced glutathione and plasma levels of α‐tocopherol and vitamin C. Results: The supplemented group experienced a decrease in the levels of malondialdehyde (?9.6%, p = 0.014) and carbonyl groups (?36.1%, p = 0.006) and an increase in antioxidants (α‐tocopherol +16.1%, p = 0.006, glutathione +36.1%, p < 0.0001, and vitamin C + 94.6%, p < 0.0001). Conclusion: The mandarin juice consumption with a reduced calorie diet positively affects the antioxidant defence and produces a decrease in biomarkers of oxidative stress in obese children.     

Expression profiles of ProEx C and Ki67 in squamous cell carcinoma in situ of the skin and their relationship with human papillomavirus genotypes

Background: ProExC is a new marker for identification of precursor lesions of cervical carcinoma. Its utility in noncervical squamous cell carcinoma in situ (SCCIS) such as Bowen's disease (BD) and actinic keratosis (AK) where human papillomavirus (HPV) plays a role has not been elucidated. Our aim was to ascertain the immunohistochemical features and clinical utility of ProExC in SCCIS of the skin. Methods: HPV presence was tested in SCCIS (38 BD and 7 AK) using GP5+/6+ and Short PCR fragment (SPF) primers and subsequently genotyped. Histopathologic sections were stained for ProExC and Ki67. A set of non‐neoplastic skin proliferative lesions were included for immunohistochemical evaluation [14 psoriasis (PS) and 6 psoriasiform dermatitis (PSD)]. Results: HPV was detected in 18.9% BD. ProExC and Ki67 in the whole epidermis thickness was observed in 86.5 and 37.1% BD, respectively (p < 0.0001). ProExC and Ki67 were restricted to the lower third of the epidermis in PS and PSD. Conclusions: ProExC expression is not associated with HPV in SCCIS of the skin. Proliferating cells are better delineated in SCCIS by ProExC which may be useful to assess the extent of these lesions. Different immunohistochemical profiles seen in neoplasic and non‐neoplastic skin lesions suggest diverse alteration of cell‐cycle kinetics. Sánchez‐Hernández M, Conesa‐Zamora P, García‐Solano J, Corbalán‐Vélez R, Martínez‐Barba E, Pérez‐Guillermo M. Expression profiles of ProEx C and Ki67 in squamous cell carcinoma in situ of the skin and their relationship with human papillomavirus genotypes.     

Characterization of indorenate effects on brain monoamine metabolism

The effect of indorenate, a central antihypertensive agent, on the catecholamine and indolamine metabolism was studied in the rat brain. Acute administration of 10 mg/kg of indorenate causes an increase in 5-HT concentrations and a decrease on its metabolite 5-hydroxyindolacetic acid (5-HIAA) in the brain stem, cerebral cortex, hypothalamus, and striatum. Maximal effects were observed between 1.5 and 3 hr after indorenate administration. Additionally, a significant decrease in homovanilic acid (HVA) and 3,4-dihydroxyphenylacetic (DOPAC) concentrations was noted after 1.5 hr of a 10 mg/kg indorenate injection. Modification of both catecholamine and indolamine metabolites was dose related. Control values were recovered 24 hr after indorenate administration. Activity of monoamine oxidase present in crude homogenates obtained from the cerebral cortex, brain stem, hypothalamus, and striatum was not affected by indorenate. The present results suggest that indorenate acts as an agonist at serotonin receptors in the central nervous system (CNS).