From sneaker to parental male: change of reproductive traits in the black goby, Gobius niger (Teleostei, Gobiidae)

This study focuses on the consequences of the switch of tactic from parasitic to parental male in the black goby, Gobius niger (Teleostei: Gobiidae), a species showing two alternative male mating tactics. Older and larger males defend nests, court, and perform parental care on eggs, while younger and smaller ones behave as parasites, sneaking into nests while spawning occurs. Males adopting different tactics are known to present differences in primary and secondary sex traits. The social context of sneaker males was manipulated to induce a tactic switch. Sneakers were kept under two different experimental treatments with or without a female, and under exclusion of male-male competition. Males changed tactics, courting females, spawning, and performing parental care. All males showed substantial changes in primary sexual traits, such as a reduction in gonadal development and an increase in the investment in accessory structures. The experimental groups differed in the functionality of gonads and accessory organs and in the development of the secondary sex traits. These results demonstrate that the moment of switching is not genetically fixed in the black goby. Sneaker males are able to quickly reallocate energy in primary and secondary sex traits, in accordance with the adopted tactic. Several aspects of this flexible reproductive pattern resemble the socially controlled sex change found in sequential hermaphrodites.     

Interactions Crucial for Three-Dimensional Domain Swapping in the HP-RNase Variant PM8

The structural determinants that are responsible for the formation of higher order associations of folded proteins remain unknown. We have investigated the role on the dimerization process of different residues of a domain-swapped dimer human pancreatic ribonuclease variant. This variant is a good model to study the dimerization and swapping processes because dimer and monomer forms interconvert, are easily isolated, and only one dimeric species is produced. Thus, simple models for the swapping process can be proposed. The dimerization (dissociation constant) and swapping propensity have been studied using different variants with changes in residues that belong to different putative molecular determinants of dimerization. Using NMR spectroscopy, we show that these mutations do not substantially alter the overall conformation and flexibility, but affect the residue level stability. Overall, the most critical residues for the swapping process are those of one subunit that interact with the hinge loop of another one-subunit residue, stabilizing it in a conformation that favors the interchange. Tyr²⁵, Gln¹⁰¹, and Pro¹⁹, with Asn¹⁷, Ser²¹, and Ser²³, are found to be the most significant; notably, Glu¹⁰³ and Arg¹⁰⁴, which were postulated to form salt bridges that would stabilize the dimer, are not critical for dimerization.     

New,rare and noteworthy lichens in the Giant Mountains

A commented list of 19 particularly interesting and noteworthy lichen species collected recently in the Giant Mts (Karkonosze, Krkonoše) is given. Most of them were found on the basalt outcrop in the western wall of the Mały Śnieżny Kocioł cirque (germ. Kleine Schneegrube), which is the most valuable and most conserved area in this mountain range. Two species are new to Poland: Lecanora gangaleoides and Lecidea praenubila. Umbilicaria cinereorufescens is reported for the first time from the Sudety Mts as a whole. Three species are new for the Giant Mts: Buellia ocellata, Diplotomma lutosum and Fuscidea praeruptorum. Eight species: Aspicilia microlepis, Belonia russula, Caloplaca crenularia, C. nivalis, Gyalecta biformis, Koerberiella wimmeriana, Miriquidica complanata and Polyblastia cruenta were re-discovered after over 100 years on the historical locality in the Mały Śnieżny Kocioł cirque.     

Structural, Biochemical, and Functional Characterization of the Cyclic Nucleotide Binding Homology Domain from the Mouse EAG1 Potassium Channel

KCNH channels are voltage-gated potassium channels with important physiological functions. In these channels, a C-terminal cytoplasmic region, known as the cyclic nucleotide binding homology (CNB-homology) domain displays strong sequence similarity to cyclic nucleotide binding (CNB) domains. However, the isolated domain does not bind cyclic nucleotides. Here, we report the X-ray structure of the CNB-homology domain from the mouse EAG1 channel. Through comparison with the recently determined structure of the CNB-homology domain from the zebrafish ELK (eag-like K(+)) channel and the CNB domains from the MlotiK1 and HCN (hyperpolarization-activated cyclic nucleotide-gated) potassium channels, we establish the structural features of CNB-homology domains that explain the low affinity for cyclic nucleotides. Our structure establishes that the "self-liganded" conformation, where two residues of the C-terminus of the domain are bound in an equivalent position to cyclic nucleotides in CNB domains, is a conserved feature of CNB-homology domains. Importantly, we provide biochemical evidence that suggests that there is also an unliganded conformation where the C-terminus of the domain peels away from its bound position. A functional characterization of this unliganded conformation reveals a role of the CNB-homology domain in channel gating.     

Construct validity of the Short Form-36 Health Survey and its relationship with BMI in obese outpatients

Objective: To investigate the construct validity of the Short Form‐36 (SF‐36) Health Survey questionnaire in obese patients. Research Methods and Procedures: Our series consisted of 1735 obese patients (age, 44.7 ± 11.0 years; 1346 women) consecutively enrolled in the QUOVADIS study, an observational multicenter study of obese treatment‐seeking outpatients. The construct validity of the SF‐36 was assessed by main component analysis. Age‐, gender‐, and education‐adjusted general linear models were used to investigate the relationship between BMI and SF‐36 domains or factors identified by main component analysis. Results: BMI was significantly associated with poor health‐related quality of life in all eight SF‐36 domains, and the strongest association was observed with physical activity. Main components analysis generated a six‐factor solution explaining 59% of the observed variance. BMI was strongly associated with factors based on the loading of items regarding the physical activity domain and factors based on role‐physical and role‐emotional items or general health and bodily pain items. In contrast, mental health‐, vitality‐, and social functioning‐based factors were not related to BMI. Discussion: In obese treatment‐seeking outpatients, the clustering of SF‐36 items in main components is not significantly different from the domain‐based approach generally used, thus confirming the robustness of such a generic questionnaire in this specific condition. However, the peculiar clustering of some SF‐36 items and their relationship with BMI suggest that the health‐related quality of life profile of subjects belonging to that population may be better described with alternative aggregations of the SF‐36 items or with disease‐tailored questionnaires.     

Host suitability, respiration rate and the outcome of larval competition in strains of the cowpea weevil, Callosobruchus maculatus

Abstract.  Variation between strains of Callosobruchus maculatus in several life-history traits is well known. Differences in functional anatomy of egg pores and larval respiration rates have also been reported in strains from Brazil and Yemen. The response of five strains of C. maculatus to seeds of two host species, cowpea ( Vigna unguiculata ) and mung bean ( Vigna radiata ), was measured along with the larval respiration rates of the same strains on both hosts. There was significant variability of response to the two hosts. Strains with higher larval respiration rate (µL O₂/insect/day) showed higher seed consumption, which significantly affected adult emergence per seed on both hosts. This finding provides support for the hypothesis that differential feeding rate is an important mechanistic component of the larval competition outcome observed in strains of C. maculatus .     

Next generation sequencing demonstrates association between tumor suppressor gene aberrations and poor outcome in patients with cancer

Next generation sequencing is transforming patient care by allowing physicians to customize and match treatment to their patients’ tumor alterations. Our goal was to study the association between key molecular alterations and outcome parameters. We evaluated the characteristics and outcomes (overall survival (OS), time to metastasis/recurrence, and best progression-free survival (PFS)) of 392 patients for whom next generation sequencing (182 or 236 genes) had been performed. The Kaplan-Meier method and Cox regression models were used for our analysis, and results were subjected to internal validation using a resampling method (bootstrap analysis). In a multivariable analysis (Cox regression model), the parameters that were statistically associated with a poorer overall survival were the presence of metastases at diagnosis (P = 0.014), gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDKN2A alterations (P = 0.0001). The variables associated with a shorter time to metastases/recurrence were gastrointestinal histology (P = 0.004), APC (P = 0.008), PTEN (P = 0.026) and TP53 (P = 0.044) alterations. TP53 (P = 0.003) and PTEN (P = 0.034) alterations were independent predictors of a shorter best PFS. A personalized treatment approach (matching the molecular aberration with a cognate targeted drug) also correlated with a longer best PFS (P = 0.046). Our study demonstrated that, across diverse cancers, anomalies in specific tumor suppressor genes (PTEN, CDKN2A, APC, and/or TP53) were independently associated with a worse outcome, as reflected by time to metastases/recurrence, best PFS on treatment, and/or overall survival. These observations suggest that molecular diagnostic tests may provide important prognostic information in patients with cancer.     

Multiple effects of paclitaxel are modulated by a high c-myc amplification level

Paclitaxel affects microtubule stability by binding to beta-tubulin, thus leading to cell accumulation in the G(2)/M phase, polyploidization, and apoptosis. Because both cell proliferation and apoptosis could be somehow regulated by the protooncogene c-myc, in this work we have investigated whether the c-myc amplification level could modulate the multiple effects of paclitaxel. To this aim, paclitaxel was administered to SW613-12A1 and -B3 human colon carcinoma cell lines (which are characterized by a high and low c-myc endogenous amplification level, respectively), and to the B3mycC5 cell line, with an enforced exogenous expression of c-myc copies. In this experimental system, we previously demonstrated that a high endogenous/exogenous level of amplification of c-myc enhances serum deprivation- and DNA damage-induced apoptosis. Accordingly, the present results indicate that a high c-myc amplification level potentiates paclitaxel cytotoxicity, confers a multinucleated phenotype, and promotes apoptosis to a great extent, thus suggesting that c-myc expression level is relevant in modulating the cellular responses to paclitaxel. We have recently shown in HeLa cells that the phosphorylated form of c-Myc accumulates in the nucleus, as distinct nucleolar and extranucleolar spots; here, we demonstrated that, after the treatment with paclitaxel, phosphorylated c-Myc undergoes redistribution, becoming diffused in the nucleoplasm.     

Beta-alanine protection against hypoxic liver injury in the rat

Liver hypoxia still represents an important cause of liver injury during shock and liver transplantation. We have investigated the protective effects of beta-alanine against hypoxic injury using isolated perfused rat livers and isolated rat hepatocyte suspensions. Perfusion with hypoxic Krebs-Henseleit buffer increased liver weight and caused a progressive release of lactate dehydrogenase (LDH) in the effluent perfusate. The addition of 5 mmol/l beta-alanine to the perfusion buffer completely prevented both weight increase and LDH leakage. These findings were confirmed by histological examinations showing that beta-alanine blocked the staining by trypan blue of either liver parenchymal and sinusoidal cells. Studies performed in isolated hepatocytes revealed that beta-alanine exerted its protective effects by interfering with Na+ accumulation induced by hypoxia. The addition of gamma-amino-butyric acid, which interfered with beta-alanine uptake by the hepatocytes or of Na+/H+ ionophore monensin, reverted beta-alanine protection in either hepatocyte suspensions or isolated perfused livers. We also observed that liver receiving beta-alanine were also protected against LDH leakage and weight increase caused by the perfusion with an hyposmotic (205 mosm) hypoxic buffer obtained by decreasing NaCl content from 118 to 60 mmol/l. This latter effect was not reverted by blocking K+ efflux from hepatocyte with BaCl(2) (1mmol/l). Altogether these results indicated that beta-alanine protected against hypoxic liver injury by preventing Na+ overload and by increasing liver resistance to osmotic stress consequent to the impairment of ion homeostasis during hypoxia.