First Late Ordovician conodont fauna in the Betic Cordillera (South Spain): a palaeobiogeographical contribution

The youngest Ordovician conodont fauna in SW Europe has been found in the Malaguide Complex of the Betic Cordillera, SE Spain. It is also the first Ordovician conodont fauna in the Western Mediterranean Alpine Orogen. The conodont association, attributed to the Hirnantian (upper part of the Amorphognathus ordovicicus Biozone), is characterized by the predominance of Walliserodus amplissimus and Scabbardella altipes and by the absence of Sagittodontina and Istorinus, typical of the Mediterranean Province. This fauna differs markedly from those of the same biozone recorded in the Spanish Variscan Orogen of the Iberian Massif, which are attributed to the Katian. The Malaguide fauna shows, however, striking similarity to faunas of the Carnic Alps and some resemblance to those of the Pyrenees, Northern England and North Wales. These features suggest that Palaeozoic terranes of the Betic Cordillera were located far to the east of their present location and displaced westward during the Alpine Orogeny

ALK inhibition activates LC3B-independent, protective autophagy in EML4-ALK positive lung cancer cells.

ALK inhibitors effectively target EML4-ALK positive non-small cell lung cancer, but their effects are hampered by treatment resistance. In the present study, we asked whether ALK inhibition affects autophagy, and whether this may influence treatment response. Whereas the impact of targeted therapies on autophagic activity previously have been assessed by surrogate marker proteins such as LC3B, we here thoroughly examined effects on functional autophagic activity, i.e. on the sequestration and degradation of autophagic cargo, in addition to autophagic markers. Interestingly, the ALK inhibitor Ceritinib decreased mTOR activity and increased GFP-WIPI1 dot formation in H3122 and H2228 EML4-ALK <sup>+</sup> lung cancer cells, suggesting autophagy activation. Moreover, an mCherry-EGFP-LC3B based assay indicated elevated LC3B carrier flux upon ALK inhibition. In accordance, autophagic cargo sequestration and long-lived protein degradation significantly increased upon ALK inhibition. Intriguingly, autophagic cargo flux was dependent on VPS34 and ULK1, but not LC3B. Co-treating H3122 cells with Ceritinib and a VPS34 inhibitor or Bafilomycin A1 resulted in reduced cell numbers. Moreover, VPS34 inhibition reduced clonogenic recovery of Ceritinib-treated cells. In summary, our results indicate that ALK inhibition triggers LC3B-independent macroautophagic flux in EML4-ALK <sup>+</sup> cells to support cancer cell survival and clonogenic growth

Correlation between preoperative CT scan and lung metastases according to surgical approach in patients with colorectal cancer

Introduction: The number of lung metastases (M1) of colorectal carcinoma (CRC) in relation to the findings of computed tomography (CT) is the object of study. Methods: Prospective and multicenter study of the Spanish Group for Surgery of CRC lung metastases (GECMP-CCR). The role of CT in the detection of pulmonary M1 is evaluated in 522 patients who underwent a pulmonary metastasectomy for CRC. We define M1/CT as the ratio between metastatic nodules and those found on preoperative CT. Disease-specific survival (DSS), disease-free survival (DFS), and surgical approach were analyzed using the Kaplan–Meier method. Results: 93 patients were performed by video-assisted surgery (VATS) and 429 by thoracotomy. In 90%, the M1/CT ratio was =1, with no differences between VATS and thoracotomy (94.1% vs 89.7%, p = 0.874). In the remaining 10% there were more M1s than those predicted by CT (M1/CT > 1), with no differences between approaches (8.6% vs 10%, p = 0.874). 51 patients with M1/CT > 1, showed a lower median DSS (35.4 months vs 55.8; p = 0.002) and DFS (14.2 months vs 29.3; p = 0.025) compared to 470 with M1/CT = 1. No differences were observed in DSS and DFS according to VATS or thoracotomy. Conclusions: Our study shows equivalent oncological results in the resection of M1 of CRC using VATS or thoracotomy approach. The group of patients with an M1/CT ratio >1 have a worse DSS and DFS, which may mean a more advanced disease than predicted preoperatively. Introducción El número de metástasis pulmonares (M1) de carcinoma colorrectal (CCR) en relación con los hallazgos de la tomografía computarizada (TC), es objeto de estudio. Métodos Estudio prospectivo y multicéntrico del Grupo Español de Cirugía de las metástasis pulmonares del CCR (GCMP-CCR). Se evalúa el papel de la TC en la detección de M1 pulmonares en 522 pacientes intervenidos de una metastasectomía pulmonar por CCR. Definimos como M1/CT al cociente entre los nódulos metastásicos y los hallados en la TC preoperatoria. Se analizó la supervivencia específica de enfermedad (SEE), la supervivencia libre de enfermedad (SLE) y el abordaje quirúrgico mediante el método de Kaplan-Meier. Resultados En 93 pacientes se utilizó la cirugía videoasistida (VATS) y 429 toracotomías. En un 90% el cociente M1/TC fue =1, sin diferencias entre VATS y toracotomía (94,1 vs. 89,7%; p = 0,874). En el 10% restante existían más M1 que las predichas por la TC (M1/CT > 1), sin diferencias entre abordajes (8,6 vs. 10%; p = 0,874). Cincuenta y un pacientes con M1/CT > 1, mostraron una menor mediana de SEE (35,4 vs. 55,8 meses; p = 0,002) y SLE (14,2 vs. 29,3 meses; p = 0,025) en comparación con 470 con M1/CT = 1. No se observaron diferencias en la SEE y la SLE según VATS o toracotomía. Conclusiones Nuestro estudio muestra unos resultados oncológicos equivalentes en la resección de M1 de CCR mediante abordaje VATS o toracotomía. El grupo de pacientes con un cociente M1/CT > 1 presentan una peor SEE y SLE, pudiendo significar una enfermedad más avanzada de la predicha preoperatoriamente

Determination of annual periodicity in annuli formation in Atlantic bluefin tuna otoliths.

Controversies remain regarding the periodicity, or seasonality, of otolith growth band formation which directly influences a correct age determination of Atlantic bluefin tuna using otoliths. Thereby, the aim of this work was to apply marginal increment analysis (MIA) and marginal edge analysis (EA) to determine the timing of band deposition. The index of completion (MIA) was also analyzed using General Additive Models. Results indicated that the opaque band begin to form in July and would finish forming in November. From the end of the year and the beginning of the following year there is minimal marginal edge growth and this is when the translucent band begins to form and reaches its maximum development in June. MIA and EA has evidenced that the annulus has been formed in November in the Atlantic Bluefin tuna otolith. This would mean to delay the date of the current July 1st adjustment criterion to November 30

An experimental test of host’s life history traits modulation in response to cuckoo parasitism risk

Hosts can counteract parasites through defences based on resistance and/or tolerance. The mechanistic basis of tolerance, which involve defensive mechanisms minimizing parasite damage after a successful parasitic attack, remains poorly explored in the study of cuckoo-host interactions. Here, we experimentally explore the possibility that the risk of great spotted cuckoo Clamator glandarius parasitism may induce tolerance defences in magpie Pica pica hosts through plasticity in life-history traits. We predict that magpies exposed to auditory cues indicating high parasitism risk will more likely exhibit resistance and/or modify their life-history traits to minimize parasitism costs (i.e. tolerance) compared to magpies under low parasitism risk. We found that manipulating the perceived parasitism risk did not affect host resistance (i.e. rejection of parasitic eggs) nor host life-history traits. Unexpectedly, host's egg volume increased over the season in nests exposed to auditory cues of control non-harmful hoopoes Upupa epops. Our results do not provide support for inducible defences (either based on resistance or tolerance) in response to risk of parasitism in magpie hosts. Even so, we encourage studying plastic expression of breeding strategies in response to risk of cuckoo parasitism to achieve a better understanding of the mechanistic basis of tolerance defences.This work was supported by the Spanish Ministry of Education and Science/FEDER (Projects CGL2011-27561/BOS and CGL2014-56769-P to D. P. and J.M.A.). D.P. was supported by the Government of Extremadura while writing (contract number TA13002). M.E.G. was supported by the Spanish Ministry of Economy and Competitiveness (grant number BES-2012-051898).

Studying the effects of multiple invasive mammals on Cory’s shearwater nest survival

The most common invasive mammals—mice, rats, and cats—have been introduced to islands around the world, where they continue to negatively affect native biodiversity. The eradication of those invasive mammals has had positive effects on many species of seabirds. However, the removal of one invasive mammal species may result in abundance changes of other species due to trophic and competitive interactions among species. Understanding the overall impact of several invasive species is a key challenge when evaluating the possible effects of eradication programmes. Here we assess the influence of the three most common invasive mammals on nest survival of Cory’s shearwater (Calonectris diomedea). We monitored six breeding colonies over 3 years and measured the activity of mice, rats and cats to examine the influence of invasive mammals on nest survival. We found that nest survival showed a similar temporal trend in all years, with lowest weekly survival probabilities shortly after chicks hatched. Cats were identified as major predators of chicks, but no measure of colony-specific cat activity was able to adequately explain variation in shearwater nest survival. Nest survival was on average 0.38 (95 % confidence interval 0.20–0.53) and varied among colonies as well as over time. We found a small positive influence of rats on nest survival, which may indicate that the presence of small rodents as alternative prey may reduce cat predation of chicks. Our findings suggest that the eradication of rodents alone may exacerbate the adverse effects of cats on shearwater nest survival.This work was included in the project LIFE07 NAT/P/000649 ‘Safe Islands for Seabirds’, coordinated by the Portuguese Society for the Study of Birds and co-financed by the European Commission.Peer Reviewe

Polyphenolic Contents and Antioxidant Potential of Stem Bark Extracts from Jatropha curcas (Linn)

We assessed the polyphenolic contents and antioxidant potential of the aqueous, ethanol and methanol stem bark extracts of Jatropha curcas. The total phenol, flavonoids, flavonols and proanthocyanidin contents of the extracts were evaluated to determine their effect on the antioxidant property of this plant, using standard phytochemical methods. The antioxidant and free radical scavenging activity of ethanol, methanol and aqueous extracts of the plant were also assessed against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), ferric reducing, nitric oxide (NO), superoxide anion, (O2−) and hydrogen peroxide (H2O2) using spectroscopic methods and results were compared with that of butylated hydroxyl toluene (BHT) and ascorbic acid as standards. The concentrations of different classes of phenolic compounds were higher in methanol and ethanol extracts compared to aqueous extracts. There was correlation between total phenol, total flavonoids, total flavonol and total proanthocyanidins (r = 0.996, 0.978, 0.908, and 0.985) respectively. There was correlations between the amount of phenolic compounds and percentage inhibition of DPPH radicals scavenging activity of the extract (r = 0.98). Findings from the present study indicated that J. curcas is a potential source of natural antioxidants and may be a good candidate for pharmaceutical plant based products

Role of PTPN22 and CSK gene polymorphisms as predictors of susceptibility and clinical heterogeneity in patients with Henoch-Schönlein purpura (IgA vasculitis)

INTRODUCTION: To determine whether the PTPN22 (protein tyrosine phosphatase nonreceptor 22)/CSK (c-src tyrosine kinase) pathway is implicated in the susceptibility and clinical heterogeneity of Henoch-Schönlein purpura (HSP) in the largest series of Caucasian HSP patients ever assessed for genetic studies. METHODS: A set of 329 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al. classification criteria and 515 sex and ethnically matched controls were recruited in this study. Two well-known CSK (CSK rs34933034 and CSK rs1378942) and two functional PTPN22 (PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q)) polymorphisms, previously associated with autoimmunity, were genotyped with TaqMan single nucleotide polymorphism (SNP) genotyping assays. RESULTS: No significant differences in the genotype and allele frequencies between HSP patients and controls were observed when the CSK rs34933034, CSK rs1378942, PTPN22 rs2476601 (R620W) and PTPN22 rs33996649 (R263Q) polymorphisms were analyzed independently. In keeping with this observation, no significant differences were found when we assessed these polymorphisms combined conforming haplotypes. In addition, there were no differences in the allele or genotype frequencies when HSP patients were stratified according the age at disease onset, sex, presence of arthralgia/arthritis, nephritis or gastrointestinal manifestations. CONCLUSIONS: Our results do not support association between PTPN22/CSK and HSP