An ontogenetic perspective on migratory strategy of a long-lived pelagic seabird: Timings and destinations change progressively during maturation

The processes that drive the ontogeny of migratory strategies in long-lived animals with slow maturation remain enigmatic. While some short-lived migrants are known or believed to repeat the same migratory patterns throughout their lives, little is known on the time required for immature long-lived migrants to progressively acquire adult-like migratory behaviours, or which aspects take longer to refine during the maturation process. Here, we studied the ontogeny of long-distance migratory strategies and related patterns of spatial distribution in a long-lived seabird species during the annual cycle. To do so, we deployed light-level geolocators on 4- to 9-year-old immature Cory's shearwaters (Calonectris borealis) and on breeding adults. We revealed that migratory timings and destinations of young shearwaters progressively changed with age. The effect of ageing was remarkably evident on spring migratory performance and phenology. Birds gradually shortened the duration of the non-breeding period by advancing departure date and reducing travelling time, which resulted in a sequential arrival at the colony of the various age contingents. Ageing immatures gradually changed from a more exploratory strategy to a more conservative way of exploiting resources, reducing both their year-round spatial spread across oceanic domains and the total distance travelled. Immatures always performed a trans-equatorial migration to the Southern Hemisphere, contrasting with 17% of the adults which remained in the North Atlantic year-round. Finally, during the breeding season immatures were widely dispersed through the North Atlantic reducing their overlap with breeding adults. Our long-term study provides empirical support to the hypothesis that in long-lived species, the refinement of migratory behaviour and year-round spatial distribution is a progressive process mediated by age and experience, where life stage constraints and competition for resources may also play a role. The emerging pattern suggests that for some avian taxa, the ontogeny of migratory strategy is a prolonged, complex and dynamic process.FEDER; FCT-Fundação para a Ciência e Tecnologiainfo:eu-repo/semantics/publishedVersio

Colony attendance and moult pattern of Cory's Shearwaters (Calonectris borealis) differing in breeding status and age

Migratory birds must fit three costly life-history events within the annual cycle, reproduction, moult and migration, to minimize their overlap and maximize survival and breeding success. However, some seabirds, such as Cory’s Shearwater Calonectris borealis, overlap body moult and breeding, with flight feather renewal occurring in late chick-rearing. In contrast, the moult patterns of non-breeding adult (sabbatical) and immature Cory’s Shearwaters, which also attend the colony during the breeding season, remain poorly understood. Furthermore, the potential implications of life-stage and breeding status trade-offs on moult status and colony attendance in non-breeders has rarely been investigated. Surveying different areas within one colony between June and September 2013 and 2014, we studied the age and breeding status composition of birds attending the breeding colony and scored moult of their body (breast and upper-neck), wing and tail feathers. We found that in addition to breeders (n = 165), 57.6% of the birds (n = 389) attending the colony were 4- to 10-year-old immatures (n = 132) and adult sabbatical shearwaters (n = 92). Sabbaticals and 8- to 10-year-old immatures (n = 28) were present at the colony during incubation, whereas only three sabbatical birds and no 8- to 10-year-old immatures were captured in late chick-rearing. Conversely, 4- to 7-year-old immatures arrived later in the season but were still present in late chick-rearing. Sabbatical and 8- to 10-year-old immatures were moulting body feathers at the same time as adult breeders, whereas, among 4- to 7-year-old immatures, older birds moulted earlier than younger birds. A larger proportion of sabbatical birds were replacing tail feathers compared with adult breeders. However, there was no evidence that sabbaticals or 8- to 10-year-old immatures differed in wing moult from adult breeders until August. Overall, our study shows that colony attendance by non-breeding adults and immatures is widespread in this population. The synchronous moult schedule of flight and body feathers across age groups at different life-history stages may suggest that this aspect of moult is controlled by environmental conditions.Fundação para a Ciência e Tecnologia - FCTinfo:eu-repo/semantics/publishedVersio

Tumor Suppressors and Cell-Cycle Proteins in Lung Cancer

The cell cycle is the cascade of events that allows a growing cell to duplicate all its components and split into two daughter cells. Cell cycle progression is mediated by the activation of a highly conserved family of protein kinases, the cyclin-dependent kinases (CDKs). CDKs are also regulated by related proteins called cdk inhibitors grouped into two families: the INK4 inhibitors (p16, p15, p19, and p18) and the Cip/Kip inhibitors (p21, p27, and p53). Several studies report the importance of cell-cycle proteins in the pathogenesis and the prognosis of lung cancer. This paper will review the most recent data from the literature about the regulation of cell cycle. Finally, based essentially on the data generated in our laboratory, the expression, the diagnostic, and prognostic significance of cell-cycle molecules in lung cancer will be examined

Identification of genes down-regulated during lung cancer progression: A cDNA array study

<p>Abstract</p> <p>Background</p> <p>Lung cancer remains a major health challenge in the world. Survival for patients with stage I disease ranges between 40–70%. This suggests that a significant proportion of patients with stage I NSCLC may actually be under-staged.</p> <p>Methods</p> <p>In order to identify genes relevant for lung cancer development, we carried out cDNA array experiments employing 64 consecutive patients (58 men and 6 women) with a median age of 58 years and stage 1 or stage 2 non-small-cell lung cancer (NSCLC).</p> <p>Results</p> <p>Basic cDNA array data identified 14 genes as differentially regulated in the two groups. Quantitative RT-PCR analysis confirmed an effective different transcriptional regulation of 8 out of 14 genes analyzed. The products of these genes belong to different functional protein types, such as extra-cellular matrix proteins and proteases (<it>Decorin </it>and <it>MMP11</it>), genes involved in DNA repair (<it>XRCC1</it>), regulator of angiogenesis (<it>VEGF</it>), cell cycle regulators (<it>Cyclin D1</it>) and tumor-suppressor genes (<it>Semaphorin 3B</it>, <it>WNT-5A </it>and retinoblastoma-related <it>Rb2/p130</it>). Some previously described differences in expression patterns were confirmed by our array data. In addition, we identified and validated for the first time the reduced expression level of some genes during lung cancer progression.</p> <p>Conclusion</p> <p>Comparative hybridization by means of cDNA arrays assisted in identifying a series of novel progression-associated changes in gene expression, confirming, at the same time, a number of previously described results.</p

Individual quality assessment of autografting by probability estimation for clinical endpoints: a prospective validation study from the European group for blood and marrow transplantation.

The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (ie, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (≤7 days on antibiotics and no transfusions; ≤21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and 7 days on antibiotics, >3 but 30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of ≥4 × 106/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) ≥5 × 106/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P 500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care

Identification of protein-protein interactions of human HtrA1.

The human heat shock protein HtrA1, a member of the HtrA family of serine proteases, is a evolutionarily highly conserved factor which displays a widespread pattern of expression. The yeast two-hybrid technique was employed to identify new cellular proteins physically interacting with HtrA1, and thus potential targets of this serine protease. An enzymatically inactive HtrA1 point mutant, HtrA1-S328A, was generated and used as bait in a yeast two-hybrid system. Fifty-two plasmids were isolated from primary positive yeast clones. Subsequent sequencing and BLAST analysis revealed cDNAs encoding for 13 different proteins. These putative binding partners of HtrA1 appeared to be a) components of extracellular matrix; b) factors related to signal pathways, and c) unknown proteins. Among the 13 positive clones identified and reported here, it is worth of note that the interaction of HtrA1 with tubulin and collagen (extracellular matrix proteins) and with tuberin (cytoplasmic protein) is confirmed by other studies, and this further supports previous findings in which HtrA1 can be found active as an intracytoplasmic protein or as secreted protein as well

Prophylactic heparin and risk of orotracheal intubation or death in patients with mild or moderate COVID-19 pneumonia

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO_{2}/FiO_{2} ratio aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO_{2}/FiO_{2} ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO_{2}/FiO_{2} > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed

Evaluation of whole genome sequencing for outbreak detection of Salmonella enterica

Salmonella enterica is a common cause of minor and large food borne outbreaks. To achieve successful and nearly 'real-time' monitoring and identification of outbreaks, reliable sub-typing is essential. Whole genome sequencing (WGS) shows great promises for using as a routine epidemiological typing tool. Here we evaluate WGS for typing of S. Typhimurium including different approaches for analyzing and comparing the data. A collection of 34 S. Typhimurium isolates was sequenced. This consisted of 18 isolates from six outbreaks and 16 epidemiologically unrelated background strains. In addition, 8 S. Enteritidis and 5 S. Derby were also sequenced and used for comparison. A number of different bioinformatics approaches were applied on the data; including pan-genome tree, k-mer tree, nucleotide difference tree and SNP tree. The outcome of each approach was evaluated in relation to the association of the isolates to specific outbreaks. The pan-genome tree clustered 65% of the S. Typhimurium isolates according to the pre-defined epidemiology, the k-mer tree 88%, the nucleotide difference tree 100% and the SNP tree 100% of the strains within S. Typhimurium. The resulting outcome of the four phylogenetic analyses were also compared to PFGE revealing that WGS typing achieved the greater performance than the traditional method. In conclusion, for S. Typhimurium, SNP analysis and nucleotide difference approach of WGS data seem to be the superior methods for epidemiological typing compared to other phylogenetic analytic approaches that may be used on WGS. These approaches were also superior to the more classical typing method, PFGE. Our study also indicates that WGS alone is insufficient to determine whether strains are related or un-related to outbreaks. This still requires the combination of epidemiological data and whole genome sequencing results

Endothelial Cells Obtained from Patients Affected by Chronic Venous Disease Exhibit a Pro-Inflammatory Phenotype

The inflammatory properties of vein endothelium in relation to chronic venous disease (CVD) have been poorly investigated. Therefore, new insights on the characteristics of large vein endothelium would increase our knowledge of large vessel physiopathology. METHODOLOGY/PRINCIPAL FINDINGS: Surgical specimens of veins were obtained from the tertiary venous network (R3) and/or saphenous vein (SF) of patients affected by CVD and from control individuals. Highly purified venous endothelial cell (VEC) cultures obtained from CVD patients were characterized for morphological, phenotypic and functional properties compared to control VEC. An increase of CD31/PECAM-1, CD146 and ICAM-1 surface levels was documented at flow cytometry in pathological VEC with respect to normal controls. Of note, the strongest expression of these pro-inflammatory markers was observed in VEC obtained from patients with more advanced disease. Similarly, spontaneous cell proliferation and resistance to starvation was higher in pathological than in normal VEC, while the migratory response of VEC showed an opposite trend, being significantly lower in VEC obtained from pathological specimens. In addition, in keeping with a higher baseline transcriptional activity of NF-kB, the release of the pro-inflammatory cytokines osteoprotegerin (OPG) and vascular endothelial growth factor (VEGF) was higher in pathological VEC cultures with respect to control VEC. Interestingly, there was a systemic correlation to these in vitro data, as demonstrated by higher serum OPG and VEGF levels in CVD patients with respect to normal healthy controls. CONCLUSION/SIGNIFICANCE: Taken together, these data indicate that large vein endothelial cells obtained from CVD patients exhibit a pro-inflammatory phenotype, which might significantly contribute to systemic inflammation in CVD patients

Ifosfamide, cisplatin and etoposide combination in locally advanced inoperable non-small-cell lung cancer: a phase II study

From March 1993 to February 1997, 43 eligible patients with inoperable stage IIIA (ten patients) and stage IIIB (33 patients), histologically confirmed NSCLC received 3 courses of the ICE combination (ifosfamide 1.5 g m−2 and mesna 750 mg m−2 two times a day, cisplatin 25 mg m−2 and etoposide 100 mg m−2, all administered intravenously (i.v.) on days 1–3 every 3 weeks) with G-CSF support. After three cycles, patients were submitted to radical surgery or received two additional courses of the ICE regimen and/or curative radiotherapy. Grade 3–4 neutropenia occurred in 21% of 114 evaluable courses, but was of short duration, leading to neutropenic fever in 5% of the courses. Severe thrombocytopenia and anaemia were observed in 13% and 3% of the courses respectively. Non-haematological toxicity was generally mild with only two episodes of reversible renal impairment. The overall response rate after three chemotherapy courses was 69% (28 partial responses, one complete response). Ten patients (8/10 patients in stage IIIA, 2/33 patients in stage IIIB) underwent radical surgery. Median TTP for patients not undergoing surgery (n = 33) was 8 months (range 3–34+); median DFS for patients rendered NED by surgery (n = 10) was 26 months (range 1–54+). Median OS for the entire group was 12.5 months (range 2–57+). The ICE regimen is active in locally advanced NSCLC with acceptable toxicity and warrants further exploration as induction chemotherapy in larger series. © 1999 Cancer Research Campaig