Monoclonal Antibodies for Asthma Management

Asthma is a multifactorial and complex disease, with different degrees of risks and severity, as well as the response to treatment. Medications currently available are most effective in severe asthma; nonetheless, there is a percentage of patients that have no response to the treatment that guidelines suggest in their recommendations. In the last years, there have been new insights in inflammatory molecules that contribute to asthma physiopathology and a lot of them have been considered to be possible targets in the management of severe asthma. As a consequence of this, a few monoclonal antibodies have been developed evidencing their effectiveness in the treatment of the disease. The study of these new therapies has allowed the identification of specific inflammatory pathways. This chapter intends to offer a critical perspective of the current guidelines for the management of severe asthma, as well as to discuss current treatments and the future on new molecules. Through an adequate characterization, different phenotypes will be recognized and associated with a determinate biomarker and should be used to select the treatment that can offer the highest efficiency in these patients. In this way, the treatment will be directed to a personalized medicine

Active management in mutual funds with concentrated benchmarks: A major dilemma to fulfill the EU directive on portfolio concentration limits.

his doctoral thesis is focused on the increasing importance of mutual funds as saving vehicles for the finances of individuals in the economies of developed countries over the last half of the twentieth century. Among them, the equity funds that take the form of open-end funds like mutual funds are becoming one of the most relevant instruments. Mutual funds collect money from investors and invest it in stocks, bonds, other funds, and so on, and their performance depends on the mix of the allocated securities. Its main objectives were to contribute to the topic of the Active Share (AS) as applied to mutual funds in Eurozone countries. This investigation was mainly motivated by the need to analyse how both the level of concentration of the benchmarks and the level of concentration of the mutual fund industries in the Eurozone affect active management. Due to the scarce number of studies focused on this topic in Europe our results have relevant implications to investors, market supervisors, and policymakers. In Chapter 1, we analysed how article 52 in Directive 2009/65/EC (UCITS IV) on risk of portfolio diversification could distort the accuracy of AS due to the higher level of concentration in Eurozone domestic benchmarks. In this chapter, we were able to identify truly active management in Eurozone mutual funds. Thus, we developed an algorithm to capture the spurious AS (sAS), which is defined as the minimum AS, that is not a consequence of active decisions made by equity fund managers. The results provide evidence that the Directive negatively influences the accuracy of the AS shown for managers who work with very concentrated domestic Eurozone benchmarks such as the PSI 20 (Portugal), ATX 20 (Austria), and IBEX 35 (Spain). In contrast, the evidence from the sAS for the least concentrated domestic Eurozone benchmarks shows that AS reported by managers who work in France, Germany, and Finland are much more accurate. Hence, these results prove that direct AS comparisons in the Eurozone are not feasible and lead us to obtain three AS thresholds per domestic equity benchmark, which are the minimum values of AS needed to confirm that domestic equity funds are significantly active at 90%, 95%, and 99% confidence levels.We also analysed the level of active management in the domestic equity funds registered in each Eurozone country. Our findings also show that the high concentration level and the heterogeneity present in the domestic equity funds in the Eurozone prevent the direct comparability of the AS. Therefore, we had to consider the level of AS over the spurious level and the characteristics of each market that produces significant and different styles of active management. For that, we formulated an actual active share (aAS) that considered the level of concentration in the domestic equity funds of the Eurozone markets and the limits of the portfolio concentration on European regulation. We define aAS as the difference between the monthly AS obtained for each domestic equity fund minus its monthly AS threshold obtained previously at 90%, 95%, and 99% confidence levels. Focusing on the most relevant mutual fund industries in the Eurozone countries, we find that France is the most active domestic equity fund market. Spanish and Italian markets also show high levels of actual active management despite the large concentration in their domestic benchmarks. Conversely, domestic equity funds registered in Germany show lower levels of active management. Our research results support the hypothesis that aAS corrects the potential bias in the original AS caused by both the domestic benchmark concentration and the EU portfolio diversification rules.In summary, our study is the first to evaluate the consequences of both the assorted characteristics of domestic Eurozone benchmarks and the European regulation that prevents portfolio concentration (UCITS IV) in the appropriate estimation of AS. Furthermore, our study identifies truly active management in domestic equity funds in the Eurozone markets. This chapter has important implications for policymakers and practitioners of the domestic equity funds in the Eurozone. In the strongly regulated European markets, our unbiased approach allows both investors and market supervisors to identify the accurate levels of active management of each industry after considering both the regulation of portfolio diversification and the concentrated domestic equity benchmarks. Market supervisors will have a better picture of the active management map to develop appropriate regulations for the mutual fund industry. In addition, our approach should help practitioners and investors to effectively find out the level of active management of domestic equity funds and therefore provide information for fund management companies to replace actual performing managers. Further, our results should help to reduce the opacity in the management fees that funds charge by providing accurate measures of active management. In Chapter 2, we analysed how some market and fund characteristics play a crucial role in explaining the portfolio concentration default on Directive 2009/65/EC (UCITS IV). This chapter should help market supervisors to improve the monitoring process of defaults by domestic equity funds in the Eurozone mutual fund industries. On the one hand, the origin of UCITS directives was considered the beginning towards market protection and increased transparency in the Eurozone. On the other hand, the structure of mutual funds allows retail investors to access sophisticated active strategies that comply with liquidity and transparency restrictions protected by regulatory oversight. Their rules are based on a certain degree of portfolio diversification with the goal of reducing their vulnerability to portfolio risks. This chapter is the first to analyse how concentrated strategies could lead to non-compliance with article 52 in UCITS IV. First, we analysed several market characteristics that may influence the probability of a fund manager failing to meet the portfolio concentration limits. Using a logic panel data model (fixed effects), we estimated the probability of incurring defaults. Our findings provide evidence that should lead market supervisors to pay attention to concentrated fund industries with concentrated domestic benchmarks to prevent defaults on Eurozone concentration limit. The level of concentration of the domestic equity benchmarks would make the defaults almost twice as likely to occur. The level of concentration of the domestic fund industry also has positive and significant effects on the likelihood of incurring defaults. That is, defaults are approximately 12% to 17% more likely to occur when the level of concentration in the domestic fund industry increases. This evidence is consistent with the findings in the literature that link competition with active management strategies such as concentrated portfolios (see Dyck et al., 2013). Second, in the same line of Chapter 1, we analysed several funds characteristics that may influence the probability of a fund manager failing to meet the portfolio concentration limits. In Eurozone markets, market supervisors should especially monitor the most experienced funds that are solo-managed to prevent portfolio weights over the 10% limit. This finding is in accordance with Goldman et al., (2016) who shows that individual managers have much more concentrated portfolios than management teams. The fund’s age has a positive and significant influence on the likelihood of defaults. That is, the probability of incurring defaults is approximately 18% to 26% higher among older funds. Thus, this evidence is in accordance with the literature that links older funds with higher levels of idiosyncratic risk as a consequence of having more concentrated portfolios (see Amihud and Goyenko, 2013). Further, we analysed the characteristics of those stocks that were especially subject to more concentrated strategies and, therefore, more vulnerable to mutual funds’ investment policies. For that, we applied a multinomial logic panel data model (fixed effects) and found that the weight of the stocks in their benchmarks had a positive and significant effect on default on the EU portfolio concentration limit. The results show how the probability of a stock being subject to default is approximately 8% to 25% higher when the stock weight in the domestic benchmark increases. Thus, market supervisors should monitor stocks with large weights in domestic equity benchmarks.In addition, we also find how the stocks of domestic benchmarks that have been held longer are likely to be subject to concentration defaults. That is, defaults are approximately 13% to 24% more likely to occur when choosing stocks that belong to the benchmarks during the last 24 months. Thus, this result is consistent with the literature that argues the local advantage of reducing information asymmetry problems.Thus, we find how stocks that present low volatility have a greater likelihood of being subject to non-compliance with EU portfolio concentration limits. In terms of percentages, the probability approximately lowers between 19% to 27% when stock volatility increases. This finding is in accordance with the commitment to controlled risk strategies (see Huang et al., 2011). Therefore, market supervisors should pay more attention to these stock characteristics to monitor stocks that are more frequently overweighted above EU concentration limits. In summary, this chapter is the first to both analyse and identify the determinants of domestic equity funds’ failure to comply with the portfolio concentration limits of EU Directive 2009/65/EC. Furthermore, our study also determines the characteristics of the stocks subject to these non-compliant portfolios in domestic equity funds in the Eurozone. This chapter has important implications for market supervisors and policymakers in the mutual fund industries of the Eurozone. Our approach allows market supervisors with limited resources to identify and control non-compliant domestic equity funds by monitoring only some fund-specific characteristics. The improvement of this monitoring process should contribute to the financial stability of the EU asset management industry in terms of investor protection and market transparency. That is, mutual fund unitholders should be completely certain that their money is allocated to portfolios fulfilling the concentration limits required by the EU. Our findings also show a tool to assist EU market supervisors in identifying some explanatory mechanisms for stock weights that are over the EU concentration limits. Thus, our results may help supervisors identify what kind of domestic equity funds are more inclined to default and what kind of stocks are likely overweighted by these funds. Market supervisors could especially monitor these stocks to verify that domestic equity funds are meeting the concentration limits. Market supervisors should focus their limited resources on these types of stocks held by domestic equity funds to prevent defaults in portfolio concentration. Finally, our approach could also help retail investors control their risk profiles in terms of exceeding portfolio concentration limits. This application is in line with the reinforcement of investor protection of portfolio concentration. Investors could be sure that domestic equity funds fully follow the diversification requirements and market transparency provided by the UCITS directives.Chapter 3 presents a new perspective in the analysis of active management. We introduced dynamism by proposing a new version of AS that considers how the managers deviate their portfolios in two consecutive periods. We define dynamic Active Share (dAS) as a measure to capture over time the actual level of activity by comparing the differences against the benchmark in two consecutive periods. Our measure captures not only the long and short static positions in each stock included in the benchmark but also the previous long (short) positions that have been overweighted (underweighted) in the next period. Thus, dAS allows us to divide between investment decisions driven to spread portfolio weights closer to the benchmark (i.e., decisions that lead to a lower differentiation to the benchmark) and the other which is further from the benchmark (i.e., decisions that lead to a higher differentiation). Focusing on the most relevant fund industries in the Eurozone, we analysed the predictive power of AS first. The best results were found in the Spanish industry and, with less robustness, in Germany, the Netherlands, Austria, and Belgium. France only shows this relationship in the long term when we consider the CAPM alpha; while Italy, Finland, Portugal, and Greece fail to offer significant results or even present negative relationships. These results indicate that the prediction ability of AS presents assorted results as this relation is less clear than that presented in the literature (Cremers and Petajisto, 2009) Second, we examined the influence on the prediction power for performance of AS by splitting stocks in the portfolios of our sample into benchmark and non-benchmark . The results allow us to identify how the high proportion of prediction ability for performance of AS is explained by the investment in non-benchmark stocks. Although the AS’s share of overweight or underweight benchmark stocks is really related to stock picking ability, investing in overweighted stocks may mean distortions in their performance evaluations that can lead to spurious contributions to portfolio performance.Third, we applied and analysed the predictive power of dAS. The results provided evidence that the performance of non-benchmark stocks in high AS funds did not extend to mutual funds with high dAS. Thus, this measure is less sensitive to the weight of the portfolio that is invested in non-benchmark securities that is very relevant in Eurozone countries where domestic benchmarks are highly concentrated. The main advantage of the dAS compared to the AS is that our measure provides more information and can be split according to different investment decisions. For that reason, we proposed splitting up the dAS to examine which trading decisions add value to the portfolio. Our most interesting results showed that German funds presents a robust relationship between selling investment decisions and subsequently better performance. This relationship was also found for Dutch, Austrian, and Portuguese funds but with actual limited significance. This finding is in accordance with the level of activity showed by these industries in Chapter 1.Further, we analysed the contributions to dAS that was generated by those trading decisions that might be considered as managers’ bets. These bets could be those decisions that increased holdings that were already overweighted (buy bets) or decrease those holdings that were already underweighted (sell bets). Our findings show as in Germany and in some cases in the Austrian and Portuguese industries that there is subsequent significantly better performance in buying decisions. Focusing on selling decisions, only Finnish funds show positive and strong beliefs and performance. The results for predicting performance show that those portfolios with a higher concentration of these bets offer subsequent abnormal returns as this prediction ability is even higher than the seminal AS in some of the markets in this study.Accordingly, the results shown in this chapter are an interesting addition to Cohen et al. (2010) who try to identify the trades in which the managers have more confidence. The empirical findings show that those mutual funds with trading decisions with a stronger belief from the manager (i.e., decisions that lead them to deviate even more from the benchmark) outperform the remaining funds, especially when buying decisions are considered. This evidence is consistent with Karoui and Patel (2020) who show that the benefit of AS lies in the selection decision rather than the weighting decision.In summary, Chapter 3 is the first to introduce a dynamic perspective on AS to capture managers’ activity and skill. This chapter is relevant for investors who should be interested in knowing whether their fund manager is active and whether their decisions on new investment opportunities add value to the portfolio (i.e., undervalued assets) or on the contrary, the fund manager is passive. The common argument is related to the fees because the management fees charged by these two types of funds should be different. In addition, the chapter is also relevant to regulators in order to adjust the management fees charged by management companies to the actual level of activity carried out by mutual funds. Several fields for further investigation have been identified in this dissertation. Regarding the EU Directive, an extensive test of the level of enforcement that the UCITS IV has implemented in each Eurozone country (including emerging markets) could be useful for making decisions about possible changes in the regulation. Furthermore, a complementary analysis of chapter VII in UCITS IV in terms of its appropriateness with the characteristics of each Eurozone country could allow a more complete assessment of the limits of portfolio concentration and the implementation of the protection to investors. In addition, this dissertation makes an important advance in the topic of active management to help further an analysis in other areas or regions with similar characteristics that could be relevant to the financial literature. <br /

Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure - demographics, etiologic and pulmonary histologic analysis

OBJECTIVES: Acute respiratory failure is present in 5&#37; of patients with acute myocardial infarction and is responsible for 20&#37; to 30&#37; of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life. METHODS: This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63&#37;) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression. RESULTS: In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9&#37; of patients. Bacterial bronchopneumonia was present in 11.9&#37; of patients, systemic arterial hypertension in 10.1&#37; and dilated cardiomyopathy in 6.9&#37;. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5&#37; were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported

Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is an important aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Pathway analyses identified several deregulated functions including cell proliferation, migration, DNA damage, regulation of stem cell differentiation and reversion of the epithelial-mesenchymal transition (EMT) phenotype, among others. Combination studies showed a synergistic interaction of EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124 had a good pharmacokinetic profile. In conclusion these experiments demonstrate the antitumor activity of EC-70124 in TNBC paving the way for the future clinical development of this drug alone or in combination with chemotherapy.Ministry of Economy and Competitiveness of Spain (BFU2012-39151 and RD12/0036/0003 to AP), and the AECC (to AP). Instituto de Salud Carlos III (PI13/01444) ACEPAIN and CRIS Cancer Foundation (to AO). JCM is a recipient of a Miguel Servet fellowship program (CP12/03073).Peer Reviewe

Gaidropsarus gallaeciae (Gadiformes: Gaidropsaridae), a New Northeast Atlantic Rockling Fish, with Commentary on the Taxonomy of the Genus

A new species of rockling fish genus Gaidropsarus is described based on six specimens collected in Galicia and Porcupine Banks, in Atlantic European waters. An analysis of morphological characters has confirmed the specific status of specimens of a previously described clade by comparison of DNA sequences. Gaidropsarus gallaeciae sp. nov. it is distinguished from congeners by the following combination of characters: 43–44 vertebrae; 54–60 third dorsal fin rays; 44–52 anal fin rays; 21–23 pectoral fin rays; head length 21.1–25.2% of standard length (SL); length of the pelvic fin 16.2–19% SL; length of the first dorsal fin ray 15.8–27% of head length (%HL); eye diameter 15.8–20.5% HL; and interorbital space 21.7–28% HL. Using the nucleotide sequence of the 5’ end of the mitochondrial COI gene as a molecular marker, the genetic p-distance between the new species and its congeners far exceeds the usual 2%, granting the former the status of an independent taxon, which is in accordance with the morphological identification. A comparison with the other 12 valid species of the genus is presented. The study also highlights the morphological diversity resulting from the meristic and biometric variability of Gaidropsarus species and lays the groundwork for future taxonomic studies on this genus.Versión del editor5,82

Mobile phone text messaging to improve medication adherence in secondary prevention of cardiovascular disease.

BACKGROUND: Worldwide at least 100 million people are thought to have prevalent cardiovascular disease (CVD). This population has a five times greater chance of suffering a recurrent cardiovascular event than people without known CVD. Secondary CVD prevention is defined as action aimed to reduce the probability of recurrence of such events. Drug interventions have been shown to be cost-effective in reducing this risk and are recommended in international guidelines. However, adherence to recommended treatments remains sub-optimal. In order to influence non-adherence, there is a need to develop scalable and cost-effective behaviour-change interventions. OBJECTIVES: To assess the effects of mobile phone text messaging in patients with established arterial occlusive events on adherence to treatment, fatal and non-fatal cardiovascular events, and adverse effects. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Conference Proceedings Citation Index - Science on Web of Science on 7 November 2016, and two clinical trial registers on 12 November 2016. We contacted authors of included studies for missing information and searched reference lists of relevant papers. We applied no language or date restrictions. SELECTION CRITERIA: We included randomised trials with at least 50% of the participants with established arterial occlusive events. We included trials investigating interventions using short message service (SMS) or multimedia messaging service (MMS) with the aim to improve adherence to medication for the secondary prevention of cardiovascular events. Eligible comparators were no intervention or other modes of communication. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. In addition, we attempted to contact all authors on how the SMS were developed. MAIN RESULTS: We included seven trials (reported in 13 reports) with 1310 participants randomised. Follow-up ranged from one month to 12 months. Due to heterogeneity in the methods, population and outcome measures, we were unable to conduct meta-analysis on these studies. All seven studies reported on adherence, but using different methods and scales. Six out of seven trials showed a beneficial effect of mobile phone text messaging for medication adherence. Dale 2015a, reported significantly greater medication adherence score in the intervention group (Mean Difference (MD) 0.58, 95% confidence interval (CI) 0.19 to 0.97; 123 participants randomised) at six months. Khonsari 2015 reported less adherence in the control group (Relative Risk (RR) 4.09, 95% CI 1.82 to 9.18; 62 participants randomised) at eight weeks. Pandey 2014 (34 participants randomised) assessed medication adherence through self-reported logs with 90% adherence in the intervention group compared to 70% in the control group at 12 months. Park 2014a (90 participants randomised) reported a greater increase of the medication adherence score in the control group, but also measured adherence with an event monitoring system for a number of medications with adherence levels ranging from 84.1% adherence to 86.2% in the intervention group and 79.7% to 85.7% in the control group at 30 days. Quilici 2013, reported reduced odds of non-adherence in the intervention group (Odds Ratio (OR) 0.43, 95% CI 0.22 to 0.86, 521 participants randomised) at 30 days. Fang 2016, reported that participants given SMS alone had reduced odds of being non-adherent compared to telephone reminders (OR 0.40 95% CI 0.18 to 0.63; 280 patients randomised). Kamal 2015 reported higher levels of adherence in the intervention arm (adjusted MD 0.54, 95% CI 0.22 to 0.85; 200 participants randomised). Khonsari 2015 was the only study to report fatal cardiovascular events and only reported two events, both in the control arm. No study reported on the other primary outcomes. No study reported repetitive thumb injury or road traffic crashes or other adverse events that were related to the intervention.Four authors replied to our questionnaire on SMS development. No study reported examining causes of non-adherence or provided SMS tailored to individual patient characteristics.The included studies were small, heterogeneous and included participants recruited directly after acute events. All studies were assessed as having high risk of bias across at least one domain. Most of the studies came from high-income countries, with two studies conducted in an upper middle-income country (China, Malaysia), and one study from a lower middle-income country (Pakistan). The quality of the evidence was found to be very low. There was no obvious conflicts of interest from authors, although only two declared their funding. AUTHORS' CONCLUSIONS: While the results of this systematic review are promising, there is insufficient evidence to draw conclusions on the effectiveness of text message-based interventions for adherence to medications for secondary prevention of CVD. Sufficiently powered, high-quality randomised trials are needed, particularly in low- and middle-income countries

The South Bank Exhibition, Londres 1951: un análisis desde The Architectural Review

La exposición Festival of Britain de Londres de 1951 ocupa un destacado lugar en la historia de la arquitectura inglesa de la postguerra por ser el punto de arranque de la recuperación urbana del South Bank de Londres. Tuvo un gran apoyo y protagonismo en The Architectural Review, que publicó varios artículos y un número monográfico con el fin de mostrar como el master plan de la exposición se ajustaba a los ideales del Visual Planning y del Townscape que la revista venía difundiendo desde hacía unos años. Pero también fue criticada por un grupo de jóvenes arquitectos liderados por Reyner Banham que como reacción propondrían una arquitectura alternativa que fue denominada como el New Brutalism.The Festival of Britain exhibition held in London in 1951 occupies a noteworthy place in the history of British architecture of the post-war period. This is because it constituted the starting point for the urban renewal of London’s South Bank. It was given strong support and great prominence by The Architectural Review, which published several articles and a monographic issue about it, in order to show how the master plan for the exhibition matched the ideals of Visual Planning and Townscape that the journal had been putting forward for some years previously. However, it was also the subject of criticism from a group of young architects, headed by Reyner Banham, who reacted to it by advocating an alternative style of architecture that was termed New Brutalism

Descriptive Analysis of LAP1 Distribution and That of Associated Proteins throughout Spermatogenesis

Spermatogenesis comprises highly complex differentiation processes. Nuclear envelope (NE) proteins have been associated with these processes, including lamins, lamina-associated polypeptide (LAP) 2 and the lamin B-receptor. LAP1 is an important NE protein whose function has not been fully elucidated, but several binding partners allow predicting putative LAP1 functions. To date, LAP1 had not been associated with spermatogenesis. In this study, LAP1 expression and cellular/subcellular localization during spermatogenesis in human and mouse testes is established for the first time. The fact that LAP1 is expressed during nuclear elongation in spermiogenesis and is located at the spermatids' centriolar pole is singularly important. LAP1 binds to members of the protein phosphatase 1 (PP1) family. Similar localization of LAP1 and PP12, a testis-specific PP1 isoform, suggests a shared function for both proteins during spermiogenesis. Furthermore, this study suggests an involvement of LAP1 in manchette development and chromatin regulation possibly via interaction with acetylated-tubulin and lamins, respectively. Taken together, the present results indicate that, by moving to the posterior pole in spermatids, LAP1 can contribute to the achievement of non-random, sperm-specific chromatin distribution, as well as modulate cellular remodeling during spermiogenesis. In addition, LAP1 seems to be associated with dynamic microtubule changes related to manchette formation and flagella development.Institute for Biomedicine (Project UID/BIM/04501/2013), the Fundação para a Ciência e Tecnologia of the Ministério da Educação e Ciência (Project PTDC/BEX-BCM/0493/2012), the COMPETE program (Programa Operacional Factores de Competitividade), the QREN (Quadro de Referência Estratégica Nacional) and the European Union (Fundo Europeu de Desenvolvimento Regional). Filipa Martins was the recipient of an FCT fellowship. The authors would also like to thank William Dauer (Columbia University, USA) for providing the anti-LAP1 antibodyinfo:eu-repo/semantics/publishedVersio

Genetic Diversity and Population Structure of Capirona (Calycophyllum spruceanum Benth.) from the Peruvian Amazon Revealed by RAPD Markers

Capirona (Calycophyllum spruceanum Benth.) is a tree species of commercial importance widely distributed in South American forests that is traditionally used for its medicinal properties and wood quality. Studies on this tree species have been focused mainly on wood properties, propagation, and growth. However, genetic studies on capirona have been very limited to date. Currently, it is possible to explore genetic diversity and population structure in a fast and reliable manner by using molecular markers. We here used 10 random amplified polymorphic DNA (RAPD) markers to analyze the genetic diversity and population structure of 59 samples of capirona that were sampled from four provinces located in the eastern region of the Peruvian amazon. A total of 186 bands were manually scored, generating a 59 × 186 presence/absence matrix. A dendrogram was generated using the UPGMA clustering algorithm, and, similar to the principal coordinate analysis (PCoA), it showed four groups that correspond to the geographic origin of the capirona samples (LBS, Irazola, Masisea, Iñapari). Similarly, a discriminant analysis of principal components (DAPC) and STRUCTURE analysis confirmed that capirona is grouped into four clusters. However, we also noticed that a few samples were intermingled. Genetic diversity estimation was conducted considering the four groups (populations) identified by STRUCTURE software. AMOVA revealed the greatest variation within populations (71.56%) and indicated that variability among populations is 28.44%. Population divergence (Fst) between clusters 1 and 4 revealed the highest genetic difference (0.269), and the lowest Fst was observed between clusters 3 and 4 (0.123). RAPD markers were successful and effective. However, more studies are needed, employing other molecular tools. To the best of our knowledge, this is the first investigation employing molecular markers in capirona in Peru considering its natural distribution, and as such it is hoped that this helps to pave the way towards its genetic improvement and the urgent sustainable management of forests in Peru

The use of sociocultural animation techniques at the University improve interpersonal relationships between teachers and students

La relación existente entre el profesor y los alumnos puede depender de muchas circunstancias. De entre ellas, este estudio se centra en confirmar que el uso de técnicas de animación sociocultural en el aula hace que se vean mejoradas las relaciones interpersonales entre estos agentes educativos. El procedimiento metodológico seguido se centra en un enfoque interpretativo-descriptivo mediante el uso de unos cuestionarios como técnicas de recogida de datos. Los resultados encontrados confirman nuestra hipótesis inicial y a la vez nos abren las puertas hacia futuras líneas de investigación.Relationships between teachers and students can depend on many circumstances. Specifically, this study focuses on confirming that the use of sociocultural animation techniques in the classroom can improve interpersonal relationships between them. The methodological approach adopted was interpretive-descriptive using questionnaires as a data collection technique. The results confirm our initial hypothesis and also open the doors to future research.Departamento de Psicología Socia