Functions of MICRORNA172 and APETALA2-LIKE genes during floral transition at the shoot apical meristem

The integration of environmental and internal signals controls floral transition at the shoot apical meristem (SAM), which contains one of the stem-cell niches that generate aerial organs. During floral transition, the identity of the SAM changes from a vegetative meristem that initiates leaf primordia at its periphery, to an inflorescence meristem that produces floral primordia. Five MICRORNA172 (MIR172) genes encode microRNA172 (miR172), which is a small RNA molecule that accumulates at the SAM during floral transition and promotes flowering by repressing the expression of the APETALA2-LIKE (AP2-LIKE) genes. MIR172A, MIR172B and MIR172D are expressed at the SAM during floral transition, and their onset of expression is earlier under inductive long days compared to short days. Notably, miR172 is also a positive regulator of inflorescence meristem size, largely by down-regulating the expression of the positive SAM area regulator AP2. Considering the earlier expression of MIR172 genes at the SAM under inductive long days, the genetic relationships between the main components of the photoperiodic pathway and MIR172 and AP2-LIKE genes were characterised. In the second chapter of this dissertation, it is shown that although the regulation of flowering time by MIR172 and AP2-LIKE genes is influenced by inductive photoperiods, these genes also regulate flowering time in a photoperiod-independent manner. In light of the negative role of miR172 and the positive role of APETALA2 (AP2) in the regulation of inflorescence meristem size, the involvement of MIR172 and AP2 genes in the enlargement of the SAM during floral transition was explored. The results in the third chapter of this dissertation show that AP2 is a positive regulator of shoot meristem size during floral transition and is essential for changes in SAM size. A genetic relation between AP2 and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1, which encodes a MADS domain transcription factor, was proposed as a mechanism that couples changes in SAM morphology and floral transition. The involvement of MIR172 genes in the regulation of flowering time was analysed by comparing the transcriptome profile of dissected plant apices from Col-0 vs. mir172 mutants. The constant mRNA levels of TARGET OF EAT 2, an AP2-LIKE gene, are a candidate main alteration that underlies the late-flowering of mir172 mutants. The transcription factor TOE2 was then characterised and a genetic relation between TOE2, AP2 and SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 4 is proposed. This work provides a framework for understanding the positive role of miR172 in the regulation of flowering time by repressing AP2-LIKE genes and constitutes evidence for the involvement of flowering-time regulators in the changes of SAM morphology during floral transition

Prevention of HIV and other sexually transmitted infections by geofencing and contextualized messages with a gamified APP, UBESAFE : Design and creation study

Advances in the development of information and communication technologies have facilitated social and sexual interrelationships, thanks to the websites and apps created to this end. However, these resources can also encourage sexual contacts without appropriate preventive measures in relation to HIV and other sexually transmitted infections (STIs). How can users be helped to benefit from the advantages of these apps while keeping in mind those preventive measures? This study aimed to prevent STIs by helping users to remember preventive measures in the risky situations. We have used the design and creation methodology and have developed a software system. This system has two parts: an Android operating system app with emphasis on ubiquitous computing and gamification as well as a server with a webpage. First, a functional test with 5 men who have sex with men (MSM) allowed us to test the app with end users. In addition, a feasibility test with 4 MSM for a month allowed us to try the UBESAFE system with all its functionalities. The main output is a system called UBESAFE that is addressed to MSM. The system has two main parts: (1) an app that sends preventive contextualized messages to users when they use a contact app or when they are near a point where sexual contacts are likely and (2) a server part that was managed by the public health agency of Barcelona (ASPB), which preserves the quality and pertinence of messages and places and offers instant help to users. To increase users' adherence, UBESAFE uses a gamified system to engage users in the creation of preventive messages. Users increased the initial pool of messages by more than 100% (34/30) and created more than 56% (9/16) of places (named hot zones). The system helped MSM who used it to become conscious about HIV and other STIs. The system also helped the ASPB to stay in contact with MSM and to detect behaviors that could benefit from preventive measures. All functions were performed in a nonintrusive manner because users used the app privately. Furthermore, the system has shown how important it is to make users a part of the creation process as well as to develop apps that work by themselves and thus become useful to the users

Presence of the transmembrane protein neuropilin in cytokine-induced killer cells

Background/Aim: Cytokine-induced killer (CIK) cells are a heterogenous population of immune cells showing promising applications in immunotherapeutic cancer treatment. Neuropilin (NRP) proteins have been proven to play an important role in cancer development and prognosis. In this study, CIK cells were tested for expression of NRPs, transmembrane proteins playing a role in the proliferation and survival of cancer cells. Materials and Methods: CIK cells were analyzed at different time points via flow cytometry and quantitative real-time polymerase chain reaction for neuropilin expression. Results: Phenotyping results showed CIK cells having developed properly, and low levels of NRP2 were detected. On the other hand, no NRP1 expression was found. Two cancer cell lines were tested by flow cytometry: A549 cells expressed NRP1 and NRP2; U251-MG cells expressed high amounts of NRP2. CIK cell showed low levels of NRP2 expression on day 14. Conclusion: The presence of NRP2, but not NRP1, was shown for CIK cells. Recognizing NRP2 in CIK cells might help to improve CIK cell cytotoxicity

Epidemiology of imported malaria among children and young adults in Barcelona (1990-2008)

<p>Abstract</p> <p>Background</p> <p>Increasing international travel and migration is producing changes in trends in infectious diseases, especially in children from many European cities. The objective of this study was to describe the epidemiology and determine the trends of imported malaria in patients under 20 years old in the city of Barcelona, Spain, during an 18-year period.</p> <p>Methods</p> <p>The study included malaria cases that were laboratory confirmed and reported to the malaria register at the Public Health Agency of Barcelona from 1990 to 2008, residing in Barcelona and less than 20 years old. Patients were classified as natives (born in Spain) or immigrants. Differences in the distribution of demographic, clinical characteristics, and incidence per 100,000 person-year evolution were analysed. Natives and immigrants were compared by logistic regression by calculating the <it>odds ratio </it>(OR) with a 95% confidence interval (CI) and Chi-square for a linear trend (p < 0.05).</p> <p>Results</p> <p>Of the total 174 cases, 143 (82.1%) were immigrants, 100 (57.5%) were female, 121 (69.5%) <it>Plasmodium falciparum</it>, and 108 (62.1%) were visiting friends and relatives (VFR) as the reason for travel. Among the immigrants, 99 (67.8%) were from Equatorial Guinea. Immigrant cases more frequently travelled to Africa than natives (p = 0.02). The factors associated with imported malaria among immigrant residents was travelling for VFR (OR: 6.2 CI 1.9-20.2) and age 15-19 (OR: 3.7 CI 1-13.3). The incidence increased from 1990 to 1999 (p < 0.001) and decreased from 2000 to 2008 (p = 0.01), although the global linear trend was not statistically significant (p = 0.41). The fatality rate was 0.5%.</p> <p>Conclusions</p> <p>The majority of cases of malaria in population less than 20 years in Barcelona were immigrants, travelling to Africa for VFR and <it>Plasmodium falciparum </it>was most frequently detected. The trend analysis of the entire study period did not show a statistically significant decline. It is recommended to be aware of malaria, especially among children of immigrants who travel to their parent's home country for VFR. Better access to pre travel advice should be provided.</p

Successful clinical outcomes following decentralization of tertiary paediatric HIV care to a community-based paediatric antiretroviral treatment network, Chiangrai, Thailand, 2002 to 2008

Introduction: Most paediatric antiretroviral treatments (ARTs) in Thailand are limited to tertiary care hospitals. To decentralize paediatric HIV treatment and care, Chiangrai Prachanukroh Hospital (CRH) strengthened a provincial paediatric HIV care network by training community hospital (CH) care teams to receive referrals of children for community follow-up. In this study, we assessed factors associated with death and clinical outcomes of HIV-infected children who received care at CRH and CHs after implementation of a community-based paediatric HIV care network. Methods: Clinical records were abstracted for all children who initiated ART at CRH. Paired Wilcoxon signed rank tests were used to assess CD4% and virological change among all children. Cox proportional hazard models were used to assess factors associated with death. Treatment outcomes (CD4%, viral load (VL) and weight-for-age Z-score (WAZ)) were compared between CRH and CH children who met the criteria for analysis. Results: Between February 2002 and April 2008, 423 HIV-infected children initiated ART and 410 included in the cohort analysis. Median follow-up for the cohort was 28 months (interquartile range (IQR)=12 to 42); 169 (41%) children were referred for follow-up at CH. As of 31 March 2008, 42 (10%) children had died. Baseline WAZ (&#60;&#x2212;2 (p=0.001)) and baseline CD4% (&#60;5% (p=0.015)) were independently associated with death. At 48 months, 86% of ART-na&#x00EF;ve children in follow-up had VL&#60;400 copies/ml. For sub-group analysis, 133 children at CRH and 154 at CHs were included for comparison. Median baseline WAZ was lower in CH children than in CRH children (p=0.001); in both groups, WAZ, CD4% and VL improved after ART with no difference in rate of WAZ and CD4% gain (p=0.421 and 0.207, respectively). Conclusions: Children at CHs had more severe immunological suppression and low WAZ at baseline. Community- and tertiary care-based paediatric ART follow-ups result in equally beneficial outcomes with the strengthening of a provincial referral network between tertiary and community care. Nutrition interventions may benefit children in community-based HIV treatment and care

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias

<p>Abstract</p> <p>Background</p> <p>Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias.</p> <p>Methods</p> <p>A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and pre-hospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables.</p> <p>Results</p> <p>Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93).</p> <p>Conclusion</p> <p>Pre-hospital oral antibiotherapy appears to reduce IMD mortality.</p

Generation of an induced pluripotent stem cell line (ESi107-A) from a transthyretin amyloid cardiomyopathy (ATTR-CM) patient carrying a p.Ser43Asn mutation in the TTR gene

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a life-threatening disease caused by the abnormal production of misfolded TTR protein by liver cells, which is then released systemically. Its amyloid deposition in the heart is linked to cardiac toxicity and progression toward heart failure. A human induced pluripotent stem cell (iPSC) line was generated from peripheral blood mononuclear cells (PBMCs) from a patient suffering familial transthyretin amyloid cardiomyopathy carrying a c.128G>A (p.Ser43Asn) mutation in the TTR gene. This iPSC line offers a useful resource to study the disease pathophysiology and a cell-based model for therapeutic discovery

Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers.

HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL &gt;2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs