Regulation of the floral transition and inflorescence development by the bZIP transcription factor FD in Arabidopsis thaliana

The integration of signals in response to endogenous and exogenous stimuli at the shoot apical meristem (SAM) determines the timing of the transition from vegetative to reproductive development in Arabidopsis. Under inductive long-day (LD) photoperiods, FLOWERING LOCUS T (FT) and the bZIP transcription factor FD form the large transcriptional complex FD–(14-3-3)–FT/TSF at the SAM. Within this complex, FD is the DNA-binding component and some target genes of FD have been well characterized. The fd mutant is late flowering under LD conditions due to the improper regulation of its targets. Despite increased knowledge on the regulatory pathways that act through the FD–(14-3-3)–FT/TSF complex, the cis-regulatory elements that are required for the binding of FD to its targets remain poorly defined, and it is unclear how different targets show distinct spatiotemporal expression patterns. For example, although FD enhances FRUITFULL (FUL) transcription within the SAM, APETALA1 (AP1) transcription is promoted by FD later in development and AP1 transcripts are specific to floral primordia. Furthermore, the subset of direct targets that are involved in the floral transition before the upregulation of FUL and AP1 remain uncharacterized. During this PhD, I generated a transgenic fd mutant line in which the translocation of FD into the nucleus can be induced at different developmental time points. Induction of FD in this line promoted flowering, and showed that FD activity was required for several days to complete floral transition. I performed RNA-seq on apices of these plants following FD induction and identified putative additional components of the FD transcriptional network. The earliest targets of FD from this whole-transcriptome analysis could not be linked to floral transition, although FUL and AP1 were upregulated at later stages, confirming that floral transition occurred following FD induction. Much evidence exists to support that FUL is regulated by FD and I identified two putative conserved binding sites in the proximal promoter of FUL. However, mutation of these cis-elements did not affect flowering time nor the accumulation or pattern of FUL protein at the SAM. Under non-inductive short-day (SD) conditions, the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 15 (SPL15) protein also binds to FUL and regulates its expression. Although FD and SPL15 regulate FUL through the LD and SD pathways, respectively, I hypothesise that they do not compete at the promoter level and that activation of FUL by FD can occur indirectly through FD-mediated activation of other transcription factors or that FD binds to redundant sites at the FUL locus under LDs. Abscisic acid (ABA) regulates stress responses such as the drought-escape response, and aspects of plant development, including axillary meristem growth and meristem arrest. The FD protein is phylogenetically closely related to bZIP transcription factors involved in ABA signalling; however, evidence for the involvement of FD in ABA signalling is weak. I disrupted ABA signalling specifically within the FD expression domain, which resulted in defects in plant shoot architecture under LDs. In legumes, FD paralogues mediate the floral transition but also determine inflorescence architecture. I identified HOMEOBOX PROTEIN 21 (HB-21), which is involved in ABA signalling, to be a direct downstream target of FD. The level of HB-21 mRNA was lower in fd than in wild-type inflorescences. The hb21 and fd mutants produced taller shoots with more siliques on the main shoot compared with wild type; thus, the regulation of HB-21 by FD links FD with inflorescence development in Arabidopsis potentially through ABA signalling. This PhD focuses on the bZIP transcription factor FD and how it regulates flowering time and inflorescence development in Arabidopsis. Collectively, the results show that FD functions throughout the Arabidopsis life cycle, and provide insight into the temporal FD-mediated transcriptional network at the SAM

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis : a phase I first-in-human study

Background: Nanoparticles hold considerable promise for aerosol-based intraperitoneal delivery in patients with carcinomatosis. Recently, results from preclinical and early clinical trials suggested that albumin-bound paclitaxel (ABP, Abraxane (TM)) may result in superior efficacy in the treatment of peritoneal metastases (PM) compared to the standard solvent-based paclitaxel formulation (Taxol (TM)). Here, we propose a phase I study of pressurized intraperitoneal aerosol chemotherapy (PIPAC) using ABP in patients with upper Gastrointestinal, breast, or ovarian cancer. Methods: Eligible patients with advanced, biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin will undergo three PIPAC treatments using ABP with a 4-week interval. The dose of ABP will be escalated from 35 to 140 mg/m(2) using a Bayesian approach until the maximally tolerated dose is determined. The primary end point is dose-limiting toxicity. Secondary analyses include surgical morbidity, non-access rate, pharmacokinetic and pharmacodynamic analyses, quality of life, and exploratory circulating biomarker analyses. Discussion: ABP holds considerable promise for intraperitoneal aerosol delivery. The aim of this study is to determine the dose level for future randomized phase II trials using ABP in PIPAC therapy

Intraperitoneal aerosolization of albumin-stabilized paclitaxel nanoparticles (Abraxane™) for peritoneal carcinomatosis : a phase I first-in-human study

Background: Nanoparticles hold considerable promise for aerosol-based intraperitoneal delivery in patients with carcinomatosis. Recently, results from preclinical and early clinical trials suggested that albumin-bound paclitaxel (ABP, Abraxane (TM)) may result in superior efficacy in the treatment of peritoneal metastases (PM) compared to the standard solvent-based paclitaxel formulation (Taxol (TM)). Here, we propose a phase I study of pressurized intraperitoneal aerosol chemotherapy (PIPAC) using ABP in patients with upper Gastrointestinal, breast, or ovarian cancer. Methods: Eligible patients with advanced, biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin will undergo three PIPAC treatments using ABP with a 4-week interval. The dose of ABP will be escalated from 35 to 140 mg/m(2) using a Bayesian approach until the maximally tolerated dose is determined. The primary end point is dose-limiting toxicity. Secondary analyses include surgical morbidity, non-access rate, pharmacokinetic and pharmacodynamic analyses, quality of life, and exploratory circulating biomarker analyses. Discussion: ABP holds considerable promise for intraperitoneal aerosol delivery. The aim of this study is to determine the dose level for future randomized phase II trials using ABP in PIPAC therapy

Beneficios de la actividad física sobre la enfermedad del Alzheimer

Nowadays, the prevalence of individuals suffering from neurodegenerative disease is steadily increasing due to the rising mean age of the world's population. Alzheimer's disease is the most common form of diagnosed these dementia. As the efficacy of pharmacological treatment is often questioned, it is necessary to resort to other non-pharmacological therapeutic possibilities, such as movement therapies and, in particular, physical activity. The aim of this systematic literature review is to demonstrate the benefits of physical activity on the state of brain structures, functional, cognitive, and mental capacities in patients diagnosed with Alzheimer's disease. To this end, a review of the current state of the art in databases was carried out: CINAHL with Full Text, MEDLINE Complete, APA PsycInfo, Rehabilitation & Sports Medicine Source, SPORTDiscus with Full Text y eBook Collection (EBSCOhost). A total of 14 studies that met the selection criteria were chosen from these databases, analyzed, and discussed. This review shows that there is considerable evidence that physical activity has several benefits on the physical and psychological variables mentioned above for the population affected by Alzheimer's. However, this favorable effect seems to disappear when physical stimulation is interrupted. In summary, it seems that physical exercise is an appropriate therapeutic approach to combat the different degenerations found in these patients and has a great potential for future intervention plans.Hoy en día, la prevalencia de individuos que padecen enfermedad neurodegenerativa está en crecimiento debido al envejecimiento de la población mundial. La enfermedad de Alzheimer es la forma más común de demencia diagnosticada. Como la eficacia del tratamiento farmacológico sigue siendo cuestionada, se hace necesario recurrir a otras posibilidades terapéuticas no farmacológicas, como las terapias de movimiento y, en particular, la actividad física. El objetivo de esta revisión bibliográfica es demostrar los beneficios de la actividad física sobre el estado de las estructuras cerebrales, las capacidades funcionales, cognitivas y mentales en enfermos que han sido diagnosticados del Alzheimer. Con este fin, se realizó una revisión del estado actual de investigación en las bases de datos: CINAHL with Full Text, MEDLINE Complete, APA PsycInfo, Rehabilitation & Sports Medicine Source, SPORTDiscus with Full Text y eBook Collection (EBSCOhost). Se escogieron, analizaron y discutieron un total de 14 estudios que cumplían con los criterios de selección. Esta revisión muestra que hay evidencia considerable para decir que la actividad física puede tener varios beneficios sobre las variables físico-psicológicas previamente expuestas en la población afectada por el Alzheimer. No obstante, la revisión también evidencia que este efecto favorable parece desaparecer cuando el entrenamiento se detiene. Para concluir, el ejercicio físico se muestra como vía terapéutica apropiada para combatir las diferentes degeneraciones que se encuentran en estos pacientes y por lo tanto tiene un gran potencial para integrarle en futuros planes de intervención.Universidad Europea de MadridDoble Grado en Ciencias de la Actividad Física y del Deporte + FisioterapiaPresencia

Capter le théâtre dans le monde d’après – enquête sur les effets de la crise COVID-19 sur les pratiques de captation de spectacle vivant

Mémoire de recherche de M2 Archives Numériques enquêtant sur les effets de la crise COVID-19 concernant les pratiques de captation de spectacle vivant

VAMP7 modulates ciliary biogenesis in kidney cells

Epithelial cells elaborate specialized domains that have distinct protein and lipid compositions, including the apical and basolateral surfaces and primary cilia. Maintaining the identity of these domains is required for proper cell function, and requires the efficient and selective SNARE-mediated fusion of vesicles containing newly synthesized and recycling proteins with the proper target membrane. Multiple pathways exist to deliver newly synthesized proteins to the apical surface of kidney cells, and the post-Golgi SNAREs, or VAMPs, involved in these distinct pathways have not been identified. VAMP7 has been implicated in apical protein delivery in other cell types, and we hypothesized that this SNARE would have differential effects on the trafficking of apical proteins known to take distinct routes to the apical surface in kidney cells. VAMP7 expressed in polarized Madin Darby canine kidney cells colocalized primarily with LAMP2-positive compartments, and siRNA-mediated knockdown modulated lysosome size, consistent with the known function of VAMP7 in lysosomal delivery. Surprisingly, VAMP7 knockdown had no effect on apical delivery of numerous cargoes tested, but did decrease the length and frequency of primary cilia. Additionally, VAMP7 knockdown disrupted cystogenesis in cells grown in a three-dimensional basement membrane matrix. The effects of VAMP7 depletion on ciliogenesis and cystogenesis are not directly linked to the disruption of lysosomal function, as cilia lengths and cyst morphology were unaffected in an MDCK lysosomal storage disorder model. Together, our data suggest that VAMP7 plays an essential role in ciliogenesis and lumen formation. To our knowledge, this is the first study implicating an R-SNARE in ciliogenesis and cystogenesis. © 2014 Szalinski et al

Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method used in patients with peritoneal cancer (PC) of primary or secondary origin. Intraperitoneal use of oxaliplatin raises concerns about toxicity, especially abdominal pain. The objective of this study was to assess the tolerance of PIPAC with oxaliplatin (PIPAC-Ox) in a large cohort of patients and to identify the risk factors for high grade toxicity, discontinuation of treatment and impaired survival. This retrospective cohort study included all consecutive patients treated with PIPAC-Ox (92 mg/m <sup>2</sup> ) in five centers specialized in the treatment of PC. The procedure was repeated every 6 weeks. Outcomes of interest were Common Terminology Criteria for Adverse Events (CTCAE), symptoms and survival (Kaplan-Meier). Univariate risk factors were included in a multinominal regression model to control for bias. Overall, 251 PIPAC-Ox treatments were performed in 101 patients (45 female) having unresectable PC of various origins: 66 colorectal, 15 gastric, 5 ovarian, 3 mesothelioma, 2 pseudomyxoma, 10 other malignancies (biliary, pancreatic, endocrine) respectively. The median PCI was 19 (IQR: 10-28). Postoperative abdominal pain was present in 23 patients. Out of the 9 patients with grade 3 abdominal pain, only 3 needed a change of PIPAC drug. CTCAE 4.0 toxicity grade 4 or higher was encountered in 16(15.9%) patients. The patients had a mean of 2.5 procedures/patient (SD = 1.5). 50 subjects presented with symptom improvement. Oxaliplatin-based PIPAC appears to be a safe treatment that offers good symptom control and promising survival for patients with advanced peritoneal disease

Innovative Approaches to Analysing Carbon Sequestration as a Mitigation Strategy in Tropical Pasture Landscapes in Two Emblematic Contexts, the Amazon and the West African Sahel

The relationship between ruminant production systems and climate change is complex. As a major contributor to greenhouse gas (GHG) emissions, the sector has been the subject of considerable controversy, with particularly severe criticism in the 2000s. However, ten years ago, the attitude towards grazing lands began to change. Their efficient use of non-renewable energy and their contribution to carbon (C) sequestration were considered as key factors in the new environmental challenge. The reality of this mitigation potential was recently called into question once again in the global agriculture and climate change debate, including that of sequestration in the soil where grazing lands occupy a major position (30-40% of the land surface representing 30% of the soil organic C of the world). Few scientific references are available on these questions in tropical regions, and the standard metrics and methods used may turn out to be unsuitable for the correct evaluation of grazed ecosystems in these regions. Significant work is therefore required to establish baselines and design strategies to ensure sustainable grazing in these regions where the global sequestration potential is high relative to the surface areas concerned. To contribute to this debate, we focus on mitigation options offered by rangelands and grasslands and their management in two emblematic tropical contexts, humid and dry tropics, where field studies have been based on original and holistic approaches at different levels. In Amazonia, if curbing deforestation remains a priority, it needs to be accompanied by sustainable management of deforested areas. In the French Amazon (French Guiana), monitoring fields using chronosequences and flux towers has produced scientific knowledge on the significant mitigation capacities of grassland ecosystems. In the Brazilian Amazon, the spatial logic of the agro-ecological intensification of forage production has enabled a transition from individual extractive systems to farm management at communal levels. In the West African Sahelian region (Northern Senegal), an integrative study at landscape scale revealed the unexpected capacity of soil and shrubs for C sequestration that can offset the GHG emissions for which pastoralism in dry tropical zones is usually blamed

Radio-Frequency Plasma Polymerized Biodegradable Carrier for in vivo Release of Cis-Platinum

A low pressure plasma process based on plasma deposition has been used to develop a drug delivery strategy. In this study, a drug delivery system based on different layers of plasma co-polymerized Poly ε-caprolactone-Polyethylene glycol (PCL-PEG) co-polymers was deposited on biocompatible substrates. Cis-platinum (118 μgm/cm2) was used as an anti-cancer drug and incorporated for local delivery of the chemotherapeutic agent. The co-polymer layers and their interaction with cancer cells were analyzed by scanning electron microscopy. Our study showed that the plasma-PCL-PEG coated cellophane membranes, in which the drug, was included did not modify the flexibility and appearance of the membranes. This system was actively investigated as an alternative method of controlling localized delivery of drug in vivo. The loading of the anti-cancer drug was investigated by UV-VIS spectroscopy and its release from plasma deposited implants against BALB/c mice liver tissues were analyzed through histological examination and apoptosis by TUNEL assay. The histological examination of liver tissues revealed that when the plasma-modified membranes encapsulated the cis-platinum, the Glisson\u27s capsule and liver parenchyma were damaged. In all cases, inflammatory tissues and fibrosis cells were observed in contact zones between the implant and the liver parenchyma. In conclusion, low pressure plasma deposited uniform nano-layers of the co-polymers can be used for controlled release of the drug in vivo