60 research outputs found
REM34 and REM35 control female and male gametophyte development in Arabidopsis thaliana
The REproductive Meristem (REM) gene family encodes for transcription factors belonging to the B3 DNA binding domain superfamily. In Arabidopsis thaliana the REM gene family is composed of 45 members, preferentially expressed during flower, ovule and seed development. Only a few members of this family have been functionally characterized: VERNALIZATION1 (VRN1) and most recently TARGET OF FLC AND SVP1 (TFS1) regulate flowering time and VERDANDI (VDD), together with VALKYRIE (VAL) control the death of the receptive synergid cell in the female gametophyte. We investigated the role of REM34, REM35 and REM36, three closely related and linked genes similarly expressed in both female and male gametophytes. Simultaneous silencing by RNA interference (RNAi) caused about 50% of the ovules to remain unfertilized. Careful evaluation of both ovule and pollen development showed that this partial sterility of the transgenic RNAi lines was due to a post meiotic block in both female and male gametophytes. Furthermore, protein interaction assays revealed that REM34 and REM35 interact, which suggests that they work together during the first stages of gametogenesis
Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.
Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG)
QT-prolonging properties are combined is generally supposed but not well studied. Based on
available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT)
classification defines the risk of QT prolongation for exposure to single drugs. We aimed to
investigate how combining AZCERT drug categories impacts QT duration and how relative drug
exposure affects the extent of pharmacodynamic drug–drug interactions.
Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether
AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed
rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other
QTc-prolonging risk factors. We concurrently considered administered drug doses and
pharmacokinetic interactions modulating drug clearance to calculate individual weights of
relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we
estimated individual drug exposure with these drugs and included this information as weights
in weighted regression analyses.
Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the
largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging
drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with
95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for
the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor.
Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging
drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation
caused by drug combinations strongly depends on the nature of the combination partners and
individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also
for the risk prediction of combination therapies with QT-prolonging drugs
Identification and Characterization of RcMADS1, an AGL24 Ortholog from the Holoparasitic Plant Rafflesia cantleyi Solms-Laubach (Rafflesiaceae)
10.1371/journal.pone.0067243PLoS ONE86-POLN
Transcriptomic Characterization of a Synergistic Genetic Interaction during Carpel Margin Meristem Development in Arabidopsis thaliana
In flowering plants the gynoecium is the female reproductive structure. In Arabidopsis thaliana ovules initiate within the developing gynoecium from meristematic tissue located along the margins of the floral carpels. When fertilized the ovules will develop into seeds. SEUSS (SEU) and AINTEGUMENTA (ANT) encode transcriptional regulators that are critical for the proper formation of ovules from the carpel margin meristem (CMM). The synergistic loss of ovule initiation observed in the seu ant double mutant suggests that SEU and ANT share overlapping functions during CMM development. However the molecular mechanism underlying this synergistic interaction is unknown. Using the ATH1 transcriptomics platform we identified transcripts that were differentially expressed in seu ant double mutant relative to wild type and single mutant gynoecia. In particular we sought to identify transcripts whose expression was dependent on the coordinated activities of the SEU and ANT gene products. Our analysis identifies a diverse set of transcripts that display altered expression in the seu ant double mutant tissues. The analysis of overrepresented Gene Ontology classifications suggests a preponderance of transcriptional regulators including multiple members of the REPRODUCTIVE MERISTEMS (REM) and GROWTH-REGULATING FACTOR (GRF) families are mis-regulated in the seu ant gynoecia. Our in situ hybridization analyses indicate that many of these genes are preferentially expressed within the developing CMM. This study is the first step toward a detailed description of the transcriptional regulatory hierarchies that control the development of the CMM and ovule initiation. Understanding the regulatory hierarchy controlled by SEU and ANT will clarify the molecular mechanism of the functional redundancy of these two genes and illuminate the developmental and molecular events required for CMM development and ovule initiation
Combinatorial activities of SHORT VEGETATIVE PHASE and FLOWERING LOCUS C define distinct modes of flowering regulation in Arabidopsis
Descartáveis urbanos: discutindo a complexidade da população de rua e o desafio para políticas de saúde
Comment on: outpatient parenteral antibiotic therapy (OPAT) for bone and joint infections: experience from a UK teaching hospital-based service.
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