A critical appraisal of controlled studies investigating malformation risks following pregabalin use in early pregnancy.

In March 2022, the Summary of Product Characteristics for the Lyrica brand of pregabalin was updated with warnings regarding malformation risks. This literature review and critical appraisal aims to explore whether these Summary of Product Characteristics updates are justified and provide clarity on the risk-benefit balance for pregabalin use in early pregnancy. A literature review was conducted in May 2022 to identify English language comparative studies of any design providing data about first trimester maternal pregabalin use and malformation risk.

Fetotoxic risk of AT1 blockers exceeds that of angiotensin-converting enzyme inhibitors: an observational study.

Objective: The fetotoxic potential of prenatal exposure to angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) has been known for many years. Symptoms range from transient oligohydramnios to neonatal anuria and permanent renal damage, joint contractures, hypocalvaria, lung hypoplasia and intrauterine or neonatal death. This study aims to investigate the critical gestational time for renin-angiotensin system inhibitor (RAS-I)-induced fetopathy, to quantify the fetopathy risk and to evaluate factors associated with the occurrence and severity of fetopathy.

Analysing time course microarray data using Bioconductor: a case study using yeast2 Affymetrix arrays.

Background: Large scale microarray experiments are becoming increasingly routine, particularly those which track a number of different cell lines through time. This time-course information provides valuable insight into the dynamic mechanisms underlying the biological processes being observed. However, proper statistical analysis of time-course data requires the use of more sophisticated tools and complex statistical models.

A genome wide analysis of the response to uncapped telomeres in budding yeast reveals a novel role for the NAD+ biosynthetic gene BNA2 in chromosome end protection.

Background: Telomeres prevent the ends of eukaryotic chromosomes from being recognized as damaged DNA and protect against cancer and ageing. When telomere structure is perturbed, a co-ordinated series of events promote arrest of the cell cycle so that cells carrying damaged telomeres do not divide. In order to better understand the eukaryotic response to telomere damage, budding yeast strains harboring a temperature sensitive allele of an essential telomere capping gene (cdc13-1) were subjected to a transcriptomic study.

Checkpoint-dependent phosphorylation of Exo1 modulates the DNA damage response.

Exo1 is a nuclease involved in mismatch repair, DSB repair, stalled replication fork processing and in the DNA damage response triggered by dysfunctional telomeres. In budding yeast and mice, Exo1 creates single-stranded DNA (ssDNA) at uncapped telomeres. This ssDNA accumulation activates the checkpoint response resulting in cell cycle arrest.

The LIM domain protein LPP is a coactivator for the ETS domain transcription factor PEA3.

PEA3 is a member of a subfamily of ETS domain transcription factors which is regulated by a number of signaling cascades, including the mitogen-activated protein (MAP) kinase pathways. PEA3 activates gene expression and is thought to play an important role in promoting tumor metastasis and also in neuronal development. Here, we have identified the LIM domain protein LPP as a novel coregulatory binding partner for PEA3.

Hip3 interacts with the HIRA proteins Hip1 and Slm9 and is required for transcriptional silencing and accurate chromosome segregation.

The fission yeast HIRA proteins Hip1 and Slm9 are members of an evolutionarily conserved family of histone chaperones that are implicated in nucleosome assembly. Here we have used single-step affinity purification and mass spectrometry to identify factors that interact with both Hip1 and Slm9. This analysis identified Hip3, a previously uncharacterized 187-kDa protein, with similarity to S.

The Schizosaccharomyces pombe HIRA-like protein Hip1 is required for the periodic expression of histone genes and contributes to the function of complex centromeres.

HIRA-like (Hir) proteins are evolutionarily conserved and are implicated in the assembly of repressive chromatin. In Saccharomyces cerevisiae, Hir proteins contribute to the function of centromeres. However, S.

Role of fission yeast Tup1-like repressors and Prr1 transcription factor in response to salt stress.

In Schizosaccharomyces pombe, the Sty1 mitogen-activated protein kinase and the Atf1 transcription factor control transcriptional induction in response to elevated salt concentrations. Herein, we demonstrate that two repressors, Tup11 and Tup12, and the Prr1 transcription factor also function in the response to salt shock. We find that deletion of both tup genes together results in hypersensitivity to elevated cation concentrations (K(+) and Ca(2+)) and we identify cta3(+), which encodes an intracellular cation transporter, as a novel stress gene whose expression is positively controlled by the Sty1 pathway and negatively regulated by Tup repressors.