ASY1 acts as a dosage-dependent antagonist of telomere-led recombination and mediates crossover interference in Arabidopsis.

During meiosis, interhomolog recombination produces crossovers and noncrossovers to create genetic diversity. Meiotic recombination frequency varies at multiple scales, with high subtelomeric recombination and suppressed centromeric recombination typical in many eukaryotes. During recombination, sister chromatids are tethered as loops to a polymerized chromosome axis, which, in plants, includes the ASY1 HORMA domain protein and REC8-cohesin complexes. Using chromatin immunoprecipitation, we show an ascending telomere-to-centromere gradient of ASY1 enrichment, which correlates strongly with REC8-cohesin ChIP-seq data. We mapped crossovers genome-wide in the absence of ASY1 and observe that telomere-led recombination becomes dominant. Surprisingly, asy1/+ heterozygotes also remodel crossovers toward subtelomeric regions at the expense of the pericentromeres. Telomeric recombination increases in asy1/+ occur in distal regions where ASY1 and REC8 ChIP enrichment are lowest in wild type. In wild type, the majority of crossovers show interference, meaning that they are more widely spaced along the chromosomes than expected by chance. To measure interference, we analyzed double crossover distances, MLH1 foci, and fluorescent pollen tetrads. Interestingly, while crossover interference is normal in asy1/+, it is undetectable in asy1 mutants, indicating that ASY1 is required to mediate crossover interference. Together, this is consistent with ASY1 antagonizing telomere-led recombination and promoting spaced crossover formation along the chromosomes via interference. These findings provide insight into the role of the meiotic axis in patterning recombination frequency within plant genomes.

Interacting Genomic Landscapes of REC8-Cohesin, Chromatin, and Meiotic Recombination in Arabidopsis.

Meiosis recombines genetic variation and influences eukaryote genome evolution. During meiosis, DNA double-strand breaks (DSBs) enter interhomolog repair to yield crossovers and noncrossovers. DSB repair occurs as replicated sister chromatids are connected to a polymerized axis. Cohesin rings containing the REC8 kleisin subunit bind sister chromatids and anchor chromosomes to the axis. Here, we report the genomic landscape of REC8 using chromatin immunoprecipitation sequencing (ChIP-seq) in Arabidopsis (Arabidopsis thaliana). REC8 associates with regions of high nucleosome occupancy in multiple chromatin states, including histone methylation at H3K4 (expressed genes), H3K27 (silent genes), and H3K9 (silent transposons). REC8 enrichment is associated with suppression of meiotic DSBs and crossovers at the chromosome and fine scales. As REC8 enrichment is greatest in transposon-dense heterochromatin, we repeated ChIP-seq in kyp suvh5 suvh6 H3K9me2 mutants. Surprisingly, REC8 enrichment is maintained in kyp suvh5 suvh6 heterochromatin and no defects in centromeric cohesion were observed. REC8 occupancy within genes anti-correlates with transcription and is reduced in COPIA transposons that reactivate expression in kyp suvh5 suvh6 Abnormal axis structures form in rec8 that recruit DSB-associated protein foci and undergo synapsis, which is followed by chromosome fragmentation. Therefore, REC8 occupancy correlates with multiple chromatin states and is required to organize meiotic chromosome architecture and interhomolog recombination.

Bacteriological, biochemical, and immunological modifications in human colostrum after Holder pasteurisation.

OBJECTIVE: The objective of this work was to evaluate the effect of Holder pasteurisation of human colostrum on a variety of microbiological, biochemical, and immunological parameters. METHODS: Colostrum samples from 10 donors, and 8 samples of mature milk used as controls, were heated at 62.5°C for 30 minutes. Bacterial counts and the concentration of furosine, lactose, myoinositol, glucose, lactulose, cytokines, and immunoglobulins were determined before and after the heat treatment. RESULTS: Mean bacterial counts in nonpasteurised colostrum samples oscillated between 2.72 and 4.13 log10 colony-forming units per millilitre in the agar media tested. Holder pasteurisation led to the destruction of the bacteria originally present in the samples. Furosine was detected in all samples before pasteurisation and increased significantly after the heat treatment (from 6.60 to 20.59 mg/100 g protein). Lactulose content was below the detection limit in nonpasteurised colostrum, but it was detected in all samples and quantified in 7 of them (from 10.68 to 38.02 mg/L) after Holder pasteurisation. Lactose, glucose, and myoinositol concentrations did not change after Holder pasteurisation. The concentrations of most cytokines and immunoglobulins were significantly higher in colostrum than in mature milk samples. Immunoglobulin content, both in colostrum and in milk samples, was reduced during pasteurisation, whereas, among cytokines, only macrophage inflammatory protein-1ß, interleukin-7, and granulocyte-macrophage-colony-stimulating factor concentrations were affected by this heat treatment. CONCLUSIONS: Lactulose and furosine content could be used as heat treatment indicators in colostrum samples. Holder pasteurisation modified the immunological profile of both colostrum and mature milk.

Congenital chylothorax: from foetal life to adolescence.

AIM: To analyse the main prenatal and postnatal features of congenital chylothorax (CC), and the outcome including mid-term follow-up. METHODS: We searched our databases for CC diagnosed between 1990 and 2006. Data of 29 cases were retrieved and analysed. Follow-up until 3 years of age was available for all patients. RESULTS: Most patients were diagnosed prenatally (94%) and most cases were complicated by foetal hydrops (66.7%). The overall survival rate at 3 years was 56%. A significantly poorer outcome was observed when foetal hydrops, preterm birth < 34 weeks, large effusions and/or early-onset pneumothorax were present. An important but not significant improvement in the survival rate was observed through the study period; while in 1990-1998, the survival rate was 41.7%, from 1999 to 2006 it was 66.7% (p = 0.19). In the mid-term follow-up, we did not observe any recurrence of CC and most infants remain asymptomatic. However, 27% of survivors were diagnosed as having asthma in early infancy. CONCLUSION: CC still carries a significant risk of perinatal mortality. However, continuous advances in foetal and neonatal medicine are improving the prognosis of these patients, and nowadays most of them are likely to survive. Beyond the neonatal period, most survivors have an uneventful outcome.

A comprehensive review of assay methods to determine drugs in breast milk and the safety of breastfeeding when taking drugs.

Most of the licit and illicit drugs consumed by the breastfeeding woman pass into the milk and can modify the production, volume and composition of the milk, as well as hypothetically have short- and long-term harmful effects on the infant. There is much confusion in the scientific community regarding this issue: should a woman breastfeed her baby while continuing to use prescription drugs and/or drugs of abuse? There are many case reports of clinically significant toxicity in breast-fed infants from some substances used by mothers (such as irritability, vomiting, sedation, respiratory depression, shock), but there are too few data on studies conducted in breastfeeding women and their infants to make a realistic risk assessment. The objective measurement of a drug and/or metabolites in maternal milk is the first step when investigating the amount of drug excreted in milk and subsequently calculating the daily dose administered to the breast-fed infant. The present review reports the analytical methods developed to detect different drugs in the breast milk, listing the principal characteristics and validation parameters, advantages and disadvantages. Furthermore, the mechanisms of drug transfer into breast milk are discussed, the correlation between the concentration of the drug in breast milk and potential adverse outcomes on the infant are described for each drug, and suggested harm minimization strategies and approved breastfeeding recommendations are indicated.

Caracteres biológicos de Hemophilus influenzae aislado de diferentes poblaciones infantiles / Biological characteristics of Haemophilus influenzae isolated from different infantile populations

Las características biológicas de Hemophilus influenzae aisladas de áreas normalmente estériles o de la orofaringe de niños, no han sido descritas en el Uruguay. Esta información tiene importante implicancia en la comprensión de la patogenia de esas infecciones y en los requisitos para lograr una vacuna adecuada. Con tal fin se determinaron los serotipos y biotipos en 54.3 por ciento de las cepas aisladas entre 1986 y 1992. Además en la totalidad de las cepas conservadas (n=311) se investigó la producción de ß lactamasas. Se demostró que la resistecia a los ß lactámicos era poco frecuente (5.9 por ciento ). Las cepas invasivas, recuperadas de la sangre, derrame pleural o LCR, pertenecían en su mayoría, al serotipo b y al biotipo I (83.4 por ciento ). En las infecciones del oído medio predominaron los H. influenzae no tipificables, así como entre las cepas que colonizaban la orofaringe de pacientes y niños sanos, pero en estos casos los biotipos fueron diversos, con 38 por ciento correspondiendo al biotipo II. Las vacunas conjugadas conteniendo polisacárido capsular del serotipo b, prevendrían los cuadros invasivos, pero no se lograría el control de infecciones por otros serotipos y por cepas no tipificables

Echocardiographic diagnosis of effusive-constrictive pericarditis due to staphylococcal pericarditis after cardiac surgery.

Two weeks after coronary artery bypass surgery, a 43-year-old man was readmitted with fever, pneumonia, left pleural effusion, and pericarditis. Echocardiography showed a localized posterior pericardial effusion, pericardial thickening, and bulging of the ventricular septum toward the left ventricle. Right-sided catheterization indicated pericardial constriction. Effusive-constrictive pericarditis was confirmed at surgery. Cardiac imaging played an important role in diagnosis of this unusual complication of cardiac surgery.