A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders.

Chromosome map of Xanthomonas campestris pv. campestris 17 with locations of genes involved in xanthan gum synthesis and yellow pigmentation.

No plasmid was detected in Xanthomonas campestris pv. campestris 17, a strain of the causative agent of black rot in cruciferous plants isolated in Taiwan. Its chromosome was cut by PacI, PmeI, and SwaI into five, two, and six fragments, respectively, and a size of 4.8 Mb was estimated by summing the fragment lengths in these digests. Based on the data obtained from partial digestion and Southern hybridization using probes common to pairs of the overlapping fragments or prepared from linking fragments, a circular physical map bearing the PacI, PmeI, and SwaI sites was constructed for the X. campestris pv. campestris 17 chromosome. Locations of eight eps loci involved in exopolysaccharide (xanthan gum) synthesis, two rrn operons each possessing an unique I-CeuI site, one pig cluster required for yellow pigmentation, and nine auxotrophic markers were determined, using mutants isolated by mutagenesis with Tn5(pfm)CmKm. This transposon contains a polylinker with sites for several rare-cutting restriction endonucleases located between the chloramphenicol resistance and kanamycin resistance (Kmr) genes, which upon insertion introduced additional sites into the chromosome. The recA and tdh genes, with known sequences, were mapped by tagging with the polylinker-Kmr segment from Tn5(pfm)CmKm. This is the first map for X. campestris and would be useful for genetic studies of this and related Xanthomonas species.

Choice and changes of contraceptive methods after primiparous delivery in Shanghai.

PIP: This study assessed the contraceptive method of choice and tendency of method switching of women after their first birth in Shanghai, China. The assessment was based on 15 months follow-up after the first delivery. Included in the study were 3701 primiparous women aged 18-43 years, with 1833 women living in an urban area and 1868 living in a rural area. Results showed that 15 months after delivery 95.46% had already used a contraceptive method. The leading first choice among urban women was the condom (50.72%), followed by the IUD (29.09%), while the leading first choice among rural women was the IUD (56.65%), followed by the condom (30.60%). Among women who had never used a contraceptive method, 33.77% of urban women and 18.52% of rural women switched method 15 months after delivery. The major reason for the contraceptive method switching was method failure attributed to improper use. Furthermore, the choice of contraceptive method after first birth varied significantly by women's characteristics. Urban, well-educated women, breast-feeding women and older women preferred the condom and the rhythm method over oral contraceptives. Family planning workers should increase women's awareness of the benefits and disadvantages of different contraceptive methods, dispel myths, and improve women's informed choice.^ieng

Interval to delivery in high-risk patients: do tocolytic agents really work?

Some question whether tocolytic drugs reduce uterine activity and prolong gestation. The interval from discontinuance of tocolytics until spontaneous labor and delivery in patients (n = 69) with documented preterm labor (PTL) versus subjects receiving prophylactic tocolytic therapy (n = 41) was studied. Women with documented PTL delivered sooner after cessation of tocolytics (6.1 +/- 6.9 days) than control (C) patients (14.7 +/- 10.8 days, P less than 0.001). Also, 28 of the 69 (41%) patients in the PTL group delivered within 24 h of discontinuation of tocolysis compared to 4 (10%) in the C group (P less than 0.0004). We conclude that tocolytic therapy for documented preterm labor suppresses uterine activity and when these agents are discontinued, contractions return and labor ensues.

Subcutaneous tocolytic infusion therapy for patients at very high risk for preterm birth.

Patients with multiple gestations or recalcitrant preterm labor are at very high risk for preterm birth in spite of adequate tocolysis. Subcutaneous infusion of tocolytic medications on an ambulatory basis has been used in several small series and has effectively prolonged gestation. This retrospective analysis presents data from 992 patients at very high risk for preterm delivery who were prescribed this therapy. The amount of tocolytic medication was individualized by utilizing the patient's volume of distribution and clearance. Pharmacists adjusted the dosage based on uterine activity strips received by nursing personnel. The average basal rate was .073 +/- .020 mg/h. Patients received an average of seven scheduled boluses per day and 1.54 +/- .93 unscheduled boluses per week (.25 +/- .03 mg each). The therapy extended the gestation a mean of 38 +/- 23 days and average gestational age at delivery was 36.3 +/- 2.6 weeks with a mean birthweight of 2759 +/- 681 g. This study, utilizing a large number of patients, confirms earlier reports that for women at very high risk for preterm delivery subcutaneous tocolytic infusion therapy is beneficial. Prospective studies evaluating such treatment on a randomized basis are indicated.