SummaryProduction of nitric oxide (NO) and nitrous oxide (N 2 O) by ammonia (NH 3 )-oxidizing bacteria in natural and man-made habitats is thought to contribute to the undesirable emission of NO and N 2 O into the earth's atmosphere. The NH 3 -oxidizing bacterium Nitrosomonas europaea expresses nitrite reductase (NirK), an enzyme that has so far been studied predominantly in heterotrophic denitrifying bacteria where it is involved in the production of these nitrogenous gases. The finding of nirK homologues in other NH 3 -oxidizing bacteria suggests that NirK is widespread among this group; however, its role in these nitrifying bacteria remains unresolved. We identified a gene, nsrR , which encodes a novel nitrite (NO 2 -)-sensitive transcription repressor that plays a pivotal role in the regulation of NirK expression in N. europaea . NsrR is a member of the Rrf2 family of putative transcription regulators. NirK was expressed aerobically in response to increasing concentrations of NO 2 -and decreasing pH. Disruption of nsrR resulted in the constitutive expression of NirK. NsrR repressed transcription from the nirK gene cluster promoter (P nir ), the activity of which correlated with NirK expression. Reconstruction of the NsrR-P nir system in Escherichia coli revealed that repression by NsrR was reversed by NO 2 -in a pH-dependent manner. The findings are consistent with the hypothesis that N. europaea expresses NirK as a defence against the toxic NO 2 -that is produced during nitrification.

Large genomic deletions of SMAD4, BMPR1A and PTEN are a common cause of JPS. Using direct sequencing and MLPA, a germline defect was detected in 48.1% of JPS patients. MLPA identified 14.8% (4/27) of these mutations. Since a substantial percentage of JPS patients carry a germline deletion and MLPA is a reliable and user-friendly technique, it is concluded that MLPA is a valuable adjunct in JPS diagnosis.

In this paper, we report the identification of a norCBQD gene cluster that encodes a functional nitric oxide reductase (Nor) in Nitrosomonas europaea. Disruption of the norB gene resulted in a strongly diminished nitric oxide (NO) consumption by cells and membrane protein fractions, which was restored by the introduction of an intact norCBQD gene cluster in trans. NorB-deficient cells produced amounts of nitrous oxide (N 2 O) equal to that of wild-type cells. NorCB-dependent activity was present during aerobic growth and was not affected by the inactivation of the putative fnr gene. The findings demonstrate the presence of an alternative site of N 2 O production in N. europaea.

Nitrite reductase (NirK) of Nitrosomonas europaea confers tolerance to nitrite (NO 2 ؊ ). The nirK gene is clustered with three genes of unknown physiological function: ncgABC. At present, this organization is unique to nitrifying bacteria. Here we report that the ncgABC gene products facilitate NirK-dependent NO 2 ؊ tolerance by reversing the negative physiological effect that is associated with the activity of NirK in their absence. We hypothesize that the ncg gene products are involved in the detoxification of nitric oxide that is produced by NirK.

Spinal Muscular Atrophy (SMA) is a disorder characterized by the degeneration of motor neurons in the spinal cord, leading to muscular atrophy. In the majority of cases, SMA is caused by the homozygous absence of the SMN1 gene. The disease severity of SMA is strongly influenced by the copy number of the closely related SMN2 gene. In addition, an SMN variant lacking exons 7 and 8 has been reported in 8% and 23% of healthy Swedish and Spanish individuals respectively. We tested 1255 samples from the 1000 Genomes Project using a new version of the multiplex ligation-dependent probe amplification (MLPA) P021 probemix that covers each SMN exon. The SMN variant lacking exons 7 and 8 was present in up to 20% of individuals in several Caucasian populations, while being almost completely absent in various Asian and African populations. This SMN1/2Δ7–8 variant appears to be derived from an ancient deletion event as the deletion size is identical in 99% of samples tested. The average total copy number of SMN1 , SMN2 and the SMN1/2Δ7–8 variant combined was remarkably comparable in all populations tested, ranging from 3.64 in Asian to 3.75 in African samples.