Survival of Male Patients with Incontinentia Pigmenti Carrying a Lethal Mutation Can Be Explained by Somatic Mosaicism or Klinefelter Syndrome

Incontinentia pigmenti (IP), or "Bloch-Sulzberger syndrome," is an X-linked dominant disorder characterized by abnormalities of skin, teeth, hair, and eyes; skewed X-inactivation; and recurrent miscarriages of male fetuses. IP results from mutations in the gene for NF-kappaB essential modulator (NEMO), with deletion of exons 4-10 of NEMO accounting for >80% of new mutations. Male fetuses inheriting this mutation and other "null" mutations of NEMO usually die in utero. Less deleterious mutations can result in survival of males subjects, but with ectodermal dysplasia and immunodeficiency. Male patients with skin, dental, and ocular abnormalities typical of those seen in female patients with IP (without immunodeficiency) are rare. We investigated four male patients with clinical hallmarks of IP. All four were found to carry the deletion normally associated with male lethality in utero. Survival in one patient is explained by a 47,XXY karyotype and skewed X inactivation. Three other patients possess a normal 46,XY karyotype. We demonstrate that these patients have both wild-type and deleted copies of the NEMO gene and are therefore mosaic for the common mutation. Therefore, the repeat-mediated rearrangement leading to the common deletion does not require meiotic division. Hypomorphic alleles, a 47,XXY karyotype, and somatic mosaicism therefore represent three mechanisms for survival of males carrying a NEMO mutation.     

Water ingestion affects orthostatic challenge-induced blood pressure and heart rate responses in young healthy subjects: gender implications

Evidence exists that women have lower orthostatic tolerance than men during quiescent standing. Water ingestion has been demonstrated to improve orthostatic tolerance in patients with severe autonomic dysfunction. We therefore sought to test the hypothesis that water ingestion would improve orthostatic tolerance in healthy young women more than in aged-matched men. Thirty seven (22 men and 15 women) healthy subjects aged 22.5± 1.7 and 21.5±1.4 (means±SD) respectively, ingested 50ml (control) and 500ml of water 40min before orthostatic challenge on two separate days of appointment in a randomized controlled, cross-over design. Seated and standing blood pressure and heart rate were determined. Orthostatic tolerance was assessed as the time to presyncope during standing. Ingesting 500ml of water significantly improves orthostatic tolerance by 22% (32.0 ± 5.2 vs 26.2 ± 2.4min; p< 0.05) in men and by 33% (24.2±2.8 vs 18.3 ± 3.2; p< 0.05) in women. Thirty minutes after ingesting 500ml of water, seated systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure rose significantly in men while only systolic blood pressure and pulse pressure rose significantly in women. However ingesting 500ml of water did not have significant effect on seated heart rate in both men and women. Ingestion of 500ml of water significantly attenuated both the orthostatic challenge-induced increased heart rate and decreased pulse pressure responses especially in women. Diastolic blood pressure tended to be positively correlated with orthostatic tolerance strongly in men than in women. Pulse pressure correlated positively while heart rate correlated negatively to orthostatic tolerance in women but not in men independent of other correlates. Water ingestion is associated with orthostatic tolerance strongly in women but weakly in men independent of other correlates. In conclusion, the findings in the present study demonstrated that water ingestion caused improvement strongly in young women than in young men. This improvement is associated with increased pulse pressure and decreased tachycardiac responses during orthostatic challenge. Keywords: Gender, Heart rate, orthostatic challenge, Pulse pressure, Water ingestion.     

The European carbon balance. Part 3: forests

We present a new synthesis, based on a suite of complementary approaches, of the primary production and carbon sink in forests of the 25 member states of the European Union (EU‐25) during 1990–2005. Upscaled terrestrial observations and model‐based approaches agree within 25% on the mean net primary production (NPP) of forests, i.e. 520±75 g C m^?2 yr^?1 over a forest area of 1.32 × 10⁶ km² to 1.55 × 10⁶ km² (EU‐25). New estimates of the mean long‐term carbon forest sink (net biome production, NBP) of EU‐25 forests amounts 75±20 g C m^?2 yr^?1. The ratio of NBP to NPP is 0.15±0.05. Estimates of the fate of the carbon inputs via NPP in wood harvests, forest fires, losses to lakes and rivers and heterotrophic respiration remain uncertain, which explains the considerable uncertainty of NBP. Inventory‐based assessments and assumptions suggest that 29±15% of the NBP (i.e., 22 g C m^?2 yr^?1) is sequestered in the forest soil, but large uncertainty remains concerning the drivers and future of the soil organic carbon. The remaining 71±15% of the NBP (i.e., 53 g C m^?2 yr^?1) is realized as woody biomass increments. In the EU‐25, the relatively large forest NBP is thought to be the result of a sustained difference between NPP, which increased during the past decades, and carbon losses primarily by harvest and heterotrophic respiration, which increased less over the same period.     

Nucleotide sequence of the genes for tryptophan synthase in Pseudomonas aeruginosa

We have determined the DNA sequence of the two adjacent genes for the alpha and beta chains of tryptophan synthase in Pseudomonas aeruginosa, along with 34 5'-flanking and 799 3'-flanking base pairs. The gene order is trpBA as predicted from earlier genetic studies, and the two cistrons overlap by 4 bp; a ribosome binding site for the second gene is evident in the coding sequence of the first gene. We have also determined the location of three large deletions eliminating portions of each gene. A detailed comparison of the deduced P. aeruginosa amino acid sequence with those published for E. coli, Bacillus subtilis, and Saccharomyces cerevisiae shows much similarity throughout the beta and most of the alpha subunit. Most of the residues implicated by chemical modification or mutation as being critical for enzymatic activity are conserved, along with many others, suggesting that three-dimensional structure has remained largely constant during evolution. We also report the construction of a recombinant plasmid that overproduces a slightly modified alpha subunit from P. aeruginosa that can form a functionally effective multimer with normal E. coli beta 2 subunit in vivo.      

Effects of oral administration of nicotine on organ weight, serum testosterone level and testicular histology in adult male rats

This study investigated the effects of oral administration of nicotine on body and reproductive organ weight, serum testosterone level and testicular histology in adult male rats. Forty male rats divided into five groups and treated for a period of 30 days with 0.5mg/kg (low dose) and 1.0 mg/kg (high dose) body weight of nicotine while the control rats received 0.2 ml/kg normal saline. The fourth and fifth groups were gavaged with 0.5mg/kg and 1.0mg/kg body weight of nicotine but were left untreated for another 30 days. These groups served as the recovery groups.  At the end of each experimental period, the animals were scarified and their reproductive organs were removed and weighed immediately. There was no significant change in the body weight. There was a significant decrease (p <0.05) in the testicular and epididymal weight of rats for both treatments while the decrease in the seminal vesicle weight for both treatment groups was not significant. The prostate weight was not significantly increased in both groups. The recovery groups showed appreciable recovery in their organ weight. Serum level of testosterone of both groups was significantly decreased in a dose dependent manner when compared with those of the control rats. The histological section showed testicular degeneration and disorganization in the cytoarchitecture, as the observed changes were pronounced in the high dose group than the low dose group. However, there were both regeneration of the germinal epithelium and restructuring of the interstitum towards normal in the recovery groups. No lesion was observed in the epididymis of the rats. The results suggest that nicotine has deleterious effect on the male reproductive organ of albino rats ameliorated by nicotine cessation.     

Water quality assessment of the Siluko River,southern Nigeria

The water quality of the Siluko River, Edo State, Nigeria was investigated from March to August 2015 to determine its suitability for drinking and usage for domestic purposes. Water samples collected from three stations were tested for thirteen physico-chemical parameters using standard analytical procedures. Temperature, phosphate and chloride were significantly different across the three stations. All other parameters, with the exception of turbidity, dissolved oxygen and phosphate, were within the permissible limits recommended by the Nigerian Standard for Drinking Water Quality (NSDWQ) and World Health Organization (WHO). Water Quality Index (WQI) values ranged from 11.24 to 16.15, indicating excellent water quality. While the quality of the water from the Siluko River is suitable for drinking and domestic usage, to prevent future deterioration of the water, it is recommended that the regulating authorities monitor effluents discharged into the river from human activities.     

Genetic evidence of intercontinental movement of avian influenza in a migratory bird: the northern pintail (Anas acuta)

The role of migratory birds in the movement of the highly pathogenic (HP) avian influenza H5N1 remains a subject of debate. Testing hypotheses regarding intercontinental movement of low pathogenic avian influenza (LPAI) viruses will help evaluate the potential that wild birds could carry Asian-origin strains of HP avian influenza to North America during migration. Previous North American assessments of LPAI genetic variation have found few Asian reassortment events. Here, we present results from whole-genome analyses of LPAI isolates collected in Alaska from the northern pintail (Anas acuta), a species that migrates between North America and Asia. Phylogenetic analyses confirmed the genetic divergence between Asian and North American strains of LPAI, but also suggested inter-continental virus exchange and at a higher frequency than previously documented. In 38 isolates from Alaska, nearly half (44.7%) had at least one gene segment more closely related to Asian than to North American strains of LPAI. Additionally, sequences of several Asian LPAI isolates from GenBank clustered more closely with North American northern pintail isolates than with other Asian origin viruses. Our data support the role of wild birds in the intercontinental transfer of influenza viruses, and reveal a higher degree of transfer in Alaska than elsewhere in North America.     

Structure and regulation of the anthranilate synthase genes in Pseudomonas aeruginosa: II. Cloning and expression in Escherichia coli

The genes for the large and small subunits of anthranilate synthase (trpE and trpG, respectively) have been cloned from Pseudomonas aeruginosa PAC174 into E. coli by R-prime formation with the broad-host- range plasmid R68.44. Sequential subcloning into plasmid vectors reduced the active Pseudomonas DNA fragment to a length of 3.1 kb. We obtained evidence that this region contains the promoter for its own expression and retains a vestigial regulatory response to tryptophan scarcity or excess.