Incorporating non-equilibrium dynamics into demographic history inferences of a migratory marine species.

Understanding how dispersal and gene flow link geographically separated the populations over evolutionary history is challenging, particularly in migratory marine species. In southern right whales (SRWs, Eubalaena australis), patterns of genetic diversity are likely influenced by the glacial climate cycle and recent history of whaling. Here we use a dataset of mitochondrial DNA (mtDNA) sequences (n = 1327) and nuclear markers (17 microsatellite loci, n = 222) from major wintering grounds to investigate circumpolar population structure, historical demography and effective population size. Analyses of nuclear genetic variation identify two population clusters that correspond to the South Atlantic and Indo-Pacific ocean basins that have similar effective breeder estimates. In contrast, all wintering grounds show significant differentiation for mtDNA, but no sex-biased dispersal was detected using the microsatellite genotypes. An approximate Bayesian computation (ABC) approach with microsatellite markers compared the scenarios with gene flow through time, or isolation and secondary contact between ocean basins, while modelling declines in abundance linked to whaling. Secondary-contact scenarios yield the highest posterior probabilities, implying that populations in different ocean basins were largely isolated and came into secondary contact within the last 25,000 years, but the role of whaling in changes in genetic diversity and gene flow over recent generations could not be resolved. We hypothesise that these findings are driven by factors that promote isolation, such as female philopatry, and factors that could promote dispersal, such as oceanographic changes. These findings highlight the application of ABC approaches to infer the connectivity in mobile species with complex population histories and, currently, low levels of differentiation.

Exposure to Mycobacterium avium decreases the protective effect of the DNA vaccine pVAXhsp65 against Mycobacterium tuberculosis-induced inflammation of the pulmonary parenchyma.

This work investigated the effect of previous Mycobacterium avium exposure on the protective ability of the DNA vaccine pVAXhsp65 against inflammation in the pulmonary parenchyma. BALB/c mice were presensitized with heat-killed M. avium and then immunized with three doses of pVAXhsp65 prior to challenge with Mycobacterium tuberculosis. M. avium sensitization induced high levels of spontaneous IL-5 production that were concomitant with a positive delayed-type hypersensitivity reaction; antigen-specific IFN-γ production was also observed upon splenocyte stimulation. Prior exposure to M. avium resulted in altered cytokine and antibody production induced by immunization with pVAXhsp65; instead of a Th1 response, vaccinated mice previously exposed to M. avium developed a strong Th2 response. This switch to a Th2 response coincided with the loss of the anti-inflammatory effect of pVAXhsp65 vaccination previously observed in the pulmonary parenchyma of mice infected with M. tuberculosis. These results suggest that exposure to environmental mycobacteria can modulate immune responses induced by mycobacterial vaccines other than bacillus Calmette-Guérin.

Neonatal BCG immunization followed by DNAhsp65 boosters: highly immunogenic but not protective against tuberculosis - a paradoxical effect of the vector?

A new tuberculosis vaccine is urgently needed. Prime-boost strategies are considered very promising and the inclusion of BCG is highly desirable. In this investigation, we tested the protective efficacy of BCG delivered in the neonatal period followed by boosters in the adult phase with a DNA vaccine containing the hsp65 gene from Mycobacterium leprae (pVAXhsp65). Immune responses were characterized by serum anti-hsp65 antibody levels and IFN-gamma and IL-5 production by the spleen. Amounts of these cytokines were also determined in lung homogenates. Protective efficacy was established by the number of colony-forming units (CFU) and histopathological analysis of the lungs after challenge with Mycobacterium tuberculosis. Immunization with BCG alone triggered a significant reduction of CFU in the lungs and also clearly preserved the pulmonary parenchyma. BCG priming also increased the immunogenicity of pVAXhsp65. However, boosters with pVAXhsp65 or the empty vector abolished the protective efficacy of BCG. Also, higher IL-5 levels were produced by spleen and lungs after DNA boosters. These results demonstrated that neonatal BCG immunization followed by DNAhsp65 boosters is highly immunogenic but is not protective against tuberculosis.

Characterization and Assessment of a Novel Plate and Frame MD Module for Single Pass Wastewater Concentration-FEED Gap Air Gap Membrane Distillation.

Membrane distillation (MD) is an up and coming technology for concentration and separation on the verge of reaching commercialization. One of the remaining boundaries is the lack of available full-scale MD modules and systems suitable to meet the requirements of potential industrial applications. In this work a new type of feed gap air gap MD (FGAGMD) plate and frame module is introduced, designed and characterized with tap water and NaCl-H2O solution. The main feature of the new channel configuration is the separation of the heating and cooling channel from the feed channel, enabling a very high recovery ratio in a single pass. Key performance indicators (KPIs) such as flux, gained output ratio (GOR), recovery ratio and thermal efficiency are used to analyze the performance of the novel module concept within this work. A recovery rate of 93% was reached with tap water and between 53%-32% with salt solutions ranging between 117 and 214 g NaCl/kg solution with this particular prototype module. Other than recovery ratio, the KPIs of the FGAGMD are similar to those of an air gap membrane distillation (AGMD) channel configuration. From the experimental results, furthermore, a new MD KPI was defined as the ratio of heating and cooling flow to feed flow. This RF ratio can be used for optimization of the module design and efficiency.

Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy.

BACKGROUND: We recently reported a mutation in the PRKAG2 gene to be responsible for a familial syndrome of ventricular preexcitation, atrial fibrillation, conduction defects, and cardiac hypertrophy. We now report a novel mutation in PRKAG2 causing Wolff-Parkinson-White syndrome and conduction system disease with onset in childhood and the absence of cardiac hypertrophy. METHODS AND RESULTS: DNA was extracted from white blood cells obtained from family members. PRKAG2 exons were amplified by polymerase chain reaction and were screened for mutations by direct sequencing. The genomic organization of the PRKAG2 gene was determined using inter-exon long-range polymerase chain reaction for cDNA sequence not available in the genome database. A missense mutation, Arg531Gly, was identified in all affected individuals but was absent in 150 unrelated individuals. The PRKAG2 gene was determined to consist of 16 exons and is at least 280 kb in size. CONCLUSIONS: We identified a novel mutation (Arg531Gly) in the gamma-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase (AMPK) to be responsible for a syndrome associated with ventricular preexcitation and early onset of atrial fibrillation and conduction disease. These observations confirm an important functional role of AMPK in the regulation of ion channels specific to cardiac tissue. The identification of the cardiac ion channel(s) serving as substrate for AMPK not only would provide insight into the molecular basis of atrial fibrillation and heart block but also may suggest targets for the development of more specific therapy for these common rhythm disturbances.

Coexistent Mahaim and Kent accessory connections: diagnostic and therapeutic implications.

Six patients with coexistent Mahaim and Kent accessory connections are described. Two had left nodoventricular Mahaim connections, the first reported cases demonstrating these findings. In neither were the left-sided Mahaim connections components of a tachycardia and their presence was incidental. In two of four with nodoventricular connections, associated atrioventricular (AV) node conduction and coexistent posteroseptal accessory pathways were found. One of these had the unusual finding of a right-sided Mahaim connection arising from a "fast" AV node pathway. In only one patient did the tachycardia incorporate the Mahaim connection. In this patient, anterograde conduction during tachycardia occurred over a right nodoventricular connection whereas retrograde conduction occurred through a concealed right free wall Kent connection. Two patients had fasciculoventricular connections that were associated with either septal (one patient) or left free wall (one patient) Kent connections. The latter also had evidence of enhanced AV node conduction. This report is unique in that it describes in detail two patients with left nodoventricular connections (Mahaim) inserting in or near the left posterior fascicle. Combined Kent and Mahaim connections, present in the six patients, appear to occur in approximately 5% of patients with the Wolff-Parkinson-White syndrome. Precise identification of bypass connections critical for reentrant circuits is essential for intelligent application of treatment options.

Evolution of odorant receptors expressed in mammalian testes.

About 10% of mammalian odorant receptors are transcribed in testes, and odorant-receptor proteins have been detected on mature spermatozoa. Testis-expressed odorant receptors (TORs) are hypothesized to play roles in sperm chemotaxis, but they might also be ordinary nasal odorant receptors (NORs) that are expressed gratuitously in testes. Under the sperm-chemotaxis hypothesis, TORs should be subject to intense sexual selection and therefore should show higher rates of amino acid substitution than NORs, but under the gratuitous-expression hypothesis, TORs are misidentified NORs and therefore should evolve like other NORs. To test these predictions, we estimated synonymous and nonsynonymous divergences of orthologous NOR and TOR coding sequences from rat and mouse. Contrary to both hypotheses, TORs are on average more highly conserved than NORs, especially in certain domains of the OR protein. This pattern suggests that some TORs might perform internal nonolfactory functions in testes; for example, they might participate in the regulation of sperm development. However, the pattern is also consistent with a modified gratuitous-expression model in which NORs with specialized ligand specificities are both more highly conserved than typical NORs and more likely to be expressed in testes.

Studies on an isolated West Indies population. VII. Genetic linkage studies of hearing loss.

Linkage analysis was performed between the locus of sensorineural hearing loss and 14 polymorphic genetic markers on 108 informative families with a total of 721 individuals in the island of Saint-Barthélémy. No significant linkage was found, and only for Gm could tight linkage be excluded.

Frequency of red cell adenosine deaminase phenotypes in a unique Breton community, the Bigoudens.

The adenosine deaminase gene frequencies were calculated in 405 subjects randomly chosen from the Bigouden district. A rather high frequency (0.0765 +/- 0.0093) was found for the ADA2 gene. The possible effect of Celtic influences is considered.

Current status of the implantable cardioverter-defibrillator.

Clinical trials have established the superiority of the implantable cardioverter-defibrillator (ICD) over antiarrhythmic drug therapy in survivors of sudden cardiac death and in high-risk patients with coronary artery disease. The ICD has evolved to overcome the limitation of earlier devices that required thoracotomy for implantation and were fraught with inappropriate shock delivery. Current ICDs are implanted in a similar manner to cardiac pacemakers and incorporate sophisticated rhythm-discrimination algorithms to prevent inappropriate therapy. Managing the patient with an ICD requires an understanding of the multiprogrammable features of modern devices. Drug interactions and potential sources of electromagnetic interference may adversely affect ICD function. Driving restrictions may be necessary under certain conditions. The cost-effectiveness of ICD therapy appears favorable, given the marked survival benefit seen in randomized trials relative to antiarrhythmic drug treatment. The growing number of ICD recipients necessitates an understanding of the specialized features of the modern ICD and the role of device therapy in clinical practice.

Cytogenetic forms of retinoblastoma: their incidence in a survey of 66 patients.

Sixty-six retinoblastoma patients were investigated using high resolution banding techniques, sister chromatid exchange (SCE) studies, and esterase-D phenotype determination and dosage. Seven patients (in six families) were found to be carriers of a rearrangement of band 13q14 due to de novo deletions, apparently balanced de novo translocations, or parental insertions. The possible role of submicroscopic parental insertions is suggested to explain transmission of nonchromosomal forms through unaffected carriers.

Electrical therapy of arrhythmias.

Pacing, cardioversion, and defibrillation may be used separately or in sequence for the termination of certain cardiac arrhythmias. Each is presently available in the form of an implantable device for long-term tachycardia therapy. The purpose of this article is to review the current applications and future directions of these new modalities.

Running on land and in water: comparative exercise physiology.

The effect of water immersion on cardiorespiratory and blood lactate responses during running was investigated. Wearing a buoyant vest, 10 trained runners (mean age 26 yr) ran in water at four different and specified submaximal loads (target heart rates 115, 130, 145, and 155-160 beats.min-1) and at maximal exercise intensity. Oxygen uptakes (VO2), heart rates, perceived exertion, and blood lactate concentrations were measured. Values were compared with levels obtained during treadmill running. For a given VO2, heart rate was 8-11 beats.min-1 lower during water running than during treadmill running, irrespective of exercise intensity. Both the maximal oxygen uptake (4.03 vs 4.60 1 x min-1) and heart rate (172 vs 188 beats.min-1) were lower during water running. Perceived exertion (legs and breathing) and the respiratory exchange ratio (RER) were higher during submaximal water running than during treadmill running, while ventilation (1 x min-1) was similar. The blood lactate concentrations were consistently higher in water than on the treadmill, both when related to VO2 and to %VO2max. Partly in conformity with earlier cycle ergometer studies, these data suggest that immersion induces acute cardiac adjustments that extend up to the maximal exercise level. Furthermore, both the external hydrostatic load and an altered running technique may add to an increased anaerobic metabolism during supported water running.

Isoacceleration: a new concept of resistive exercise.

This study presents the concept of constant (iso-) accelerative and decelerative exercise and compares concentric and eccentric torque output during isoaccelerative and isodecelerative movements with that during comparable constant velocity (isokinetic) conditions. Twelve men (19-42 yr) performed maximal voluntary concentric and eccentric knee extensions at velocities of 120 and 240 degrees.s-1 (isokinetic) and at accelerations of 180 and 720 degrees.s-2 (both isoaccelerative and isodecelerative) between 10 degrees and 90 degrees knee angles. At 50 degrees, the 180 and 720 degrees.s-2 tests had velocities of 120 and 240 degrees.s-1, respectively, and thus torque comparisons could be made at a corresponding position and velocity. No difference was seen among the isoaccelerative, isodecelerative, or isokinetic angle- and velocity-specific torques for either the concentric or eccentric tests (P greater than 0.05). The results demonstrated that, under conditions of maximal voluntary effort, movement speed as such (within the range studied) was the essential determinant of muscle force--not whether this speed was attained during accelerative, decelerative, or constant velocity movements. As a testing and training modality, the controlled acceleration technique, particularly eccentric deceleration and concentric accleration, appears to offer advantages as compared with existing methods, since it more faithfully reflects the contraction conditions during natural strength-requiring movements.

The Murein Types of Listeria grayi, Listeria murrayi and Listeria denitrificans.

The amino acid sequences of the mureins of the type strains Listeria grayi ATCC 19120, Listeria murrayi ATCC 25401 and Listeria denitrificans ATCC 14870 were determined. L. grayi and L. murrayi contain the murein variation A1γ (A(2)pm-direct-type) which is also present in the type strain of L. monocytogenes. L. denitrificans has a different murein. It belongs to the variation A4α, exhibiting a γ-D-glutamyl-L-seryl-interpeptide bridge between alanyl-γ-D-glutamyl-lysyl-D-alanine peptide subunits (Lys-Ser-D-Glu-type). The taxonomic implications are discussed.