Universal heteroplasmy of human mitochondrial DNA.

Mammalian cells contain thousands of copies of mitochondrial DNA (mtDNA). At birth, these are thought to be identical in most humans. Here, we use long read length ultra-deep resequencing-by-synthesis to interrogate regions of the mtDNA genome from related and unrelated individuals at unprecedented resolution. We show that very low-level heteroplasmic variance is present in all tested healthy individuals, and is likely to be due to both inherited and somatic single base substitutions. Using this approach, we demonstrate an increase in mtDNA mutations in the skeletal muscle of patients with a proofreading-deficient mtDNA polymerase γ due to POLG mutations. In contrast, we show that OPA1 mutations, which indirectly affect mtDNA maintenance, do not increase point mutation load. The demonstration of universal mtDNA heteroplasmy has fundamental implications for our understanding of mtDNA inheritance and evolution. Ostensibly de novo somatic mtDNA mutations, seen in mtDNA maintenance disorders and neurodegenerative disease and aging, will partly be due to the clonal expansion of low-level inherited variants

Simulating offshore wind contract for difference auctions to prepare bid strategies

This paper presents a novel agent-based, stochastic model, which uses game-theoretic principles to simulate Contract for Difference (CfD) auctions. The framework has use cases and implications for policymakers and renewable generators alike, and can be used by developers to prepare bidding strategy and for policymakers to empirically test auction design. The model is demonstrated through replication of the offshore wind CfD Allocation Round 3 (AR3) pot, and utilises high-level cost modelling distribution data to estimate bid prices for the competing projects. The model produces a distribution of most likely results which better categorises uncertainty, and through comparison of AR3 and simulation results, demonstrates how outcomes can be predicted with reasonable confidence by developers. Analysis show that the transmission network and grid connection charges are a significant barrier for projects in some geographical regions to be awarded a CfD contract, potentially hindering renewable deployment in those areas. Moreover, this paper demonstrates how players can use probability theory to select an optimum bidding strategy which maximises expected profit while factoring the uncertainty inherent in CfD auctions. Results show that a 1200 MW wind farm development can increase potential profits by £135 million over the CfD contract length in exchange for a 25 p.p. chance reduction in being awarded a subsidy

Stratus Ocean Reference Station (20˚S, 85˚W), mooring recovery and deployment cruise, R/V Ron Brown cruise 04-11, December 5 - December 24, 2004

The Ocean Reference Station at 20° S, 85° W under the stratus clouds west of northern Chile and Peru is being maintained to provide ongoing, climate-quality records of surface meteorology, of air-sea fluxes of heat, freshwater, and momentum, and of upper ocean temperature, salinity, and velocity variability. The Stratus Ocean Reference Station (ORS Stratus) is supported by the National Oceanic and Atmospheric Administration’s (NOAA) Climate Observation Program. It is recovered and redeployed annually, with cruises that have come between October and December. During the December 2004 cruise of NOAA's R/V Ronald H. Brown to the ORS Stratus site, the primary activities where the recovery of the WHOI surface mooring that had been deployed in November 2003, the deployment of a new WHOI surface mooring at that site, the in-situ calibration of the buoy meteorological sensors by comparison with instrumentation put on board by staff of the NOAA Environmental Technology Laboratory (ETL), and observations of the stratus clouds and lower atmosphere by NOAA ETL and Jason Tomlinson from Texas A&M. The ORS Stratus buoys are equipped with two Improved Meteorological systems, which provide surface wind speed and direction, air temperature, relative humidity, barometric pressure, incoming shortwave radiation, incoming longwave radiation, precipitation rate, and sea surface temperature. The IMET data are made available in near real time using satellite telemetry. The mooring line carries instruments to measure ocean salinity, temperature, and currents. The ETL instrumentation used during the 2004 cruise included cloud radar, radiosonde balloons, and sensors for mean and turbulent surface meteorology. The atmospheric observations also benefited from the C-Band radar mounted on the R/V Ronald H. Brown. In addition to this work, buoy work was done in support of the Chilean Navy Hydrographic and Oceanographic Service (SHOA). A tsunami warning mooring was reinstalled at 75°W, 20°S for SHOA, after the previous buoy installed last year failed. SHOA personnel were onboard to direct the deployment and to gain experience. Four students from the University of Concepcion collected hydrographic data and water samples. One other Chilean student from the University of Chile was involved in the atmospheric sampling program, with a particular focus on the near coast jet. Finally, the cruise hosted a teacher participating in NOAA's Teacher at Sea Program, Mary Esther Cook, who used her experience to develop lessons for her class back in Arkansas.Funding was provided by the National Oceanic and Atmospheric Administration under Contract Number NA17RJ1225

Acute febrile illness is associated with Rickettsia spp infection in dogs

BACKGROUND: Rickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. METHODS: Dogs from southern Italy with acute fever (n = 99) were compared with case–control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. RESULTS: The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank®, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. CONCLUSIONS: This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR

Rickettsia slovaca Infection: DEBONEL/TIBOLA

Producción CientíficaThis study describes the epidemiological, clinical, and microbiological characteristics of a new tick-borne disease in Spain—Dermacentor-borne necrosis erythema lymphadenopathy (DEBONEL). The clinical presentations include an eschar at the site of the tick bite, surrounded by an erythema and painful regional lymphadenopathy. The disease appears during the colder months and its vector is Dermacentor marginatus (D. marginatus). From January 1990 to December 2004, 54 patients presented at Hospital of La Rioja with these clinical and epidemiological data. The ratio of females to males was 32/22. The average age was 37 years. In all cases tick bites were located on the upper body (90% on the scalp). The median incubation period was 4.7 days. Signs and symptoms were mild in all cases. Only a small number of patients presented mild and nonspecific abnormalities in a complete blood cell count and mild elevation of erythrocyte sedimentation rates and C-protein reactive and liver enzyme levels. Serological evidence of acute rickettsiosis was observed in 19 patients (61%). In 29% sera tested by polymerase chain reactions (PCRs) were positive. The sequence obtained from a PCR product revealed 98% identity with Rickettsia sp. strains RpA4, DnS14, and DnS28. All ticks removed from patients were PCR-positive. Sequencing showed 8 of them identified as R. slovaca and 2 as Rickettsia sp. strains RpA4, DnS14, and DnS28

Optimization of sequence alignment for simple sequence repeat regions

Abstract Background Microsatellites, or simple sequence repeats (SSRs), are tandemly repeated DNA sequences, including tandem copies of specific sequences no longer than six bases, that are distributed in the genome. SSR has been used as a molecular marker because it is easy to detect and is used in a range of applications, including genetic diversity, genome mapping, and marker assisted selection. It is also very mutable because of slipping in the DNA polymerase during DNA replication. This unique mutation increases the insertion/deletion (INDELs) mutation frequency to a high ratio - more than other types of molecular markers such as single nucleotide polymorphism (SNPs). SNPs are more frequent than INDELs. Therefore, all designed algorithms for sequence alignment fit the vast majority of the genomic sequence without considering microsatellite regions, as unique sequences that require special consideration. The old algorithm is limited in its application because there are many overlaps between different repeat units which result in false evolutionary relationships. Findings To overcome the limitation of the aligning algorithm when dealing with SSR loci, a new algorithm was developed using PERL script with a Tk graphical interface. This program is based on aligning sequences after determining the repeated units first, and the last SSR nucleotides positions. This results in a shifting process according to the inserted repeated unit type. When studying the phylogenic relations before and after applying the new algorithm, many differences in the trees were obtained by increasing the SSR length and complexity. However, less distance between different linage had been observed after applying the new algorithm. Conclusions The new algorithm produces better estimates for aligning SSR loci because it reflects more reliable evolutionary relations between different linages. It reduces overlapping during SSR alignment, which results in a more realistic phylogenic relationship.</p

A success story: HIV prevention for injection drug users in Rhode Island

BACKGROUND: New HIV diagnoses related to injection drug use (IDU) have declined in the United States. Access to clean syringes and decreasing HIV transmission among injection drug users have been HIV prevention priorities of the Rhode Island (RI) HIV community. To examine trends in IDU-related new HIV diagnoses in RI, we performed a retrospective analysis of new HIV diagnoses according to HIV risk factor from 1990–2003. RESULTS: There has been an 80% absolute reduction in IDU-related new HIV diagnoses in RI coincident with IDU-specific prevention efforts. CONCLUSION: There has been a greater decline in IDU-related new HIV diagnoses in Rhode Island compared to national data reported by the Centers for Disease Control and Prevention. We hypothesize that this dramatic decline in Rhode Island is related to extensive HIV prevention efforts targeting IDUs. Further research is needed to examine the impact of specific HIV prevention interventions for injection drug users