De Novo Assembly of the Pneumocystis jirovecii Genome from a Single Bronchoalveolar Lavage Fluid Specimen from a Patient.

ABSTRACT Pneumocystis jirovecii is a fungus that causes severe pneumonia in immunocompromised patients. However, its study is hindered by the lack of an in vitro culture method. We report here the genome of P. jirovecii that was obtained from a single bronchoalveolar lavage fluid specimen from a patient. The major challenge was the in silico sorting of the reads from a mixture representing the different organisms of the lung microbiome. This genome lacks virulence factors and most amino acid biosynthesis enzymes and presents reduced GC content and size. Together with epidemiological observations, these features suggest that P. jirovecii is an obligate parasite specialized in the colonization of human lungs, which causes disease only in immune-deficient individuals. This genome sequence will boost research on this deadly pathogen. IMPORTANCE Pneumocystis pneumonia is a major cause of mortality in patients with impaired immune systems. The availability of the P. jirovecii genome sequence allows new analyses to be performed which open avenues to solve critical issues for this deadly human disease. The most important ones are (i) identification of nutritional supplements for development of culture in vitro, which is still lacking 100 years after discovery of the pathogen; (ii) identification of new targets for development of new drugs, given the paucity of present treatments and emerging resistance; and (iii) identification of targets for development of vaccines.

Numerical simulation of ambient seismic wavefield modification caused by pore-fluid effects in an oil reservoir

We have modeled numerically the seismic response of a poroelastic inclusion with properties applicable to an oil reservoir that interacts with an ambient wavefield. The model includes wave-induced fluid flow caused by pressure differences between mesoscopic-scale (i.e., in the order of centimeters to meters) heterogeneities. We used a viscoelastic approximation on the macroscopic scale to implement the attenuation and dispersion resulting from this mesoscopic-scale theory in numerical simulations of wave propagation on the kilometer scale. This upscaling method includes finite-element modeling of wave-induced fluid flow to determine effective seismic properties of the poroelastic media, such as attenuation of P- and S-waves. The fitted, equivalent, viscoelastic behavior is implemented in finite-difference wave propagation simulations. With this two-stage process, we model numerically the quasi-poroelastic wave-propagation on the kilometer scale and study the impact of fluid properties and fluid saturation on the modeled seismic amplitudes. In particular, we addressed the question of whether poroelastic effects within an oil reservoir may be a plausible explanation for low-frequency ambient wavefield modifications observed at oil fields in recent years. Our results indicate that ambient wavefield modification is expected to occur for oil reservoirs exhibiting high attenuation. Whether or not such modifications can be detected in surface recordings, however, will depend on acquisition design and noise mitigation processing as well as site-specific conditions, such as the geologic complexity of the subsurface, the nature of the ambient wavefield, and the amount of surface noise.

The Smiling Project: development of a new program for gait and balance training

Introduction: The SMILING project, a multicentric project fundedby the European Union, aims to develop a new gait and balance trainingprogram to prevent falls in older persons. The program includes the"SMILING shoe", an innovative device that generates mechanical perturbationwhile walking by changing the soles' inclination. Induced perturbationschallenge subjects' balance and force them to react to avoidfalls. By training specifically the complex motor reactions used to maintainbalance when walking on irregular ground, the program will improvesubjects' ability to react in situation of unsteadiness and reduce theirrisk of falling. Methods: The program will be evaluated in a multicentric,cross-over randomized controlled trial. Overall, 112 subjects (aged≥65 years, ≥1 falls, POMA score 22-26/28) will be enrolled. Subjectswill be randomised in 2 groups: group A begin the training with active"SMILING shoes", group B with inactive dummy shoes. After 4 weeksof training, group A and B will exchange the shoes. Supervised trainingsessions (30 minutes twice a week for 8 weeks) include walkingtasks of progressive difficulties.To avoid a learning effect, "SMILINGshoes" perturbations will be generated in a non-linear and chaotic way.Gait performance, fear of falling, and acceptability of the program willbe assessed. Conclusion: The SMILING program is an innovative interventionfor falls prevention in older persons based on gait and balancetraining using chaotic perturbations. Because of the easy use of the"SMILING shoes", this program could be used in various settings, suchas geriatric clinics or at home.

Synovial fluid examination for the diagnosis of synovial amyloidosis in patients with chronic renal failure undergoing haemodialysis

The diagnosis of synovial amyloidosis is based upon synovial biopsy. Synovial fluid (SF) in seven patients with amyloid arthropathy associated with chronic renal failure undergoing haemodialysis were studied. The SF and synovial samples of 10 consecutive patients with seronegative mono- or oligoarthritis served as controls. Six of the seven patients with amyloid positive synovial biopsy specimens showed amyloid in their SF. No amyloid was found in the synovial tissue or fluid of the 10 patients in the control group, the sensitivity being 87.7%. The finding of amyloid in SF was highly reproducible, showing its presence in the same joint on several occasions. The deposits were Congophilia resistant to potassium permanganate pretreatment, and the immunohistochemical analysis proved that they contained beta 2 microglobulin. The high sensitivity and good reproducibility of the method shows that the finding of amyloid in SF is sufficient for the diagnosis of synovial amyloidosis. It is possible to perform immunohis

Detection of bovine foetal DNA from amniotic fluid using the polymerase chain reaction

Selostus: Sikiön DNA:n tunnistaminen naudan sikiövedestä polymeraasiketjureaktion avulla

The stationary distribution of a continuously varying strategy in a class-structured population under mutation-selection-drift balance.

Many traits and/or strategies expressed by organisms are quantitative phenotypes. Because populations are of finite size and genomes are subject to mutations, these continuously varying phenotypes are under the joint pressure of mutation, natural selection and random genetic drift. This article derives the stationary distribution for such a phenotype under a mutation-selection-drift balance in a class-structured population allowing for demographically varying class sizes and/or changing environmental conditions. The salient feature of the stationary distribution is that it can be entirely characterized in terms of the average size of the gene pool and Hamilton's inclusive fitness effect. The exploration of the phenotypic space varies exponentially with the cumulative inclusive fitness effect over state space, which determines an adaptive landscape. The peaks of the landscapes are those phenotypes that are candidate evolutionary stable strategies and can be determined by standard phenotypic selection gradient methods (e.g. evolutionary game theory, kin selection theory, adaptive dynamics). The curvature of the stationary distribution provides a measure of the stability by convergence of candidate evolutionary stable strategies, and it is evaluated explicitly for two biological scenarios: first, a coordination game, which illustrates that, for a multipeaked adaptive landscape, stochastically stable strategies can be singled out by letting the size of the gene pool grow large; second, a sex-allocation game for diploids and haplo-diploids, which suggests that the equilibrium sex ratio follows a Beta distribution with parameters depending on the features of the genetic system.

PPARγ Agonist-Induced Fluid Retention Depends on αENaC Expression in Connecting Tubules.

BACKGROUND/AIMS: Thiazolidinediones (TZDs, like rosiglitazone (RGZ)) are peroxisome proliferator-activated receptor γ (PPARγ) agonists used to treat type 2 diabetes. Clinical limitations include TZD-induced fluid retention and body weight (BW) increase, which are inhibited by amiloride, an epithelial-sodium channel (ENaC) blocker. RGZ-induced fluid retention is maintained in mice with αENaC knockdown in the collecting duct (CD). Since ENaC in the connecting tubule (CNT) rather than in CD appears to be critical for normal NaCl retention, we aimed to further explore the role of ENaC in CNT in RGZ-induced fluid retention. METHODS: Mice with conditional inactivation of αENaC in both CNT and CD were used (αENaC lox/lox AQP2-Cre; 'αENaC-CNT/CD-KO') and compared with littermate controls (αENaC lox/lox mice; 'WT'). BW was monitored and total body water (TBW) and extracellular fluid volume (ECF) were determined by bioelectrical impedance spectroscopy (BIS) before and after RGZ (320 mg/kg diet for 10 days). RESULTS: On regular NaCl diet, αENaC-CNT/CD-KO had normal BW, TBW, ECF, hematocrit, and plasma Na(+), K(+), and creatinine, associated with an increase in plasma aldosterone compared with WT. Challenging αENaC-CNT/CD-KO with a low NaCl diet unmasked impaired NaCl and K homeostasis, consistent with effective knockdown of αENaC. In WT, RGZ increased BW (+6.1%), TBW (+8.4%) and ECF (+10%), consistent with fluid retention. These changes were significantly attenuated in αENaC-CNT/CD-KO (+3.4, 1.3, and 4.3%). CONCLUSION: Together with the previous studies, the current results are consistent with a role of αENaC in CNT in RGZ-induced fluid retention, which dovetails with the physiological relevance of ENaC in this segment. © 2014 S. Karger AG, Basel.

Investigación y desarrollo en preservación digital: un balance internacional

Se presenta una panorámica de las acciones de investigación y desarrollo en preservación digital en el ámbito internacional, incluyendo un apartado dedicado a la situación en España. La mayor atención se da en las aplicaciones de preservación digital en bibliotecas y archivos, pero también se presenta someramente la situación en otros entornos como los repositorios institucionales, los archivos administrativos, los archivos personales, la industria aeroespacial y los museos. El análisis de los protagonistas de la investigación lleva a destacar el papel preeminente de algunas bibliotecas y archivos nacionales, de determinados países y una incipiente entrada de empresas de software. En cuanto a las líneas de investigación destaca la integración de herramientas para generar sistemas de preservación integrados.

Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers.

While it was thought that most of cerebral creatine is of peripheral origin, AGAT and GAMT are well expressed in CNS where brain cells synthesize creatine. While the creatine transporter SLC6A8 is expressed by microcapillary endothelial cells (MCEC) at blood-brain barrier (BBB), it is absent from their surrounding astrocytes. This raised the concept that BBB has a limited permeability for peripheral creatine, and that the brain supplies a part of its creatine by endogenous synthesis. This review brings together the latest data on creatine and guanidinoacetate transport through BBB and blood-CSF barrier (BCSFB) with the clinical evidence of AGAT-, GAMT- and SLC6A8-deficient patients, in order to delineate a clearer view on the roles of BBB and BCSFB in the transport of creatine and guanidinoacetate between periphery and CNS, and on brain synthesis and transport of creatine. It shows that in physiological conditions, creatine is taken up by CNS from periphery through SLC6A8 at BBB, but in limited amounts, and that CNS also needs its own creatine synthesis. No uptake of guanidinoacetate from periphery occurs at BBB except under GAMT deficiency, but a net exit of guanidinoacetate seems to occur from CSF to blood at BCSFB, predominantly through the taurine transporter TauT.

Vegetation and CO2 balance in an abandoned harvested peatland in Aitoneva, southern Finland

Tiivistelmä: Kasvillisuus ja CO2-tase käytöstä vapautuneella turvetuotantoalueella Kihniön Aitonevalla

What makes a host profitable? Parasites balance host nutritive resources against immunity.

Numerous host qualities can modulate parasite fitness, and among these, host nutritive resources and immunity are of prime importance. Indeed, parasite fitness increases with the amount of nutritive resources extracted from the host body and decreases with host immune response. To maximize fitness, parasites have therefore to balance these two host components. Yet, because host nutritive resources and immunity both increase with host body condition, it is unclear whether parasites perform better on hosts in prime, intermediate, or poor condition. We investigated blood meal size and survival of the ectoparasitic louse fly Crataerina melbae in relation to body condition and cutaneous immune response of their Alpine swift (Apus melba) nestling hosts. Louse flies took a smaller blood meal and lived a shorter period of time when feeding on nestlings that were experimentally food deprived or had their cutaneous immune response boosted with methionine. Consistent with these results, louse fly survival was the highest when feeding on nonexperimental nestlings in intermediate body condition. Our findings emphasize that although hosts in poor condition had a reduced immunocompetence, parasites may have avoided them because individuals in poor condition did not provide adequate resources. These findings highlight the fact that giving host immunocompetence primary consideration can result in a biased appraisal of host-parasite interactions.

Metallogenic model of the Trepca Pb-Zn-Ag skarn deposit, Kosovo: Evidence from fluid inclusions, Rare Earth Elements, and stable isotope data

The Trepca Pb-Zn-Ag skarn deposit (29 Mt of ore at 3.45% Pb, 2.30% Zn, and 80 g/t Ag) is located in the Kopaonik block of the western Vardar zone, Kosovo. The mineralization, hosted by recrystallized limestone of Upper Triassic age, was structurally and lithologically controlled. Ore deposition is spatially and temporally related with the postcollisional magmatism of Oligocene age (23-26 Ma). The deposit was formed during two distinct mineralization stages: an early prograde closed-system and a later retrograde open-system stage. The prograde mineralization consisting mainly of pyroxenes (Hd(54-100)Jo(0-45)Di(0-45)) resulted from the interaction of magmatic fluids associated with Oligocene (23-26 Ma) postcollisional magmatism. Whereas there is no direct contact between magmatic rocks and the mineralization, the deposit is classified as a distal Pb-Zn-Ag skarn. Abundant pyroxene reflects low oxygen fugacity (<10(-31) bar) and anhydrous environment. Fluid inclusion data and mineral assemblage limit the prograde stage within a temperature range between 390 degrees and 475 degrees C. Formation pressure is estimated below 900 bars. Isotopic composition of aqueous fluid, inclusions hosted by hedenbergite (delta D = -108 to -130 parts per thousand; delta O-18 = 7.5-8.0 parts per thousand), Mn-enriched mineralogy and high REE content of the host carbonates at the contact with the skarn mineralization suggest that a magmatic fluid was modified during its infiltration through the country rocks. The retrograde mineral assemblage comprises ilvaite, magnetite, arsenopyrite, pyrrhotite, marcasite, pyrite, quartz, and various carbonates. Increases in oxygen and sulfur fugacities, as well as a hydrous character of mineralization, require an open-system model. The opening of the system is related to phreatomagmatic explosion and formation of the breccia. Arsenopyrite geothermometer limits the retrograde stage within the temperature range between 350 degrees and 380 degrees C and sulfur fugacity between 10(-8.8) and 10(-7.2) bars. The principal ore minerals, galena, sphalerite, pyrite, and minor chalcopyrite, were deposited from a moderately saline Ca-Na chloride fluid at around 350 degrees C. According to the isotopic composition of fluid inclusions hosted by sphalerite (delta D = -55 to -74 parts per thousand; delta O-18 = -9.6 to -13.6 parts per thousand), the fluid responsible for ore deposition was dominantly meteoric in origin. The delta S-31 values of the sulfides spanning between -5.5 and +10 parts per thousand point to a magmatic origin of sulfur. Ore deposition appears to have been largely contemporaneous with the retrograde stage of the skarn development. Postore stage accompanied the precipitation of significant amount of carbonates including the travertine deposits at the deposit surface. Mineralogical composition of travertine varies from calcite to siderite and all carbonates contain significant amounts of Mn. Decreased formation temperature and depletion in the REE content point to an influence of pH-neutralized cold ground water and dying magmatic system.