Bovine IFNGR2, IL12RB1, IL12RB2, and IL23R polymorphisms and MAP infection status

Mycobacterium avium ssp. paratuberculosis (MAP) infection causes a chronic granulomatous inflammatory condition of the bovine gut that is characterized by diarrhea, progressive weight loss, and emaciation, and ultimately leads to loss in productivity and profitability of dairy operations. The host cytokine machinery is known to play an important role in protecting against MAP infection. Therefore, the goal of the present study was to assess whether polymorphisms in candidate genes encoding important cytokines and cytokine receptors are associated with MAP infection status of dairy cattle. MAP infection status was evaluated based on serum and milk enzyme-linked immunosorbent assays (ELISAs) for MAP-specific antibodies. Twenty previously reported polymorphisms in genes encoding bovine interferon gamma (IFNG), IFNGR1, IFNGR2, IL22, IL22RA1, IL12RB1, IL12RB2, and IL23R were genotyped in a resource population of 446 dairy Holsteins with known MAP infection status, and logistic regression was used to assess the statistical association with a binomial MAP infection status phenotype. Four SNPs in IFNGR2, IL12RB1, IL12RB2, and IL23R were found to be associated with the MAP infection status of the resource population. These results underscore the importance of cytokines and their receptors in conferring protection against MAP infection and warrant further functional characterization of these associations.     

Status of Exosphaeroma amplicauda (Stimpson, 1857), E. aphrodita (Boone, 1923) and description of three new species (Crustacea,Isopoda, Sphaeromatidae) from the north-eastern Pacific

Exosphaeroma amplicauda (Stimpson, 1857) from the west coast of North America is reviewed and redescribed and revealed to be a group of closely related species. A neotype is designated and the species redescribed based on the neotype and topotypic specimens. Exosphaeroma amplicauda is known only from the coast of California, at Marin, Sonoma and San Mateo Counties. Exosphaeroma aphrodita (Boone, 1923), type locality La Jolla, California and previously considered nomen dubium is taken out of synonymy and re-validated. A further three species: Exosphaeroma paydenae sp. n., Exosphaeroma russellhansoni sp. n., and Exosphaeroma pentcheffi sp. n. are described herein. Sphaeroma octonctum Richardson, 1899 is placed into junior synonymy with Exosphaeroma amplicauda. A key to the Pacific West Coast Exosphaeroma is provided.     

Optimizing agent-based transmission models for infectious diseases

Background

Infectious disease modeling and computational power have evolved such that large-scale agent-based models (ABMs) have become feasible. However, the increasing hardware complexity requires adapted software designs to achieve the full potential of current high-performance workstations.

Results

We have found large performance differences with a discrete-time ABM for close-contact disease transmission due to data locality. Sorting the population according to the social contact clusters reduced simulation time by a factor of two. Data locality and model performance can also be improved by storing person attributes separately instead of using person objects. Next, decreasing the number of operations by sorting people by health status before processing disease transmission has also a large impact on model performance. Depending of the clinical attack rate, target population and computer hardware, the introduction of the sort phase decreased the run time from 26 % up to more than 70 %. We have investigated the application of parallel programming techniques and found that the speedup is significant but it drops quickly with the number of cores. We observed that the effect of scheduling and workload chunk size is model specific and can make a large difference.

Conclusions

Investment in performance optimization of ABM simulator code can lead to significant run time reductions. The key steps are straightforward: the data structure for the population and sorting people on health status before effecting disease propagation. We believe these conclusions to be valid for a wide range of infectious disease ABMs. We recommend that future studies evaluate the impact of data management, algorithmic procedures and parallelization on model performance.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0612-2) contains supplementary material, which is available to authorized users.     

Endosomally stored MHC class II does not contribute to antigen presentation by dendritic cells at inflammatory conditions

Major histocompatibility complex (MHC) class II (MHCII) is constitutively expressed by immature dendritic cells (DC), but has a short half-life as a consequence of its transport to and degradation in lysosomes. For its transfer to lysosomes, MHCII is actively sorted to the intraluminal vesicles (ILV) of multivesicular bodies (MVB), a process driven by its ubiquitination. ILV have, besides their role as an intermediate compartment in lysosomal transfer, also been proposed to function as a site for MHCII antigen loading and temporal storage. In that scenario, DC would recruit antigen-loaded MHCII to the cell surface in response to a maturation stimulus by allowing ILV to fuse back with the MVB delimiting membrane. Other studies, however, explained the increase in cell surface expression during DC maturation by transient upregulation of MHCII synthesis and reduced sorting of newly synthesized MHCII to lysosomes. Here, we have characterized the relative contributions from the biosynthetic and endocytic pathways and found that the vast majority of antigen-loaded MHCII that is stably expressed at the plasma membrane by mature DC is synthesized after exposure to inflammatory stimuli. Pre-existing endosomal MHCII contributed only when it was not yet sorted to ILV at the moment of DC activation. Together with previous records, our current data are consistent with a model in which passage of MHCII through ILV is not required for antigen loading in maturing DC and in which sorting to ILV in immature DC provides a one-way ticket for lysosomal degradation.     

Probing the redox metabolism in the strictly anaerobic,extremely thermophilic,hydrogen-producing <Emphasis Type="Italic">Caldicellulosiruptor</Emphasis><Emphasis Type="Italic">saccharolyticus</Emphasis> using amperometry

Changes in the redox metabolism in the anaerobic, extremely thermophilic, hydrogen-forming bacterium Caldicellulosiruptor saccharolyticus were probed for the first time in vivo using mediated amperometry with ferricyanide as a thermotolerant external mediator. Clear differences in the intracellular electron flow were observed when cells were supplied with different carbon sources. A higher electrochemical response was detected when cells were supplied with xylose than with sucrose or glucose. Moreover, using the mediated electrochemical method, it was possible to detect differences in the electron flow between cells harvested in the exponential and stationary growth phases. The electron flow of C. saccharolyticus was dependent on the NADH- and reduced ferredoxin generation flux and the competitive behavior of cytosolic and membrane-associated oxidoreductases. Sodium oxamate was used to inhibit the NADH-dependent lactate dehydrogenase, upon which more NADH was directed to membrane-associated enzymes for ferricyanide reduction, leading to a higher electrochemical signal. The method is noninvasive and the results presented here demonstrate that this method can be used to accurately detect changes in the intracellular electron flow and to probe redox enzyme properties of a strictly anaerobic thermophile in vivo.     

The high prevalence of Torque teno virus DNA in blood donors and haemodialysis patients in southern Brazil

This study investigates the frequency of Torque teno virus (TTV) infection in 150 blood donors and 77 patients requiring haemodialysis in southern Brazil. Plasma samples were screened for TTV DNA using polymerase chain reaction (PCR). The prevalences of TTV among blood donors and patients requiring haemodialysis were 73.3% and 68.8%, respectively. The presence of TTV was correlated with age in the blood donors (p = 0.024). In haemodialysis patients, no association was found between TTV infection and the demographic parameters (age, sex and education), the duration of haemodialysis or a history of blood transfusion. This study is the first to evaluate the prevalence of TTV infection in Brazilian patients requiring haemodialysis.     

Global diversity of marine isopods (except asellota and crustacean symbionts)

The crustacean order Isopoda (excluding Asellota, crustacean symbionts and freshwater taxa) comprise 3154 described marine species in 379 genera in 37 families according to the WoRMS catalogue. The history of taxonomic discovery over the last two centuries is reviewed. Although a well defined order with the Peracarida, their relationship to other orders is not yet resolved but systematics of the major subordinal taxa is relatively well understood. Isopods range in size from less than 1 mm to Bathynomus giganteus at 365 mm long. They inhabit all marine habitats down to 7280 m depth but with few doubtful exceptions species have restricted biogeographic and bathymetric ranges. Four feeding categories are recognised as much on the basis of anecdotal evidence as hard data: detritus feeders and browsers, carnivores, parasites, and filter feeders. Notable among these are the Cymothooidea that range from predators and scavengers to external blood-sucking micropredators and parasites. Isopods brood 10-1600 eggs depending on individual species. Strong sexual dimorphism is characteristic of several families, notably in Gnathiidae where sessile males live with a harem of females while juvenile praniza stages are ectoparasites of fish. Protandry is known in Cymothoidae and protogyny in Anthuroidea. Some Paranthuridae are neotenous. About half of all coastal, shelf and upper bathyal species have been recorded in the MEOW temperate realms, 40% in tropical regions and the remainder in polar seas. The greatest concentration of temperate species is in Australasia; more have been recorded from temperate North Pacific than the North Atlantic. Of tropical regions, the Central Indo-Pacific is home to more species any other region. Isopods are decidedly asymmetrical latitudinally with 1.35 times as many species in temperate Southern Hemisphere than the temperate North Atlantic and northern Pacific, and almost four times as many Antarctic as Arctic species. More species are known from the bathyal and abyssal Antarctic than Arctic GOODS provinces, and more from the larger Pacific than Atlantic oceans. Two areas with many species known are the New Zealand-Kermadec and the Northern North Pacific provinces. Deep hard substrates such as found on seamounts and the slopes are underrepresented in samples. This, the documented numbers of undescribed species in recent collections and probable cryptic species suggest a large as yet undocumented fauna, potentially an order of magnitude greater than presently known.     

Sampling site matters when counting lymphocyte subpopulations

Clinical and scientific work routinely relies on antecubital venipunctures for hematological, immunological or other analyses on blood. This study tested the hypothesis that antecubital veins can be considered to be a good proxy for other sampling sites. Using a hematocytometer and a flow cytometer, we analyzed the cell counts from samples coming from the radial artery, the dorsal hand veins and the antecubital veins from 18 volunteers. Most surprisingly, we identified the greatest difference not to exist between arterial and venous circulation, but between the distal (radial artery & dorsal hand veins) and proximal (antecubital veins) sampling sites. Naïve T cells had a higher cell count distally compared to proximally and the reverse was true for effector memory T cells. Despite these differences there were high correlations between the different sampling sites, which partially supports our initial hypothesis. Our findings are crucial for the future design and interpretation of immunological research, and for clinical practice. Furthermore, our results suggest a role for interval lymph nodes in the trafficking of lymphocytes.     

Turning sex inside-out: Peripheral contributions to sexual differentiation of the central nervous system

ABSTRACT: Sexual differentiation of the nervous system occurs via the interplay of genetics, endocrinology and social experience through development. Much of the research into mechanisms of sexual differentiation has been driven by an implicit theoretical framework in which these causal factors act primarily and directly on sexually dimorphic neural populations within the central nervous system. This review will examine an alternative explanation by describing what is known about the role of peripheral structures and mechanisms (both neural and non-neural) in producing sex differences in the central nervous system. The focus of the review will be on experimental evidence obtained from studies of androgenic masculinization of the spinal nucleus of the bulbocavernosus, but other systems will also be considered.