Spontaneously-resolving episodes of cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: Virological features and clinical outcomes

It has been reported that low-plasma cytomegalovirus (CMV) DNA loads are associated with an increased risk of overall mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Utilizing a conservative strategy for initiation of preemptive antiviral therapy (>1500 IU/mL), we characterized the virological features of spontaneously-resolving episodes of CMV DNAemia and assessed their impact on mortality through the first year after transplantation. We reviewed the CMV DNA polymerase chain reaction results and clinical charts of 230 consecutive adult patients who underwent T-cell replete allo-HSCT at our center. A total of 280 episodes of CMV DNAemia were registered in 164 patients, of which 144 episodes cleared spontaneously. Clearance of CMV DNAemia was significantly delayed in initial and recurrent self-resolving episodes featuring CMV DNA peak loads > 250 IU/mL compared with those displaying lower values. All-cause mortality in patients with self-resolving episodes of CMV DNAemia was comparable (P = 0.7) to that in patients with no CMV DNAemia and was not related to the CMV DNA peak load (≥250 IU/mL vs <250 IU/mL) (P = 0.6). In summary, in our setting, the magnitude of the CMV DNA peak load reached during self-resolving episodes of CMV DNAemia correlated directly with duration of episodes, but had no apparent impact on all-cause mortality taking patients with no documented CMV DNAemia as a reference.     

Germinal center B cell initiation,GC maturation,and the coevolution of its stromal cell niches

Throughout the developing GC response, B cell survival and fate choices made at the single cell level are dependent on signals received largely through interactions with other cells, often with cognate T cells. The type of signals that a given B cell can encounter is dictated by its location within tissue microarchitecture. The focus of this review is on the initiation and evolution of the GC response at the earliest time points. Here, we review the key factors influencing the progression of GC B cell differentiation that are both stage and context dependent. Finally, we describe the coevolution of niches within and surrounding the GC that influence the outcome of the GC response.     

Diversity and distribution of Maize-associated totivirus strains from Tanzania

Virus Genes - Typically associated with fungal species, members of the viral family Totiviridae have recently been shown to be associated with plants, including important crop species, such as...     

Description of two new species of allocreadiid trematodes (Digenea: Allocreadiidae) in middle American freshwater fishes using an integrative taxonomy approach

Parasitology Research - Integrative taxonomy uses several sources of information to establish more robust species delimitation criteria. In this study, we followed that approach to describe two new...     

Taxonomic status of Rhabdochona ictaluri (Nematoda: Rhabdochonidae) based on molecular and morphological evidence

The genus Rhabdochona includes more than 100 species infecting freshwater fishes in all zoogeographical regions of the world. In Mexico, 12 nominal species of Rhabdochona have been recorded. Of these, Rhabdochona ictaluri was originally described as a parasite of endemic catfishes of the family Ictaluridae; however, the species was later considered on morphological grounds as a junior synonym of Rhabdochona kidderi. In this study, newly sampled specimens of R. ictaluri were obtained from the type host and type locality and were used to perform a detailed morphological analysis and molecular phylogenetic inferences through one mitochondrial and two nuclear genes; data were used in an integrative taxonomy context to test the taxonomic status of R. ictaluri. This approach proved to be very useful to confirm the validity of this species, and robust species limits were established between these two putative species considering morphology, molecular data, host association, and biogeography.

     

Prion neurotoxicity

Although the mechanisms underlying prion propagation and infectivity are now well established, the processes accounting for prion toxicity and pathogenesis have remained mysterious. These processes are of enormous clinical relevance as they hold the key to identification of new molecular targets for therapeutic intervention. In this review, we will discuss two broad areas of investigation relevant to understanding prion neurotoxicity. The first is the use of in vitro experimental systems that model key events in prion pathogenesis. In this context, we will describe a hippocampal neuronal culture system we developed that reproduces the earliest pathological alterations in synaptic morphology and function in response to PrP^Sc. This system has allowed us to define a core synaptotoxic signaling pathway involving the activation of NMDA and AMPA receptors, stimulation of p38 MAPK phosphorylation and collapse of the actin cytoskeleton in dendritic spines. The second area concerns a striking and unexpected phenomenon in which certain structural manipulations of the PrP^C molecule itself, including introduction of N‐terminal deletion mutations or binding of antibodies to C‐terminal epitopes, unleash powerful toxic effects in cultured cells and transgenic mice. We will describe our studies of this phenomenon, which led to the recognition that it is related to the induction of large, abnormal ionic currents by the structurally altered PrP molecules. Our results suggest a model in which the flexible N‐terminal domain of PrP^C serves as a toxic effector which is regulated by intramolecular interactions with the globular C‐terminal domain. Taken together, these two areas of study have provided important clues to underlying cellular and molecular mechanisms of prion neurotoxicity. Nevertheless, much remains to be done on this next frontier of prion science.