Late Stage Infection in Sleeping Sickness

At the turn of the 19th century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles

Immunological aspects in chronic lymphocytic leukemia (CLL) development

Chronic lymphocytic leukemia (CLL) is unique among B cell malignancies in that the malignant clones can be featured either somatically mutated or unmutated IGVH genes. CLL cells that express unmutated immunoglobulin variable domains likely underwent final development prior to their entry into the germinal center, whereas those that express mutated variable domains likely transited through the germinal center and then underwent final development. Regardless, the cellular origin of CLL remains unknown. The aim of this review is to summarize immunological aspects involved in this process and to provide insights about the complex biology and pathogenesis of this disease. We propose a mechanistic hypothesis to explain the origin of B-CLL clones into our current picture of normal B cell development. In particular, we suggest that unmutated CLL arises from normal B cells with self-reactivity for apoptotic bodies that have undergone receptor editing, CD5 expression, and anergic processes in the bone marrow. Similarly, mutated CLL would arise from cells that, while acquiring self-reactivity for autoantigens—including apoptotic bodies—in germinal centers, are also still subject to tolerization mechanisms, including receptor editing and anergy. We believe that CLL is a proliferation of B lymphocytes selected during clonal expansion through multiple encounters with (auto)antigens, despite the fact that they differ in their state of activation and maturation. Autoantigens and microbial pathogens activate BCR signaling and promote tolerogenic mechanisms such as receptor editing/revision, anergy, CD5+ expression, and somatic hypermutation in CLL B cells. The result of these tolerogenic mechanisms is the survival of CLL B cell clones with similar surface markers and homogeneous gene expression signatures. We suggest that both immunophenotypic surface markers and homogenous gene expression might represent the evidence of several attempts to re-educate self-reactive B cells

The immunopathology of ANCA-associated vasculitis.

The small-vessel vasculitides are a group of disorders characterised by variable patterns of small blood vessel inflammation producing a markedly heterogeneous clinical phenotype. While any vessel in any organ may be involved, distinct but often overlapping sets of clinical features have allowed the description of three subtypes associated with the presence of circulating anti-neutrophil cytoplasmic antibodies (ANCA), namely granulomatosis with polyangiitis (GPA, formerly known as Wegener's Granulomatosis), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (eGPA, formerly known as Churg-Strauss syndrome). Together, these conditions are called the ANCA-associated vasculitidies (AAV). Both formal nomenclature and classification criteria for the syndromes have changed repeatedly since their description over 100 years ago and may conceivably do so again following recent reports showing distinct genetic associations of patients with detectable ANCA of distinct specificities. ANCA are not only useful in classifying the syndromes but substantial evidence implicates them in driving disease pathogenesis although the mechanism by which they develop and tolerance is broken remains controversial. Advances in our understanding of the pathogenesis of the syndromes have been accompanied by some progress in treatment, although much remains to be done to improve the chronic morbidity associated with the immunosuppression required for disease control

Imports and isotopes: a modern baseline study for interpreting Iron Age and Roman trade in fallow deer antlers

The European Fallow deer (Dama dama dama) became extinct in the British Isles and most of continental Europe at the time of the Last Glacial Maximum, with the species becoming restricted to an Anatolian refugium (Masseti et al. 2008). Human-mediated reintroductions resulted in fallow populations in Rhodes, Sicily, Mallorca, Iberia and other parts of western Europe (Sykes et al. 2013). Eventually, the species was brought to Britain by the Romans during the 1st century AD, with a breeding population being established at Fishbourne Roman Palace (Sykes et al. 2011). The human influence on the present-day distribution of the species makes it particularly interesting from a zooarchaeological perspective. This paper describes my MSc research, as part of the AHRC-funded project Dama International: Fallow Deer and European Society 6000 BC–AD 1600, looking at antlers from Iron Age and Roman sites in Britain for evidence of trade in body parts and whether this can be elucidated by a parallel stable isotope study of modern fallow antlers of known provenance

A mountaintop swarm of the hemipteran Nysius raphanus in New Mexico, with notes on other insects

Volume: 51Start Page: 166End Page: 16

Notes on the group of Andrena carlini Cookorell, with description of a new species from California (Hymenoptera: Apoidea)

Volume: 25Start Page: 33End Page: 3

A new species of Andrena at the Micrandrena-Scaphandrena boundary (Hymenoptera: Apoidea)

Volume: 63Start Page: 325End Page: 32

The modified hind wing of Euglossa (Hymenoptera: Apoidea.)

Volume: 27Start Page: 181End Page: 18