Persistence of Epstein-Barr Virus in Self-Reactive Memory B Cells

Epstein-Barr virus infection has been epidemiologically associated with the development of multiple autoimmune diseases, particularly systemic lupus erythematosus and multiple sclerosis. Currently, there is no known mechanism that can account for these associations. The germinal-center (GC) model of EBV infection and persistence proposes that EBV gains access to the memory B cell compartment via GC reactions by driving infected cells to differentiate using the virus-encoded LMP1 and LMP2a proteins, which act as functional homologues of CD40 and the B cell receptor, respectively. The ability of LMP2a, when expressed in mice, to allow escape of autoreactive B cells suggests that it could perform a similar role in infected GC B cells, permitting the survival of potentially pathogenic autoreactive B cells. To test this hypothesis, we cloned and expressed antibodies from EBV⁺ and EBV⁻ memory B cells present during acute infection and profiled their self- and polyreactivity. We find that EBV does persist within self- and polyreactive B cells but find no evidence that it favors the survival of pathogenic autoreactive B cells. On the contrary, EBV⁺ memory B cells express lower levels of self-reactive and especially polyreactive antibodies than their uninfected counterparts do. Our work suggests that EBV has only a modest effect on the GC process, which allows it to access and persist within a subtly unique niche of the memory compartment characterized by relatively low levels of self- and polyreactivity. We suggest that this might reflect an active process where EBV and its human host have coevolved so as to minimize the virus''s potential to contribute to autoimmune disease.     

Diversity and geographic distribution of benthic foraminifera: a molecular perspective

The diversity and distribution of modern benthic foraminifera has been extensively studied in order to aid the paleoecological interpretation of their fossil record. Traditionally, foraminiferal species are identified based on morphological characters of their organic, agglutinated or calcareous tests. Recently, however, new molecular techniques based on analysis of DNA sequences have been introduced to study the genetic variation in foraminifera. Although the number of species for which DNA sequence data exist is still very limited, it appears that morphology-based studies largely underestimated foraminiferal diversity. Here, we present two examples of the use of DNA sequences to examine the diversity of benthic foraminifera. The first case deals with molecular and morphological variations in the well-known and common calcareous genus Ammonia. The second case presents molecular diversity in the poorly documented group of monothalamous (single-chambered) foraminifera. Both examples perfectly illustrate high cryptic diversity revealed in almost all molecular studies. Molecular results also confirm that the majority of foraminiferal species have a restricted geographic distribution and that globally distributed species are rare. This is in opposition to the theory that biogeography has no impact on the diversity of small-sized eukaryotes. At least in the case of foraminifera, size does not seem to have a main impact on dispersal capacities. However, the factors responsible for the dispersal of foraminiferal species and the extension of their geographic ranges remain largely unknown. Special Issue: Protist diversity and geographic distribution. Guest editor: W. Foissner.     

Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study

Detecting left ventricular (LV) dysfunction at an early stage is key in addressing the heart failure epidemic. In proteome profiling experiments in mice subjected either to aortic banding or sham, the circulating CXCR3 ligands monokine induced by interferon-γ (MIG) and interferon-γ inducible protein 10 (IP10) were 5 to 40 fold up-regulated at eight weeks. We assessed the diagnostic value of circulating NT-pro BNP and CXCR3 ligands (MIG, IP10, Interferon-inducible T-cell alpha chemo-attractant [I–TAC]) in patients with hypertension (≥140/90 mm Hg) associated with subclinical (n = 19) or symptomatic (n = 16) diastolic LV dysfunction on echocardiography and healthy controls. NT–pro BNP, MIG, IP10, I–TAC all increased (p ≤ 0.014) across the categories of worsening left ventricular dysfunction. In patients with symptomatic disease, MIG, IP10, and I–TAC increased 210% (p = 0.015), 140% (p = 0.007) and 120% (p = 0.035) more than NT-pro BNP. The optimal discrimination limits, obtained by maximizing Youden’s index were 246 pmol/L, 65 pg/mL, 93 pg/mL, and 24 pg/mL, respectively. The odds ratios associated with the four biomarkers were significant (p ≤ 0.010), ranging from 4.00 for IP10 to 9.69 for MIG. With adjustment for NT–pro BNP, the CXCR3 ligands retained significance (p ≤ 0.028). Adding optimized thresholds for the CXCR3 ligands to NT–pro BNP enhanced (p ≤ 0.014) the integrated discrimination improvement and the net reclassification improvement. In conclusion, congruent with the concept that inflammation plays a key role in the pathogenesis of LV dysfunction, MIG, IP10 and I–TAC add diagnostic accuracy over and beyond NT–pro BNP.     

Hydrological regulation drives regime shifts: evidence from paleolimnology and ecosystem modeling of a large shallow Chinese lake

Quantitative evidence of sudden shifts in ecological structure and function in large shallow lakes is rare, even though they provide essential benefits to society. Such ‘regime shifts’ can be driven by human activities which degrade ecological stability including water level control (WLC) and nutrient loading. Interactions between WLC and nutrient loading on the long‐term dynamics of shallow lake ecosystems are, however, often overlooked and largely underestimated, which has hampered the effectiveness of lake management. Here, we focus on a large shallow lake (Lake Chaohu) located in one of the most densely populated areas in China, the lower Yangtze River floodplain, which has undergone both WLC and increasing nutrient loading over the last several decades. We applied a novel methodology that combines consistent evidence from both paleolimnological records and ecosystem modeling to overcome the hurdle of data insufficiency and to unravel the drivers and underlying mechanisms in ecosystem dynamics. We identified the occurrence of two regime shifts: one in 1963, characterized by the abrupt disappearance of submerged vegetation, and another around 1980, with strong algal blooms being observed thereafter. Using model scenarios, we further disentangled the roles of WLC and nutrient loading, showing that the 1963 shift was predominantly triggered by WLC, whereas the shift ca. 1980 was attributed to aggravated nutrient loading. Our analysis also shows interactions between these two stressors. Compared to the dynamics driven by nutrient loading alone, WLC reduced the critical P loading and resulted in earlier disappearance of submerged vegetation and emergence of algal blooms by approximately 26 and 10 years, respectively. Overall, our study reveals the significant role of hydrological regulation in driving shallow lake ecosystem dynamics, and it highlights the urgency of using multi‐objective management criteria that includes ecological sustainability perspectives when implementing hydrological regulation for aquatic ecosystems around the globe.     

A new chromosomal race (2n=44) of Nannospalax xanthodon from Turkey (Mammalia: Rodentia)

A new karyotype for blind mole rats was recorded in Tunceli province in Eastern Turkey. The karyotype contained 44 chromosomes, including 13 biarmed pairs, 7 acrocentric pairs, and one heteromorphic pair with a submetacentric and an acrocentric homologue in the autosomal complement (FNa=69). The X chromosome was submetacentric and the Y chromosome medium-sized subtelocentric (FN=73). Distinct dark centromeric C-bands were observed on most of the biarmed and three pairs of the acrocentric autosomes. The NORs were detected on short arms of three subtelocentric pairs and one acrocentric pair of autosomes. The diploid number of chromosomes and the karyotype characteristics observed are obviously unique among hitherto studied populations of blind mole rats and the complement can be evaluated as a new chromosome race of Nannospalax xanthodon. The distribution ranges of individual chromosome races of the species recorded in Eastern Anatolia are revised and possible interracial hybridization is discussed in respect of the finding of a new race.