Characterizing a hybrid zone between a cryptic species pair of freshwater snails

Characterizing hybrid zones and their dynamics is a central goal in evolutionary biology, but this is particularly challenging for morphologically cryptic species. The lack of conspicuous divergence between parental types means intermediate hybrid forms often go undetected. We aimed to detect and characterize a suspected hybrid zone between a pair of morphologically cryptic lineages of the freshwater snail, Radix. We sampled Radix from across a contact zone between two mitochondrial lineages (Radix balthica and an undescribed lineage termed ‘MOTU3’) and detected admixture between two nuclear genotype clusters, which were significantly but not categorically associated with the mitochondrial lineages. Using a model selection approach, we show that the admixture cline is best explained by an interaction between precipitation and temperature gradients over the area, rather than geographic distance. We thus hypothesize that the correlation with climatic gradients suggests environmental selection has played a role in maintaining the hybrid zone. In a 2050 climate change scenario, we furthermore predict an expansion of one of the nuclear clusters and a widening of the hybrid zone as the climate warms and dries.     

Distribution and cellular localization of caldendrin immunoreactivity in adult human forebrain.

We investigated by immunohistochemistry (IHC) the distribution of caldendrin, the founding member of a novel family of neuronal calcium-binding proteins closely related to calmodulin, in human forebrain. Caldendrin immunoreactivity was unevenly distributed, with prominent staining in the paleo- and neocortex, hippocampus, and hypothalamus. With the exception of the hypothalamus, labeling was restricted to the somato-dendritic compartment of neurons. This distribution completely matches that reported in rat, indicating that the cellular function is most likely conserved among species. Therefore, one prerequisite for functional studies in rodent models aimed at elucidation of mechanisms with relevance for humans can be based on the present findings.     

The replacement histone H2A.Z in a hyperacetylated form is a feature of active genes in the chicken

The replacement histone H2A.Z is variously reported as being linked to gene expression and preventing the spread of heterochromatin in yeast, or concentrated at heterochromatin in mammals. To resolve this apparent dichotomy, affinity-purified antibodies against the N-terminal region of H2A.Z, in both a triacetylated and non-acetylated state, are used in native chromatin immmuno-precipitation experiments with mononucleosomes from three chicken cell types. The hyperacetylated species concentrates at the 5′ end of active genes, both tissue specific and housekeeping but is absent from inactive genes, while the unacetylated form is absent from both active and inactive genes. A concentration of H2A.Z is also found at insulators under circumstances implying a link to barrier activity but not to enhancer blocking. Although acetylated H2A.Z is widespread throughout the interphase genome, at mitosis its acetylation is erased, the unmodified form remaining. Thus, although H2A.Z may operate as an epigenetic marker for active genes, its N-terminal acetylation does not.     

Freezing tolerance in two Norway spruce (Picea abies [L.] Karst.) progenies is physiologically correlated with drought tolerance

The goal of the present study was to investigate whether seedlings of Norway spruce (Picea abies [L.] Karst.) from a frost tolerant progeny (P2), were more drought tolerant than seedlings from a less frost tolerant progeny (P1). Progenies differing in freezing tolerance were identified by exposing seedlings in autumn in a large-scale trial to temperatures from -11 to -15 degrees C and scoring the degree of needle injury. Seedlings from P1 and P2 were grown from seeds for about 1 year under controlled conditions in a climatized growth room and were exposed to drought stress by withholding water for about 3 weeks. Drought caused reductions in biomass in both progenies but to a stronger extent in P1 than in P2. Seedlings of P2 were able to fully maintain root biomass. They also showed less water loss in different tissues. Decreases in quantum yield efficiency of photosystem II of dark-adapted plants occurred several days later in P2 than in P1. New proteins of molecular masses of 24.3 and 25.5 kDa appeared during drought stress. Since they occurred in both progenies a role of these proteins in progeny-related differences in drought performance is unlikely. Progeny 2 contained inherently higher superoxide dismutase and lower peroxidase activities than progeny 1. In conclusion, freezing and drought-tolerance respective -sensitivity were co-occurring traits in the spruce progenies studied here. Pre-existing high activities of enzymes protecting against oxidative stress in seedlings may have contributed to increase stress tolerance in P2 compared with P1.     

Identification of low molecular weight pyroglutamate A{beta} oligomers in Alzheimer disease: a novel tool for therapy and diagnosis

N-terminally truncated Aβ peptides starting with pyroglutamate (AβpE3) represent a major fraction of all Aβ peptides in the brain of Alzheimer disease (AD) patients. AβpE3 has a higher aggregation propensity and stability and shows increased toxicity compared with full-length Aβ. In the present work, we generated a novel monoclonal antibody (9D5) that selectively recognizes oligomeric assemblies of AβpE3 and studied the potential involvement of oligomeric AβpE3 in vivo using transgenic mouse models as well as human brains from sporadic and familial AD cases. 9D5 showed an unusual staining pattern with almost nondetectable plaques in sporadic AD patients and non-demented controls. Interestingly, in sporadic and familial AD cases prominent intraneuronal and blood vessel staining was observed. Using a novel sandwich ELISA significantly decreased levels of oligomers in plasma samples from patients with AD compared with healthy controls were identified. Moreover, passive immunization of 5XFAD mice with 9D5 significantly reduced overall Aβ plaque load and AβpE3 levels, and normalized behavioral deficits. These data indicate that 9D5 is a therapeutically and diagnostically effective monoclonal antibody targeting low molecular weight AβpE3 oligomers.     

Dietary intake of plant sterols stably increases plant sterol levels in the murine brain

Plant sterols such as sitosterol and campesterol are frequently administered as cholesterol-lowering supplements in food. Recently, it has been shown in mice that, in contrast to the structurally related cholesterol, circulating plant sterols can enter the brain. We questioned whether the accumulation of plant sterols in murine brain is reversible. After being fed a plant sterol ester-enriched diet for 6 weeks, C57BL/6NCrl mice displayed significantly increased concentrations of plant sterols in serum, liver, and brain by 2- to 3-fold. Blocking intestinal sterol uptake for the next 6 months while feeding the mice with a plant stanol ester-enriched diet resulted in strongly decreased plant sterol levels in serum and liver, without affecting brain plant sterol levels. Relative to plasma concentrations, brain levels of campesterol were higher than sitosterol, suggesting that campesterol traverses the blood-brain barrier more efficiently. In vitro experiments with brain endothelial cell cultures showed that campesterol crossed the blood-brain barrier more efficiently than sitosterol. We conclude that, over a 6-month period, plant sterol accumulation in murine brain is virtually irreversible.     

AKAP79/150 interacts with the neuronal calcium-binding protein caldendrin

The A kinase-anchoring protein AKAP79/150 is a postsynaptic scaffold molecule and a key regulator of signaling events. At the postsynapse it coordinates phosphorylation and dephosphorylation of receptors via anchoring kinases and phosphatases near their substrates. Interactions between AKAP79 and two Ca(2+) -binding proteins caldendrin and calmodulin have been investigated here. Calmodulin is a known interaction partner of AKAP79/150 that has been shown to regulate activity of the kinase PKC in a Ca(2+) -dependent manner. Pull-down experiments and surface plasmon resonance biosensor analyses have been used here to demonstrate that AKAP79 can also interact with caldendrin, a neuronal calcium-binding protein implicated in regulation of Ca(2+) -influx and release. We demonstrate that calmodulin and caldendrin compete for a partially overlapping binding site on AKAP79 and that their binding is differentially dependent on calcium. Therefore, this competition is regulated by calcium levels. Moreover, both proteins have different binding characteristics suggesting that the two proteins might play complementary roles. The postsynaptic enrichment, the complex binding mechanism, and the competition with calmodulin, makes caldendrin an interesting novel player in the signaling toolkit of the AKAP interactome.