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.     

Structurally and functionally unique complexins at retinal ribbon synapses

Ribbon synapses in retinal sensory neurons maintain large pools of readily releasable synaptic vesicles. This allows them to release several hundreds of vesicles per second at every presynaptic release site. The molecular components that cause this high transmitter release efficiency of ribbon synapses are unknown. In the present study, we identified and characterized two novel vertebrate complexins (CPXs), CPXs III and IV, that are the only CPX isoforms present in retinal ribbon synapses. CPXs III and IV are COOH-terminally farnesylated, and, like CPXs I and II, bind to SNAP receptor complexes. CPXs III and IV can functionally replace CPXs I and II, and their COOH-terminal farnesylation regulates their synaptic targeting and modulatory function in transmitter release. The novel CPXs III and IV may contribute to the unique release efficacy of retinal sensory neurons.     

11β-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches

The inhibition of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), which catalyzes the conversion of inactive 11-ketoglucocorticoids to active 11β-hydroxyglucocorticoids, emerged as promising strategy to treat symptoms of the metabolic syndrome, including obesity and type 2 diabetes. In this study the leaves of the anti-diabetic medicinal plant loquat (Eriobotrya japonica) were phytochemically investigated following hints from a pharmacophore-based virtual screening and a bioactivity-guided approach. Determination of the 11β-HSD1 and 11β-HSD2 inhibitory activities in cell lysates revealed triterpenes from the ursane type as selective, low micro-molar inhibitors of 11β-HSD1, that is, corosolic acid (1), 3-epicorosolic acid methyl ester (4), 2-α hydroxy-3-oxo urs-12-en-28-oic acid (6), tormentic acid methyl ester (8), and ursolic acid (9). Importantly, a mixture of loquat constituents with moderate activities displayed a pronounced additive effect. By means of molecular modeling studies and the identification of the 11β-HSD1-inhibiting 11-keto-ursolic acid (17) and 3-acetyl-11-keto-ursolic acid (18) a structure–activity relationship was deduced for this group of pentacyclic triterpenes. The mechanism of action elucidated in the present work together with the previously determined pharmacological activities provides these natural products with an astonishing multi-targeted anti-diabetic profile.     

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.     

The circadian system of ruin lizards: a seasonally changing neuroendocrine loop?

Previous studies have shown that the amplitude of daily melatonin production in cultured ruin lizard pineal organs explanted in the summer is significantly higher than that from organs explanted in the winter. To test whether seasonal photoperiodic changes are decoded autonomously by the pineal gland, pineals explanted in summer were cultured in vitro and exposed to changes between winter and summer photoperiods. The changes in photoperiod duration did not affect the daily profiles of in vitro melatonin production. The discrepancy between the present in vitro results and those from lizards exposed to winter or summer photoperiods before pineal explantation supports the view that circadian information entering the pineal gland via its innervation is involved in determining seasonal changes of melatonin production in ruin lizards. We further examined whether a central component of the circadian system of ruin lizards, specifically the retinae of the lateral eyes, expresses similar seasonal changes in function as does the pineal gland. We did not find any difference between summer and autumn-winter in the effectiveness of either bilateral retinalectomy or optic nerve lesion-at the level of the optic chiasm-in altering circadian locomotor behavior in constant conditions. Both surgical procedures mostly induced a shortening of the free-running period of the locomotor rhythm of similar magnitude in all seasons. Thus, the retinae do not appear to participate in the seasonal reorganization of the circadian system in ruin lizards.     

Detection of viral sequences in semen of honeybees (Apis mellifera): evidence for vertical transmission of viruses through drones

Honeybees (Apis mellifera) can be attacked by many eukaryotic parasites, and bacterial as well as viral pathogens. Especially in combination with the ectoparasitic mite Varroa destructor, viral honeybee diseases are becoming a major problem in apiculture, causing economic losses worldwide. Several horizontal transmission routes are described for some honeybee viruses. Here, we report for the first time the detection of viral sequences in semen of honeybee drones suggesting mating as another horizontal and/or vertical route of virus transmission. Since artificial insemination and controlled mating is widely used in honeybee breeding, the impact of our findings for disease transmission is discussed.     

Simvastatin prolongs survival times in prion infections of the central nervous system

Prion diseases are fatal and at present there are neither cures nor palliative therapies known/available, which delay disease onset or progression. Cholesterol-lowering drugs have been reported to inhibit prion replication in infected cell cultures and to modulate inflammatory reactions. We aimed to determine whether simvastatin-treatment could delay disease onset in a murine prion model. Groups of mice were intracerebrally infected with two doses of scrapie strain 139A. Simvastatin-treatment commenced 100 days postinfection. The treatment did not affect deposition of misfolded prion protein PrP(res). However, expression of marker proteins for glia activation like major histocompatibility class II and galectin-3 was found to be affected. Analysis of brain cholesterol synthesis and metabolism revealed a mild reduction in cholesterol precursor levels, whereas levels of cholesterol and cholesterol metabolites were unchanged. Simvastatin-treatment significantly delayed disease progression and prolonged survival times in established prion infection of the CNS (p < or = 0.0003). The results suggest that modulation of glial responses and the therapeutic benefit observed in our murine prion model of simvastatin is not due to the cholesterol-lowering effect of this drug.     

Hepatitis E: an overview

The hepatitis E virus (HEV) is a non-enveloped, positive-sense, single-stranded RNA virus with icosahedral symmetry. Although it is related to the alpha-virus superfamily, the HEV is classified as a separate Hepatitis E-like viruses genus. Infection in humans occurs in sporadic and epidemic forms and can cause an acute, self-limited, icteric hepatitis. Recent studies indicate the existence of a reservoir in animals.