Differential expression of TGF-β isoforms during postlactational mammary gland involution

After cessation of lactation, the mammary gland undergoes involution, which is characterized by a massive epithelial cell death and proteolytic degradation of the extracellular matrix. Whereas the expression patterns and also the function of TGF-beta isoforms during mammary gland branching morphogenesis and lactation are well understood, their expression during postlactational involution and therefore a possible role in this process is poorly known. In this study we show that TGF-beta3 expression is dramatically induced (>fivefold) during mouse mammary gland involution when compared to that of virgin mouse, reaching a maximal expression level at day 4 after weaning. In contrast, other TGF-beta isoforms do not display significant increase in expression during involution (TGF-beta1, 1.3-fold and TGF-beta2, <1.5-fold) when compared to that of virgin or lactating mice. During mammary gland involution, TGF-beta3 is expressed in the epithelial layer and particularly in myoepithelial cells. A comparison of the kinetics of TGF-beta3 expression to that of programmed cell death and degradation of the basement membrane suggests that TGF-beta3 functions in the remodeling events of the extracellular matrix during the second stage of involution.     

Astrocytic Gap Junctional Communication Decreases Neuronal Vulnerability to Oxidative Stress-Induced Disruption of Ca2+ Homeostasis and Cell Death

Abstract: We investigated the effect of uncoupling astrocytic gap junctions on neuronal vulnerability to oxidative injury in embryonic rat hippocampal cell cultures. Mixed cultures (neurons growing on an astrocyte monolayer) treated with 18-α-glycyrrhetinic acid (GA), an uncoupler of gap junctions, showed markedly enhanced generation of intracellular peroxides (2,7-dichlorofluorescein fluorescence), impairment of mitochondrial function [(dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction], and cell death (lactate dehydrogenase release) following exposure to oxidative insults (FeSO₄ and 4-hydroxynonenal). GA alone had little or no effect on basal levels of peroxides, mitochondrial function, or neuronal survival. Intercellular dye transfer analyses revealed extensive astrocyte-astrocyte coupling but no astrocyte-neuron or neuron-neuron coupling in the mixed cultures. Studies of pure astrocyte cultures and microscope analyses of neurons in mixed cultures showed that the increased oxidative stress and cell death in GA-treated cultures occurred only in neurons and not in astrocytes. Antioxidants (propyl gallate and glutathione) blocked the death of neurons exposed to FeSO₄/GA. Elevations of neuronal intracellular calcium levels ([Ca²⁺]_i) induced by FeSO₄ were enhanced in neurons in mixed cultures exposed to GA. Removal of extracellular Ca²⁺ and the L-type Ca²⁺ channel blocker nimodipine prevented impairment of mitochondrial function and cell death induced by FeSO₄ and GA, whereas glutamate receptor antagonists were ineffective. Finally, GA exacerbated kainate- and FeSO₄-induced injury to pyramidal neurons in organotypic hippocampal slice cultures. The data suggest that interastrocytic gap junctional communication decreases neuronal vulnerability to oxidative injury by a mechanism involving stabilization of cellular calcium homeostasis and dissipation of oxidative stress.     

Analyses of quantitative trait loci associated with resistance to shape Sclerotinia sclerotiorum in sunflowers (shape Helianthus annuus L.) using molecular markers

Restriction fragment length polymorphism and isoenzyme markers were used to investigate quantitative trait loci involved in sunflower resistance to mycelial extension of Sclerotinia sclerotiorum on leaves and capitula. Seed weight, oil content and flowering data were also evaluated. Four quantitative trait loci were demonstrated for leaf resistance and two for capitulum resistance. One of these zones appears involved in resistance to both types of S. sclerotiorum attack while the others appear specific for resistance of one part of the plant. Two quantitative trait loci were detected for seed weight, three for oil content and three for flowering date. Individual quantitative trait loci explained 9% to 48% of the phenotypic variability, confirming the polygenic basis of the quantitative traits studied. Overall, the quantitative trait loci explain 60% of the genetic variation for leaf resistance and 38% for capitulum resistance to S. sclerotiorum. One linkage group is particularly interesting since it includes quantitative trait loci for all the five quantitative traits measured. Hypotheses for linkage versus pleiotropy and consequences of all the results in resistance breeding are discussed.     

OPA1 (dys)functions

Mitochondrial morphology varies according to cell type and cellular context from an interconnected filamentous network to isolated dots. This morphological plasticity depends on mitochondrial dynamics, a balance between antagonistic forces of fission and fusion. DRP1 and FIS1 control mitochondrial outer membrane fission and Mitofusins its fusion. This review focuses on OPA1, one of the few known actors of inner membrane dynamics, whose mutations provoke an optic neuropathy. Since its first identification in 2000 the characterization of the functions of OPA1 has made rapid progress thus providing numerous clues to unravel the pathogenetic mechanisms of ADOA-1.     

Parental Use of Corporal Punishment in Europe: Intersection between Public Health and Policy

Studies have linked the use of corporal punishment of children to the development of mental health disorders. Despite the recommendation of international governing bodies for a complete ban of the practice, there is little European data available on the effects of corporal punishment on mental health and the influence of laws banning corporal punishment. Using data from the School Children Mental Health Europe survey, the objective of this cross-sectional study was to examine the prevalence and legal status of corporal punishment across six European countries and to evaluate the association between parental use of corporal punishment and children’s mental health. The study found that odds of having parents who reported using occasional to frequent corporal punishment were 1.7 times higher in countries where its use is legal, controlling for socio-demographic factors. Children with parents who reported using corporal punishment had higher rates of both externalized and internalized mental health disorders.     

Behavioural Effects of Tourism on Oceanic Common Dolphins,Delphinus sp., in New Zealand: The Effects of Markov Analysis Variations and Current Tour Operator Compliance with Regulations

Common dolphins, Delphinus sp., are one of the marine mammal species tourism operations in New Zealand focus on. While effects of cetacean-watching activities have previously been examined in coastal regions in New Zealand, this study is the first to investigate effects of commercial tourism and recreational vessels on common dolphins in an open oceanic habitat. Observations from both an independent research vessel and aboard commercial tour vessels operating off the central and east coast Bay of Plenty, North Island, New Zealand were used to assess dolphin behaviour and record the level of compliance by permitted commercial tour operators and private recreational vessels with New Zealand regulations. Dolphin behaviour was assessed using two different approaches to Markov chain analysis in order to examine variation of responses of dolphins to vessels. Results showed that, regardless of the variance in Markov methods, dolphin foraging behaviour was significantly altered by boat interactions. Dolphins spent less time foraging during interactions and took significantly longer to return to foraging once disrupted by vessel presence. This research raises concerns about the potential disruption to feeding, a biologically critical behaviour. This may be particularly important in an open oceanic habitat, where prey resources are typically widely dispersed and unpredictable in abundance. Furthermore, because tourism in this region focuses on common dolphins transiting between adjacent coastal locations, the potential for cumulative effects could exacerbate the local effects demonstrated in this study. While the overall level of compliance by commercial operators was relatively high, non-compliance to the regulations was observed with time restriction, number or speed of vessels interacting with dolphins not being respected. Additionally, prohibited swimming with calves did occur. The effects shown in this study should be carefully considered within conservation management plans, in order to reduce the risk of detrimental effects on common dolphins within the region.     

Viral Dose and Immunosuppression Modulate the Progression of Acute BVDV-1 Infection in Calves: Evidence of Long Term Persistence after Intra-Nasal Infection

Bovine viral diarrhoea virus (BVDV) infection of cattle causes a diverse range of clinical outcomes from being asymptomatic, or a transient mild disease, to producing severe cases of acute disease leading to death. Four groups of calves were challenged with a type 1 BVDV strain, originating from a severe outbreak of BVDV in England, to study the effect of viral dose and immunosuppression on the viral replication and transmission of BVDV. Three groups received increasing amounts of virus: Group A received 10^2.55TCID₅₀/ml, group B 10^5.25TCID₅₀/ml and group C 10^6.7TCID ₅₀/ml. A fourth group (D) was inoculated with a medium dose (10^5.25TCID₅₀/ml) and concomitantly treated with dexamethasone (DMS) to assess the effects of chemically induced immunosuppression. Naïve calves were added as sentinel animals to assess virus transmission. The outcome of infection was dose dependent with animals given a higher dose developing severe disease and more pronounced viral replication. Despite virus being shed by the low-dose infection group, BVD was not transmitted to sentinel calves. Administration of dexamethasone (DMS) resulted in more severe clinical signs, prolonged viraemia and virus shedding. Using PCR techniques, viral RNA was detected in blood, several weeks after the limit of infectious virus recovery. Finally, a recently developed strand-specific RT-PCR detected negative strand viral RNA, indicative of actively replicating virus, in blood samples from convalescent animals, as late as 85 days post inoculation. This detection of long term replicating virus may indicate the way in which the virus persists and/or is reintroduced within herds.