Habitat‐driven population structure of bottlenose dolphins,Tursiops truncatus,in the North‐East Atlantic

Despite no obvious barrier to gene flow, historical environmental processes and ecological specializations can lead to genetic differentiation in highly mobile animals. Ecotypes emerged in several large mammal species as a result of niche specializations and/or social organization. In the North‐West Atlantic, two distinct bottlenose dolphin (Tursiops truncatus) ecotypes (i.e. ‘coastal’ and ‘pelagic’) have been identified. Here, we investigated the genetic population structure of North‐East Atlantic (NEA) bottlenose dolphins on a large scale through the analysis of 381 biopsy‐sampled or stranded animals using 25 microsatellites and a 682‐bp portion of the mitochondrial control region. We shed light on the likely origin of stranded animals using a carcass drift prediction model. We showed, for the first time, that coastal and pelagic bottlenose dolphins were highly differentiated in the NEA. Finer‐scale population structure was found within the two groups. We suggest that distinct founding events followed by parallel adaptation may have occurred independently from a large Atlantic pelagic population in the two sides of the basin. Divergence could be maintained by philopatry possibly as a result of foraging specializations and social organization. As coastal environments are under increasing anthropogenic pressures, small and isolated populations might be at risk and require appropriate conservation policies to preserve their habitats. While genetics can be a powerful first step to delineate ecotypes in protected and difficult to access taxa, ecotype distinction should be further documented through diet studies and the examination of cranial skull features associated with feeding.     

Multiple-binding-site mechanism explains concentration-dependent unbinding rates of DNA-binding proteins

Recent work has demonstrated concentration-dependent unbinding rates of proteins from DNA, using fluorescence visualization of the bacterial nucleoid protein Fis [Graham et al. (2011) (Concentration-dependent exchange accelerates turnover of proteins bound to double-stranded DNA. Nucleic Acids Res., 39:2249)]. The physical origin of this concentration-dependence is unexplained. We use a combination of coarse-grained simulation and theory to demonstrate that this behavior can be explained by taking into account the dimeric nature of the protein, which permits partial dissociation and exchange with other proteins in solution. Concentration-dependent unbinding is generated by this simple model, quantitatively explaining experimental data. This effect is likely to play a major role in determining binding lifetimes of proteins in vivo where there are very high concentrations of solvated molecules.     

The effect of habitat temperature on serum antifreeze glycoprotein (AFGP) activity in Notothenia rossii (Pisces: Nototheniidae) in the Southern Ocean

The marble notothen, Notothenia rossii, is widely distributed around the waters of sub-Antarctic islands in the Southern Ocean and is exposed to different temperatures that range from ?1.5 to 8 °C. This study investigates whether the different environmental conditions experienced by N. rossii at different latitudes in the Southern Ocean affect the levels of its blood serum antifreeze glycoprotein (AFGP). N. rossii specimens were collected from four localities, including the Ob’ Seamount in the Indian Ocean sector, and South Georgia Island, South Shetland Islands and Dallman Bay in the Atlantic Ocean sector. Serum AFGP activity was determined in terms of thermal hysteresis, i.e. the difference between the equilibrium melting and non-equilibrium freezing points (f.p.s.). Among the four populations, the Ob’ Seamount specimen had the lowest serum AFGP activity (0.44 °C) and concentration (4.88 mg/mL), and the highest non-equilibrium f.p. (?1.39 °C). These results are consistent with the warmer, ice-free waters around the Ob’ Seamount. The other three higher latitude populations have 2–3 times greater serum AFGP activity and concentration, and much lower non-equilibrium f.p.s. In contrast, the physiological profiles of serum AFGP size isoforms revealed that all N. rossii populations, including the Ob’ Seamount specimen, possess an extensive complements of AFGP proteins. Isoform variation was observed, especially in the large size isoforms (AFGPs 1–5), when compared to AFGP of the high Antarctic Dissostichus mawsoni. The lower levels of AFGP and the absence of some of the large isoforms are likely responsible for higher non-equilibrium f.p.s. of the Ob’ seamount specimen.     

Impact of sulphur dioxide on the viability,culturability, and volatile phenol production of Dekkera bruxellensis in wine

Viability and culturability of eight Dekkera bruxellensis strains in wine along with the accumulation of volatile phenols in response to increasing concentrations of molecular sulphur dioxide (mSO₂) were investigated. mSO₂ concentrations up to 1 mg/L induced the non-culturable state of a portion of the population in all the strains to a different extent for each strain, although the cells were still viable. At 1.4 mg/L mSO₂, cells were non-culturable, though 0.38–29.01 % of cells retained their viability. When exposed to 2.1 mg/L mSO₂, viable cells were not detected. Up to 0.24 mg/L 4-vinylguaiacol and up to 0.73 mg/L 4-ethylphenol were accumulated by non-culturable and dead Dekkera bruxellensis strains, respectively. The concentration of mSO₂ needed for the transition from viable to non-culturable state of D. bruxellensis strains was higher in wine than in synthetic wine medium. The volatile phenols accumulated in wine were different from those produced in synthetic wine medium, although their accumulation kinetics were similar.     

Protein profiling in the gut of Penaeus monodon gavaged with oral WSSV‐vaccines and live white spot syndrome virus

White spot syndrome virus (WSSV) is a pathogen that causes considerable mortality of the farmed shrimp, Penaeus monodon. Candidate ‘vaccines’, WSSV envelope protein VP28 and formalin‐inactivated WSSV, can provide short‐lived protection against the virus. In this study, P. monodon was orally intubated with the aforementioned vaccine candidates, and protein expression in the gut of immunised shrimps was profiled. The alterations in protein profiles in shrimps infected orally with live‐WSSV were also examined. Seventeen of the identified proteins in the vaccine and WSSV‐intubated shrimps varied significantly compared to those in the control shrimps. These proteins, classified under exoskeletal, cytoskeletal, immune‐related, intracellular organelle part, intracellular calcium‐binding or energy metabolism, are thought to directly or indirectly affect shrimp's immunity. The changes in the expression levels of crustacyanin, serine proteases, myosin light chain, and ER protein 57 observed in orally vaccinated shrimp may probably be linked to immunoprotective responses. On the other hand, altered expression of proteins linked to exoskeleton, calcium regulation and energy metabolism in WSSV‐intubated shrimps is likely to symbolise disturbances in calcium homeostasis and energy metabolism.     

The psychosis spectrum in a young U.S. community sample: findings from the Philadelphia Neurodevelopmental Cohort

Little is known about the occurrence and predictors of the psychosis spectrum in large non‐clinical community samples of U.S. youths. We aimed to bridge this gap through assessment of psychosis spectrum symptoms in the Philadelphia Neurodevelopmental Cohort, a collaborative investigation of clinical and neurobehavioral phenotypes in a prospectively accrued cohort of youths, funded by the National Institute of Mental Health. Youths (age 11‐21; N=7,054) and collateral informants (caregiver/legal guardian) were recruited through the Children's Hospital of Philadelphia and administered structured screens of psychosis spectrum symptoms, other major psychopathology domains, and substance use. Youths were also administered a computerized neurocognitive battery assessing five neurobehavioral domains. Predictors of psychosis spectrum status in physically healthy participants (N=4,848) were examined using logistic regression. Among medically healthy youths, 3.7% reported threshold psychotic symptoms (delusions and/or hallucinations). An additional 12.3% reported significant sub‐psychotic positive symptoms, with odd/unusual thoughts and auditory perceptions, followed by reality confusion, being the most discriminating and widely endorsed attenuated symptoms. A minority of youths (2.3%) endorsed subclinical negative/disorganized symptoms in the absence of positive symptoms. Caregivers reported lower symptom levels than their children. Male gender, younger age, and non‐European American ethnicity were significant predictors of spectrum status. Youths with spectrum symptoms had reduced accuracy across neurocognitive domains, reduced global functioning, and increased odds of depression, anxiety, behavioral disorders, substance use and suicidal ideation. These findings have public health relevance for prevention and early intervention.     

WASH‐driven actin polymerization is required for efficient mycobacterial phagosome maturation arrest

Pathogenic mycobacteria survive in phagocytic host cells primarily as a result of their ability to prevent fusion of their vacuole with lysosomes, thereby avoiding a bactericidal environment. The molecular mechanisms to establish and maintain this replication compartment are not well understood. By combining molecular and microscopical approaches we show here that after phagocytosis the actin nucleation‐promoting factor WASH associates and generates F‐actin on the mycobacterial vacuole. Disruption of WASH or depolymerization of F‐actin leads to the accumulation of the proton‐pumping V‐ATPase around the mycobacterial vacuole, its acidification and reduces the viability of intracellular mycobacteria. This effect is observed for M. marinum in the model phagocyte Dictyostelium but also for M. marinum and M. tuberculosis in mammalian phagocytes. This demonstrates an evolutionarily conserved mechanism by which pathogenic mycobacteria subvert the actin‐polymerization activity of WASH to prevent phagosome acidification and maturation, as a prerequisite to generate and maintain a replicative niche.     

Spinal cord pathology is ameliorated by P2X7 antagonism in a SOD1-mutant mouse model of amyotrophic lateral sclerosis

In recent years there has been an increasing awareness of the role of P2X7, a receptor for extracellular ATP, in modulating physiopathological mechanisms in the central nervous system. In particular, P2X7 has been shown to be implicated in neuropsychiatry, chronic pain, neurodegeneration and neuroinflammation. Remarkably, P2X7 has also been shown to be a ‘gene modifier’ in amyotrophic lateral sclerosis (ALS): the receptor is upregulated in spinal cord microglia in human and rat at advanced stages of the disease; in vitro, activation of P2X7 exacerbates pro-inflammatory responses in microglia that have an ALS phenotype, as well as toxicity towards neuronal cells. Despite this detrimental in vitro role of P2X7, in SOD1-G93A mice lacking P2X7, the clinical onset of ALS was significantly accelerated and disease progression worsened, thus indicating that the receptor might have some beneficial effects, at least at certain stages of disease. In order to clarify this dual action of P2X7 in ALS pathogenesis, in the present work we used the antagonist Brilliant Blue G (BBG), a blood-brain barrier permeable and safe drug that has already been proven to reduce neuroinflammation in traumatic brain injury, cerebral ischemia-reperfusion, neuropathic pain and experimental autoimmune encephalitis. We tested BBG in the SOD1-G93A ALS mouse model at asymptomatic, pre-symptomatic and late pre-symptomatic phases of disease. BBG at late pre-onset significantly enhanced motor neuron survival and reduced microgliosis in lumbar spinal cord, modulating inflammatory markers such as NF-κB, NADPH oxidase 2, interleukin-1β, interleukin-10 and brain-derived neurotrophic factor. This was accompanied by delayed onset and improved general conditions and motor performance, in both male and female mice, although survival appeared unaffected. Our results prove the twofold role of P2X7 in the course of ALS and establish that P2X7 modulation might represent a promising therapeutic strategy by interfering with the neuroinflammatory component of the disease.KEY WORDS: ALS, Brilliant Blue G, Microglia, Motor neuron, P2X7