Mutagenesis of nisin’s leader peptide proline strongly modulates export of precursor nisin

The lantibiotic nisin is produced by Lactococcus lactis as a precursor peptide comprising a 23 amino acid leader peptide and a 34 amino acid post-translationally modifiable core peptide. We previously demonstrated that the conserved FNLD part of the leader is essential for intracellular enzyme-catalyzed introduction of lanthionines in the core peptide and also for transporter-mediated export, whereas other positions are subject to large mutational freedom. We here demonstrate that, in the absence of the extracellular leader peptidase, NisP, export of precursor nisin via the modification and transporter enzymes, NisBTC, is strongly affected by multiple substitutions of the leader residue at position -2, but not by substitution of positions in the vicinity of this site. Export levels of precursor nisin increased by more than 70% for position -2 mutants Asp, Thr, Ser, Trp, Lys, Val and decreased more than 70% for Cys, His, Met. In a strain with leader peptidase, the Pro-2Lys and Pro-2Asp precursor nisins were less efficiently cleaved by NisP than wild type precursor nisin. Taken together, the wild type precursor nisin with a proline at position -2 allows balanced export and cleavage efficiencies by precursor nisin’s transporter and leader peptidase.     

Altered Community Flammability in Florida’s Apalachicola Ravines and Implications for the Persistence of the Endangered Conifer Torreya taxifolia

Plant species and communities often reflect historic fire regimes via ecological and evolutionary responses to recurrent fires. Plant communities of the southeastern USA experience a wide array of fire regimes, perhaps nowhere more marked than the juxtaposition of fire-prone uplands and adjacent mesic ravines along Florida’s Apalachicola River. The ravines contain many endemic and disjunct species, most notably the endangered endemic conifer Torreya taxifolia. A rapid decline in T. taxifolia over the past 60 years has been associated with widespread replacement by other tree species. To understand the changes accompanying the shift in ravine composition, we compared leaf litter flammability of nine historic and contemporary species. We measured maximum flame height, flame duration, smoldering duration, mass loss, absorptive capacity, and drying rate. Ordination and perMANOVA suggest the nine species segregated into three distinct groups: the fire-impeding T. taxifolia and Taxus floridana; an intermediate group of three deciduous angiosperms; and a mixed cluster of four flammable species. Results suggest T. taxifolia and T. floridana were fire-impeding species in these communities, while contemporary dominants burn similarly to the upslope pyric species. The increasing presence of fire-facilitating species may portend a shifting fire regime that further imperils T. taxifolia and other rare species in the formerly fire-safe ravines.     

The derivation of D’Arcy Thompson’s theory of transformations from the theory of optimal design

It is shown informally that Cohn’s theory of Optimal Forms can be construed as a comparative theory, and that when this is done the celebrated theory of transformations of D’Arcy Thompson follows as a consequence. The implications of this type of theoretical foundation for the Thompson theory with regard to problems of comparative morphology are discussed, and some suggestions for the further implementation of the theory are described. This research was supported by the United States Air Force through the Air Force Office of Scientific Research of the Air Research and Development Command, under Contract No. AF 49(638)-917.     

Expectant Parents’ Understanding of the Implications and Management of Fever in the Neonate

Objective

We estimated the extent to which Canadian expectant parents would seek medical care in a febrile neonate (age 30 days or less). We also evaluated expectant parents’ knowledge of signs and symptoms of fever in a neonate, and explored the actions Canadian expectant parents would take to optimize the health of their child.

Methods

We conducted a cross-sectional survey of a sample of expectant parents from a large urban center in Canada. We recruited participants from waiting rooms in an obstetrical ultrasound clinic located in an urban tertiary care hospital in Montreal, Canada. We asked participants nine questions about fever in neonates including if, and how, they would seek care for their neonate if they suspected he/she were febrile.

Results

Among the 355 respondents, (response rate 87%) we found that 75% of parents reported that they would take their febrile neonate for immediate medical assessment, with nearly one fifth of the sample reporting that they would not seek medical care. We found no significant associations between the choice to seek medical care and expectant parents socio-demographic characteristics.

Conclusions

Despite universal access to high quality health care in Canada, our study highlights concerning gaps in the knowledge of the care of the febrile infant in one fifth of expectant parents. Physicians and health providers should strive to provide early education to expectant parents about how to recognize signs of fever in the neonate and how best to seek medical care. This may improve neonatal health outcomes in Canada.     

Effects of oxysterols on the blood–brain barrier: Implications for Alzheimer’s disease

Altered brain cholesterol homeostasis plays a key role in neurodegenerative diseases such as Alzheimer’s disease (AD). For a long time, the blood–brain barrier (BBB) was basically considered as a barrier isolating the brain from circulating cholesterol, however, several lines of evidence now suggest that the BBB strictly regulates the exchanges of sterol between the brain and the peripheral circulation. Oxysterols, synthesized by neurons or by peripheral cells, cross the BBB easily and modulate the expression of several enzymes, receptors and transporters which are involved not only in cholesterol metabolism but also in other brain functions. This review article deals with the way oxysterols impact BBB cells. These perspectives open new routes for designing certain therapeutical approaches that target the BBB so that the onset and/or progression of brain diseases such as AD may be modulated.     

Consequences of Environmental Fluctuations on Taylor’s Power Law and Implications for the Dynamics and Persistence of Populations

Conservation Biologists have found that demographic stochasticity causes the mean time to extinction to increase exponentially with population size. This has proved helpful in analyses determining extinction times and characterizing the pathway to extinction. The aim of this investigation is to explore the possible interactions between environmental/demographic noises and the scaling effect of the mean population size with its variance, which is expected to follow Taylor’s power law relationship. We showed that the combined effects of environmental/demographic noises and the scaling of population size variability interact with the population dynamics and affect the mean time to extinction.     

Predicting the Outcome of Sjogren’s Syndrome-Associated Non-Hodgkin’s Lymphoma Patients

BackgroundNon-Hodgkin''s lymphoma (NHL) development in Sjögren’s syndrome (SS) remains a potentially lethal complication and efforts should focus on the identification of predictors that could aid in appropriate therapeutic decisions.MethodsIn order to identify potential prognostic factors for outcome in SS-associated NHL, we retrospectively analyzed a cohort of 77 patients, diagnosed with NHL according to WHO classification criteria and meeting the American-European Consensus Classification (AECC) criteria for SS and examined the effect of SS-activity (defined as the EULAR SS disease activity index-ESSDAI) in the prognosis of SS-related NHLs, as defined in terms of overall and event-free survivals (OS and EFS). An event was defined as lymphoma relapse, treatment failure, disease progression, histological transformation or death. The effect of NHL clinical and laboratory characteristics was also investigated.ResultsMALT lymphomas constituted the majority (66.2%) of lymphomas. During the follow-up (median = 57.93 months), the 5-year OS was 90.91% (95% CI: 82.14–95.80%) and the EFS was 77.92% (95% CI: 67.37–85.82%). Patients with high ESSDAI score at lymphoma diagnosis had a greater risk for death (OR = 5.241, 95% CI: 1.034–26.568) or for event (OR = 4.317, 95% CI: 1.146–9.699, p = 0.008). These patients had also significantly worse EFS (HR = 4.541, 95% CI: 1.772–11.637) and OS (HR = 5.946, 95% CI: 1.259–28.077). In addition, post-chemotherapy ESSDAI improvement was significantly lower in patients who had experienced an event (p = 0.005). An unfavorable International prognostic index (IPI) score (high-intermediate/high) was associated with high risk of death and event (OR = 13.867, 95% CI: 2.656–72.387 and OR = 12.589, 95% CI: 3.911–40.526, respectively), worse EFS (log-rank p<0.001, HR = 8.718, 95% CI: 3.477–21.858), as well as with worse OS (log-rank p<0.001, HR = 11.414, 95% CI: 2.414–53.974). After adjustment for identified risk factors, IPI score retained a significant prognostic role following by a strong effect of ESSDAI in survival outcomes.ConclusionsAt the point of NHL diagnosis, IPI and ESSDAI might be proved useful predictive tools in SS-associated lymphoma prognosis, directing to a more patient-tailored approach.     

Development of the Partner’s Treatment of Animals Scale

Although studies of the relationship between animal abuse and intimate partner violence have proliferated in recent years, building upon previous work and making cross-study comparisons have been rendered difficult by the utilization of differing operationalizations of animal maltreatment within this literature. This paper aims to mitigate this problem by introducing and detailing a scale of animal maltreatment by romantic partners, developed and tested with a sample of 55 women in domestic violence shelters who self-identified as victims of intimate partner violence. The Partner’s Treatment of Animals Scale (PTAS) is comprised of five scales (emotional animal abuse, threats to harm animals, animal neglect, physical animal abuse, and severe physical animal abuse) that have strong demonstrated reliability. The construction of the scales is presented in this paper, and recommendations are made for employing the PTAS in subsequent studies.     

Alzheimer’s Disease-Related Protein Expression in the Retina of Octodon degus

New studies show that the retina also undergoes pathological changes during the development of Alzheimer’s disease (AD). While transgenic mouse models used in these previous studies have offered insight into this phenomenon, they do not model human sporadic AD, which is the most common form. Recently, the Octodon degus has been established as a sporadic model of AD. Degus display age-related cognitive impairment associated with Aβ aggregates and phosphorylated tau in the brain. Our aim for this study was to examine the expression of AD-related proteins in young, adult and old degus retina using enzyme-linked or fluorescence immunohistochemistry and to quantify the expression using slot blot and western blot assays. Aβ4G8 and Aβ6E10 detected Aβ peptides in some of the young animals but the expression was higher in the adults. Aβ peptides were observed in the inner and outer segment of the photoreceptors, the nerve fiber layer (NFL) and ganglion cell layer (GCL). Expression was higher in the central retinal region than in the retinal periphery. Using an anti-oligomer antibody we detected Aβ oligomer expression in the young, adult and old retina. Immunohistochemical labeling showed small discrete labeling of oligomers in the GCL that did not resemble plaques. Congo red staining did not result in green birefringence in any of the animals analyzed except for one old (84 months) animal. We also investigated expression of tau and phosphorylated tau. Expression was seen at all ages studied and in adults it was more consistently observed in the NFL-GCL. Hyperphosphorylated tau detected with AT8 antibody was significantly higher in the adult retina and it was localized to the GCL. We confirm for the first time that Aβ peptides and phosphorylated tau are expressed in the retina of degus. This is consistent with the proposal that AD biomarkers are present in the eye.     

Phosphorus Cycling in Montreal’s Food and Urban Agriculture Systems

Cities are a key system in anthropogenic phosphorus (P) cycling because they concentrate both P demand and waste production. Urban agriculture (UA) has been proposed as a means to improve P management by recycling cities’ P-rich waste back into local food production. However, we have a limited understanding of the role UA currently plays in the P cycle of cities or its potential to recycle local P waste. Using existing data combined with surveys of local UA practitioners, we quantified the role of UA in the P cycle of Montreal, Canada to explore the potential for UA to recycle local P waste. We also used existing data to complete a substance flow analysis of P flows in the overall food system of Montreal. In 2012, Montreal imported 3.5 Gg of P in food, of which 2.63 Gg ultimately accumulated in landfills, 0.36 Gg were discharged to local waters, and only 0.09 Gg were recycled through composting. We found that UA is only a small sub-system in the overall P cycle of the city, contributing just 0.44% of the P consumed as food in the city. However, within the UA system, the rate of recycling is high: 73% of inputs applied to soil were from recycled sources. While a Quebec mandate to recycle 100% of all organic waste by 2020 might increase the role of UA in P recycling, the area of land in UA is too small to accommodate all P waste produced on the island. UA may, however, be a valuable pathway to improve urban P sustainability by acting as an activity that changes residents’ relationship to, and understanding of, the food system and increases their acceptance of composting.     

Stress contributes to the development of central insulin resistance during aging: Implications for Alzheimer’s disease

It is becoming evident that chronic exposure to stress not only might result in insulin resistance or cognitive deficits, but may also be considered a risk factor for pathologies such as depression or Alzheimer's disease (AD). There is great interest in determining the molecular mechanisms underlying interactions between stress, aging, memory and Alzheimer's disease (AD). We have used the chronic mild stress (CMS) model to study the effects of chronic stress on the aging process and the development of central insulin resistance and AD pathology. CMS aged mice showed cognitive impairments in the novel object recognition test. In addition, CMS aged mice displayed both peripheral insulin resistance, as shown by HOMA index, and decreased hippocampal levels of pIRS and downstream intracellular signaling (pAKT, pGSK and pERK1/2). Interestingly, there was a significant increase in both C99:C83 ratio and BACE1 levels in the hippocampus of CMS aged mice. Increased expression of the AD marker pTau was also found in stressed aged mice. Increased expression of the stress-activated protein kinase JNK was found in CMS aged mice, accompanied by significant decreases in glucocorticoid receptor (GR) expression and increases in mineralocorticoid receptor (MR) expression. It is suggested that the interaction of stress with aging should be considered when studying determinants of the onset and progression of AD.