Major histocompatibility complex variation in insular populations of the Egyptian vulture: inferences about the roles of genetic drift and selection

Insular populations have attracted the attention of evolutionary biologists because of their morphological and ecological peculiarities with respect to their mainland counterparts. Founder effects and genetic drift are known to distribute neutral genetic variability in these demes. However, elucidating whether these evolutionary forces have also shaped adaptive variation is crucial to evaluate the real impact of reduced genetic variation in small populations. Genes of the major histocompatibility complex (MHC) are classical examples of evolutionarily relevant loci because of their well-known role in pathogen confrontation and clearance. In this study, we aim to disentangle the partial roles of genetic drift and natural selection in the spatial distribution of MHC variation in insular populations. To this end, we integrate the study of neutral (22 microsatellites and one mtDNA locus) and MHC class II variation in one mainland (Iberia) and two insular populations (Fuerteventura and Menorca) of the endangered Egyptian vulture (Neophron percnopterus). Overall, the distribution of the frequencies of individual MHC alleles (n=17 alleles from two class II B loci) does not significantly depart from neutral expectations, which indicates a prominent role for genetic drift over selection. However, our results point towards an interesting co-evolution of gene duplicates that maintains different pairs of divergent alleles in strong linkage disequilibrium on islands. We hypothesize that the co-evolution of genes may counteract the loss of genetic diversity in insular demes, maximize antigen recognition capabilities when gene diversity is reduced, and promote the co-segregation of the most efficient allele combinations to cope with local pathogen communities.     

Biodegradation of bisphenols with immobilized laccase or tyrosinase on polyacrylonitrile beads

The biodegradation of waters polluted by some bisphenols, endowed with endocrine activity, has been studied by means of laccase or tyrosinase immobilized on polyacrylonitrile (PAN) beads. Bisphenol A (BPA), Bisphenol B (BPB), Bisphenol F (BPF) and Tetrachlorobisphenol A (TCBPA) have been used. The laccase-PAN beads system has been characterized as a function of pH, temperature and substrate concentration. The biochemical parameters so obtained have been compared with those of the free enzyme to evidence the modification induced by the immobilization process. Once characterized, the laccase-PAN beads have been employed in a fluidized bed reactor to determine for each of the four bisphenols the degradation rate constant (k); the τ(50), i.e., the time to obtain the 50% of degradation, and the removal efficiency (RE(90)) after 90 min of enzyme treatment. The same parameters have been measured for each of the four pollutants with the same fluidized bed bioreactor loaded with tyrosinase-PAN beads. The internal comparison, i.e., in each of the two catalytic systems, has shown that both enzymes exhibit a removal efficiency in the following order BPF>BPA>BPB>TCBPA. The external comparison, i.e., the comparison between the two catalytic system, has shown that the catalytic power of laccase were higher than that of tyrosinase. The operational stability of both catalytic systems resulted excellent, since they maintained more than 80% of the initial activity after 30 days of work.     

Continuous live imaging of adult neural stem cell division and lineage progression in vitro

Little is known about the intrinsic specification of adult neural stem cells (NSCs) and to what extent they depend on their local niche. To observe adult NSC division and lineage progression independent of their niche, we isolated cells from the adult mouse subependymal zone (SEZ) and cultured them at low density without growth factors. We demonstrate here that SEZ cells in this culture system are primarily neurogenic and that adult NSCs progress through stereotypic lineage trees consisting of asymmetric stem cell divisions, symmetric transit-amplifying divisions and final symmetric neurogenic divisions. Stem cells, identified by their astro/radial glial identity and their slow-dividing nature, were observed to generate asymmetrically and fast-dividing cells that maintained an astro/radial glia identity. These, in turn, gave rise to symmetrically and fast-dividing cells that lost glial hallmarks, but had not yet acquired neuronal features. The number of amplifying divisions was limited to a maximum of five in this system. Moreover, we found that cell growth correlated with the number of subsequent divisions of SEZ cells, with slow-dividing astro/radial glia exhibiting the most substantial growth prior to division. The fact that in the absence both of exogenously supplied growth factors and of signals provided by the local niche neurogenic lineage progression takes place in such stereotypic fashion, suggests that lineage progression is, to a significant degree, cell intrinsic or pre-programmed at the beginning of the lineage.     

Are grasslands important habitats for soil microarthropod conservation?

Biodiversity has been a focal aim of environmental protection since the Rio conference, but only with the beginning of the new millennium did soil biodiversity become an important aspect of international policy. Edaphic fauna play a key role in many soil functions, such as organic matter decomposition, humus formation and nutrient element cycling; moreover, affect the porosity, aeration, infiltration and distribution of organic matter in soil horizons, modifying soil structure and improving its fertility. The ecosystem services provided by soil animals are becoming progressively lost due to agricultural practice intensification, which causes a reduction in both abundance and taxonomic diversity of soil communities. In the present study, a permanent grassland habitat was studied in order to evaluate its potential as a soil biodiversity reservoir in agroecosystems. Grassland samples were compared with samples from a semi-natural woodland area and an arable land site. Microarthropod abundances, Acari/Collembola ratio (A/C), Shannon diversity index (H′) and evenness index (E) were calculated. QBS-ar index was used in order to evaluate soil biological quality. Microarthropod communities of the three land use typologies differed in both the observed groups and their abundance. Steady soil taxa characterized both woodland and grassland soils, whereas their abundances were significantly higher in woodland soil. Taxon diversity and soil biological quality in the grasslands did not differ from the woodland samples. The microarthropod community in the arable land showed a reduction both in taxa numbers and soil biological quality compared with the other sites. Soil biological quality and edaphic community composition highlighted the importance of grassland habitats in the protection of soil biodiversity.     

Dosimetric impact of volumetric modulated arc therapy for nasopharyngeal cancer treatment

BackgroundThe purpose of the study was to evaluate the toxicity and outcome of nasopharyngeal carcinoma patients treated using 3-dimensional conformal radiotherapy (3DCRT) or volumetric modulated arc therapy (VMAT) technique.Materials and methods68 patients treated between 2006 and 2018 were retrospectively analysed. Since 2009 patients received 3DCRT with 50/70 Gy to the elective/boost volumes in 35 fractions; from then, VMAT with simultaneous integrated boost (SIB) with 54.45/69.96 Gy in 33, or 54/66 Gy in 30 fractions. Induction chemotherapy was administered in 74% of the patients, concomitant cisplatinum in 87%. Acute and late toxicity data, progression-free survival PSF and overall survival OS, and toxicity correlations with dose metrics were reported.ResultsWith a median follow-up of 64 months, complete remission at the last evaluation was in 68% of the patients, while 28% and 9% had locoregional relapse and distant disease, respectively. The 5- and 10-year progression free survival (PFS) rates were 62.7 ± 6.5% and 53.2 ± 8.7%, respectively. The 5- and 10-year OS rates were 78.9 ± 5.5% and 61.4 ± 9.2%, respectively. At the multivariate Cox analysis TNM stage (p = 0.02) and concomitant chemotherapy (p = 0.01) resulted significant for PFS, concomitant chemotherapy (p = 0.04) for OS.Improvements in acute toxicity were presented for VMAT patients due to its ability to spare OARs. Odds ratio (OR) for acute salivary toxicity, between VMAT and 3DCRT, was 4.67 (p = 0.02). Dosimetrically, salivary toxicity correlated with mean parotid dose (p = 0.05), dysphagia with laryngeal (p = 0.04) and mean oral cavity (p = 0.06) doses, when dose-volume histograms (DVHs) are corrected for fractionation.ConclusionThis study is a proof of a significant benefit of the VMAT technique compared with 3DCRT in terms of side effects in nasopharynx patients, and adds dosimetric correlations.     

Evidence of connectivity between continental and differentiated insular populations in a highly mobile species

Aim Genetically differentiated insular populations are candidates for independent units for conservation. However, occasional immigration to reduced island populations may occur and potentially have important consequences in their future viability and evolutionary potential. In this study, we investigate the conservation implications of population structure and connectivity of insular and continental populations of a migratory raptor as determined using genetic tools and satellite tracking. Location Western European populations in the Iberian Peninsula and two insular populations in the Mediterranean Sea (Balearic Islands) and Atlantic Ocean (Canary Islands). Methods We genotyped 22 microsatellite loci in 96 Egyptian vultures (Neophron percnopterus) from the Iberian Peninsula, 36 from Menorca (Balearic archipelago) and 242 (85% of the current population) from Fuerteventura (Canary Islands). We analysed genetic variation to estimate structure, gene flow, genetic diversity, effective size and recent demographic history of the populations. Additionally, 19 vultures were marked with satellite transmitters to track their migration routes. Results Insular populations were genetically differentiated from those of the mainland. We detected immigration in the insular populations and within the continental counterpart. We found similar levels of genetic variability between the continent and the islands, and a bottleneck analysis indicated recent sharp population declines in both archipelagos but not on the continent. Main conclusions Our study provides evidence that, in spite of significant differentiation, insular populations of highly mobile species may remain connected with the mainland. Conservation programmes should take into account population connectivity and integrate differentiated units of management within complex units of conservation that can best maintain processes and potential for evolutionary change.     

Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer

Two major mechanisms have been causally implicated in the establishment of cellular senescence: the activation of the DNA damage response (DDR) pathway and the formation of senescence-associated heterochromatic foci (SAHF). Here we show that in human fibroblasts resistant to premature p16(INK4a) induction, SAHF are preferentially formed following oncogene activation but are not detected during replicative cellular senescence or on exposure to a variety of senescence-inducing stimuli. Oncogene-induced SAHF formation depends on DNA replication and ATR (ataxia telangiectasia and Rad3-related). Inactivation of ATM (ataxia telangiectasia mutated) or p53 allows the proliferation of oncogene-expressing cells that retain increased heterochromatin induction. In human cancers, levels of heterochromatin markers are higher than in normal tissues, and are independent of the proliferative index or stage of the tumours. Pharmacological and genetic perturbation of heterochromatin in oncogene-expressing cells increase DDR signalling and lead to apoptosis. In vivo, a histone deacetylase inhibitor (HDACi) causes heterochromatin relaxation, increased DDR, apoptosis and tumour regression. These results indicate that heterochromatin induced by oncogenic stress restrains DDR and suggest that the use of chromatin-modifying drugs in cancer therapies may benefit from the study of chromatin and DDR status of tumours.     

The role of microvesicles in tissue repair

Microvesicles (MVs) are released by almost all cells in resting and activated conditions. First described several years ago, it is only recently that their mechanisms of action are being elucidated, and their potential role in health and disease is drawing increasing attention. The main function of MVs is signaling through specific interactions with target cells and the transferring of gene products. Gaining further insights into the molecular specificity of MVs has allowed identification of the cellular source and may provide new diagnostic tools in the future. Indeed, an increasing body of evidence indicates that MVs are capable of mediating tissue repair in models of acute kidney and liver injury. In this review, we will discuss the mechanisms through which MVs from stem cells may act on target cells and may modify the response to injury. Furthermore, MVs from inflammatory cells are suspected to be involved in various diseases, such as cardiovascular and renal diseases, pathological pregnancy, tumors and sepsis. MVs are no doubt also involved in modulating immunity, and future studies will clarify their functional role in negatively modulating the cell response. Their role in physiological and pathological processes is increasingly appreciated. Depending on the cell source and the condition, MVs may be either beneficial or detrimental to the host. The recognition of their pathogenetic role may suggest new approaches to future therapies.     

High-resolution measurements of face-to-face contact patterns in a primary school

Background

Little quantitative information is available on the mixing patterns of children in school environments. Describing and understanding contacts between children at school would help quantify the transmission opportunities of respiratory infections and identify situations within schools where the risk of transmission is higher. We report on measurements carried out in a French school (6–12 years children), where we collected data on the time-resolved face-to-face proximity of children and teachers using a proximity-sensing infrastructure based on radio frequency identification devices.

Methods and Findings

Data on face-to-face interactions were collected on Thursday, October 1^st and Friday, October 2^nd 2009. We recorded 77,602 contact events between 242 individuals (232 children and 10 teachers). In this setting, each child has on average 323 contacts per day with 47 other children, leading to an average daily interaction time of 176 minutes. Most contacts are brief, but long contacts are also observed. Contacts occur mostly within each class, and each child spends on average three times more time in contact with classmates than with children of other classes. We describe the temporal evolution of the contact network and the trajectories followed by the children in the school, which constrain the contact patterns. We determine an exposure matrix aimed at informing mathematical models. This matrix exhibits a class and age structure which is very different from the homogeneous mixing hypothesis.

Conclusions

We report on important properties of the contact patterns between school children that are relevant for modeling the propagation of diseases and for evaluating control measures. We discuss public health implications related to the management of schools in case of epidemics and pandemics. Our results can help define a prioritization of control measures based on preventive measures, case isolation, classes and school closures, that could reduce the disruption to education during epidemics.     

Astroglial inhibition of NF-κB does not ameliorate disease onset and progression in a mouse model for amyotrophic lateral sclerosis (ALS)

Motor neuron death in amyotrophic lateral sclerosis (ALS) is considered a "non-cell autonomous" process, with astrocytes playing a critical role in disease progression. Glial cells are activated early in transgenic mice expressing mutant SOD1, suggesting that neuroinflammation has a relevant role in the cascade of events that trigger the death of motor neurons. An inflammatory cascade including COX2 expression, secretion of cytokines and release of NO from astrocytes may descend from activation of a NF-κB-mediated pathway observed in astrocytes from ALS patients and in experimental models. We have attempted rescue of transgenic mutant SOD1 mice through the inhibition of the NF-κB pathway selectively in astrocytes. Here we show that despite efficient inhibition of this major pathway, double transgenic mice expressing the mutant SOD1(G93A) ubiquitously and the dominant negative form of IκBα (IκBαAA) in astrocytes under control of the GFAP promoter show no benefit in terms of onset and progression of disease. Our data indicate that motor neuron death in ALS cannot be prevented by inhibition of a single inflammatory pathway because alternative pathways are activated in the presence of a persistent toxic stimulus.