Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium

The innate immune system is present throughout the female reproductive tract and functions in synchrony with the adaptive immune system to provide protection in a way that enhances the chances for fetal survival, while protecting against potential pathogens. Recent data show that activation of Toll-like receptor (TLR)2 and 4 by low-molecular weight hyaluronic acid (LMW-HA) in the epidermis induces secretion of the antimicrobial peptide β-defensin 2. In the present work, we show that LMW-HA induces vaginal epithelial cells to release different antimicrobial peptides, via activation of TLR2 and TLR4. Further, we found that LMW-HA favors repair of vaginal epithelial injury, involving TLR2 and TLR4, and independently from its classical receptor CD44. This wound-healing activity of LMW-HA is dependent from an Akt/phosphatidylinositol 3 kinase pathway. Therefore, these findings suggest that the vaginal epithelium is more than a simple physical barrier to protect against invading pathogens: on the contrary, this surface acts as efficient player of innate host defense, which may modulate its antimicrobial properties and injury restitution activity, following LMW-HA stimulation; this activity may furnish an additional protective activity to this body compartment, highly and constantly exposed to microbiota, ameliorating the self-defense of the vaginal epithelium in both basal and pathological conditions.     

Effects of somatic mutations on CDR loop flexibility during affinity maturation

Prior studies suggest that antibody affinity maturation is achieved, in part, via prearranging the CDRs for binding. The implication is that the entropy cost of binding is reduced and that this rigidification occurs as a consequence of somatic mutations during maturation. However, how these mutations modulate CDR flexibility is unclear. Here, molecular dynamics simulations captured CDR flexibility differences between four mature antibodies (7G12, AZ28, 28B4, and 48G7) and their germline predecessors. Analysis of their trajectories: (1) rationalized how mutations during affinity maturation restrict CDR motility, (2) captured the equilibrium between bound and unbound conformations for the H3 loop of unliganded 7G12, and (3) predicted a set of new mutations that, according to our simulations, should diminish binding by increasing flexibility.     

Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells

4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy.     

Relationship between mammary morphology traits and milk yield of Sicilo-Sarde dairy sheep in Tunisia

Sicilo-Sarde is a local breed from northern Tunisia resulting from crossing Sarda and Comisana dairy sheep and is traditionally used for cheese production after lamb weaning. A sample of 52 adult Sicilo-Sarde lactating ewes was used for studying their udder morphological traits and milk yield potential during weeks 4-8 (milking-suckling period) and 10 (milking period) of lactation. Daily milk yield was estimated on a daily basis by using the double oxytocin injection method 4 h after machine-milking at d 30 and 45. Udder and teat morphology were also measured at d 45 of lactation. Cisternal area (by ultrasonography) and udder compartments (cisternal and alveolar milk) were evaluated 8 h after milking by using atosiban and oxytocin on d 72 of lactation. Milk yield averaged 0.56 ± 0.10 L/d and ewes had small (volume, 496 ± 28 mL) and healthy udders (CMT, <1), with medium sized teats (length, 18.5 ± 4.9 mm; diameter, 10.0 ± 2.0 mm) attached at 45 ± 10°. A drop in milk production (49%) was found in the transition from suckling (day 30) to milking (week 10). Udder cisterns were multilocular and small sized (half udder area, 11.6 ± 4.5 cm²), although cisternal milk accounted for 54% of the total milk in the udder. Correlation between cisternal milk and cisternal area was moderate (R² = 0.48; P < 0.05). Lag time and total milking time were 1.9 ± 0.1 and 31 ± 5 s, respectively. In conclusion, the Sicilo-Sarde ewes evaluated showed medium sized cisterns and teats which were morphologically adequate for machine milking, although milk production needs to be improved.     

Phylogenetic placement and population structure of Indo‐Pacific bottlenose dolphins (Tursiops aduncus) off Zanzibar,Tanzania, based on mtDNA sequences

Phylogenetic placement of bottlenose dolphins from Zanzibar, East Africa and putative population differentiation between animals found off southern and northern Zanzibar were examined using variation in mtDNA control region sequences. Samples (n= 45) from animals bycaught in fishing gear and skin biopsies collected during boat surveys were compared to published sequences (n= 173) of Indo‐Pacific bottlenose dolphin, Tursiops aduncus, from southeast Australian waters, Chinese/Indonesian waters, and South African waters (which recently was proposed as a new species) and to published sequences of common bottlenose dolphin, Tursiops truncatus. Bayesian and maximum parsimony analyses indicated a close relationship between Zanzibar and South African haplotypes, which are differentiated from both Chinese/Indonesian and Australian T. aduncus haplotypes. Our results suggest that the dolphins found off Zanzibar should be classified as T. aduncus alongside the South African animals. Further, analyses of genetic differentiation showed significant separation between the T. aduncus found off northern and southern Zanzibar despite the relatively short distance (approximately 80 km) between these areas. Much less differentiation was found between southern Zanzibar and South Africa, suggesting a more recent common evolutionary history for these populations than for the northern and southern Zanzibar populations.     

Cotton cultivation and textile production in the Arabian Peninsula during antiquity; the evidence from Mada��in Salih (Saudi Arabia) and Qal��at al-Bahrain (Bahrain)

The discovery of seeds and textiles from Gossypium (cotton) in Achaemenian levels of the mid-6th–late 4th century b.c. at Qal’at al-Bahrain, Bahrain and in early 1st millennium a.d. at Mada’in Salih, Saudi Arabia, reveals the role played by the Arabian Peninsula as a textile production centre during the centuries before and after the beginning of the Christian era. Both these sites were situated on important trade routes, overseas (Qal’at al-Bahrain) and overland (Mada’in Salih), and it is likely that at least part of the cotton production was intended for trade, complementing and perhaps competing with other sources of cotton textiles in the contemporary Middle East. In the arid climate of the Arabian Peninsula, cotton was probably grown in association with irrigated date palm gardens where a wide array of other crops was grown, as is shown by the analysis of charred seeds and wood from occupation levels at both sites. The present article places these particular finds in the larger context of cotton cultivation in the Middle East and India.     

Expanding hybrid zone between Solea aegyptiaca and Solea senegalensis: genetic evidence over two decades

Several marine hybrid zones have been described and studied during the last years. Assessing the movements of extending hybrid zones is central to improve our understanding of evolutionary processes. We have re-examined the hybrid zone between Solea aegyptiaca and Solea senegalensis that was first described 22 years ago in northern Tunisia when introgressed S. senegalensis individuals were found in the Gulf of Tunis, whereas locally caught S. aegyptiaca were genetically pure. Six population samples harvested both inside and outside the area where the two fish species coexist were genotyped for allozymes and exon-primed intron length polymorphism. Both types of markers were congruent and revealed that introgression takes place indeed in both directions. A high introgression level (36.4%) in the Bizerta lagoon and much less outside indicate that this is the main area where hybridization occurs while introgression clines towards the south in S. aegyptiaca and towards the north in S. senegalensis plead in favour of the existence of a unimodal hybrid zone. The higher introgression level calculated in the current study (when compared to 16% reported formerly) and the newly found introgressed S. aegyptiaca in Bizerta lagoon seem to indicate that the genetic exchanges occurring between the two taxa are evolving and not stabilized yet.     

Molecular epidemiology of malaria prevalence and parasitaemia in a wild bird population

Avian malaria (Plasmodium spp.) and other blood parasitic infections of birds constitute increasingly popular model systems in ecological and evolutionary host-parasite studies. Field studies of these parasites commonly use two traits in hypothesis testing: infection status (or prevalence at the population level) and parasitaemia, yet the causes of variation in these traits remain poorly understood. Here, we use quantitative PCR to investigate fine-scale environmental and host predictors of malaria infection status and parasitaemia in a large 4-year data set from a well-characterized population of blue tits (Cyanistes caeruleus). We also examine the temporal dynamics of both traits within individuals. Both infection status and parasitaemia showed marked temporal and spatial variation within this population. However, spatiotemporal patterns of prevalence and parasitaemia were non-parallel, suggesting that different biological processes underpin variation in these two traits at this scale. Infection probability and parasitaemia both increased with host age, and parasitaemia was higher in individuals investing more in reproduction (those with larger clutch sizes). Several local environmental characteristics predicted parasitaemia, including food availability, altitude, and distance from the woodland edge. Although infection status and parasitaemia were somewhat repeatable within individuals, infections were clearly dynamic: patent infections frequently disappeared from the bloodstream, with up to 26% being lost between years, and parasitaemia also fluctuated within individuals across years in a pattern that mirrored annual population-level changes. Overall, these findings highlight the ecological complexity of avian malaria infections in natural populations, while providing valuable insight into the fundamental biology of this system that will increase its utility as a model host-parasite system.     

The impact of seasonal and year-round transmission regimes on the evolution of influenza A virus

Punctuated antigenic change is believed to be a key element in the evolution of influenza A; clusters of antigenically similar strains predominate worldwide for several years until an antigenically distant mutant emerges and instigates a selective sweep. It is thought that a region of East-Southeast Asia with year-round transmission acts as a source of antigenic diversity for influenza A and seasonal epidemics in temperate regions make little contribution to antigenic evolution. We use a mathematical model to examine how different transmission regimes affect the evolutionary dynamics of influenza over the lifespan of an antigenic cluster. Our model indicates that, in non-seasonal regions, mutants that cause significant outbreaks appear before the peak of the wild-type epidemic. A relatively large proportion of these mutants spread globally. In seasonal regions, mutants that cause significant local outbreaks appear each year before the seasonal peak of the wild-type epidemic, but only a small proportion spread globally. The potential for global spread is strongly influenced by the intensity of non-seasonal circulation and coupling between non-seasonal and seasonal regions. Results are similar if mutations are neutral, or confer a weak to moderate antigenic advantage. However, there is a threshold antigenic advantage, depending on the non-seasonal transmission intensity, beyond which mutants can escape herd immunity in the non-seasonal region and there is a global explosion in diversity. We conclude that non-seasonal transmission regions are fundamental to the generation and maintenance of influenza diversity owing to their epidemiology. More extensive sampling of viral diversity in such regions could facilitate earlier identification of antigenically novel strains and extend the critical window for vaccine development.