Rabbit haemorrhagic disease virus (RHDV) is a calicivirus of the genus Lagovirus that causes rabbit haemorrhagic disease (RHD) in adult European rabbits (Oryctolagus cuniculus). First described in ...China in 1984, the virus rapidly spread worldwide and is nowadays considered as endemic in several countries. In Australia and New Zealand where rabbits are pests, RHDV was purposely introduced for rabbit biocontrol. Factors that may have precipitated RHD emergence remain unclear, but non-pathogenic strains seem to pre-date the appearance of the pathogenic strains suggesting a key role for the comprehension of the virus origins. All pathogenic strains are classified within one single serotype, but two subtypes are recognised, RHDV and RHDVa. RHD causes high mortality in both domestic and wild adult animals, with individuals succumbing between 48-72 h post-infection. No other species has been reported to be fatally susceptible to RHD. The disease is characterised by acute necrotising hepatitis, but haemorrhages may also be found in other organs, in particular the lungs, heart, and kidneys due to disseminated intravascular coagulation. Resistance to the disease might be explained in part by genetically determined absence or weak expression of attachment factors, but humoral immunity is also important. Disease control in rabbitries relies mainly on vaccination and biosecurity measures. Such measures are difficult to be implemented in wild populations. More recent research has indicated that RHDV might be used as a molecular tool for therapeutic applications. Although the study of RHDV and RHD has been hampered by the lack of an appropriate cell culture system for the virus, several aspects of the replication, epizootology, epidemiology and evolution have been disclosed. This review provides a broad coverage and description of the current knowledge on the disease and the virus.
Toll-like receptors (TLRs) are a major class of pattern recognition receptors (PRRs) expressed in the cell surface or membrane compartments of immune and non-immune cells. TLRs are encoded by a ...multigene family and represent the first line of defense against pathogens by detecting foreigner microbial molecular motifs, the pathogen-associated molecular patterns (PAMPs). TLRs are also important by triggering the adaptive immunity in vertebrates. They are characterized by the presence of leucine-rich repeats (LRRs) in the ectodomain, which are associated with the PAMPs recognition. The direct recognition of different pathogens by TLRs might result in different evolutionary adaptations important to understand the dynamics of the host-pathogen interplay. Ten mammal TLR genes, viral (TLR3, 7, 8, 9) and non-viral (TLR1-6, 10), were selected to identify signatures of positive selection that might have been imposed by interacting pathogens and to clarify if viral and non-viral TLRs might display different patterns of molecular evolution.
By using Maximum Likelihood approaches, evidence of positive selection was found in all the TLRs studied. The number of positively selected codons (PSC) ranged between 2-26 codons (0.25%-2.65%) with the non-viral TLR4 as the receptor with higher percentage of positively selected codons (2.65%), followed by the viral TLR8 (2.50%). The results indicated that viral and non-viral TLRs are similarly under positive selection. Almost all TLRs have at least one PSC located in the LRR ectodomain which underlies the importance of the pathogen recognition by this region.
Our results are not in line with previous studies on primates and birds that identified more codons under positive selection in non-viral TLRs. This might be explained by the fact that both primates and birds are homogeneous groups probably being affected by only a restricted number of related viruses with equivalent motifs to be recognized. The analyses performed in this work encompassed a large number of species covering some of the most representative mammalian groups - Artiodactyla, Rodents, Carnivores, Lagomorphs and Primates - that are affected by different families of viruses. This might explain the role of adaptive evolution in shaping viral TLR genes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The discovery of osteocalcin, a protein synthetized by osteoblasts, as a hormone that has positive effects on insulin resistance, contributed to support the concept of bone as an endocrine organ. ...However, very little is known about the molecular pathways involved in osteocalcin improved-insulin resistance. The present study aimed to investigate the mechanisms of action of osteocalcin on insulin resistance and inflammation in obese mice and 3T3-L1 adipocytes.
Lean control, saline-treated obese and uncarboxylated osteocalcin (uOC)-treated obese mice were subjected to insulin tolerance test in vivo. Blood was collect for biochemical/metabolic profile analysis; and, skeletal muscle, white adipose tissue (WAT) and bone were collected for protein (Western blotting) and mRNA (RT-qPCR) analysis. uOC effects on insulin resistance and inflammation were also investigated in 3T3-L1 adipocytes challenged with tumor necrosis factor. Osteocalcin treatment improved in vivo insulin resistance in obese mice. In WAT, osteocalcin had positive effects such as (1) WAT weight reduction; (2) upregulation of glucose transporter (GLUT) 4 protein and its mRNA (Slc2a4); (3) improved insulin-induced AKT phosphorylation; (4) downregulation of several genes involved in inflammation and inflammassome transcriptional machinery, and (5) reduction of the density of macrophage in crown-like structures (histomorphometrical analysis). Notably, in 3T3-L1 adipocytes, osteocalcin restored Slc2a4/GLUT4 content and reduced the expression of inflammatory genes after TNF-a challenge; moreover, osteocalcin treatment increased AKT phosphorylation induced by insulin. Finally, it was observed that in bone, osteocalcin improves insulin resistance by increasing insulin-induced AKT phosphorylation and reducing the expression of genes involved in bone insulin resistance, resulting in increased secretion of uncarboxylated osteocalcin in circulation.
We provided some mechanisms of action for osteocalcin in the amelioration of insulin resistance in obesity: in WAT, osteocalcin improves insulin resistance by decreasing inflammation, and increasing insulin signaling and the expression of Slc2a4/GLUT4; and, in bone, osteocalcin increases the secretion of uncarboxylated osteocalcin by improving insulin resistance.
•Mechanisms for osteocalcin in improving insulin resistance in obesity are provided.•Osteocalcin improves insulin resistance and inflammation in adipose tissue.•Osteocalcin improves insulin resistance in bone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The control of infections by the vertebrate adaptive immune system requires careful modulation to optimize defense and minimize harm to the host. The Fc receptor-like (
) genes encode ...immunoregulatory molecules homologous to the receptors for the Fc portion of immunoglobulin (FCR). To date, nine different genes (
,
,
and
) have been identified in mammalian organisms.
is located at a separate chromosomal position from the
locus, has conserved synteny in mammals and is situated between the
and
genes. Here, we show that this three gene block underwent repeated duplication in
(nine-banded armadillo) resulting in six
copies, of which five appear functional. Among 21 mammalian genomes analyzed, this expansion was unique to
. Ig-like domains that derive from the five clustered
functional gene copies show high structural conservation and sequence identity. However, the presence of multiple non-synonymous amino acid changes that would diversify individual receptor function has led to the hypothesis that
endured subfunctionalization during evolution in
. Interestingly,
is noteworthy for its natural resistance to the
pathogen that causes leprosy. Because
is chiefly expressed by cytotoxic T and NK cells, which are important in cellular defense responses against
, we speculate that
subfunctionalization could be relevant for the adaptation of
to leprosy. These findings highlight the species-specific diversification of
family members and the genetic complexity underlying evolving multigene families critical for modulating adaptive immune protection.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Friction spot joining of Aluminum AA6181-T4/CF-PPS double-lap joints was successfully demonstrated.•The individual influence of joining parameters on joint mechanical performance was ...determined.•Changes in heat input, microstructure and joint strength were studied by Taguchi and ANOVA methods.•Strong joints with lap shear resistance varying from 2107N to 3523N were obtained.
Friction spot joining is an alternative technique to produce metal-composite overlap joints. The main process parameters are tool rotational speed, plunge depth, joining time and joining force. In this study, the individual effect of the process parameters on the microstructure and mechanical strength of hybrid AA6181-T4/CF-PPS double lap joints was investigated using Taguchi method and analysis of variance (ANOVA). Produced joints presented mechanical performance from 2107N to 3523N. Joints failed by brittle fracture at the interface between aluminum alloy and composite, with displacement-at-peak load values from 0.7mm to 0.9mm. Tool rotational speed was the parameter with the largest influence on the joint shear resistance, followed by the joining time, plunge depth and joining force. Higher strength was correlated to the extension of the bonding area and macro-mechanical interlocking related to the formation of a metallic indentation (metallic nub) slightly inserted into the composite. Larger bonding areas were shown to be related to higher heat input (as a result of longer joining times and intermediate rotational speeds) leading to larger consolidated polymeric layers at the metal-composite interface. Higher macro-mechanical interlocking was obtained at larger plunge depths. Joining force was shown to be related to crevice and pore filling of the metal surface by supporting spreading of the molten polymer. Higher joining forces led to better wetting of the interface, increasing adhesive forces and joint mechanical performance. Nevertheless excessive joining forces caused squeezing flow of the molten layer reducing joint strength, since a large adhesive area was lost.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary
Objective
The goal of this study was to evaluate the influence of high‐intensity interval training (HIIT) on anthropometric variables in adults afflicted with overweight or obesity and to ...compare the effects with those of moderate‐intensity continuous training.
Methods
A computer literature search was performed for HIIT intervention studies that evaluated anthropometric variables in adults afflicted with overweight or obesity.
Results
Of the 857 articles retrieved in the electronic search, 48 met the inclusion criteria. The analyses demonstrated that HIIT was effective in decreasing body mass (−1.45 kg 95% CI: −1.85 to −1.05 kg), body mass index (−0.44 kg m−2 95% CI: −0.59 to −0.30 kg m−2), waist circumference (−2.3 cm 95% CI: −3.1 to −1.4 cm), waist/hip ratio (−0.01 95% CI: −0.02 to −0.00), body fat percentage (−1.29% 95% CI: −1.70% to −0.87%) and abdominal visceral fat area (−6.83 cm2 95% CI: −11.95 to −1.71 cm2). When considering equalization between the two methods (energy expenditure or workload matched), no differences were found in any measure except body mass (for which HIIT was superior).
Conclusions
High‐intensity interval training and moderate‐intensity continuous training results were similar, particularly when equalization between the two methods was considered. Thus, HIIT can be used as a secondary method for the treatment of obesity in adults.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Understanding recent speciation history requires merging phylogenetic and population genetics approaches, taking into account the persistence of ancestral polymorphism and possible introgression. The ...emergence of a clear phylogeny of hares (genus Lepus) has been hampered by poor genomic sampling and possible occurrence of mitochondrial DNA (mtDNA) introgression from the arctic/boreal Lepus timidus into several European temperate and possibly American boreal species. However, no formal test of introgression, taking also incomplete lineage sorting into account, has been done. Here, to clarify the yet poorly resolved species phylogeny of hares and test hypotheses of mtDNA introgression, we sequenced 14 nuclear DNA and 2 mtDNA fragments (8205 and 1113 bp, respectively) in 50 specimens from 11 hare species from Eurasia, North America, and Africa. By applying an isolation-with-migration model to the nuclear data on subsets of species, we find evidence for very limited gene flow from L. timidus into most temperate European species, and not into the American boreal ones. Using a multilocus coalescent–based method, we infer the species phylogeny, which we find highly incongruent with mtDNA phylogeny using parametric bootstrap. Simulations of mtDNA evolution under the speciation history inferred from nuclear genes did not support the hypothesis of mtDNA introgression from L. timidus into the American L. townsendii but did suggest introgression from L. timidus into 4 temperate European species. One such event likely resulted in the complete replacement of the aboriginal mtDNA of L. castroviejoi and of its sister species L. corsicanus. It is remarkable that mtDNA introgression in hares is frequent, extensive, and always from the same donor arctic species. We discuss possible explanations for the phenomenon in relation to the dynamics of range expansions and species replacements during the climatic oscillations of the Pleistocene.
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BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Immunoglobulin A (IgA) is the mammalian mucosal antibody, providing an important line of defense against pathogens. With 15 IgA subclasses, the European rabbit has an extremely complex IgA ...system, strikingly more complex than most other mammals, which have only one IgA or, in the case of hominoids, two IgA subclasses. Similar to the two hominoid primate
IGHA
genes, the expansion of the rabbit
IGHA
genes appears to have begun in an ancestral lagomorph since multiple IgA copies were found by Southern blot analysis for the genera
Sylvilagus
,
Lepus
, and
Ochotona
.
Results
To gain a better insight into the extraordinary lagomorph IgA evolution, we sequenced, for the first time, expressed IgA genes for two
Lepus
species,
L. europaeus
and
L. granatensis
. These were aligned with the 15 rabbit IgA isotypes, and evolutionary analyses were conducted. The obtained phylogenetic tree shows that the
Lepus
IgA sequences cluster with and among the rabbit IgA isotypes, and the interspecies and intraspecies nucleotide genetic distances are similar. A comparison of the amino acid sequences of the
Lepus
and rabbit IgA confirms that there are two trans-species polymorphisms and that the rabbit and
Lepus
sequences share a common genetic pool. In fact, the main differences between the studied leporids IgAs reside in the characteristics of the hinge region.
Conclusion
The
Lepus
IgA sequences we have obtained strongly suggest that the great expansion of the leporid
IGHA
genes occurred in a common ancestral species and was then maintained in the descendants. A strong selective pressure caused the extraordinary expansion of the
IGHA
genes but then subsided, leading to the maintenance of the acquired polymorphisms in the descendants, with little subsequent divergence. This is a unique evolutionary pattern in which an ancient gene expansion has been maintained for approximately 18 million years.
This review presents some examples of studies using the European rabbit (Oryctolagus cuniculus) that have led to, and continue to, contribute to advancement of understanding of human diseases as well ...as therapeutics development. In addition, we tabulate FDA-approved rabbit polyclonal and rabbit monoclonal antibodies (mAbs) that are used for diagnostic applications, as well as an overview of some “humanized” or otherwise altered rabbit mAbs that are in initial phase I, II, or advanced to phase III clinical trials. Information about endogenous retriviruses learned from studies of rabbits and other members of the order Lagomorpha are summarized as this knowledge now applies to new therapeutics being developed for several human diseases including Multiple Sclerosis, Type 1 Diabetes and Cancer.
•The laboratory rabbit is a valuable model for studies of human diseases.•The rabbit's genome is more similar to the human genome than are rodents' genomes.•Rabbits produce highly specific high affinity antibodies.•Clinical trials of humanized rabbit monoclonal antibodies are in progress.•New information about engogenous retroviruses may lead to human therapeutics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Several strands of evidence indicate the presence of marked similarities between human brain and testis. Understanding these similarities and their implications has become a topic of interest among ...the scientific community. Indeed, an association of intelligence with some semen quality parameters has been reported and a relation between dysfunctions of the human brain and testis has also been evident. Numerous common molecular features are evident when these tissues are compared, which is reflected in the huge number of common proteins. At the functional level, human neurons and sperm share a number of characteristics, including the importance of the exocytotic process and the presence of similar receptors and signalling pathways. The common proteins are mainly involved in exocytosis, tissue development and neuron/brain-associated biological processes. With this analysis, we conclude that human brain and testis share several biochemical characteristics which, in addition to their involvement in the speciation process, could, at least in part, be responsible for the expression of a huge number of common proteins. Nonetheless, this is an underexplored topic, and the connection between these tissues needs to be clarified, which could help to understand the dysfunctions affecting brain and testis, as well as to develop improved therapeutic strategies.
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