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Pangolins, considered the most-trafficked mammals on Earth, are rapidly heading to extinction. Eight extant species of these African and Asian scale-bodied anteaters are commonly recognized, but their evolutionary relationships remain largely unexplored. Here, we present the most comprehensive phylogenetic assessment of pangolins, based on genetic variation of complete mitogenomes and 9 nuclear genes. We confirm deep divergence among Asian and African pangolins occurring not later than the Oligocene-Miocene boundary ca. 23 million years ago (Ma) (95% HPD = 18.7-27.2), limited fossil evidence suggesting dispersals from Europe. We recognize 3 genera including Manis (Asian pangolins), Smutsia (large African pangolins), and Phataginus (small African pangolins), which first diversified in the Middle-Upper Miocene (9.8-13.3 Ma) through a period of gradual cooling coinciding with a worldwide taxonomic diversification among mammals. Based on large mitogenomic distances among the 3 genera (18.3-22.8%) and numerous (18) morphological traits unique to Phataginus, we propose the subfamily Phatagininae subfam. nov. to designate small African pangolins. In contrast with the morphological-based literature, our results establish that the thick-tailed pangolin (Mams crassicaudata) is sister-species of the Sunda (Manis javanica) and Palawan (Manis culionensis) pangolins. Mitogenomic phylogenetic delineations supported additional pangolin species subdivisions (n = 13), including 6 African common pangolin (Phataginus tricuspis) lineages, but these patterns were not fully supported by our multi-locus approach. Finally, we identified more than 5000 informative mitogenomic sites and diagnostic variation from 5 nuclear genes among all species and lineages of pangolins, providing an important resource for further research and for effectively tracing the worldwide pangolin trade.

Big cat genomes reveal a history of interspecies admixture and adaptive evolution of genes underlying development and sensory perception., The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages.

The content of repetitive DNA in avian genomes is considerably less than in other investigated vertebrates. The first descriptions of tandem repeats were based on the results of routine biochemical and molecular biological experiments. Both satellite DNA and interspersed repetitive elements were annotated using library-based approach and de novo repeat identification in assembled genome. The development of deep-sequencing methods provides datasets of high quality without preassembly allowing one to annotate repetitive elements from unassembled part of genomes. In this work, we search the chicken assembly and annotate high copy number tandem repeats from unassembled short raw reads. Tandem repeat (GGAAA)n has been identified and found to be the second after telomeric repeat (TTAGGG)n most abundant in the chicken genome. Furthermore, (GGAAA)n repeat forms expanded arrays on the both arms of the chicken W chromosome. Our results highlight the complexity of repetitive sequences and update data about organization of sex W chromosome in chicken.

Background: Data regarding risk factors for revision surgery after superior labral anterior-posterior (SLAP) repair are limited to institutional series. Purpose: To define risk factors for revision surgery after SLAP repair among patients in a large national database. Study Design: Case-control study; Level of evidence, 3. Methods: A national insurance database was queried for patients undergoing arthroscopic SLAP repair (Current Procedural Terminology [CPT] code 29807) for the diagnosis of a SLAP tear. Patients without a CPT modifier for laterality were excluded. Revision surgery was defined as (1) subsequent ipsilateral SLAP repair (CPT 29807), (2) ipsilateral arthroscopic debridement for the diagnosis of a SLAP tear (CPT 29822 or 29823, with diagnosis code 840.7), (3) subsequent ipsilateral arthroscopic biceps tenodesis (CPT 29828), (4) subsequent ipsilateral open biceps tenodesis (CPT 23430), and (5) subsequent biceps tenotomy (CPT 23405). Multivariable binomial logistic regression analysis was performed to identify risk factors for revision surgery after SLAP repair, including patient demographics/comorbidities, concomitant diagnoses, and concomitant procedures performed. Odds ratios (ORs), 95% CIs, and P values were calculated. The estimated financial impact of revision surgery was also calculated. Results: There were 4751 patients who met inclusion and exclusion criteria. Overall, 121 patients (2.5%) required revision surgery after SLAP repair. Regression analysis identified numerous risk factors for revision surgery, including age >40 years (OR, 1.5; 95% CI, 1.2-1.8; P = .045), female sex (OR, 1.5; 95% CI, 1.3-1.8; P = .010), obesity (OR, 1.8; 95% CI, 1.5-2.2; P = .001), smoking (OR, 2.0; 95% CI, 1.6-2.4; P < .0001), and diagnosis of biceps tendinitis (OR, 3.5; 95% CI, 3.0-4.2; P < .0001) or long head of the biceps tearing (OR, 5.1; 95% CI, 4.1-6.3; P < .0001) at or before the time of surgery. Concomitant rotator cuff repair and distal clavicle excision were not significant risk factors for revision surgery. The cost of revision surgery averaged almost $9000. Conclusion: Risk factors for revision surgery after SLAP repair include age >40 years, female sex, obesity, smoking, and diagnosis of biceps tendinitis or long head of the biceps tearing. The diagnosis of biceps tendinitis (OR, 3.5) or long head of the biceps tearing (OR, 5.1) at or before the time of surgery was an especially significant risk factor for revision surgery. The high cost of revision surgery highlights the importance of appropriate indications to avoid the need for subsequent procedures.

Acetabular extrusion of cement during total hip arthroplasty is a well-recognised occurrence. We report a case of femoral neuropathy secondary to an extruded cement mass nine years after primary cemented total hip arthroplasty. Removal of the cement resulted in resolution of the patients symptoms. (Hip International 2005; 15: 182-3).

Clinical and experimental data suggest that carcinoembryonic antigen (CEA, CD66e, CEACAM-5) plays a key role in the formation of hepatic metastasis from colorectal and other types of epithelial cancers. The molecular events involved in CEA-induced metastasis have yet to be defined. Our group first cloned the gene (CEAR) for CEA-binding protein from the surface of fixed liver macrophages, (Kupffer cells). In this study to further elucidate the role of CEAR in colorectal cancer progression, its expression in colorectal cancer cells was suppressed by short hairpin RNAs (shRNAs) in CEA-overexpressing and CEA - negative MIP-101 colorectal cancer cell lines. The data show that targeted suppression of endogenous CEAR in tumor cells resulted in changes in cell invasiveness. RT-PCR data indicated reduced levels of E-cadherin, Snail, MMP-2, and Oct-4 in the clones with suppressed CEAR suggesting a role in the epithelial mesenchymal transition. The comparative analysis of tumorigenic activity to the liver of the cell lines with suppressed CEAR has also been conducted using an intrasplenic injection model in immuno-deficient mice. This data shows a decrease in tumor progression associated with CEAR suppression. In summary the results of this study revealed a novel role for CEAR gene in the regulation of colorectal cancer cell invasiveness and progression.

International audience; To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.

Background: Attempts to improve proximal load transfer and minimize stress shielding have included reducing the stiffness of femoral stems and using alternative stem materials, including carbon fiber composites. An uncemented implant (SR71) composed of a carbon-fiber-composite distal section and a porous-coated titanium-alloy proximal section, designed to improve proximal load transfer and provide good fixation, was clinically evaluated in a prospective randomized study. Methods: Sixty patients were enrolled and randomized to receive either the SR71 stem or an all-metal stem (Stability). All patients received a cemented all-polyethylene acetabular component and a 28-mm metal femoral head. All uncemented stems were implanted by the same surgeon. Patients were followed for up to ten years with repeated assessments of bone mineral density, radiographs, Harris hip scores (HHS), and visual analog scale (VAS) pain scores. Results: Ten years postoperatively, nineteen patients who had been treated with the SR71 stem and not lost to follow-up showed a significantly greater increase in proximal bone mineral density (Gruen zones 1 [p = 0.003] and 7 [p = 0.0007]) from baseline than did the twenty-two who had been treated with the Stability stem and not lost to follow-up. In contrast, the Stability group showed a significantly greater increase in distal bone mineral density (Gruen zones 2 [p = 0.0004], 3 [p = 0.0001], and 5 [p = 0.0035]) compared with the SR71 group. Radiographs demonstrated one case of progressive migration of an acetabular component used with an SR71 stem and one case of bone resorption in Gruen zones 7 and 14 in a patient treated with a Stability stem. There was no significant difference between the SR71 and Stability stems in terms of changes in the total HHS, HHS for pain, HHS for range of motion, or VAS pain scores ten years postoperatively relative to preoperative levels. There was one reported revision of an SR71 femoral stem at the ten-year review. Conclusions: The investigational SR71 implant provided increased proximal bone density and reduced distal bone density. The implant showed promising results at the time of early follow-up, and the clinical outcomes were similar to those of an all-metal stem at the time of a ten-year follow-up. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

The tyrosine kinase inhibitor (TKI) imatinib has revolutionized the management of chronic myeloid leukaemia (CML). However, around 25% of patients fail to sustain an adequate response. We sought to identify gene-expression biomarkers that could be used to predict imatinib response. The expression of 29 genes, previously implicated in CML pathogenesis, were measured by TaqMan Low Density Array in 73 CML patient samples. Patients were divided into low and high expression for each gene and imatinib failure (IF), probability of achieving CCyR, progression free survival and CML related OS were compared by Kaplan-Meier and log-rank. Results were validated in a second cohort of 56 patients, with a further technical validation using custom gene-expression assays in a conventional RT-qPCR in a sub-cohort of 37 patients. Patients with low PTCH1 expression showed a worse clinical response for all variables in all cohorts. PTCH1 was the most significant predictor in the multivariate analysis compared with Sokal, age and EUTOS. PTCH1 expression assay showed the adequate sensitivity, specificity and predictive values to predict for IF. Given the different treatments available for CML, measuring PTCH1 expression at diagnosis may help establish who will benefit best from imatinib and who is better selected for second generation TKI.

The dynamic geological and climatological history of Southeast Asia has spawned a complex array of ecosystems and 12 of the 37 known cat species, making it the most felid-rich region in the world. To examine the evolutionary histories of these poorly studied fauna, we compared phylogeography of six species (leopard cat Prionailurus bengalensis, fishing cat P. viverrinus, Asiatic golden cat Pardofelis temminckii, marbled cat P. marmorata, tiger Panthera tigris and leopard P. pardus) by sequencing over 5 kb of DNA each from 445 specimens at multiple loci of mtDNA, Y and X chromosomes. All species except the leopard displayed significant phylogenetic partitions between Indochina and Sundaland, with the central Thai-Malay Peninsula serving as the biogeographic boundary. Concordant mtDNA and nuclear DNA genealogies revealed deep Indochinese-Sundaic divergences around 2 MYA in both P. bengalensis and P. marmorata comparable to previously described interspecific distances within Felidae. The divergence coincided with serial sea level rises during the late Pliocene and early Pleistocene, and was probably reinforced by repeated isolation events associated with environmental changes throughout the Pleistocene. Indochinese-Sundaic differentiations within P. tigris and P. temminckii were more recent at 72-108 and 250-1570 kya, respectively. Overall, these results illuminate unexpected, deep vicariance events in Southeast Asian felids and provide compelling evidence of species-level distinction between the Indochinese and Sundaic populations in the leopard cat and marbled cat. Broader sampling and further molecular and morphometric analyses of these species will be instrumental in defining conservation units and effectively preserving Southeast Asian biodiversity.

Diversity within the major histocompatibility complex (MHC) reflects the immunological fitness of a population. MHC-linked microsatellite markers provide a simple and an inexpensive method for studying MHC diversity in large-scale studies. We have developed 6 MHC-linked microsatellite markers in the domestic cat and used these, in conjunction with 5 neutral microsatellites, to assess MHC diversity in domestic mixed breed (n = 129) and purebred Burmese (n = 61) cat populations in Australia. The MHC of outbred Australian cats is polymorphic (average allelic richness = 8.52), whereas the Burmese population has significantly lower MHC diversity (average allelic richness = 6.81; P < 0.01). The MHC-linked microsatellites along with MHC cloning and sequencing demonstrated moderate MHC diversity in cheetahs (n = 13) and extremely low diversity in Gir lions (n = 13). Our MHC-linked microsatellite markers have potential future use in diversity and disease studies in other populations and breeds of cats as well as in wild felid species.

The guigna (Leopardus guigna) is the smallest and most-restricted New World cat species, inhabiting only around 160,000 km2 of temperate rain forests in southern South America and is currently threatened by habitat loss, fragmentation and human persecution. We investigated phylogeographic patterns of genetic diversity, demographic history and barriers to gene flow with 116 individuals sampled across the species geographic range by analyzing 1,798 base pairs of the mtDNA (496 bp HVSI region, 720 bp NADH-5 gene, 364 bp from 16S gene and 218 bp from ATP-8 gene) and 15 microsatellite loci. Mitochondrial DNA data revealed a clear phylogeographic pattern with moderate separation between northern and southern Chilean populations supporting recognized subspecific partitions based on morphology. A recent demographic expansion was inferred for the southern-most group (San Rafael Lake), presumably due to the complete coverage of this area during the last glacial period, 28000–16000 years BP. Geographical barriers such as the Andes Mountains and the Chacao Channel have partially restricted historic and more-recent gene flow and the Chiloe Island population has diverged genetically since being separated from the mainland 7000 years BP. This is the first study of the genetic structure of this threatened species throughout its whole geographic range.

Summary Black and white rhinoceros ( Diceros bicornis and Ceratotherium simum ) are iconic African species that are classified by the International Union for the Conservation of Nature (IUCN) as Critically Endangered and Near Threatened (http://www.iucnredlist.org/), respectively [1]. At the end of the 19 th century, Southern white rhinoceros ( Ceratotherium simum simum ) numbers had declined to fewer than 50 animals in the Hluhluwe-iMfolozi region of the KwaZulu-Natal (KZN) province of South Africa, mainly due to uncontrolled hunting [2,3]. Efforts by the Natal Parks Board facilitated an increase in population to over 20,000 in 2015 through aggressive conservation management [2]. Black rhinoceros ( Diceros bicornis ) populations declined from several hundred thousand in the early 19 th century to ∼65,000 in 1970 and to ∼2,400 by 1995 [1] with subsequent genetic reduction, also due to hunting, land clearances and later poaching [4]. In South Africa, rhinoceros poaching incidents have increased from 13 in 2007 to 1,215 in 2014 [1]. This has occurred despite strict trade bans on rhinoceros products and strict enforcement in recent years.

South-central Africa is characterized by an archipelago of wetlands, which has evolved in time and space since at least the Miocene, providing refugia for animal species during Pleistocene arid episodes. Their importance for biodiversity in the region is reflected in the evolution of a variety of specialist mammal and bird species, adapted to exploit these wetland habitats. Populations of lions (Panthera leo) across south-central and east Africa have contrasting signatures of mitochondrial DNA haplotypes and biparental nuclear DNA in wetland and savannah habitats, respectively, pointing to the evolution of distinct habitat preferences. This explains the absence of genetic admixture of populations from the Kalahari savannah of southwest Botswana and the Okavango wetland of northern Botswana, despite separation by only 500 km. We postulate that ancestral lions were wetland specialists and that the savannah lions evolved from populations that were isolated during arid Pleistocene episodes. Expansion of grasslands and the resultant increase in herbivore populations during mesic Pleistocene climatic episodes provided the stimulus for the rapid population expansion and diversification of the highly successful savannah lion specialists. Our model has important implications for lion conservation.

Over 95% of all metazoan (animal) species comprise the “invertebrates,” but very few genomes from these organisms have been sequenced. We have, therefore, formed a “Global Invertebrate Genomics Alliance” (GIGA). Our intent is to build a collaborative network of diverse scientists to tackle major challenges (e.g., species selection, sample collection and storage, sequence assembly, annotation, analytical tools) associated with genome/transcriptome sequencing across a large taxonomic spectrum. We aim to promote standards that will facilitate comparative approaches to invertebrate genomics and collaborations across the international scientific community. Candidate study taxa include species from Porifera, Ctenophora, Cnidaria, Placozoa, Mollusca, Arthropoda, Echinodermata, Annelida, Bryozoa, and Platyhelminthes, among others. GIGA will target 7000 noninsect/nonnematode species, with an emphasis on marine taxa because of the unrivaled phyletic diversity in the oceans. Priorities for selecting invertebrates for sequencing will include, but are not restricted to, their phylogenetic placement; relevance to organismal, ecological, and conservation research; and their importance to fisheries and human health. We highlight benefits of sequencing both whole genomes (DNA) and transcriptomes and also suggest policies for genomic-level data access and sharing based on transparency and inclusiveness. The GIGA Web site (http://giga.nova.edu) has been launched to facilitate this collaborative venture.

Shoulder instability is a relatively common problem. Even with contemporary surgical techniques, instability can recur following both open and arthroscopic fixation. Surgical management of capsular insufficiency in anterior shoulder stabilization represents a significant challenge, particularly in young, active patients. There are a limited number of surgical treatment options. The Laterjet technique can present with a number of intraoperative challenges and postoperative complication.We report an arthroscopic subscapularis tenodesis technique as a salvage procedure for challenging glenohumeral instability cases. Sutures are passed through the subscapularis tendon and capsule before they are tied as one in the subdeltoid psace. The rotator interval is closed with superior and medial advancement of anterior and inferior tissue. This technical note carefully describes this procedure with useful technical tips, illustrations, and diagrams.Two clinical cases are described involving patients with recurrent instability following failed surgery who were successfully managed with this procedure.Both cases described resulted in improved shoulder stability, range of motion, and function following management with this surgical technique. This arthroscopic subscapularis tenodesis procedure is proposed as a useful alternative repair technique for cases of recurrent instability after failed surgery with isolated capsular insufficiency.It is believed that this arthroscopic subscapularis tenodesis technique can potentially provide similar outcomes to open bone block stabilization procedures, while reducing the risks associated with those procedures.

Surgical management of shoulder pathologies has evolved tremendously during the past 3 decades, such that many lesions previously treated with open techniques are now addressed arthroscopically. Despite this movement, many surgeons and outcome studies continue to prefer open repairs as the gold standard, criticizing--with good reason--the reliability, reproducibility, and extended operative time of arthroscopic repairs, particularly with respect to anterior stabilizations and subscapularis repairs. With this in mind, we present the arthroscopic "subdeltoid approach," a novel standardized exposure technique for extracompartmental anterior shoulder arthroscopy. We define the subdeltoid space as the fascial plane bound superiorly by the acromion and coracoacromial ligament, medially by the coracoid and the conjoint tendon, inferiorly by the musculotendinous insertion of the pectoralis major to the humerus, and laterally by the lateral border of the humerus. When coupled with existing arthroscopic tools, this space dramatically enhances our ability to apply open techniques to some of the more challenging anterior shoulder pathoanatomy and expand the indications and efficacy of arthroscopy. This exposure technique has been used in more than 300 cases during the past decade to treat a myriad of shoulder pathologies, without any longstanding postoperative complications.

With greater numbers of younger patients undergoing total hip replacement (THR), the effect of patient age on the diameter of the femoral canal may become more relevant. This study aimed to investigate the relationship between the diameter of the diaphysis of the femoral canal with increasing age in a large number of patients who underwent THR. A total of 1685 patients scheduled for THR had their femoral dimensions recorded from calibrated radiographs. There were 736 males and 949 females with mean ages of 67.1 years (34 to 92) and 70.2 years (29 to 92), respectively. The mean diameter of the femoral canal was 13.3 mm (8.0 to 23.0) for males and 12.7 mm (6.0 to 26.0) for females. There was a poor correlation between age and the diameter of the canal in males (r = 0.071, p = 0.05) but a stronger correlation in females (r = 0.31, p < 0.001). The diameter of the femoral canal diameter of a female patient undergoing THR could be predicted to increase by 3.2 mm between the ages of 40 and 80 years, in contrast a male would be expected to experience only a 0.6 mm increase during the same period. This increase in the diameter of the canal with age might affect the long-term survival of the femoral component in female patients. Cite this article: Bone Joint J 2013;95-B:339–42.

The puma is an iconic predator that ranges throughout the Americas, occupying diverse habitats. Previous phylogeographic analyses have revealed that it exhibits moderate levels of genetic structure across its range, with few of the classically recognized subspecies being supported as distinct demographic units. Moreover, most of the species' molecular diversity was found to be in South America. To further investigate the phylogeographic structure and demographic history of pumas we analyzed mtDNA sequences from 186 individuals sampled throughout their range, with emphasis on South America. Our objectives were to refine the phylogeographic assessment within South America and to investigate the demographic history of pumas using a coalescent approach. Our results extend previous phylogeographic findings, reassessing the delimitation of historical population units in South America and demonstrating that this species experienced a considerable demographic expansion in the Holocene, ca. 8,000 years ago. Our analyses indicate that this expansion occurred in South America, prior to the hypothesized re-colonization of North America, which was therefore inferred to be even more recent. The estimated demographic history supports the interpretation that pumas suffered a severe demographic decline in the Late Pleistocene throughout their distribution, followed by population expansion and re-colonization of the range, initiating from South America.

Biceps-labrum complex (BLC) disease is a well recognized source of shoulder pain. The BLC can be divided into 3 anatomical zones: inside, junction, and bicipital tunnel. Despite our evolving understanding, diagnosis of BLC pathology through physical examination, standard imaging techniques, and standard diagnostic glenohumeral arthroscopy can be challenging. Selection of the most appropriate surgical technique in refractory cases should take into account decompression of the extra-articular bicipital tunnel. In this article we review the recent literature regarding diagnosis and treatment options for BLC disease.

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics.

Pangolins, unique mammals with scales over most of their body, no teeth, poor vision, and an acute olfactory system, comprise the only placental order (Pholidota) without a whole-genome map. To investigate pangolin biology and evolution, we developed genome assemblies of the Malayan (Manis javanica) and Chinese (M. pentadactyla) pangolins. Strikingly, we found that interferon epsilon (IFNE), exclusively expressed in epithelial cells and important in skin and mucosal immunity, is pseudogenized in all African and Asian pangolin species that we examined, perhaps impacting resistance to infection. We propose that scale development was an innovation that provided protection against injuries or stress and reduced pangolin vulnerability to infection. Further evidence of specialized adaptations was evident from positively selected genes involving immunity-related pathways, inflammation, energy storage and metabolism, muscular and nervous systems, and scale/hair development. Olfactory receptor gene families are significantly expanded in pangolins, reflecting their well-developed olfaction system. This study provides insights into mammalian adaptation and functional diversification, new research tools and questions, and perhaps a new natural IFNE-deficient animal model for studying mammalian immunity.

Pangolins are scale-covered mammals, containing eight endangered species. Maintaining pangolins in captivity is a significant challenge, in part because little is known about their genetics. Here we provide the first large-scale sequencing of the critically endangered Manis javanica transcriptomes from eight different organs using Illumina HiSeq technology, yielding ~75 Giga bases and 89,754 unigenes. We found some unigenes involved in the insect hormone biosynthesis pathway and also 747 lipids metabolism-related unigenes that may be insightful to understand the lipid metabolism system in pangolins. Comparative analysis between M. javanica and other mammals revealed many pangolin-specific genes significantly over-represented in stress-related processes, cell proliferation and external stimulus, probably reflecting the traits and adaptations of the analyzed pregnant female M. javanica. Our study provides an invaluable resource for future functional works that may be highly relevant for the conservation of pangolins.

Сarcinoembryonic antigen (CEA, CEACAM5, CD66) is a promoter of metastasis in epithelial cancers that is widely used as a prognostic clinical marker of metastasis. The aim of this study is to identify the network of genes that are associated with CEA-induced colorectal cancer liver metastasis. We compared the genome-wide transcriptomic profiles of CEA positive (MIP101 clone 8) and CEA negative (MIP 101) colorectal cancer cell lines with different metastatic potential in vivo. The CEA-producing cells displayed quantitative changes in the level of expression for 100 genes (over-expressed or down-regulated). They were confirmed by quantitative RT-PCR. The KEGG pathway analysis identified 4 significantly enriched pathways: cytokine-cytokine receptor interaction, MAPK signaling pathway, TGF-beta signaling pathway and pyrimidine metabolism. Our results suggest that CEA production by colorectal cancer cells triggers colorectal cancer progression by inducing the epithelial- mesenchymal transition, increasing tumor cell invasiveness into the surrounding tissues and suppressing stress and apoptotic signaling. The novel gene expression distinctions establish the relationships between the existing cancer markers and implicate new potential biomarkers for colorectal cancer hepatic metastasis.

Background B chromosomes are dispensable and variable karyotypic elements found in some species of animals, plants and fungi. They often originate from duplications and translocations of host genomic regions or result from hybridization. In most species, little is known about their DNA content. Here we perform high-throughput sequencing and analysis of B chromosomes of roe deer and brocket deer, the only representatives of Cetartiodactyla known to have B chromosomes. Results In this study we developed an approach to identify genomic regions present on chromosomes by high-throughput sequencing of DNA generated from flow-sorted chromosomes using degenerate-oligonucleotide-primed PCR. Application of this method on small cattle autosomes revealed a previously described KIT gene region translocation associated with colour sidedness. Implementing this approach to B chromosomes from two cervid species, Siberian roe deer (Capreolus pygargus) and grey brocket deer (Mazama gouazoubira), revealed dramatically different genetic content: roe deer B chromosomes consisted of two duplicated genomic regions (a total of 1.42-1.98 Mbp) involving three genes, while grey brocket deer B chromosomes contained 26 duplicated regions (a total of 8.28-9.31 Mbp) with 34 complete and 21 partial genes, including KIT and RET protooncogenes, previously found on supernumerary chromosomes in canids. Sequence variation analysis of roe deer B chromosomes revealed a high frequency of mutations and increased heterozygosity due to either amplification within B chromosomes or divergence between different Bs. In contrast, grey brocket deer B chromosomes were found to be more homogeneous and resembled autosomes in patterns of sequence variation. Similar tendencies were observed in repetitive DNA composition. Conclusions Our data demonstrate independent origins of B chromosomes in the grey brocket and roe deer. We hypothesize that the B chromosomes of these two cervid species represent different stages of B chromosome sequences evolution: probably nascent and similar to autosomal copies in brocket deer, highly derived in roe deer. Based on the presence of the same orthologous protooncogenes in canids and brocket deer Bs we argue that genomic regions involved in B chromosome formation are not random. In addition, our approach is also applicable to the characterization of other evolutionary and clinical rearrangements. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2933-6) contains supplementary material, which is available to authorized users.

AimsOur aim was to examine the clinical and radiographic outcomes in 257 consecutive Oxford unicompartmental knee arthroplasties (OUKAs) (238 patients), five years post-operatively.Patients and MethodsA retrospective evaluation was undertaken of patients treated between April 2008 and October 2010 in a regional centre by two non-designing surgeons with no previous experience of UKAs. The Oxford Knee Scores (OKSs) were recorded and fluoroscopically aligned radiographs were assessed post-operatively at one and five years.ResultsThe median age of the 238 patients was 65.0 years (interquartile range (IQR) 59.0 to 73.0), the median body mas index was 30.0 (IQR 27.5 to 33.0) and 51.7% were male. There were no intra-operative complications. There was a significant improvement in the median OKS at six weeks (34, IQR 31.0 to 37.0), one year (38, IQR 29.0 to 43.0) and five years (37, IQR 27.0 to 42.0) when compared with the pre-operative scores (16, IQR 13.0 to 19.0) (all p = < 0.01). No patient had progressive radiolucent lines or loosening. A total of 16 patients had died by five years. The cumulative survival at five years was 98.8% and the mean survival time was 5.8 years (95% confidence interval 5.6 to 5.9). A total of seven OUKAs (2.7%) were revised; three within five years and four thereafter, between 5.1 and 5.7 years post-operatively. Five (1.9%) had re-operations within five years.ConclusionThe proportion of patients requiring revision at five years is lower than that generally reported for UKA. These findings add support for the use of the cementless OUKA outside the design centre. Longer follow-up is required. Cite this article: Bone Joint J 2017;99-B:623–31.

Unlike other domesticated creatures, the house cat contributes little to human survival. Researchers have therefore wondered how and why cats came to live among people. Experts traditionally thought that the Egyptians were the first to domesticate the cat, some 3,600 years ago. But recent genetic and archaeological discoveries indicate that cat domestication began in the Fertile Crescent, perhaps around 10,000 years ago, when agriculture was getting under way. The findings suggest that cats started making themselves at home around people to take advantage of the mice and food scraps found in their settlements.

To determine if reoperation rates are higher for patients who underwent isolated rotator cuff repair (RCR) than those who underwent RCR with concomitant biceps tenodesis using a large private-payer database.A national insurance database was queried for patients who underwent arthroscopic RCR between the years 2007 and 2014 (PearlDiver, Warsaw, IN). The Current Procedural Terminology (CPT) 29,827 (arthroscopy, shoulder, surgical; with RCR) identified RCR patients who were subdivided into 3 groups-group 1: RCR without biceps tenodesis; group 2: RCR with concomitant arthroscopic biceps tenodesis (CPT 29827 and 29,828); group 3: RCR with concomitant open biceps tenodesis (CPT 29827 and 23,430). Reoperation rates (revision RCR, subsequent biceps surgeries) and complications at 30 days, 90 days, 6 months, and 1 year were analyzed. Multivariate logistic regression was used to compare reoperations and complications between groups. Rotator cuff tear size, whether the biceps was ruptured and whether a biceps tenotomy was performed, was not available.Group 1: 27,178 patients. Group 2: 4,810 patients. Group 3: 1,493 patients. More patients underwent concomitant arthroscopic than concomitant open tenodesis (P.001). A total of 2,509 patients underwent a reoperation for RCR or biceps tenodesis within 1 year after RCR. When adjusted for age, sex, and comorbidities, no significant differences in reoperation rates at 30 days or 90 days among the 3 groups, but significantly more patients who had a tenodesis, required a reoperation compared with those who did not have a tenodesis at 6 months and 1 year (both P.001). Urinary tract infections were more common in patients who did not have a tenodesis, whereas dislocation, nerve injury, and surgical site infection were more common in tenodesis patients.Higher reoperation rates at 1 year were seen in patients who had concomitant biceps tenodesis.Level III, case-control database review study.

Background Bones have been subjected to considerable selective pressure throughout vertebrate evolution, such as occurred during the adaptations associated with the development of powered flight. Powered flight evolved independently in two extant clades of vertebrates, birds and bats. While this trait provided advantages such as in aerial foraging habits, escape from predators or long-distance travels, it also imposed great challenges, namely in the bone structure. Results We performed comparative genomic analyses of 89 bone-associated genes from 47 avian genomes (including 45 new), 39 mammalian, and 20 reptilian genomes, and demonstrate that birds, after correcting for multiple testing, have an almost two-fold increase in the number of bone-associated genes with evidence of positive selection (~52.8 %) compared with mammals (~30.3 %). Most of the positive-selected genes in birds are linked with bone regulation and remodeling and thirteen have been linked with functional pathways relevant to powered flight, including bone metabolism, bone fusion, muscle development and hyperglycemia levels. Genes encoding proteins involved in bone resorption, such as TPP1, had a high number of sites under Darwinian selection in birds. Conclusions Patterns of positive selection observed in bird ossification genes suggest that there was a period of intense selective pressure to improve flight efficiency that was closely linked with constraints on body size. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2681-7) contains supplementary material, which is available to authorized users.

High-resolution genetic and physical maps are invaluable tools for building accurate genome assemblies, and interpreting results of genome-wide association studies (GWAS). Previous genetic and physical maps anchored good quality draft assemblies of the domestic cat genome, enabling the discovery of numerous genes underlying hereditary disease and phenotypes of interest to the biomedical science and breeding communities. However, these maps lacked sufficient marker density to order thousands of shorter scaffolds in earlier assemblies, which instead relied heavily on comparative mapping with related species. A high-resolution map would aid in validating and ordering chromosome scaffolds from existing and new genome assemblies. Here, we describe a high-resolution genetic linkage map of the domestic cat genome based on genotyping 453 domestic cats from several multi-generational pedigrees on the Illumina 63K SNP array. The final maps include 58,055 SNP markers placed relative to 6637 markers with unique positions, distributed across all autosomes and the X chromosome. Our final sex-averaged maps span a total autosomal length of 4464 cM, the longest described linkage map for any mammal, confirming length estimates from a previous microsatellite-based map. The linkage map was used to order and orient the scaffolds from a substantially more contiguous domestic cat genome assembly (Felis catus v8.0), which incorporated ∼20 × coverage of Illumina fragment reads. The new genome assembly shows substantial improvements in contiguity, with a nearly fourfold increase in N50 scaffold size to 18 Mb. We use this map to report probable structural errors in previous maps and assemblies, and to describe features of the recombination landscape, including a massive (∼50 Mb) recombination desert (of virtually zero recombination) on the X chromosome that parallels a similar desert on the porcine X chromosome in both size and physical location.

The glaucomas are a group of diseases characterized by optic nerve damage that together represent a leading cause of blindness in the human population and in domestic animals. Here we report a mutation in LTBP2 that causes primary congenital glaucoma (PCG) in domestic cats. We identified a spontaneous form of PCG in cats and established a breeding colony segregating for PCG consistent with fully penetrant, autosomal recessive inheritance of the trait. Elevated intraocular pressure, globe enlargement and elongated ciliary processes were consistently observed in all affected cats by 8 weeks of age. Varying degrees of optic nerve damage resulted by 6 months of age. Although subtle lens zonular instability was a common feature in this cohort, pronounced ectopia lentis was identified in less than 10% of cats examined. Thus, glaucoma in this pedigree is attributed to histologically confirmed arrest in the early post-natal development of the aqueous humor outflow pathways in the anterior segment of the eyes of affected animals. Using a candidate gene approach, significant linkage was established on cat chromosome B3 (LOD 18.38, θ = 0.00) using tightly linked short tandem repeat (STR) loci to the candidate gene, LTBP2. A 4 base-pair insertion was identified in exon 8 of LTBP2 in affected individuals that generates a frame shift that completely alters the downstream open reading frame and eliminates functional domains. Thus, we describe the first spontaneous and highly penetrant non-rodent model of PCG identifying a valuable animal model for primary glaucoma that closely resembles the human disease, providing valuable insights into mechanisms underlying the disease and a valuable animal model for testing therapies.

Faurby, Werdelin, and Svenning raise some interesting and valid points around the interpretation of the genomics and fossil data on the history of the African cheetah, a species that has fascinated humankind for millennia. They emphasize a controversy to which we alluded in our article [1] and they offer an alternative explanation to the scenario we had suggested for the time and place of demographic events that preceded modern African cheetah populations. We fully agree that there are important areas of uncertainty in this conundrum and welcome the opportunity to reconsider and to offer our view into the natural history of Acinonyx jubatus. We do believe that the integration of fossil and molecular data seems a good way to get toward the truth, so we shall try to emphasize two considerations in our comments: first, the most parsimonious interpretation of data; and second, the robustness of available and relevant fossil and molecular data. Some aspects to consider: The extreme genetic depletion of modern cheetahs seems true and validated by Dobrynin et al., as has been suggested with multiple metrics across several decades [1–3]. Two possible historic events that could account for the genetic reduction are extended continental migration events and/or population bottlenecks (a.k.a. founder effect). We offered possible (but not proven) explanations based upon dating the latest founder effect at 10,000–12,000 during the late Pleistocene by multiple molecular methods, coincident with abrupt mammal extinction events in North America and Eurasia at that time. The genome-wide Dadi result suggested an earlier more ancient demographic contraction ~100,000 years ago. Something caused the massive diversity loss in their history. We suggested two scenarios: the earliest—a migration of North American cheetahs out of North America >100,000 years BP, and a second—when cheetahs went extinct from North America 10,000–12,000 years ago. It may be relevant that North American pumas show a near identical quantity of genomic depletion as African cheetahs, suggesting they were also extirpated form North America during the quaternary mammal extinction and repopulated from South America subsequently [3–5]. Was this an irrelevant coincidence or was a single North American or global event responsible? The answer is uncertain. Please refer to [6, 7] which detail the latest relatively robust molecular phylogenies for the Felidae and a derivative study [8] that postulates parsimonious historic migration scenarios based upon phylogeny, the fossil record, present and past geographical occurrence, and geological sea levels. That phylogenetic study reported in [6] examined 18,853 bp of nuclear sequence (autosome, X and Y chromosome), which yielded 3440 parsimony informative sites, and mtDNA sequence, from all 37 Felidae species calibrated with 16 fossil dates [6]. That molecular phylogeny (combined with paleontological, geological and present range) posited the arrival of the ancestors of three Felidae lineages (Ocelot preceding Lynx, and then preceding Puma lineage) into North America, around 8–8.5 million years ago (MYA). All three lineages have roots in North America with ocelot ancestors appearing first 8.0 MYA, Lynx ancestors 7.2 MYA, and Puma ancestors 6.7 MYA. Cheetah-like genera (Acinonyx lineage) appear first ~4.9 MYA. Support for this scenario comes from molecular evolutionary analyses that were supported by 13 cladistic synapomorphies (large insertion/deletions) [6]. Sometime thereafter, the Acinonyx lineage ancestors, derived from the North American puma lineage precursors, would make their way back to Asia from North America. The fossil record puts the oldest cheetah fossils in Asia 3 million years before present (MYBP). Fossils of Acinonyx and cheetah-looking cats were in both in Asia and North America from 3 MYA to the late Pleistocene. So the comment in their title “There were never any true cheetahs in North America” depends on what we mean by “true cheetahs.” Faurby, Werdelin, and Svenning argue cogently that North American cheetah fossils are all from the genus Miracinonyx, which is not closely related to modern Acinonyx cheetahs, which occur in Africa today and in Eurasia throughout the Pliocene and Pleistocene fossil deposits. Thus, the trivial name of North American “cheetah” is misleading (they imply we fell into that trap, although these authors themselves use the trivial name “cheetah” ten times in their note). The data supporting the distinctions of North American species in Miracinonyx from Eurasian Acinonyx are the bases of the controversy. A seminal and elegant report by Van Valkenburgh et al. [9] concluded that North American cheetah fossils (there were six specimens, one complete and five fragmented) were cladistically similar based upon ten synapomorphic morphological features that were distinct from Eurasian Acinonyx fossils. This study proposed the distinction of North America (Miracinonyx) and Eurasian (Acinonyx) genera in 1990. Faurby, Werdelin, and Svenning affirm this conclusion by stating “… No fossils of Acinonyx are known from North America, despite the extensive fossil record from the continent, while no fossils of Miracinonyx are known outside North America.” This declarative statement discounts a longstanding controversy that Van Valkenburgh et al. [9] acknowledge. First, there are several important adaptive morphometric characters that are shared between North America and Eurasian cheetah species including long slender limbs, small aerodynamic skulls, and reduced canines which Van Valkenburgh et al. [9] attribute to homoplasy or parallelisms. But at least three respected authors groups have disagreed [10–12] and opined that the adaptive similarities are evidence for homology of North American and African cheetahs supporting the modern cheetah origins in North America. Adams’ study titled “The cheetah-native American” [10], classifies the North American cheetah specimens as Acinonyx (precursors of modern Acinonyx) and suggests that pronouncing these important cursorial characters as convergence or parallelism “pushes the concept of parallel evolution to an unprecedented extreme”. Van Valkenburgh et al. [9] actually place the Eurasian Acinonyx and the North American Miracinonyx genera as sister taxa, emphasizing the difficulty in sorting this controversy cleanly. Further they state “… The common ancestor (of Acinonyx and Miracinonyx) … could have been either Old or New World.” Mark Springer, a noted expert of interpreting molecular and paleontological evidence across vertebrate taxa [13], states that “… morphological studies of eutherian … relationships have failed to separate homology and homoplasy and have consistently been misled by the latter … one of the greatest challenges ahead for mammalian systematists is to tease apart homology and homoplasy in morphological characters.” Springer’s study described explicitly how morphological inference erred in over 50 % of ordinal assignments within the mammalian radiations due to this issue [13]. Faurby, Werdelin, and Svenning refer to Barnet et al. [14] who presented a molecular phylogeny that uses ancient DNA to place the North American Miracinonyx as a sister to Puma concolor (and not modern Acinonyx), but they acknowledge the limited power of a 1302 bp mtDNA dataset. There are other details of the Barnett study that may be relevant. First, the actual nucleotide alignment is not presented which limits our ability to evaluate their conclusions or assess the extent of homoplasy. Further, when Barnet et al. performed a jack-knife analyses, excluding H. jaguarundi from the phylogenic analysis (H. jaguarundi is a sister taxon to Puma concolor [6–8]), statistical support for the sister relationship of Puma-Miracinonyx actually increased, an indication that molecular homoplasy was operative in their results [14]. Their conclusion that American cheetah Miracinonyx is not within the African-Asian Acinonyx group is tentative at best and has not been confirmed convincingly. Faurby, Werdelin, and Svenning raise an important caveat concerning the confidence interval of the Dadi and PSMC and question the average generation of modern and ancient cheetahs. We do agree these aspects are not as firm as we would prefer. They hypothesize that “… the simplest explanation of the patterns may be a gradual decline in Acinonyx as inferred by the PSMC algorithm, potentially with sharper declines in some periods as suggested by the DaDi analysis.” Their points are true and we acknowledge the tentative aspects of our derived conclusions. In sum, we welcome the engagement of Faurby, Werdelin, and Svenning in the interpretation of the new and older data around the natural history for cheetah origins. They may be correct in their interpretation that Eurasian Cheetahs are the most recent ancestors of modern African cheetahs but their North American presence at one or several stages also seems plausible from the available data. We were not there at the time, so we cannot be sure of what the timing or influence of any possible North American cheetah migration to Asia might be, but both fossil and molecular evidence would be consistent with cheetah-like cats in both Asia and North America for some 3 MY. A correct explanation for African cheetah origins would seem to be one of three possibilities: (1) Eurasian origin exclusively; (2) North American origins exclusively and a migration across Asia to Africa; or (3) a combination of continental evolution on both continents, combined with periodic migration (and perhaps admixture) allowing both continental populations to contribute to modern African cheetah genetic disposition and locations. The resolution of these alternatives represents a fascinating challenge for the genome archeologists reading this exchange.

The Asian arowana (Scleropages formosus), one of the world’s most expensive cultivated ornamental fishes, is an endangered species. It represents an ancient lineage of teleosts: the Osteoglossomorpha. Here, we provide a high-quality chromosome-level reference genome of a female golden-variety arowana using a combination of deep shotgun sequencing and high-resolution linkage mapping. In addition, we have also generated two draft genome assemblies for the red and green varieties. Phylogenomic analysis supports a sister group relationship between Osteoglossomorpha (bonytongues) and Elopomorpha (eels and relatives), with the two clades together forming a sister group of Clupeocephala which includes all the remaining teleosts. The arowana genome retains the full complement of eight Hox clusters unlike the African butterfly fish (Pantodon buchholzi), another bonytongue fish, which possess only five Hox clusters. Differential gene expression among three varieties provides insights into the genetic basis of colour variation. A potential heterogametic sex chromosome is identified in the female arowana karyotype, suggesting that the sex is determined by a ZW/ZZ sex chromosomal system. The high-quality reference genome of the golden arowana and the draft assemblies of the red and green varieties are valuable resources for understanding the biology, adaptation and behaviour of Asian arowanas.

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species’ native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics., Author Summary We describe the genome assembly of Asian seabass (Lates calcarifer), a marine teleost with aquaculture relevance. Though >500 eukaryotic genome sequences are available in public repositories, the majority are highly fragmented with incomplete assemblies, which explains why considerable effort and resources are often spent to improve their quality after publication. In our study, we employed long read sequencing combined with genetic and optical mapping, and syntenic information to produce a chromosomal level assembly. The largely continuous genome assembly will be useful for comparative genomics and offers an opportunity to look into regions less explored such as tandem repeats (the core component of centromeres and telomeres). In addition, population structure of the species was analysed based on low-coverage genome sequence information from 61 individuals representing diverse geographic locations stretching from North-Western India across South-East Asia and Australia to Papua New Guinea.

The cytochrome P450 (CYP) superfamily defends organisms from endogenous and noxious environmental compounds, and thus is crucial for survival. However, beyond mammals the molecular evolution of CYP2 subfamilies is poorly understood. Here, we characterized the CYP2 family across 48 novel avian whole genomes representing all major extant bird clades. Overall, 12 CYP2 subfamilies were identified, including the first description of the CYP2F, CYP2G and several CYP2AF genes in avian genomes. Some of the CYP2 genes previously described as being lineage-specific, such as CYP2K and CYP2W, are ubiquitous to all avian groups. Furthermore, we identified a large number of CYP2J copies, which have been associated previously with water reabsorption. We detected positive selection in the avian CYP2C, CYP2D, CYP2H, CYP2J, CYP2K and CYP2AC subfamilies. Moreover, we identified new substrate recognition sites (SRS0, SRS2_SRS3 and SRS3.1) and heme binding areas that influence CYP2 structure and function of functional importance as under significant positive selection. Some of the positively selected sites in avian CYP2D are located within the same SRS1 region that was previously linked with the metabolism of plant toxins. Additionally, we find that selective constraint variations in some avian CYP2 subfamilies are consistently associated with different feeding habits (CYP2H and CYP2J), habitats (CYP2D, CYP2H, CYP2J and CYP2K) and migratory behaviors (CYP2D, CYP2H and CYP2J). Overall, our findings indicate that there has been active enzyme site selection on CYP2 subfamilies and differential selection associated with different life history traits among birds.

The koala (Phascolarctos cinereus) suffered population declines and local extirpation due to hunting in the early 20th century, especially in southern Australia. Koalas were subsequently reintroduced to the Brisbane Ranges (BR) and Stony Rises (SR) by translocating individuals from a population on French Island descended from a small number of founders. To examine genetic diversity and north–south differentiation, we genotyped 13 microsatellite markers in 46 wild koalas from the BR and SR, and 27 Queensland koalas kept at the US zoos. The Queensland koalas displayed much higher heterozygosity (H O = 0.73) than the 2 southern Australian koala populations examined: H O = 0.49 in the BR, whereas H O = 0.41 in the SR. This is consistent with the historical accounts of bottlenecks and founder events affecting the southern populations and contrasts with reports of high genetic diversity in some southern populations. The 2 southern Australian koala populations were genetically similar (F ST = 0.018, P = 0.052). By contrast, northern and southern Australian koalas were highly differentiated (F ST = 0.27, P < 0.001), thereby suggesting that geographic structuring should be considered in the conservation management of koalas. Sequencing of 648bp of the mtDNA control region in Queensland koalas found 8 distinct haplotypes, one of which had not been previously detected among koalas. Queensland koalas displayed high mitochondrial haplotype diversity (H = 0.753) and nucleotide diversity (π = 0.0072), indicating along with the microsatellite data that North American zoos have maintained high levels of genetic diversity among their Queensland koalas.

Solenodons are insectivores found only in Hispaniola and Cuba, with a Mesozoic divergence date versus extant mainland mammals. Solenodons are the oldest lineage of living eutherian mammal for which a mitogenome sequence has not been reported. We determined complete mitogenome sequences for six Hispaniolan solenodons (Solenodon paradoxus) using next-generation sequencing. The solenodon mitogenomes were 16,454–16,457 bp long and carried the expected repertoire of genes. A mitogenomic phylogeny confirmed the basal position of solenodons relative to shrews and moles, with solenodon mitogenomes estimated to have diverged from those of other mammals ca. 78 Mya. Control region sequences of solenodons from the northern (n = 3) and southern (n = 5) Dominican Republic grouped separately in a network, with FST = 0.72 (p = 0.036) between north and south. This regional genetic divergence supports previous morphological and genetic reports recognizing northern (S. p. paradoxus) and southern (S. p. woodi) subspecies in need of separate conservation plans.

The incidence of cardiovascular events and mortality strongly correlates with serum phosphate in individuals with CKD. The Npt2b transporter contributes to maintaining phosphate homeostasis in the setting of normal renal function, but its role in CKD-associated hyperphosphatemia is not well understood. Here, we used adenine to induce uremia in both Npt2b-deficient and wild-type mice. Compared with wild-type uremic mice, Npt2b-deficient uremic mice had significantly lower levels of serum phosphate and attenuation of FGF23. Treating Npt2b-deficient mice with the phosphate binder sevelamer carbonate further reduced serum phosphate levels. Uremic mice exhibited high turnover renal osteodystrophy; treatment with sevelamer significantly decreased the number of osteoclasts and the rate of mineral apposition in Npt2b-deficient mice, but sevelamer did not affect bone formation and rate of mineral apposition in wild-type mice. Taken together, these data suggest that targeting Npt2b in addition to using dietary phosphorus binders may be a therapeutic approach to modulate serum phosphate in CKD.

What Kitty Shares with Kings Although long-studied, the underlying basis of mammalian coat patterns remains unclear. By studying a large number of cat species and varieties, Kaelin et al. (p. 1536 ) identified two genes, Taqpep and Edn3 , as critical factors in the development of feline pigment patterns. Mutations in Taqpep are responsible for the blotched tabby pattern in domestic cats and the unusual coat of wild king cheetahs. Gene expression patterns in cat and cheetah skin suggest that Edn3 is a likely regulator of felid hair color. The findings support a common model for coat and pigment pattern formation in domestic and wild cats.

Recent NHS reforms have incentivised reduction in length of stay, with the UK department of health expecting health trusts to reduce bed days and ultimately reduce overall costs. The aim of this study was to identify avoidable causes for protracted hospital admission following total hip arthroplasty (THA) or total knee arthroplasty (TKA) within a fast-track unit. During a 6-month period, 535 consecutive patients underwent primary THA or TKA under the care of a single surgeon. All patients with a post-operative stay of greater than 72 h were identified, and reasons for delayed discharge were determined. The majority of arthroplasty patients were discharged within 3 days post-operatively. Twenty-one per cent of THA patients and 25 % of TKA patients remained as inpatients for greater than 72 h. For the THA population, this equates to 43 % of bed days used by 21 % of patients, and for the TKA population, 44 % of bed days were used by 25 % of patients. The major factor within both groups for delayed discharge was attributed to inadequate social support. Delayed discharge can never be totally prevented. This unit aims to develop improvement in social work provision, with a greater focus on pre-admission discharge planning to reduce the number of delayed discharges and ultimately reduce the cost burden of joint replacement surgery. It is not conducive with the ethos of fast-track arthroplasty to only identify social circumstances upon admission.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-β-catenin was observed both in mouse and human bones. Overall repression of Wnt/β-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-κB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/β-catenin pathway is involved in the pathogenesis of renal osteodystrophy.

In the past few years, several genomewide association studies (GWASs) have been conducted to identify host genetic variants involved in control of human immunodeficiency virus type 1 (HIV-1) load and in progression to AIDS [1–10]. Overall, these GWASs emphasized the major role of the HLA chromosome 6 region, particularly the HCP5/HLA-B*57 rs2395029 signal [1–3, 5, 8], and the CXCR6 gene region [7]. These GWASs focused on viral load and disease progression, but genetic correlates of the HIV-1 acquisition phenotype have met limited success: 2 recent GWASs conducted in Malawi reported no significant determinants of HIV infection [11, 12]. Looking for new host factors correlated to HIV susceptibility is critical because the only validated association to date is the 32 base-pair deletion in the CCR5 gene: only 1%–2% of Europeans are homozygous for this mutation and exhibit a near-complete protection against infection by HIV-1 R5 strains [13, 14]. To identify additional genetic factors that might contribute to HIV-1 acquisition, we performed a meta-analysis using GWAS genotypic data from 2 European AIDS progression cohorts, comparing each group of HIV-1–infected patients with uninfected controls of the same ancestry [8, 15]. Next, we replicated the association for the single-nucleotide polymorphism (SNP) showing the smallest P value in the European meta-analysis on 2 independent US cohorts of European ancestry.

The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important new evolutionary conclusions implicating these deadly infectious agents in domestic and non-domestic felids.

The tiger population that once inhabited the Korean peninsula was initially considered a unique subspecies (Panthera tigris coreensis), distinct from the Amur tiger of the Russian Far East (P. t. altaica). However, in the following decades, the population of P. t. coreensis was classified as P. t. altaica and hence forth the two populations have been considered the same subspecies. From an ecological point of view, the classification of the Korean tiger population as P. t. altaica is a plausible conclusion. Historically, there were no major dispersal barriers between the Korean peninsula and the habitat of Amur tigers in Far Eastern Russia and northeastern China that might prevent gene flow, especially for a large carnivore with long-distance dispersal abilities. However, there has yet to be a genetic study to confirm the subspecific status of the Korean tiger. Bone samples from four tigers originally caught in the Korean peninsula were collected from two museums in Japan and the United States. Eight mitochondrial gene fragments were sequenced and compared to previously published tiger subspecies’ mtDNA sequences to assess the phylogenetic relationship of the Korean tiger. Three individuals shared an identical haplotype with the Amur tigers. One specimen grouped with Malayan tigers, perhaps due to misidentification or mislabeling of the sample. Our results support the conclusion that the Korean tiger should be classified as P. t. altaica, which has important implications for the conservation and reintroduction of Korean tigers.