African and Asian leopards are highly differentiated at the genomic level.

Leopards are the only big cats still widely distributed across the continents of Africa and Asia. They occur in a wide range of habitats and are often found in close proximity to humans. But despite their ubiquity, leopard phylogeography and population history have not yet been studied with genomic tools. Here, we present population-genomic data from 26 modern and historical samples encompassing the vast geographical distribution of this species. We find that Asian leopards are broadly monophyletic with respect to African leopards across almost their entire nuclear genomes. This profound genetic pattern persists despite the animals' high potential mobility, and despite evidence of transfer of African alleles into Middle Eastern and Central Asian leopard populations within the last 100,000 years. Our results further suggest that Asian leopards originated from a single out-of-Africa dispersal event 500-600 thousand years ago and are characterized by higher population structuring, stronger isolation by distance, and lower heterozygosity than African leopards. Taxonomic categories do not take into account the variability in depth of divergence among subspecies. The deep divergence between the African subspecies and Asian populations contrasts with the much shallower divergence among putative Asian subspecies. Reconciling genomic variation and taxonomy is likely to be a growing challenge in the genomics era.

No longer locally extinct? Tracing the origins of a lion (Panthera leo) living in Gabon.

Lions (Panthera leo) are of particular conservation concern due to evidence of recent, widespread population declines in what has hitherto been seen as a common species, robust to anthropogenic disturbance. Here we use non-invasive methods to recover complete mitochondrial genomes from single hair samples collected in the field in order to explore the identity of the Gabonese Plateaux Batéké lion. Comparison of the mitogenomes against a comprehensive dataset of African lion sequences that includes relevant geographically proximate lion populations from both contemporary and ancient sources, enabled us to identify the Plateaux Batéké lion as a close maternal relative to now extirpated populations found in Gabon and nearby Congo during the twentieth century, and to extant populations of Southern Africa. Our study demonstrates the relevance of ancient DNA methods to field conservation work, and the ability of trace field samples to provide copious genetic information about free-ranging animals.

Microwave-assisted activation and modulator removal in zirconium MOFs for buffer-free CWA hydrolysis.

A novel, facile and efficient method was developed for the activation of acetic acid modulated zirconium MOFs. The protocol involves briefly heating the material in water using microwave irradiation. MOF-808, DUT-84 and UiO-66 were all activated in this manner to remove the modulator and organic solvent from the framework post synthesis, with retention of MOF integrity post activation. The degree of activation was characterised by the use of TGA and NMR. The catalytic activity of the activated MOFs and their non-activated counterparts was investigated for chemical warfare agent (CWA) hydrolysis. Upon activation, an increase in the rate of hydrolysis was observed in the degradation of CWA simulant dimethyl 4-nitrophenyl phosphate (DMNP). MOF-808 and DUT-84 were also screened as catalysts for the hydrolysis of the V-series agent VM, with remarkable half-lives obtained for MOF-808 in the absence of any buffers. Currently employed MOF activation procedures involve the use of additional organic solvents post synthesis; we believe this method to be ideally efficacious for the organic desolvation of zirconium MOFs and removing modulator additives.

Selective complexation of divalent cations by a cyclic α,ß-peptoid hexamer: a spectroscopic and computational study.

We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and ß-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na+, K+, Ag+) but showed selectivity for divalent cations (Ca2+, Ba2+, Sr2+ and Mg2+). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca2+ and Ba2+), while 5-coordination is preferred for divalent cations with larger (Ba2+) or smaller ionic radii (Mg2+).

The evolution of bicontinuous polymeric nanospheres in aqueous solution.

Complex polymeric nanospheres in aqueous solution are desirable for their promising potential in encapsulation and templating applications. Understanding how they evolve in solution enables better control of the final structures. By unifying insights from cryoTEM and small angle X-ray scattering (SAXS), we present a mechanism for the development of bicontinuous polymeric nanospheres (BPNs) in aqueous solution from a semi-crystalline comb-like block copolymer that possesses temperature-responsive functionality. During the initial stages of water addition to THF solutions of the copolymer the aggregates are predominantly vesicles; but above a water content of 53% irregular aggregates of phase separated material appear, often microns in diameter and of indeterminate shape. We also observe a cononsolvency regime for the copolymer in THF-water mixtures from 22 to 36%. The structured large aggregates gradually decrease in size throughout dialysis, and the BPNs only appear upon cooling the fully aqueous dispersions from 35 °C to 5 °C. Thus, the final BPNs are ultimately the result of a reversible temperature-induced morphological transition.

Dexamethasone may be the most efficacious corticosteroid for use as monotherapy in castration-resistant prostate cancer.

Corticosteroids have been used in the therapy for castration-resistant prostate cancer (CRPC) for decades, both as monotherapy and in combination with additional agents. In this article the authors report the results of a phase II trial of dexamethasone versus prednisolone as monotherapy for CRPC. The study suggests improved PSA and radiographic response rates as well as improved time to PSA progression for dexamethasone over prednisolone therapy; however the differences only trend toward statistical significance. Nonetheless, in light of these data, when treating patients with corticosteroid monotherapy for CRPC it may be prudent to consider using daily dexamethasone over prednisone/prednisolone.

Mosaic maternal uniparental disomy of chromosome 11 in a patient with Silver-Russell syndrome.

Silver-Russell syndrome (SRS) is a clinically heterogeneous disorder characterised mainly by intrauterine and postnatal growth retardation. While maternal uniparental disomy of chromosome 7 is found in 5-10% of SRS patients, recently genetic and epigenetic mutations affecting the imprinting centres on chromosome 11p15 have been reported in up to 64% of patients. Chromosome 11p15 abnormalities reported in SRS include methylation defects in the imprinting centre 1 (ICR1) and maternally inherited duplications involving all or part of the imprinted region of 11p15. Here we report the first published case of SRS with mosaic maternal uniparental disomy of chromosome 11.

Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants.

Histologic variants of idiopathic focal segmental glomerulosclerosis (FSGS) may have prognostic value. A recent working classification system has distinguished five FSGS variants. We evaluated a cohort of adult patients with biopsy-proven FSGS diagnosed between March 1982 and July 2001 to determine if subtypes were associated with renal outcome. Renal biopsies were reviewed by two pathologists. Demographic and clinical data were obtained from charts. Outcomes were partial and complete remission of the nephrotic syndrome, and renal failure. The frequency of FSGS variants was: 3% cellular (N=6), 11% collapsing (N=22), 17% tip lesion (N=34), 26% perihilar (N=52), and 42% not otherwise specified (NOS) (N=83). Collapsing FSGS affected younger and more often black patients. Black race was uncommon in tip variant. Collapsing and tip variants had higher proteinuria and lower serum albumin than perihilar and NOS variants. Better renal function and less severe tubulointerstitial injury were observed in patients with tip variant. These patients were more likely to receive steroids and more often achieved complete remission (50%). After a median follow-up of 1.8 years, 23% of patients were on dialysis and 28% had renal failure. Collapsing FSGS had worse 1-year (74%) and 3-year (33%) renal survival compared to other variants (overall cohort renal survival at 1 and 3 years: 86 and 67%). Different histologic variants of FSGS have substantial differences in clinical features at the time of biopsy diagnosis and substantial differences in renal outcomes.

Chondrodysplasia punctata: case report and review of audiological and ENT features.

Chondrodysplasia punctata is a term referring to a clinically heterogeneous group of bone and cartilage dysplasias which cause characteristic epiphyseal stippling. The condition can involve the ear, nose and throat in diverse ways at many levels. We present a case of X-linked brachytelephalangic chondrodysplasia punctata, which illustrates the features of this condition particularly relevant to the audiological physician, otolaryngologist and neonatologist.

Skeletal muscle involvement in infantile systemic hyalinosis.

Infantile Systemic Hyalinosis is a rare autosomal recessive entity, characterised by deposition of hyaline material in skin and bone, often complicated by visceral involvement. The characteristic features are marked delay in motor milestones attributed to severe progressive flexion contractures of proximal and distal joints, and skin and mucosal hypertrophy and thickening, followed by failure to thrive. Pain secondary to osteolytic lesions is also a predominant feature. We report a patient with Infantile Systemic Hyalinosis, confirmed by the clinical findings, who also displayed clear evidence of proximal muscle weakness. Muscle biopsy revealed myopathic changes, which have not been reported previously. We suggest that skeletal muscle is involved in Infantile Systemic Hyalinosis and contributes to the characteristic poor outcome of these patients.

Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene.

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. We report the characterization of ALPL gene mutations in a series of 11 families from various origins affected by perinatal and infantile hypophosphatasia. Sixteen distinct mutations were found, fifteen of them not previously reported: M45V, G46R, 388-391delGTAA, 389delT, T131I, G145S, D172E, 662delG, G203A, R255L, 876-881delAGGGGA, 962delG, E294K, E435K, and A451T. This confirms that severe hypophosphatasia is due to a large spectrum of mutations in Caucasian populations.

Isolated non-compaction of the ventricular myocardium: prenatal diagnosis and natural history.

Isolated non-compaction of the ventricular myocardium (NCVM) is a rare cardiomyopathy characterized by the persistence of numerous marked ventricular trabeculations and deep intertrabecular recesses with direct vascular supply by the ventricular cavities. We report two cases diagnosed by fetal echocardiography at 27 and 30 weeks' gestation, respectively. Postnatal echocardiography verified the presence of the NCVM seen prenatally. Diagnosis was confirmed at postmortem following neonatal demise in the first case. Surgical intervention for exomphalos and extrahepatic biliary atresia was required in the second case, but there is no clinical abnormality of the cardiovascular system a year after delivery. The uncertainty of prognosis and the familial recurrence described elsewhere indicate the difficulty of counseling and the value of prenatal diagnosis, which is feasible using currently available ultrasonographic equipment.

Lamellar organic thin films through self-assembly and molecular recognition.

Molecular clips possessing U-shaped cavities have been functionalized on their convex side with long aliphatic tails. These molecules form dimers which self-assemble into malleable lamellar thin films. Upon addition of a guest (methyl 3,5-dihydroxybenzoate), a 1:1 host-guest complex is formed, which prohibits clip dimerization. As a result, the lamellar structure of the material is lost. Complexation of 3,5-dihydroxybenzoic acid in the clip results in host-guest complexes which dimerize by hydrogen bonding interactions between the carboxylic acid functions of the bound guests. This dimerization restores the lamellar type architecture of the material.

Ocular injury from the venom of the Southern walkingstick.

PURPOSE: To report a case of severe conjunctival and corneal epithelial defects resulting from exposure to the venom of the Southern walkingstick, Anisomorpha buprestoides. DESIGN: Case report. INTERVENTION: The patient was treated with cyclopentolate 1% and underwent daily examinations until the corneal and conjunctival epithelial defects resolved. MAIN OUTCOME MEASURE: Resolution of corneal and conjunctival epithelial defects. RESULTS: The corneal and conjunctival epithelial defects slowly resolved over 6 days. Visual acuity improved to 20/20 in the affected eye. No residual corneal scarring was evident. CONCLUSIONS: Slowly resolving corneal and conjunctival epithelial defects can occur from direct contact with the venom from the Southern walkingstick, A. buprestoides; therefore, this insect should be approached with caution.

Trisomy 17p10-p12 resulting from a supernumerary marker chromosome derived from chromosome 17: molecular analysis and delineation of the phenotype.

We report a 5-year-old boy with a small de novo marker chromosome derived from the proximal short arm of chromosome 17. His clinical features include hypotonia, global developmental delay, oval face with large nose and prominent ears, and ligamentous laxity of the fingers. Magnetic resonance imaging of the brain demonstrated mildly delayed myelination. G-band chromosome analysis revealed mosaicism for a small marker chromosome in 85% of the peripheral blood cells analyzed. Fluorescence in situ hybridization and microsatellite polymorphism studies showed that the der(17) was of maternal origin and included genetic material from the 17p10-p12 region, but did not contain the PMP22 gene. One breakpoint mapped within the centromere and the second breakpoint mapped adjacent to the Charcot-Marie-Tooth disease type 1A proximal low-copy repeat (CMT1A-REP). We compare the clinical characteristics of our patient with those previously reported to have a duplication involving the proximal short arm region of chromosome 17 to further delineate the phenotype of trisomy 17pl0-p12.

Sex difference in the validity of vertebral deformities as an index of prevalent vertebral osteoporotic fractures: a population survey of older men and women.

Morphometric methods have been developed for standardized assessment of vertebral deformities in clinical and epidemiologic studies of spinal osteoporosis. However, vertebral deformity may be caused by a variety of other conditions. To examine the validity of morphometrically assessed vertebral deformities as an index of osteoporotic vertebral fractures, we developed an algorithm for radiological differential classification (RDC) based on a combination of quantitative and qualitative assessment of lateral spinal radiographs. Radiographs were obtained in a population of 50- to 80-year-old German women (n = 283) and men (n = 297) surveyed in the context of the European Vertebral Osteoporosis Study (EVOS). Morphometric methods (Eastell 3 SD and 4 SD criteria, McCloskey) were validated against RDC and against bone mineral density (BMD) at the femur and the lumbar spine. According to RDC 36 persons (6.2%) had at least one osteoporotic vertebral fracture; among 516 (88.9%) nonosteoporotics 154 had severe spondylosis, 132 had other spinal disease and 219 had normal findings; 14 persons (2.4%) could not be unequivocally classified. The prevalence of morphometrically assessed vertebral deformities ranged from 7.3% to 19.2% in women and from 3.5% to 16.6% in men, depending on the stringency of the morphometric criteria. The agreement between RDC and morphometric methods was poor. In men, 62-86% of cases with vertebral deformities were classified as nonosteoporotic (severe spondylosis or other spinal disease) by RDC, compared with 31-68% in women. Among these, most had wedge deformities of the thoracic spine. On the other hand, up to 80% of osteoporotic vertebral fractures in men and up to 48% in women were missed by morphometry, in particular endplate fractures at the lumbar spine. In the group with osteoporotic vertebral fractures by RDC the proportion of persons with osteoporosis according to the WHO criteria (T-score < -2.5 SD) was 90.0% in women and 86.6% in men, compared with 67.9-85.0% in women and 20.8-50.0% in men with vertebral deformities by various methods. Although vertebral deformities by most definitions were significantly and inversely related to BMD as a continuous variable in both sexes [OR; 95% CI ranged between (1.70; 1.07-2.70) and (3.69; 1.33-10.25)], a much stronger association existed between BMD and osteoporotic fractures defined by RDC [OR; 95% CI between (4.85; 2.30-10.24) and (15.40; 4.65-51.02)]. In the nonosteoporotic group individuals with severe spondylosis had significantly higher BMD values at the femoral neck (p < 0.01) and lumbar spine (p < 0.0004) compared with the normal group. On the basis of internal (RDC) and external (BMD) validation, we conclude that assessment of vertebral osteoporotic fracture by quantitative methods alone will result in considerable misclassification, especially in men. Criteria for differential diagnosis as used within RDC can be helpful for a standardized subclassification of vertebral deformities in studies of spinal osteoporosis.