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Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the analyses in the UK Biobank, a much more homogeneously designed study. We show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population stratification. More generally, our results imply that typical constructions of polygenic scores are sensitive to population stratification and that population-level differences should be interpreted with caution., Editorial Note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter)., Competing Interests: MS, RM, AG, AB, AM, MT, CC, JH, MD, NP, IM, DR, SS No competing interests declared, BN Ben Neale is a member and on the scientific advisory board of Deep Genomics, a consultant for Camp4 Therapeutics Corporation, a consultant for Merck & Co., a consultant for Takeda Phamaceutical, and a consultant for Avanir Pharmaceuticals. None of these entities played a role in determining the content of this paper., (© 2019, Sohail et al.)

Objective: The aim of our work was to study the potential of tarsomarginal grafting technique, in canine., Animal Studied: All dogs included in this study had tumors of the upper or lower eyelid. Furthermore, resection of the tumor necessitated excision of the eyelid margin comprising 1/4 and 2/3., Procedure: Harvesting of the graft with the length of half the length of the tumor, including its free margins was performed via a full-thickness incision on the ipsilateral healthy eyelid. The cutaneous layer and all of the muscle fibers of the transplant were meticulously removed except a 3 mm strip along the free lid margin. A full-thickness tumor excision was then performed. The graft was sutured at the level of the defect to be reconstructed. A sliding H flap was generated. The resulting nourishing myocutaneous flap was then sutured along the free margin of the tarso-conjunctivo-marginal graft. The lateral edges of the advancement flap were sutured to the edges of the receiving sites., Results: The average size of the reconstructed area was 17.8 mm. The resulting stretched lid fissure length after surgery was shortened over 7 to 11 mm. This technique for grafting was used to reconstruct an eyelid that had lost tissue measuring between 1/4 and 2/3 of its length. The few complications that were encountered were mainly the occurrence of keratitis or suture dehiscence., Conclusions: This tarsomarginal grafting technique has yielded encouraging results in dogs. This technique can fill large lid defects with a physiologic lid margin but is shortening the stretched lid fissure length., (© 2018 American College of Veterinary Ophthalmologists.)

Archaeogenetic studies have described the formation of Eurasian 'steppe ancestry' as a mixture of Eastern and Caucasus hunter-gatherers. However, it remains unclear when and where this ancestry arose and whether it was related to a horizon of cultural innovations in the 4 th millennium BCE that subsequently facilitated the advance of pastoral societies in Eurasia. Here we generated genome-wide SNP data from 45 prehistoric individuals along a 3000-year temporal transect in the North Caucasus. We observe a genetic separation between the groups of the Caucasus and those of the adjacent steppe. The northern Caucasus groups are genetically similar to contemporaneous populations south of it, suggesting human movement across the mountain range during the Bronze Age. The steppe groups from Yamnaya and subsequent pastoralist cultures show evidence for previously undetected farmer-related ancestry from different contact zones, while Steppe Maykop individuals harbour additional Upper Palaeolithic Siberian and Native American related ancestry.

Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid metabolism and is often hypothesized to reflect adaptation to an agricultural diet. Here, we test the evidence for this relationship using both modern and ancient DNA data. We show that almost all the inhabitants of Europe carried the ancestral allele until the derived allele was introduced ∼8,500 years ago by Early Neolithic farming populations. However, we also show that it was not under strong selection in these populations. We find that this allele, and other proposed agricultural adaptations at LCT/MCM6 and SLC22A4, were not strongly selected until much later, perhaps as late as the Bronze Age. Similarly, increased copy number variation at the salivary amylase gene AMY1 is not linked to the development of agriculture although, in this case, the putative adaptation precedes the agricultural transition. Our analysis shows that selection at the FADS locus was not tightly linked to the initial introduction of agriculture and the Neolithic transition. Further, it suggests that the strongest signals of recent human adaptation in Europe did not coincide with the Neolithic transition but with more recent changes in environment, diet, or efficiency of selection due to increases in effective population size.

The first decade of ancient genomics has revolutionized the study of human prehistory and evolution. We review new insights based on prehistoric modern human genomes, including greatly increased resolution of the timing and structure of the out-of-Africa expansion, the diversification of present-day non-African populations, and the earliest expansions of those populations into Eurasia and America. Prehistoric genomes now document population transformations on every inhabited continent-in particular the effect of agricultural expansions in Africa, Europe, and Oceania-and record a history of natural selection that shapes present-day phenotypic diversity. Despite these advances, much remains unknown, in particular about the genomic histories of Asia (the most populous continent) and Africa (the continent that contains the most genetic diversity). Ancient genomes from these and other regions, integrated with a growing understanding of the genomic basis of human phenotypic diversity, will be in focus during the next decade of research in the field.

Farming was first introduced to Europe in the mid-seventh millennium bc, and was associated with migrants from Anatolia who settled in the southeast before spreading throughout Europe. Here, to understand the dynamics of this process, we analysed genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe and surrounding regions between 12000 and 500 bc. We document a west-east cline of ancestry in indigenous hunter-gatherers and, in eastern Europe, the early stages in the formation of Bronze Age steppe ancestry. We show that the first farmers of northern and western Europe dispersed through southeastern Europe with limited hunter-gatherer admixture, but that some early groups in the southeast mixed extensively with hunter-gatherers without the sex-biased admixture that prevailed later in the north and west. We also show that southeastern Europe continued to be a nexus between east and west after the arrival of farmers, with intermittent genetic contact with steppe populations occurring up to 2,000 years earlier than the migrations from the steppe that ultimately replaced much of the population of northern Europe.

The objective was to assess the effect of high intensity focused ultrasound (HIFU) on intraocular pressure (IOP) in dogs with primary glaucoma (PG). Seven dogs (13 eyes) presenting with PG as diagnosed by a raised IOP (> 20 mm Hg) associated with consistent gonioscopy and ultrasound biomicroscopy of the ciliary cleft, with no other ocular disease. Patients were divided into 3 groups, corresponding to their pre-operative IOP (group 1 ranging from 21 to 30 mm Hg, group 2 from 31 to 40 and group 3 for 40 and above). Ciliary process sonication was achieved with a probe containing one high-frequency transducer operating at 21 MHz during 5 seconds. Six sites were treated in patients from group 1, 8 in group 2, 10 in group 3, under general anesthesia. Post-operative treatment consisted of systemic meloxicam and topical carbonic anhydrase inhibitors, beta-blockers and prostaglandins analogues. No intraoperative complications were observed. Conjunctival hyperaemia occurred in eyes from group 2 (66%) and 3 (100%). Conjunctival burns were visible in 2 patients from group 3. One patient from group 3 experienced a hypertensive spike during the first hours post-op with associated pain. The hypotensive effect of HIFU was observed in all groups. Normotensive IOP (≤20 mm Hg) was reached in all patients until the last recheck at 6 months post op. Despite the small number of patients included in the study, HIFU appears to be a promising option for the management of PG in dogs.

The surgical resection of a squamous cell carcinoma in a cat was performed on both the palpebral and nasal aspects of the OD medial canthus. A two-stage surgical technique was employed, involving two different transposition flaps, taking care to maintain eyelid function and estheticism, with a long follow-up.

Mutations occur at vastly different rates across the genome, and populations, leading to differences in the spectrum of segregating polymorphisms. Here, we investigate variation in the rare variant spectrum in a sample of human genomes representing all major world populations. We find at least two distinct signatures of variation. One, consistent with a previously reported signature is characterized by an increased rate of TCC>TTC mutations in people from Western Eurasia and South Asia, likely related to differences in the rate, or efficiency of repair, of damage due to deamination of methylated guanine. We describe the geographic extent of this signature and show that it is detectable in the genomes of ancient, but not archaic humans. The second signature is private to certain Native American populations, and is concentrated at CpG sites. We show that this signature is not driven by differences in the CpG mutation rate, but is a result of the fact that highly mutable CpG sites are more likely to undergo multiple independent mutations across human populations, and the spectrum of such mutations is highly sensitive to recent demography. Both of these effects dramatically affect the spectrum of rare variants across human populations, and should be taken into account when using mutational clocks to make inference about demography.

Objective: To assess the use of an optical device (D-EYE; Si14 S.p.A.) attached to a modern smartphone (iPhone 5; Apple Inc.) for imaging the fundus in small animals., Animals Studied: Five dogs, five cats, and five rabbits with clear media were imaged using a prototype of the D-EYE., Procedure: The optical device was composed of lenses, polarizing filters, a beam splitter, a diaphragm, and mirrors, attached to a smartphone via a metal shell. Images were obtained 20 min after pupil dilation with topical 0.5% tropicamide in a darkened room, to ensure maximum pupillary dilation. Focus was set to the infinite when the autofocus was overwhelmed. Light intensity was adapted to each animal via the application (minimum light intensity for imaging the tapetal region, maximum light intensity for imaging the nontapetal region). Both still images and video sequences were recorded for each animal., Results: Posterior segment structures were visible in all animals: optic nerve head, tapetum lucidum (when present), nontapetal region, retinal vessels, and choroidal vessels (when the retinal pigment epithelium and the choroidal pigmentation were discreet). Focal light artifacts were common when photographing the tapetum lucidum. Recording videos allowed the visualization of dynamic phenomena., Conclusions: The D-EYE assessed appears to be an easy means of obtaining images of the posterior segment structures., (© 2016 American College of Veterinary Ophthalmologists.)

Objective: To describe the use of a porcine urinary bladder acellular matrix for surgical reconstruction of the cornea in cases of canine and feline deep corneal ulcers, and feline corneal sequestra., Materials and Methods: Twenty-seven dogs and three cats with deep corneal ulcers and seven cats with corneal sequestra were included in the study with overall 38 eyes. For each patient, the necrotic material (ie corneal sequestrum or collagenolytic tissue) was removed by circular lamellar keratectomy. The collagen graft was then cut and prepared to match the stromal defect and then sutured into the lamellar keratectomy bed using interrupted and continuous patterns of absorbable polyglactin 9-0 sutures. Postoperative medical treatment consisted of topical and systemic administration of antibiotics, combined with topical administration of atropine sulfate. The animals were examined 18, 45, and 90 days after the surgery., Results: Postoperative examination revealed complete integration of the biomaterial in 93.5% of ulceration cases in both species and in 100% of feline corneal sequestrum cases. In two cases of ulceration (1 dog and 1 cat), progression of the collagenolytic process at the graft periphery required an additional conjunctival graft 7 days after the first surgery. At 90 days post-op, 100% of the eyes were sighted., Conclusion: Use of a porcine urinary bladder acellular matrix appears to be effective in the surgical management of deep corneal ulcers and feline corneal sequestra., (© 2015 American College of Veterinary Ophthalmologists.)

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000-7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3-6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between ~37,000 and ~14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An ~35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age ~19,000 years ago. During the major warming period after ~14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.

Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 bc, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe's first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 bc, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10(-8)), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10(-9)), higher insulin resistance (P=6 × 10(-4)) and lower serum sex hormone binding globulin concentrations (P=5 × 10(-4)). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10(-8)) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10(-5)). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk.

Large whole-genome sequencing projects have provided access to much rare variation in human populations, which is highly informative about population structure and recent demography. Here, we show how the age of rare variants can be estimated from patterns of haplotype sharing and how these ages can be related to historical relationships between populations. We investigate the distribution of the age of variants occurring exactly twice (ƒ(2) variants) in a worldwide sample sequenced by the 1000 Genomes Project, revealing enormous variation across populations. The median age of haplotypes carrying ƒ(2) variants is 50 to 160 generations across populations within Europe or Asia, and 170 to 320 generations within Africa. Haplotypes shared between continents are much older with median ages for haplotypes shared between Europe and Asia ranging from 320 to 670 generations. The distribution of the ages of ƒ(2) haplotypes is informative about their demography, revealing recent bottlenecks, ancient splits, and more modern connections between populations. We see the effect of selection in the observation that functional variants are significantly younger than nonfunctional variants of the same frequency. This approach is relatively insensitive to mutation rate and complements other nonparametric methods for demographic inference.

High-throughput DNA sequencing technology has transformed genetic research and is starting to make an impact on clinical practice. However, analyzing high-throughput sequencing data remains challenging, particularly in clinical settings where accuracy and turnaround times are critical. We present a new approach to this problem, implemented in a software package called Platypus. Platypus achieves high sensitivity and specificity for SNPs, indels and complex polymorphisms by using local de novo assembly to generate candidate variants, followed by local realignment and probabilistic haplotype estimation. It is an order of magnitude faster than existing tools and generates calls from raw aligned read data without preprocessing. We demonstrate the performance of Platypus in clinically relevant experimental designs by comparing with SAMtools and GATK on whole-genome and exome-capture data, by identifying de novo variation in 15 parent-offspring trios with high sensitivity and specificity, and by estimating human leukocyte antigen genotypes directly from variant calls.

It has been assumed that radiographs are consistently used in the preoperative evaluation of hallux valgus; however, little information is available to support this assumption. To investigate the frequency of use and clinical utility of radiographs in the assessment of hallux valgus, an online survey was completed by 28 podiatrists in UK departments of podiatric surgery. Radiographs were used in the assessment of hallux valgus in all departments. Of the 28 podiatrists, 61% viewed digital radiographs only, 7% film only, and 32%, a combination of both. Also, 71% routinely took measurements from the radiographs to inform procedure selection. Of those taking measurements, the first intermetatarsal angle was the only measurement used by all participants, followed by the sesamoid position, used by 90%. For those taking measurements, the measurements influenced procedure selection for most cases before surgery, with the procedure site within the first metatarsal moving more proximally as the first metatarsal angle increased., (Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Inferring the nature and magnitude of selection is an important problem in many biological contexts. Typically when estimating a selection coefficient for an allele, it is assumed that samples are drawn from a panmictic population and that selection acts uniformly across the population. However, these assumptions are rarely satisfied. Natural populations are almost always structured, and selective pressures are likely to act differentially. Inference about selection ought therefore to take account of structure. We do this by considering evolution in a simple lattice model of spatial population structure. We develop a hidden Markov model based maximum-likelihood approach for estimating the selection coefficient in a single population from time series data of allele frequencies. We then develop an approximate extension of this to the structured case to provide a joint estimate of migration rate and spatially varying selection coefficients. We illustrate our method using classical data sets of moth pigmentation morph frequencies, but it has wide applications in settings ranging from ecology to human evolution.

Well-powered genome-wide association studies, now made possible through advances in technology and large-scale collaborative projects, promise to characterize the contribution of rare variants to complex traits and disease. However, while population structure is a known confounder of association studies, it remains unknown whether methods developed to control stratification are equally effective for rare variants. Here, we demonstrate that rare variants can show a stratification that is systematically different from, and typically stronger than, common variants, and this is not necessarily corrected by existing methods. We show that the same process leads to inflation for load-based tests and can obscure signals at truly associated variants. Furthermore, we show that populations can display spatial structure in rare variants, even when Wright's fixation index F(ST) is low, but that allele frequency-dependent metrics of allele sharing can reveal localized stratification. These results underscore the importance of collecting and integrating spatial information in the genetic analysis of complex traits.

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome., Competing Interests: The authors have declared that no competing interests exist.

The development of next generation sequencing (NGS) has radically transformed the scientific landscape, making it possible to sequence the exome of any given individual in a cost-effective way. The power of this approach has been demonstrated by a number of groups who have identified pathogenic mutations in small pedigrees that have been resistant to traditional genetic mapping. Recently it has become clear that exome sequencing has great potential with respect to sporadic disease and the identification of de novo mutations. This is highlighted by studies reporting whole-exome sequencing of patient-parental trios affected by learning disability, autism and schizophrenia. It is widely anticipated that the introduction of this technique into a clinical setting will revolutionise genetic diagnosis. However, the sensitivity of NGS exome sequencing is currently unclear. Here, we describe the exome sequencing of DNA samples from a patient with double cortex syndrome and her parents, resulting in the detection of a mosaic splicing mutation in LIS1. This variant was found at an allele frequency of just 18%, demonstrating that NGS methods have the capacity to identify pathogenic mosaic mutations present at a low level.

The rationale that subtalar joint position, reflected by calcaneal alignment, determines foot morphology was used to formulate an approach to examination of the validity of three measures of "foot type": the Staheli Arch Index, the Chippaux-Smirak Index, and navicular height. Each measure was calculated in five positions, progressively inverting from a reference position of maximal comfortable eversion. Pearson product moment correlations (Staheli Arch Index: r = 0.5; Chippaux-Smirak Index: r = 0.6; and navicular height: r = 0.8) indicated that each measure progressively increased with inversion. The change in calcaneal position required to produce significant changes in each measure was investigated using analysis of variance with Scheffé post hoc analysis. This analysis revealed that changes of 15 degrees and 20 degrees were required to produce significant differences in Chippaux-Smirak Index and Staheli Arch Index scores, respectively, threatening their validity. Navicular height was sensitive to smaller changes of 10 degrees and thus displays greater sensitivity to changes in calcaneal position than the footprint parameters tested.

Substantial evidence suggests that complete rejection of the Root model may be premature, given the inherent logic in an Aristotelian interpretation of its core philosophy. Although critics have focused on a Platonic interpretation of Root's criteria for normalcy and surrounding theories, recent theoretic shifts towards a more flexible view of the factors which can combine to produce pathologic conditions suggest that the Root model retains usefulness. Although it has been suggested that Kuhn's approach may contain a destructive element, one of its propositions--that a phase of normal science is characterized by a common vision of the research required within the paradigm--seems to hold the key to the future success of podiatric biomechanics. The approach of Lakatos seems to provide the required "modicum of self-confidence which enables us to live and practice" to smooth the transition between established and emergent approaches. Although the approaches of Kuhn and Lakatos remain incommensurable, it is certain that Kuhn would agree with one particularly relevant comment by Lakatos, that "blind commitment to a theory is not an intellectual virtue: it is an intellectual crime."

The identification of malignancies associated with transplantation has led to enhanced vigilance and care in these patients, as well as insight into the pathogenesis of select malignancies. We report a case of Merkel cell carcinoma, an uncommon cutaneous malignancy of neuroendocrine origin, diagnosed in a 65-year-old Caucasian man 6 years after renal transplantation. While it is well known that transplant patients are at increased risk for squamous cell carcinomas of the skin, other types may also have an increased frequency. We suggest that Merkel cell carcinoma could have an increased incidence in the transplant population.

The expressions of aquaporin-1 (AQP-1) in cultured mIMCD-3 cells were studied. There was no detectable AQP-1 in cells grown in serum-containing growth medium (SM, 297 +/- 2 mOsm/kg. H2O). When SM was supplemented with NaCl (406 +/- 2 mOsm/kg. H2O), cellular AQP-1 was induced. A further increase in medium osmolarity with NaCl (493 +/- 3 mOsm/kg. H2O) had conferred cells an 2.5 to 3-fold increase of AQP-1 expression over those grown in the 406 +/- 2 mOsm/kg. H2O medium. Moreover, AQP-1 was found to be translocated from cytosol to membrane. In addition, exposing the mIMCD-3 cells to vasopressin (AVP, 10(-8) M) and/or NaCl-supplemented serum-free media (496 +/- 3 mOsm/kg. H2O) for 6h did not render them to produce AQP-1. However, AQP-1 was induced after 24h of incubation, with an 1.5-fold additive effect by AVP. Our RT-PCR data had confirmed the NaCl inducibility and AVP synergism in AQP-1 expression at both mRNA and protein levels. This suggests a new role for cellular AQP-1 and AVP in overcoming osmotic stress in an in vitro system.