) and is a hydrophobic flavonoid We examined the effects

) and is a hydrophobic flavonoid. We examined the effects https://www.selleckchem.com/autophagy.html of dietary xanthohumol-rich hop extract in obese rats that was induced by feeding a high-fat diet. Dietary xanthohumol-rich hop extract significantly lowered the body weight gain of these rats compared to rats fed a high-fat diet without the extract. The increase of body weight, liver weight, and triacylglycerol levels in the plasma and liver of the rats fed a high-fat diet was ameliorated by dietary xanthohumol-rich hop extract. Dietary xanthohumol-rich

hop extract tended to reduce hepatic fatty acid synthesis through the reduction of hepatic SREBP1c mRNA expression in the rats fed a high-fat diet. The excreted of triacylglycerol into feces also was promoted by dietary xanthohumol-rich hop extract. Plasma adiponectin levels in the rats fed a high-fat Apoptosis inhibitor diet also tended to be elevated by dietary xanthohumol-rich hop extract. Thus, xanthohumol-rich hop extract may inhibit the increase of body weight, liver weight, and triacylglycerol in the plasma and liver induced

by feeding high-fat diet through the regulation of hepatic fatty acid metabolism and inhibition of intestinal fat absorption. Therefore, xanthohumol-rich hop extract may exert preventive function on the increase of body weight and tissue triacylglycerol levels by overnutrition.”
“Bones of the craniofacial skeleton are derived from two distinct cell lineages, cranial neural crest and AZD1208 concentration mesoderm, and articulate at sutures and synchondroses which represent major bone growth sites. Premature fusion of cranial suture(s) is associated with craniofacial dysmorphogenesis caused in part by alteration in the growth potential at sutures and can occur as an isolated birth defect or as part of a syndrome, such as Apert syndrome. Conditional expression of the Apert FGFR2 S252W mutation in cells derived from mesoderm was previously shown to be necessary and sufficient to cause corona] craniosynostosis. Here we used micro computed tomography images of mice expressing the Apert mutation constitutively in either

mesoderm- or neural crest-derived cells to quantify craniofacial shape variation and suture fusion patterns, and to identify shape changes in craniofacial bones derived from the lineage not expressing the mutation, referred to here as secondary shape changes. Our results show that at postnatal day 0: (i) conditional expression of the FGFR2 S252W mutation in neural crest-derived tissues causes a more severe craniofacial phenotype than when expressed in mesoderm-derived tissues; and (ii) both mesoderm- and neural crest-specific mouse models display secondary shape changes. We also show that premature suture fusion is not necessarily dependent on the expression of the FGFR2 S252W mutation in the sutural mesenchyme.

e , in the form of higher-order tensors and matrices), (ii) incom

e., in the form of higher-order tensors and matrices), (ii) incomplete, and (iii) have both shared and unshared components. In order to address these challenges, in this paper, we introduce a novel unsupervised data fusion model based on joint factorization of matrices and higher-order tensors. Results: While the traditional formulation of coupled matrix and tensor factorizations modeling only shared factors fails to capture the underlying structures in the presence of both shared and unshared factors, the proposed data fusion model has the potential to automatically reveal shared and unshared

components through modeling constraints. Using numerical experiments, we demonstrate the effectiveness of the proposed approach in terms of identifying shared and unshared components. Furthermore, we measure a set of mixtures with known chemical composition using both LC-MS (Liquid Chromatography – Mass Spectrometry) and NMR (Nuclear Magnetic SB202190 solubility dmso Resonance) and demonstrate that the structure-revealing data fusion model can (i) successfully capture the chemicals in the mixtures and extract the relative concentrations of the chemicals accurately, (ii) provide

promising results in terms of identifying shared and unshared chemicals, and (iii) reveal AG-014699 clinical trial the relevant patterns in LC-MS by coupling with the diffusion NMR data. Conclusions: We have proposed a structure-revealing data fusion model that can jointly analyze heterogeneous, incomplete data sets with shared and unshared components and demonstrated its promising performance as well as potential limitations on both simulated and real data.”
“Exciton delocalization and singlet excitation energy transfer have been systematically studied for the complete set of 16 DNA nucleobase dimers in their ideal, single-strand stacked B-DNA conformation, at theMS-CASPT2 level of theory. The extent of exciton delocalization in the two lowest (pi,pi*) states of the dimers is determined

using the symmetrized one-electron transition density matrices between mTOR inhibitor the ground and excited states, and the electronic coupling is calculated using the delocalization measure and the energy splitting between the states [see F. Plasser, A. J. A. Aquino, W. L. Hase, and H. Lischka, J. Phys. Chem. A 116, 11151-11160 (2012)]. The calculated couplings lie between 0.05 eV and 0.14 eV. In the B-DNA conformation, where the interchromophoric distance is 3.38 angstrom, our couplings deviate significantly from those calculated with the transition charges, showing the importance of orbital overlap components for the couplings in this conformation. The calculation of the couplings is based on a two-state model for exciton delocalization. However, in three stacks with a purine in the 5′ position and a pyrimidine in the 3′ one (AT, GC, and GT), there is an energetically favored charge transfer state that mixes with the two lowest excited states.

The modulation of SOCS gene expression is shown to be cytokine an

The modulation of SOCS gene expression is shown to be cytokine and cell type dependent. While interferon-gamma up-regulates the expression of all the three SOCS genes in both the fibroid RTG-2 and the monocyte/macrophage RTS-11 cell lines, interleukin-1 beta only up-regulates SOCS gene expression in the

RTG-2 cell line, with little, if any, effect in the RTS-11 cell line. (c) 2007 Elsevier Ltd. All rights reserved.”
“In a previous paper, the biological activity of a 216-amino acid recombinant truncated form of the soybean 7S globulin alpha’ subunit, known to control cholesterol and triglyceride homeostasis, was described. In this work, a shorter version of the polypeptide Stem Cell Compound high throughput screening chain, spanning 142 amino acid residues from the N-terminus and thus exclusively including the so-called extension region, was cloned and overexpressed in Pichia pastoris. The yield of the recombinant polypeptide, which was termed alpha’E. was 8-fold greater than the previous truncated version. The alpha’E

polypeptide was purified by simple conventional biochemical techniques to make it available for biological assays. Human hepatoma cell lines (Hep G2) were used to monitor the uptake and degradation of labeled low-density lipoproteins (LDL), according to an established procedure. The LDL uptake (+86%) and degradation (+94%) by cells tested at the highest alpha’E dose (2 mu M) were similar to those c-Met inhibitor found in cells incubated Adriamycin with 1 mu M simvastatin, a potent inhibitor of cholesterol biosynthesis. Additionally, the cell response to alpha’E was found to be dose-dependent. The present findings strongly suggest that this recombinant polypeptide, or a fragment thereof, is the molecular determinant for cholesterol homeostasis and open new prospects for understanding the mechanism involved in this biological response, as a gateway to its utilization in lipid-lowering therapies. (C) 2011 Elsevier

Inc. All rights reserved.”
“A novel chelated ruthenium-based metathesis catalyst bearing an N-2,6-diisopropylphenyl group is reported and displays near-perfect selectivity for the Z-olefin (>95%), as well as unparalleled TONs of up to 7400, in a variety of homodimerization and industrially relevant metathesis reactions. This derivative and other new catalytically active species were synthesized using an improved method employing sodium carboxylates to induce the salt metathesis and C-H activation of these chelated complexes. All of these new ruthenium-based catalysts are highly Z-selective in the homodimerization of terminal olefins.”
“Microstructure in two diblock methacrylic azo polymers and in some of their blends with PMMA of different molecular weights as well as their photoinduced anisotropy have been investigated. The block copolymers have similar structure but different azo content and degree of polymerization.

8% (P = 0 011), 30 7% (P < 0 001), and 35 4% (P < 0 001), r

8% (P = 0.011), 30.7% (P < 0.001), and 35.4% (P < 0.001), respectively, compared with placebo. TAG were lowered by 27.5%

(P = 0.044), 21.7% (P = 0.034), and 32.7% (P < 0.01), respectively. check details The total-:HDL-C ratio was significantly lowered in all 3 intervention groups. We found no treatment effects on the apolipoprotein CII:CIII ratio, cholesterol ester transfer protein mass, FFA concentrations, and markers for low-grade inflammation or endothelial dysfunction. This study shows that in metabolic syndrome patients, plant stanol esters lower not only non-HDL-C, but also TAG. Effects on TAG were also present in combination with statin treatment, illustrating an additional benefit of stanol esters in this CHID risk population. J. Nutr. 139: 1143-1149, 2009.”
“Background/Purpose: Because of controversy regarding timing of tourniquet release during

total knee arthroplasty (TKA), a closed arthrotomy as a tamponade for effective hemostasis was used to save ischemia time. The study was to verify the safety and efficacy on clinical issues.\n\nMethods: A prospective cohort study was conducted on 72 consecutive unilateral primary TKAs. They were divided into two groups according to different timing of tourniquet release. The study group was composed of 36 index procedures with an intra-operative release after a tight arthrotomy closure; while the remaining 36 TKAs with a tourniquet application throughout the procedure comprised the comparative group. In all operations, no drain was used to augment the intra-articular tamponade.\n\nResults: In Wnt inhibitor the study group, the tourniquet time was significantly shorter (p < 0.001), and thus ischemic duration and perioperative blood loss were reduced. The postoperative course was similar on the basis of analgesics consumption and inpatient stay, Ulixertinib clinical trial but better earlier functional recovery as well as subjective performance was observed at early postoperative follow-ups.\n\nConclusions: The results suggest that a closed tamponade with arthrotomy closure and drainage avoidance is an effective hemostasis to reduce ischemia time during TKAs. Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association.

All rights reserved.”
“A major evolutionary force driving functionally referential alarm calls is the need for different strategies to escape various predator types in complex structured habitats. In contrast, a single escape strategy appears to be sufficient in less-structured open habitats, and under such conditions urgency-dependent alarm calls may be favored. Nevertheless, some species, such as meerkats (Suricata suricatta), have evolved functionally referential alarm calls despite living in open areas, using only bolt-holes for retreat. To understand the evolution of different alarm call systems, we investigated the calls of sympatric Cape ground squirrels (Xerus inauris) and compared their antipredator and foraging behavior with that of meerkats.

To date, no specific small molecule inhibitor targeting this path

To date, no specific small molecule inhibitor targeting this pathway has been identified. Pancreatic endoplasmic reticulum kinase (PERK), one of the UPR transducers, is an eIF2 alpha kinase. Compromising PERK function inhibits tumor growth in mice, suggesting that PERK may be a cancer drug target, but identifying a specific inhibitor of any kinase is challenging. The goal of this study was to identify some

pair-wise receptor-ligand atomic contacts that confer selective PERK inhibition. Compounds selectively inhibiting PERK-mediated phosphorylation in vitro were identified using an initial virtual library screen, followed by structure-activity hypothesis testing. The most potent PERK selective inhibitors utilize three specific kinase active site contacts that, when absent from chemically Ulixertinib manufacturer similar compounds, abrogates the inhibition: (i) a strong van der Waals contact with PERK residue Met7, (ii) interactions with the N-terminal portion of the activation loop, and (iii) groups providing

selleck products electrostatic complementarity to Asp144. Interestingly, the activation loop contact is required for PERK selectivity to emerge. Understanding these structure-activity relationships may accelerate rational PERK inhibitor design.”
“Bacteria from seven Lake Vostok accretion and two deep glacial Vostok ice core sections were characterized. The cell concentrations were low, but many of the cells were viable. From the hundreds of cultures, 18 unique bacterial rRNA gene phylotypes were determined. Lake Vostok may contain a complex

microbial ecosystem.”
“The Attention Network Test (ANT) provides measures for three different components of visual attention: executive control (=conflict inhibition), orienting, and alerting. There is reasonable evidence that alterations of attention-mainly in the executive/conflict domain-are associated with susceptibility to psychiatric illness. Specific impairments may be a characteristic for a medical condition such as schizophrenia and thus shift our understanding from a neuropsychological endophenotype to a more precise ZD1839 solubility dmso genetic understanding of this disorder. Study subjects comprised 35 schizophrenic patients and 35 healthy controls (13 female and 22 male in both groups). The ANT was administered to all participants and rated individual responses for the three factors (alerting, orienting, and conflict) and their respective ratios relative to mean reaction times. With regard to gender differences, group comparisons were performed for schizophrenic patients vs. healthy controls. Significant differences between patients and controls could be detected for mean reaction time (639 vs. 538 ms) and for conflict ratio (0.158 vs. 0.191). The latter difference mainly resulted from gender-specific variances of the conflict network in opposite directions.

Methods Forty-five patients were either examined on a first, seco

Methods Forty-five patients were either examined on a first, second, or third generation DSCT in an ultra-high-resolution (UHR) temporal bone-imaging mode. On the third generation DSCT system, the tighter focal spot of 0.2 mm(2) removesthe necessity for an additional z-axis-filter, leading to an improved z-axis radiation dose efficiency. Images of 0.4 mm were reconstructed using standard filtered-back-projection or iterative reconstruction (IR) technique for previous generations of DSCT and

a novel IR algorithm for the third generation DSCT. Radiation dose and image quality were compared between the three DSCT systems. Results The statistically significantly highest subjective and objective image quality was evaluated for the third generation DSCT when compared to the first or second generation DSCT systems (all p smaller than 0.05). Total effective dose was 63 %/39 % lower for Saracatinib the third generation examination as compared to the first and second generation DSCT. Conclusions Temporal bone imaging without z-axis-UHR-filter and a novel third generation IR algorithm allows for significantly higher image quality while lowering effective dose JQ-EZ-05 when compared to the first two generations of DSCTs.”
“We investigated the anatomical organization of glomeruli in the antennal lobes

(ALs) of male silkmoths. We reconstructed 10 different ALs and established an identification procedure for individual glomeruli by using size, shape, and position relative to anatomical landmarks. Quantitative analysis of these morphological characteristics supported the validity of our identification strategy. The glomerular organization of the ALs was roughly conserved between different ALs. However, we found individual variations that were reproducibly observed. The combination of a digital atlas with other experimental techniques, such as electrophysiology, optical imaging, selleck screening library and genetics, should facilitate a more in-depth analysis of sensory information processing in silkmoth ALs.”
“Recent studies suggest trends toward more mastectomies for

primary breast cancer treatment. We assessed survival after mastectomy and breast-conserving surgery (BCS) with radiation for early-stage breast cancer among non-selected populations of women and among women similar to those in clinical trials. Using population-based data from Surveillance Epidemiology, and End Results cancer registries linked with Medicare administrative data from 1992 to 2005, we conducted propensity score analysis of survival following primary therapy for early-stage breast cancer, including BCS with radiation, BCS without radiation, mastectomy with radiation, and mastectomy without radiation. Adjusted survival was greatest among women who had BCS with radiation (median survival = 10.98 years).

Two groups of patients were enrolled: group I (38 patients with C

Two groups of patients were enrolled: group I (38 patients with CPPD) and group II (22 patients with knee OA). US/PDS examination of the heels was performed to both groups. In the CPPD group, US/PDS examination of the Achilles tendon revealed: calcification in 57.9%, enthesophytosis in 57.9%, enthesopathy

in 23.7%, vascular sign in 21%, bursitis in 13.2%, and cortical bone irregularity in 10.5%. US/PDS examination of plantar fascia in the CPPD group revealed: calcification in 15.8%, cortical bone irregularity in 78.9%, enthesophytosis in 60.5%, and planter fasciitis in 42.1%. In patients with CPPD, age was significantly correlated with enthesophytosis click here and deep retrocalcaneal bursitis (p=0.01 and p=0.04, respectively). Heel tenderness and posterior talalgia were significantly correlated with Achilles tendon enthesopathy, vascular sign, and deep retrocalcaneal bursitis (p=0.0001 for each). Inferior talalgia was significantly correlated with plantar

fasciitis (p=0.0001). The sensitivity of ultrasonography for detection of calcifications in Achilles tendon and plantar fascia was 57.9% and 15.8%, respectively, and the specificity was 100% for both. To conclude, ultrasonographic Achilles tendon and plantar fascia calcifications are frequent findings in patients with CPPD. These calcifications have a high specificity JQEZ5 price S3I-201 purchase and can be used as a useful indirect sign of CPPD.”
“Stable carbon isotope values (delta C-13) obtained from terrestrial plant leaves are increasingly being used to infer palaeoenvironmental

trends. However, there are considerable variations in delta C-13 values even among leaves of a single plant due to different microhabitats, which can bias palaeoenvironmental interpretations. One important factor causing microhabitat variations is leaf position on a tree (i.e. sun and shade leaves). It is extensively known that delta C-13 varies markedly between sun and shade leaves in modern plants, with sun leaves containing more enriched C-13. Yet, the delta C-13 variations of fossil leaves in this respect are not investigated systematically. Here, we examine bulk carbon and nitrogen isotopic variabilities of fossil Liquidambar leaves between sun and shade leaves. For comparison, bulk isotopic data are analyzed in modern Liquidambar. Our results show that carbon and nitrogen content, C/N ratio, delta C-13 and nitrogen isotope composition (delta N-15) are notably different between sun and shade morphotypes in modern Liquidambar. When these criteria are applied to fossil Liquidambar, we found that the difference in stable carbon isotope compositions between fossil sun and shade morphotypes is narrow (only 0.33 parts per thousand) and statistically not significant (P > 0.2).

This finding should be confirmed in a larger sample “
“Parti

This finding should be confirmed in a larger sample.”
“Partial substitution of various transition metals for Al

in 10Al(2)O(3)center dot 2B(2)O(3) (Al20B4O36, 10A2B) was studied to use as a thermostable support for Pd catalysts. Fe-substitution CHIR-99021 manufacturer afforded the formation of solid solutions in the range of x <= 1.5 in FexAl20-xB4O36 (Fe-10A2B) without impurities. The DFT calculations confirmed that Fe-substitution was most likely to occur on the 5-coordinated Al site and predicted a shorter Fe-O distances of 1.84-2.05 angstrom compared to 1.94 and 2.12 angstrom in Fe2O3, in accordance with Fe-K edge EXAFS results. Fe-substitution improved the catalytic NO conversion in a rich region (A/F < 14.6), because CO-H2O and subsequent NO-H-2 reactions were accelerated. The redox between Fe3+ and Fe2+ in Fe-10A2B generated the oxygen storage capacity (OSC), which yielded an efficient buffering effect GW786034 mw on air-to-fuel (A/F) fluctuation in a simulated exhaust gas stream with lean/rich perturbation. These results suggest that Fe-10A2B is expected to be used as

a multifunctional support material for Pd catalysts in automotive three-way catalysts. (C) 2013 Elsevier B.V. All rights reserved.”
“Background: Set-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological GSK621 and biochemical processes are unclear. Animal studies have established that glutamatergic pathways

in the prefrontal cortex play an important role in set-shifting ability. However, it is not yet understood whether levels of serum glutamatergic amino acids are associated with set-shifting performance in humans. The aim of this study was to determine whether serum concentrations of amino acids related to glutamatergic neurotransmission (glutamine, glutamate, glycine, L-serine, D-serine) are associated with set-shifting ability in people with acute AN and those after recovery.\n\nMethods: Serum concentrations of glutamatergic amino acids were measured in 27 women with current AN (AN group), 18 women recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST) and the Trail Making Task (TMT). Dimensional measures of psychopathology were used, including the Eating Disorder Examination Questionnaire (EDEQ), the Maudsley Obsessive-Compulsive Inventory (MOCI) and the Hospital Anxiety and Depression Scale (HADS).\n\nResults: Serum glutamine concentrations in the AN group (1,310.2 +/- 265.6 mu M, mean +/- SD) were significantly higher (by approximately 20%) than those in the HC group (1,102.9 +/- 152.7 mu M, mean +/- SD) (F-(2,F- 70) = 6.3, P = 0.003, 95% CI 61.2 to 353.4).

Phosphorylation of other Rab11 effectors also modulates polarized

Phosphorylation of other Rab11 effectors also modulates polarized trafficking in other experimental systems, which hints that similar mechanisms may be widely used to control the directionality of membrane traffic.”
“We introduce Monte Carlo simulation methods for determining the wetting properties of model systems

at geometrically rough interfaces. The techniques described here enable one to calculate the macroscopic contact angle of a droplet that organizes in one of the three wetting states commonly observed for fluids at geometrically rough surfaces: the Cassie, Wenzel, and impregnation states. We adopt an interface potential approach in which the wetting properties of a system are related to the surface density dependence of the https://www.selleckchem.com/products/dinaciclib-sch727965.html surface excess free energy of a thin liquid film in contact with the substrate. We first describe challenges and inefficiencies encountered when implementing a direct version of this approach to compute the properties of fluids at rough surfaces. Next, we detail a series of convenient thermodynamic paths that enable one to obtain free energy information at relevant surface densities over a wide range of temperatures and substrate strengths in an efficient manner. We then show how this information is assembled to construct complete wetting diagrams at a temperature

of interest. The strategy pursued Pevonedistat molecular weight within this work is general and is expected to be applicable to a wide range of molecular systems. To demonstrate the utility of the approach, we present results for a Lennard-Jones fluid in contact with a substrate containing rectangular-shaped grooves

characterized by feature sizes of order ten fluid diameters. For this particular fluid-substrate combination, we find that the macroscopic theories of Cassie and Wenzel provide a reasonable description of simulation data. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3655817]“
“Oxygen plays a critical role in plant metabolism, stress response/signaling, and adaptation to environmental changes (Lambers and Colmer, Plant Soil 274:7-15, 2005; Pitzschke et al., Antioxid Redox Signal 8:1757-1764, 2006; Van Breusegem et al., Plant Sci 161:405-414, 2001). Reactive oxygen species (ROS), by-products of various metabolic pathways in which oxygen is a key molecule, are produced during GSK1210151A adaptation responses to environmental stress. While much is known about plant adaptation to stress (e.g., detoxifying enzymes, antioxidant production), the link between ROS metabolism, O-2 transport, and stress response mechanisms is unknown. Thus, non-invasive technologies for measuring O-2 are critical for understanding the link between physiological O-2 transport and ROS signaling. New non-invasive technologies allow real-time measurement of O-2 at the single cell and even organelle levels. This review briefly summarizes currently available (i.e.

hBM-MSCs and hAT-MSCs were isolated from bone marrow aspirate and

hBM-MSCs and hAT-MSCs were isolated from bone marrow aspirate and lipoaspirate, respectively. Rat lungs were decellularized with CHAPS detergent, followed by seeding the matrix with hBM-MSCs and hAT-MSCs. Under appropriate culture conditions, both human MSC populations attached to and proliferated within the lung tissue scaffold. In addition, cells were capable of type 2 pneumocyte differentiation, as assessed by marker expression of surfactant protein C (pro-SPC) at the protein and the RNA level, and by Daporinad cost the presence of lamellar bodies by transmission electron microscopy. Additionally, hAT-MSCs

contributed to Clara-like cells that lined the airways in the lung scaffolds, whereas the hBM-MSCs did not. We also tested the differentiation

potential of MSCs on different extracellular matrix components in vitro, and found that protein substrate influences MSC epithelial differentiation. Together our data show the capacity for human MSCs to differentiate toward lung epithelial phenotypes, and the possibility of using these cells for lung cell therapies and tissue engineering.”
“By using a genome-wide N-ethyl-N-nitrosourea (ENU)-induced dominant mutagenesis screen in mice, a founder with low bone mineral density (BMD) was identified. Mapping and sequencing revealed a T to C transition in a splice donor of the collagen alpha1 type I (Col1a1) gene, resulting in the skipping of exon 9 and a predicted 18-amino acid deletion within the N-terminal region of the triple helical domain of Col1a1. Col1a1(Jrt)/+ mice were smaller in size, had lower BMD associated with decreased bone volume/tissue volume (BV/TV) and PKC412 in vitro reduced trabecular number, and furthermore exhibited mechanically weak, brittle, fracture-prone bones, a hallmark of osteogenesis imperfecta (OI). Several

markers of osteoblast differentiation were upregulated in mutant bone, and histomorphometry selleck showed that the proportion of trabecular bone surfaces covered by activated osteoblasts (Ob.S/BS and N.Ob/BS) was elevated, but bone surfaces undergoing resorption (Oc.S/BS and N.Oc/BS) were not. The number of bone marrow stromal osteoprogenitors (CFU-ALP) was unaffected, but mineralization was decreased in cultures from young Col1a1(Jrt)/+ versus +/+ mice. Total collagen and type I collagen content of matrices deposited by Col1a1(Jrt)/+ dermal fibroblasts in culture was approximate to 40% and 30%, respectively, that of +/+ cells, suggesting that mutant collagen chains exerted a dominant negative effect on type I collagen biosynthesis. Mutant collagen fibrils were also markedly smaller in diameter than +/+ fibrils in bone, tendon, and extracellular matrices deposited by dermal fibroblasts in vitro. Col1a1(Jrt)/+ mice also exhibited traits associated with Ehlers-Danlos syndrome (EDS): Their skin had reduced tensile properties, tail tendon appeared more frayed, and a third of the young adult mice had noticeable curvature of the spine.