bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reverse genetics in the tide pool: knock‐down of target gene expression via RNA interference in the copepod Tigriopus californicus
Authors: Barreto Felipe S. , Schoville Sean D. , Burton Ronald S. 
Published: December 2014

AbstractReverse genetic tools are essential for characterizing phenotypes of novel genes and testing functional hypotheses generated from next‐generation sequencing studies. RNA interference (RNAi) has been a widely used technique for describing or quantifying physiological, developmental or behavioural roles of target genes by suppressing their expression. The marine intertidal copepod Tigriopus californicus has become an emerging model for evolutionary and physiological studies, but this species is not amenable to most genetic manipulation approaches. As crustaceans are susceptible to RNAi‐mediated gene knock‐down, we developed a simple method for delivery of gene‐specific double‐stranded RNA that results in significant suppression of target gene transcription levels. The protocol was examined on five genes of interest, and for each, at least 50% knock‐down in expression was achieved. While knock‐down levels did not reach 100% in any trial, a well‐controlled experiment with one heat‐shock gene showed unambiguously that such partial gene suppression may cause dramatic changes in phenotype. Copepods with suppressed expression of heat‐shock protein beta 1 (hspb1) exhibited dramatically decreased tolerance to high temperatures, validating the importance of this gene during thermal stress, as proposed by a previous study. The application of this RNAi protocol in T. californicus will be invaluable for examining the role of genes putatively involved in reproductive isolation, mitochondrial function and local adaptation.
Early prediction of rheumatoid arthritis by magnetic resonance imaging in the absence of anti‐cyclic citrullinated peptide antibodies and radiographic erosions in undifferentiated inflammatory arthritis patients: a prospective study
Authors: Ji Lanlan , Li Guangtao , Xu Yufeng , Zhou Wei , Zhang Zhuoli 
Published: December 2014

AbstractObjectiveTo assess the practicability of magnetic resonance imaging (MRI) in confirming the diagnosis of clinically suspected rheumatoid arthritis (RA), when anti‐cyclic citrullinated peptide antibody and radiographic erosions are absent.MethodsWe prospectively involved 31 treatment‐naive patients with early inflammatory arthritis. At the initial visit, X‐rays and gadolinium‐enhanced MRI of both hands, as well as serological examinations and acute phase reactants were performed. The scores of synovitis, bone edema, bone erosion and tenosynovitis of metacarpophalangeal and wrist joints were evaluated using the RA‐MRI scoring system. For all the patients, radiographs at baseline were normal and anti‐cyclic citrullinated peptide antibodies were negative.ResultsAt the end of follow‐up(median 15 months, range 12–20 months), 22 patients were diagnosed as having RA according to 1987 American College of Rheumatology criteria. Bone edema, erosions, synovitis and tenosynovitis were observed in all the patients. However, the frequency of symmetric synovitis in wrists was significantly higher in the RA group. Moreover this group turned out to have significantly higher MRI bone erosion score in wrists. Further, receiver operating characteristic curve analysis revealed a positive wrist bone erosion score at 5, with a specificity of 78% and a sensitivity of 68%. There was no significant difference between the two groups with respect to metacarpophalangeal synovitis, metacarpophalangeal bone erosion, bone edema or tenosynovitis.ConclusionMRI evidence of symmetric synovitis at wrist and a high bone erosion score at that site may assist in making an early diagnosis of RA in those patients who are negative for anti‐cyclic citrullinated peptide antibody.
Cloninger's psychobiological model of personality and psychological distress in fibromyalgia
Authors: Garcia‐Fontanals Alba , García‐Blanco Susanna , Portell Mariona , Pujol Jesús , Poca‐Dias Violant , García‐Fructuoso Ferran , López‐Ruiz Marina , Gutiérrez‐Rosado Teresa , Gomà‐i‐Freixanet Montserrat , Deus Joan 
Published: December 2014

AbstractAimPersonality can play an important role in the clinical symptoms of fibromyalgia (FM). The aim of this study is to identify personality profiles in FM patients and the possible presence of personality disorder (PD) from the Temperament and Character Inventory‐Revised (TCI‐R), and to assess whether personality dimensions are related to psychological distress in FM.MethodThe sample consisted of 42 patients with FM and 38 healthy controls. The TCI‐R, Hospital Anxiety and Depression Scale, State‐Trait Anxiety Inventory, Short‐Form‐36 Health Survey, Fibromyalgia Impact Questionnaire and McGill Pain Questionnaire were administered.ResultsThe personality profile of the FM group based on the TCI‐R is defined by high Harm Avoidance (HA), low Novelty Seeking (NS), and low Self‐Directedness (SD). Only one‐third of patients with FM present a possible psychometric PD, principally from Cluster C. In the FM group, HA and SD are associated positively and negatively, respectively, with indicators of emotional distress. Patients with higher HA present higher perceived pain intensity rated via a verbal‐numerical scale while Determination (SD2) reduced the perceived level of pain induced by the stimulus. NS is negatively related to the number of work absences caused by FM.ConclusionsThe study suggests that HA and SD play an important role in psychological distress in FM. The fact that SD is prone to modification and has a regulatory effect on emotional impulses is a key aspect to consider from the psychotherapeutic point of view.
Towards the identification of the loci of adaptive evolution
Authors: Pardo‐Diaz Carolina , Salazar Camilo , Jiggins Chris D. 
Published: December 2014

Summary

Establishing the genetic and molecular basis underlying adaptive traits is one of the major goals of evolutionary geneticists in order to understand the connection between genotype and phenotype and elucidate the mechanisms of evolutionary change. Despite considerable effort to address this question, there remain relatively few systems in which the genes shaping adaptations have been identified.

Here, we review the experimental tools that have been applied to document the molecular basis underlying evolution in several natural systems, in order to highlight their benefits, limitations and suitability. In most cases, a combination of DNA, RNA and functional methodologies with field experiments will be needed to uncover the genes and mechanisms shaping adaptation in nature.
Reversible cell cycle inhibition and premature aging features imposed by conditional expression of p16Ink4a
Authors: Boquoi Amelie , Arora Sanjeevani , Chen Tina , Litwin Sam , Koh James , Enders Greg H. 
Published: December 2014

SummaryThe cyclin‐dependent kinase (Cdk) inhibitor p16Ink4a (p16) is a canonical mediator of cellular senescence and accumulates in aging tissues, where it constrains proliferation of some progenitor cells. However, whether p16 induction in tissues is sufficient to inhibit cell proliferation, mediate senescence, and/or impose aging features has remained unclear. To address these issues, we generated transgenic mice that permit conditional p16 expression. Broad induction at weaning inhibited proliferation of intestinal transit‐amplifying and Lgr5+ stem cells and rapidly imposed features of aging, including hair loss, skin wrinkling, reduced body weight and subcutaneous fat, an increased myeloid fraction in peripheral blood, poor dentition, and cataracts. Aging features were observed with multiple combinations of p16 transgenes and transactivators and were largely abrogated by a germline Cdk4 R24C mutation, confirming that they reflect Cdk inhibition. Senescence markers were not found, and de‐induction of p16, even after weeks of sustained expression, allowed rapid recovery of intestinal cell proliferation and reversal of aging features in most mice. These results suggest that p16‐mediated inhibition of Cdk activity is sufficient to inhibit cell proliferation and impose aging features in somatic tissues of mammals and that at least some of these aging features are reversible.
Brain function during cognitive flexibility and white matter integrity in alcohol‐dependent patients, problematic drinkers and healthy controls
Authors: Jansen Jochem M. , van Holst Ruth J. , van den Brink Wim , Veltman Dick J. , Caan Matthan W. A. , Goudriaan Anna E. 
Published: December 2014

AbstractCognitive flexibility has been associated with prefrontal white matter (WM) integrity in healthy controls (HCs), showing that lower WM integrity is associated with worse performance. Although both cognitive flexibility and WM integrity have been found to be aberrant in alcohol‐dependent (AD) patients, the relationship between the two has never been tested. In this study, we investigated the association between WM tract density and cognitive flexibility in patients with AD (n = 26) and HCs (n = 22). In order to assess the influence of AD severity, we also included a group of problematic drinkers (PrDs; n = 23) who did not meet the AD criteria. Behavioral responses and brain activity during a cognitive flexibility task were measured during functional magnetic resonance imaging. Probabilistic fiber tracking was performed between the dorsolateral prefrontal cortex and the basal ganglia; two crucial regions for task switching. Finally, the task‐related functional connectivity between these areas was assessed. There were no significant group differences in the task performance. However, compared with HCs, AD patients and PrDs showed decreased WM integrity and increased prefrontal brain activation during task switching. Evidence is presented for a compensatory mechanism, involving recruitment of additional prefrontal resources in order to compensate for WM and neural function impairments in AD patients and PrDs. Although present in both alcohol groups, the PrDs were more successful in invoking this compensatory mechanism when compared to the AD patients. We propose that this may therefore serve as a protective factor, precluding transition from problematic drinking into alcohol dependence.
Rat Articular Cartilages Change Their Tissue and Protein Compositions During Perinatal Period
Authors: Kobayashi‐Miura M. , Miura T. , Osago H. , Yamaguchi Y. , Aoyama T. , Tanabe T. , Matsumoto K.‐i. , Fujita Y. 
Published: December 2014

SummaryArticular cartilage (AC) covers the surface of bones in joints and functions as a cushion against mechanical loading. The tissue contains abundant extracellular matrix (ECM), which mainly consists of proteoglycans (PG) and collagen (COL) fibres. The property of AC is gradually changing by ageing with gravity loading. To know the property change of AC by initial gravity loading during short period after birth, we performed histological assays and proteomics assay on the AC of the femoral condyle in knee joints of perinatal rats. The water content (%) was significantly decreased in neonate AC compared with fetal AC. During the perinatal stages (E19 and P0), the localizations of glycosaminoglycan (GAG) and type I and II COLs were homogeneous. The density of chondrocytes was significantly decreased in the deeper layers comparing with the surface layer in neonate AC. In addition, we found a drastic change in the protein expression pattern on proteomic analysis. The expressions of ECM components were relatively increased in neonate AC compared with fetal AC.
Spindle cell metaplastic carcinoma of breast: A clinicopathological and immunohistochemical analysis
Authors: Zhu Hong , Li Ke , Dong Dan‐dan , Fu Jing , Liu Dan‐dan , Wang Lei , Xu Gang , Song Lin‐hong 
Published: December 2014

AbstractAimTo better characterize spindle cell metaplastic carcinoma (SpCMC) of breast, a rare variant of breast cancer that has been classified under the broad rubric of metaplastic carcinoma.MethodsWe presented herein 19 cases of metaplastic breast carcinoma with dominant spindle cell component. All cases were clinically of breast origin, showed more than 80% spindle morphology, 10 cases exhibited pure spindled morphology, 8 contained invasive ductal carcinoma (IDC) and 1 presented with ductal carcinoma in situ elements.ResultsImmunohistochemical studies showed evidence suggesting myoepithelial and epithelial differentiation as exhibited by immunoreactivity for at least one myoepithelial and epithelial markers in all pure spindle cell components. IDC group showed 21.7% of axillary lymph nodes metastasis rate, whereas the axillary lymph node metastasis rate of the SpCMC group was 1.3%, significantly lower than that of the IDC group (P < 0.001). Immunohistochemical staining of IDC exhibited higher degrees of positivity for ER, PR and Her2 (90, 60 and 30%, respectively) when compared with the SpCMC group, which showed a positive degree of 5.2, 5.2 and 10.5% for ER, PR and Her2, respectively (P < 0.001).ConclusionBased on this series, SpCMC is a rare variant of metaplastic breast carcinoma with the distinct histopathological and immunohistochemical features. The biological behaviors of SpCMC, like axillary lymph node status, were quite different from that of IDC, suggesting that it may act as an independent pathologic subtype. Immunohistochemical analysis of a panel of epithelial and myoepithelial markers could contribute to the pathologic diagnosis of SpCMC.
Ophthalmic experience over 10 years in an observational nationwide Danish cohort of Fabry patients with access to enzyme replacement
Authors: Fledelius Hans C. , Sandfeld Lisbeth , Rasmussen Åse Krogh , Madsen Christoffer V. , Feldt‐Rasmussen Ulla 
Published: December 2014

AbstractPurposeEnzyme replacement therapy (ERT) was offered from year 2001 to patients with Fabry disease. The ophthalmic experience was analysed, as part of a general 10‐year status.MethodsA retrospective observational series comprising 39 patients (25 females, 14 males) closely followed by the endocrinologists, and with regular ophthalmic control. Time of inclusion was when the option of ERT was started, at age 11–60 years. Eye data (standard eye examination, including retinal imaging) were incomplete in five, due to death or non‐attendance, and five patients had refused treatment.ResultsVision was normal throughout, except in two young males with total unilateral central retinal artery occlusion, prior to and during enzyme replacement, respectively. Cornea verticillata and conjunctival vessel ectasies were common. Tortuosity of retinal arterioles and venules was recorded in eight and 18 patients, respectively, and phlebopathy in 22, although generally without evidence of loss of vessel wall integrity. Systemic vascular lesions with or without loss of function were recorded for kidney (n = 23), heart (n = 17) and brain (n = 7), and an association was suggested between nephropathy and abnormal morphology of retinal vessels.ConclusionsThirteen of 32 patients on ERT showed a reduction of corneal deposits over the study period. Abnormal ocular vessel morphology was a frequent finding. In contrast to the function loss related to systemic ischaemic lesions, we found no indication of impairment of visual parameters in 37. Compared to other Fabry series, two of 39 patients with serious unilateral occlusive retinal disease may appear a high number. The presence of retinal tortuosity is discussed, possibly reflecting haemodynamic events related to vessel wall deposits, but could also be ‘constitutional’, as part of the Fabry inheritance.
Intra‐ocular pressure‐lowering effects of a Rho kinase inhibitor, ripasudil (K‐115), over 24 hours in primary open‐angle glaucoma and ocular hypertension: a randomized, open‐label, crossover study
Authors: Tanihara Hidenobu , Inoue Toshihiro , Yamamoto Tetsuya , Kuwayama Yasuaki , Abe Haruki , Suganami Hideki , Araie Makoto ,   the K‐115 Clinical Study Group
Published: December 2014

AbstractPurposeTo investigate the intra‐ocular pressure (IOP)‐lowering effects of a selective Rho kinase inhibitor, ripasudil (K‐115), over 24 hr in patients with primary open‐angle glaucoma (POAG) or ocular hypertension (OHT).MethodsIn this multicenter, prospective, randomized, open‐label, 3‐period, Latin‐square crossover clinical study, 28 patients with POAG or OHT whose IOP level was 21 mmHg or higher were subdivided into three groups. Each patient was treated with placebo and ripasudil in concentrations of 0.2 and 0.4%, at 9:00 and 21:00 on day 1 through a total of 3 periods separated by washout periods. IOP was measured at 9:00, 10:00, 11:00, 13:00, 16:00, 19:00, 21:00, 22:00 and 23:00 on day 1, and 1:00, 4:00, 7:00 and 9:00 on day 2 in sitting position using Goldmann applanation tonometer. Main outcome measure was the IOP reduction of placebo and ripasudil from baseline.ResultsThe mean IOP reduction was −5.2 mmHg for 0.2%, −6.4 mmHg for 0.4% and −2.0 mmHg for placebo at 2 hr after the first instillation. Also, the corresponding values were −6.8 mmHg for 0.2%, −7.3 mmHg for 0.4% and −4.1 mmHg for placebo at 2 hr after the second instillation. Statistically significant IOP reduction, compared with placebo, was found for both 0.2 and 0.4% from 1 through 7 hr after each instillation. In safety, conjunctival hyperaemia was observed in 22 patients (79%) for 0.2%, 27 patients (96%) for 0.4% and three patients (11%) for placebo.ConclusionRipasudil is a promising new topical medication to lower IOP for at least 7 hr after instillations in patients with POAG or OHT.
Systemic levels of vascular endothelial growth factor before and after intravitreal injection of aflibercept or ranibizumab in patients with age‐related macular degeneration: a randomised, prospective trial
Authors: Zehetner Claus , Kralinger Martina T. , Modi Yasha S. , Waltl Inga , Ulmer Hanno , Kirchmair Rudolf , Bechrakis Nikolaos E. , Kieselbach Gerhard F. 
Published: December 2014

AbstractPurposeTo evaluate the changes of vascular endothelial growth factor (VEGF) plasma levels after intravitreal injections of aflibercept or ranibizumab in patients with exudative age‐related macular degeneration (AMD).MethodsThirty‐eight patients with exudative AMD were included in this randomised, prospective study. Nineteen patients were randomised to treatment with intravitreal aflibercept (2.0 mg) and 19 to intravitreal ranibizumab (0.5 mg). The concentration of VEGF was measured by ELISA just before the injection, after 7 days and 1 month. Twenty‐two age‐ and sex‐matched healthy patients without chorioretinal diseases served as control.ResultsThe median baseline plasma VEGF concentration was 61.0 pg/ml in the control group, 43.0 pg/ml in the aflibercept group and 59.0 pg/ml in the ranibizumab group (p = 0.127). Seven days after intravitreal injection of aflibercept plasma levels were significantly reduced to values below the minimum detectable dose (MDD) in 17 of 19 patients (89.5%) resulting in a median VEGF concentration of <9 pg/ml (p < 0.001). The reduction persisted throughout 1 month with values below the MDD in 5 of 19 patients (26.3%) and a median measurement of 17.0 pg/ml (p < 0.001). In patients treated with ranibizumab no significant effects could be observed with a baseline VEGF of 59.0 pg/ml, 54.0 pg/ml at 7 days (p = 0.776) and 58.5 pg/ml at 4 weeks of follow‐up (p = 0.670).ConclusionAfter intravitreal aflibercept injection, the systemic VEGF levels were significantly reduced throughout the observational period of 4 weeks. No significant systemic effects of intravitreal ranibizumab on plasma VEGF were observed.
A prospective, observational, open‐label, multicentre study to investigate the daily treatment practice of ranibizumab in patients with neovascular age‐related macular degeneration
Authors: van Asten Freekje , Evers‐Birkenkamp Kim U. , van Lith‐Verhoeven Janneke J. C. , de Jong‐Hesse Yvonne , Hoppenreijs Vincent P. T. , Hommersom Richard F. , Scholten Agnes M. , Hoyng Carel B. , Klaver Johannes H. J. ,   the HELIOS study group
Published: December 2014

AbstractPurposeThe HELIOS (Health Economics with Lucentis in Observational Settings) study was designed on request of the Dutch Health Authority for an observational study to assess the effectiveness and safety of ranibizumab for neovascular age‐related macular degeneration (wet AMD) in daily practice.MethodsThe HELIOS study was a 2‐year prospective, observational, open‐label, multicentre study involving 14 sites. Patients with wet AMD were enrolled and observed for a period of 24 months. The data were collected at baseline and at the visits closest around the time‐points 3, 6, 12, 18 and 24 months after inclusion.ResultsTreatment with ranibizumab resulted in prevention of vision loss. The mean ETDRS score increased from 45.1 letters at baseline to 48.5 letters at 24 months. This was achieved with a mean of 7.8 injections over 24 months. Stabilization of visual acuity was also reflected by the scores on the quality of life EQ‐5D questionnaire, which did not significantly change over the study period. The more subjective EQ‐VAS questionnaire showed an overall improvement. The VFQ‐25 questionnaire was also mostly stable over time. After 24 months, 32.2% of the patients gained ≥1 letter and 17.1% gained >15 letters. Patients completing the loading phase were better responders, as demonstrated by increased long‐term visual acuity. In addition, ranibizumab was well tolerated and had a safety profile commonly seen in routine clinical practice.ConclusionThis study demonstrates that also in daily practice ranibizumab was effective in preventing vision loss over a period of 24 months. No new safety findings were identified.
B‐type and N‐terminal pro‐B‐type natriuretic peptides are equally useful in assessing patent ductus arteriosus in very preterm infants
Authors: König Kai , Guy Katelyn J. , Drew Sandra M. , Barfield Charles P. 
Published: December 2014

AbstractAimB‐type natriuretic peptide (BNP) and N‐terminal pro‐BNP (NTproBNP) have been shown to correlate with the size of the patent ductus arteriosus (PDA) in preterm infants. We investigated whether BNP or NTproBNP was more closely correlated with PDA size.MethodsThis prospective observational study included preterm infants born <32 weeks' gestation who had an echocardiogram performed within the first four days of life. Blood samples were taken simultaneously for BNP and NTproBNP measurements prior to echocardiographic examination.ResultsOf the 60 infants recruited, 58 had complete data sets. The cohort's mean and standard deviation (SD) gestational age was 27+3 (2+2) weeks, the mean (SD) birthweight was 1032 (315) grams, and 46 (79.3%) infants had a PDA with a mean (SD) diameter of 3.2 (0.9) mm. Median and interquartile range (IQR) BNP levels were 486.5 (219–1316) pg/mL for infants with a PDA and 190 (95.5–514.5) pg/mL for infants without a PDA. Median (IQR) NTproBNP levels were 10 858.5 (6319–42 108) pg/mL for infants with a PDA and 7488 (3363–14 227.5) pg/mL for infants without a PDA. Both BNP (R = 0.35, p = 0.0066) and NTproBNP (R = 0.31, p = 0.018) were significantly correlated with PDA size.ConclusionBNP and NTproBNP are similarly useful for assessing PDA size in preterm infants.