bluuebunny/crossref_metadata_2025_split huggingface dataset:
Removal of Hsf4 leads to cataract development in mice through down-regulation of γS-crystallin and Bfsp expression
Authors: Shi Xiaohe , Cui Bin , Wang Zhugang , Weng Lin , Xu Zhongping , Ma Jinjin , Xu Guotong , Kong Xiangyin , Hu Landian 
Published: February 2009

Abstract

Background
Heat-shock transcription factor 4 (HSF4) mutations are associated with autosomal dominant lamellar cataract and Marner cataract. Disruptions of the Hsf4 gene cause lens defects in mice, indicating a requirement for HSF4 in fiber cell differentiation during lens development. However, neither the relationship between HSF4 and crystallins nor the detailed mechanism of maintenance of lens transparency by HSF4 is fully understood.

Results
In an attempt to determine how the underlying biomedical and physiological mechanisms resulting from loss of HSF4 contribute to cataract formation, we generated an Hsf4 knockout mouse model. We showed that the Hsf4 knockout mouse (Hsf4
-/-) partially mimics the human cataract caused by HSF4 mutations. Q-PCR analysis revealed down-regulation of several cataract-relevant genes, including γS-crystallin (Crygs) and lens-specific beaded filament proteins 1 and 2 (Bfsp1 and Bfsp2), in the lens of the Hsf4
-/- mouse. Transcription activity analysis using the dual-luciferase system suggested that these cataract-relevant genes are the direct downstream targets of HSF4. The effect of HSF4 on γS-crystallin is exemplified by the cataractogenesis seen in the Hsf4
-/-,rncat intercross. The 2D electrophoretic analysis of whole-lens lysates revealed a different expression pattern in 8-week-old Hsf4
-/- mice compared with their wild-type counterparts, including the loss of some αA-crystallin modifications and reduced expression of γ-crystallin proteins.

Conclusion
Our results indicate that HSF4 is sufficiently important to lens development and disruption of the Hsf4 gene leads to cataracts via at least three pathways: 1) down-regulation of γ-crystallin, particularly γS-crystallin; 2) decreased lens beaded filament expression; and 3) loss of post-translational modification of αA-crystallin.
The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey
Authors: Wang Yiwen , Danilova Vicktoria , Cragin Tiffany , Roberts Thomas W , Koposov Alexey , Hellekant Göran 
Published: February 2009

Abstract

Background
Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers.

Results
We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers.

Conclusion
In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non-S fibers originates from other kinds of receptors. The absence of the effect of lactisole on the faint responses in some S fibers to other stimuli as well as the responses to sweet and non-sweet stimuli in non-S fibers suggest that these responses originate from other taste receptors.
Vitrification of isolated mice blastomeres using a closed loading device
Authors: Kader Amr , Agarwal Ashok , Sharma Rakesh , Falcone Tommaso 
Published: February 2009

Abstract
Isolated blastomeres obtained by embryo biopsy serve mainly for preimplantation genetic screening. Blastomeres are undifferentiated embryonic cells that include all the embryo genetic information. A lot of developing technologies may benefit by the efficient cryopreservation of blastomeres for future potential use, especially for stem cell culture and differentiation control. We are hereby reporting for the first time the feasibility of preserving individual isolated blastomeres in microvolumes in a closed vitrification system. Using a cryotip and propagation in microvolumes, isolated mice blastomeres were vitrified and warmed with 100% post-warming survival.
Ejaculate collection efficiency and post-thaw semen quality in wild-caught Griffon vultures from the Sardinian population
Authors: Madeddu Manuela , Berlinguer Fiammetta , Ledda Massimo , Leoni Giovanni G , Satta Valentina , Succu Sara , Rotta Andrea , Pasciu Valeria , Zinellu Angelo , Muzzeddu Marco , Carru Ciriaco , Naitana Salvatore 
Published: February 2009

AbstractThis study aimed to test the feasibility of a programme of semen collection and cryopreservation in Griffon vultures. Four wild-caught individuals kept in captivity because of unrecoverable traumas were used. Semen collection attempts were made twice a week during three consecutive reproductive seasons (December – March) using the abdominal massage method. Ejaculation was successfully induced between late January and late February. Semen collection efficiency was rather low (27.9%) and it did not vary among individuals (p > 0.05). No differences were found in ejaculate volumes (12.5 +/- 9.1 μl), spermatozoa concentration (28.4 +/- 30.9 million cells/ml) and viability (61.3 +/- 13.9%) among the 4 vultures. ATP values differed among the four vultures (p < 0.001); B showed higher nucleotide concentration than both C and D, while it did not differ form A, whose values were higher compared with D. After freezing and thawing, semen in vitro viability, DNA integrity and ATP intracellular concentration were determined. Spermatozoa viability after thawing did not differ among the four individuals (52.6 +/- 5.8 in A, 53.4 +/- 4.6 in B, 50.4 +/- 3.2 in C, 42.5 +/- 2.7 in D), but it decreased significantly compared to fresh semen (p < 0.05). During 4 hrs in vitro culture, spermatozoa collected from B maintained over time a higher viability in vitro when compared to A, C and D. As evaluated by the comet assay method, DNA fragmentation after freezing and thawing did not differ in the 4 vultures. ATP concentration in frozen/thawed semen was significantly lower than in fresh semen (p < 0.0001). This study indicates that semen cryopreservation can be considered as a useful tool in the conservation of Griffon vulture genetic resources, but further studies are needed to optimize this technique.
Attention Deficit Hyperactivity Disorder comorbid oppositional defiant disorder and its predominately inattentive type: evidence for an association with COMT but not MAOA in a Chinese sample
Authors: Qian Qiu-Jin , Liu Jin , Wang Yu-Feng , Yang Li , Guan Li-Li , Faraone Stephen V 
Published: February 2009

Abstract

Background
There are three childhood disruptive behavior disorders (DBDs), attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). The most common comorbid disorder in ADHD is ODD. DSM-IV describes three ADHD subtypes: predominantly inattentive type (ADHD-IA), predominantly hyperactive-impulsive type (ADHD-HI), and combined type (ADHD-C). Prior work suggests that specific candidate genes are associated with specific subtypes of ADHD in China. Our previous association studies between ADHD and functional polymorphisms of COMT and MAOA, consistently showed the low transcriptional activity alleles were preferentially transmitted to ADHD-IA boys. Thus, the goal of the present study is to test the hypothesis that COMT Val158Met and MAOA-uVNTR jointly contribute to the ODD phenotype among Chinese ADHD boys.

Methods
171 Chinese boys between 6 and 17.5 years old (mean = 10.3, SD = 2.6) with complete COMT val158met and MAOA-uVNTR genotyping information were studied. We used logistic regression with genotypes as independent variables and the binary phenotype as the dependent variable. We used p < 0.05 as the level of nominal statistical significance. Bonferroni correction procedures were used to adjust for multiple comparisons.

Results
Our results highlight the potential etiologic role of COMT in the ADHD with comorbid ODD and its predominately inattentive type in male Chinese subjects. ADHD with comorbid ODD was associated with homozygosity of the high-activity Val allele, while the predominantly inattentive ADHD subtype was associated with the low-activity Met allele. We found no evidence of association between the MAOA-uVNTR variant and ADHD with comorbid ODD or the ADHD-IA subtype.

Conclusion
Our study of attention deficit hyperactivity disorder comorbid oppositional defiant disorder and its predominately inattentive type highlights the potential etiologic role of COMT for ADHD children in China. But we failed to observe an interaction between COMT and MAOA, which suggests that epistasis between COMT and MAOA genes does not influence the phenotype of ADHD-IA with comorbid ODD in a clinical sample of Chinese male subjects. To confirm our findings further studies with a larger number of subjects and healthy controls are needed.
High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays
Authors: Wang Yuker , Carlton Victoria EH , Karlin-Neumann George , Sapolsky Ronald , Zhang Li , Moorhead Martin , Wang Zhigang C , Richardson Andrea L , Warren Robert , Walther Axel , Bondy Melissa , Sahin Aysegul , Krahe Ralf , Tuna Musaffe , Thompson Patricia A , Spellman Paul T , Gray Joe W , Mills Gordon B , Faham Malek 
Published: February 2009

AbstractBackgroundA major challenge facing DNA copy number (CN) studies of tumors is that most banked samples with extensive clinical follow-up information are Formalin-Fixed Paraffin Embedded (FFPE). DNA from FFPE samples generally underperforms or suffers high failure rates compared to fresh frozen samples because of DNA degradation and cross-linking during FFPE fixation and processing. As FFPE protocols may vary widely between labs and samples may be stored for decades at room temperature, an ideal FFPE CN technology should work on diverse sample sets. Molecular Inversion Probe (MIP) technology has been applied successfully to obtain high quality CN and genotype data from cell line and frozen tumor DNA. Since the MIP probes require only a small (~40 bp) target binding site, we reasoned they may be well suited to assess degraded FFPE DNA. We assessed CN with a MIP panel of 50,000 markers in 93 FFPE tumor samples from 7 diverse collections. For 38 FFPE samples from three collections we were also able to asses CN in matched fresh frozen tumor tissue.ResultsUsing an input of 37 ng genomic DNA, we generated high quality CN data with MIP technology in 88% of FFPE samples from seven diverse collections. When matched fresh frozen tissue was available, the performance of FFPE DNA was comparable to that of DNA obtained from matched frozen tumor (genotype concordance averaged 99.9%), with only a modest loss in performance in FFPE.ConclusionMIP technology can be used to generate high quality CN and genotype data in FFPE as well as fresh frozen samples.
Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability
Authors: Pascual-Ramos Virginia , Contreras-Yáñez Irazú , Villa Antonio R , Cabiedes Javier , Rull-Gabayet Marina 
Published: February 2009

Abstract
Introduction
Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators.

Methods
Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used.

Results
The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age at baseline was associated with therapy discontinuation (odds ratio = 1.1, 95% confidence interval = 1.007 to 1.103, P = 0.02).

Conclusions
Discontinuation of DMARDs was frequent and progressive in an early RA cohort. Patients with persistence on therapy were younger, had lower disease activity and disability during follow-up, and reached sustained remission more frequently and earlier than patients without it. MP should intentionally be evaluated during follow-up of early RA patients, as it seems to play a major role in outcome.
Global analysis of alternative splicing regulation by insulin and wingless signaling in Drosophilacells
Authors: Hartmann Britta , Castelo Robert , Blanchette Marco , Boue Stephanie , Rio Donald C , Valcárcel Juan 
Published: February 2009

Abstract
Background
Despite the prevalence and biological relevance of both signaling pathways and alternative pre-mRNA splicing, our knowledge of how intracellular signaling impacts on alternative splicing regulation remains fragmentary. We report a genome-wide analysis using splicing-sensitive microarrays of changes in alternative splicing induced by activation of two distinct signaling pathways, insulin and wingless, in Drosophila cells in culture.

Results
Alternative splicing changes induced by insulin affect more than 150 genes and more than 50 genes are regulated by wingless activation. About 40% of the genes showing changes in alternative splicing also show regulation of mRNA levels, suggesting distinct but also significantly overlapping programs of transcriptional and post-transcriptional regulation. Distinct functional sets of genes are regulated by each pathway and, remarkably, a significant overlap is observed between functional categories of genes regulated transcriptionally and at the level of alternative splicing. Functions related to carbohydrate metabolism and cellular signaling are enriched among genes regulated by insulin and wingless, respectively. Computational searches identify pathway-specific sequence motifs enriched near regulated 5' splice sites.

Conclusions
Taken together, our data indicate that signaling cascades trigger pathway-specific and biologically coherent regulatory programs of alternative splicing regulation. They also reveal that alternative splicing can provide a novel molecular mechanism for crosstalk between different signaling pathways.
Secondary CD5+ Diffuse Large B-Cell Lymphoma Not Associated With Transformation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Richter Syndrome)
Authors: Maeshima Akiko Miyagi , Taniguchi Hirokazu , Nomoto Junko , Maruyama Dai , Kim Sung-Won , Watanabe Takashi , Kobayashi Yukio , Tobinai Kensei , Matsuno Yoshihiro 
Published: February 2009

Abstract
Few cases of secondary CD5+ diffuse large B-cell lymphoma (DLBCL) that are not Richter syndrome have been reported previously. We report 9 cases of non–Richter syndrome secondary CD5+ DLBCL. Among 529 cases of DLBCL, 38 (7.2%) were CD5+ DLBCL, including 9 of secondary CD5+ DLBCL. Five cases gained CD5 expression during the clinical course of DLBCL (group 1). Three cases showed transformation from CD5− low-grade B-cell lymphoma to CD5+ DLBCL (group 2). The remaining case showed coexistence of CD5+ DLBCL and CD5+ follicular lymphoma. The clonal relationships of CD5− and CD5+ tumors were confirmed in all 4 available cases. Cases of secondary CD5+ DLBCL that were not Richter syndrome were classifiable into 3 groups. Groups 1 and 2 showed the gain of CD5 during the clinical course or transformation of the tumors, suggesting that CD5 expression is closely associated with the progression of B-cell lymphoma.
PAX-2 in the Diagnosis of Primary Renal Tumors
Authors: Ozcan Ayhan , Zhai Jim , Hamilton Candice , Shen Steven S. , Ro Jae Y. , Krishnan Bhuvaneswari , Truong Luan D. 
Published: February 2009

Abstract
The diagnosis of renal cell carcinoma (RCC) remains problematic, especially in the context of metastasis or small needle biopsy specimens. The renal cell carcinoma marker (RCCM) and kidney-specific cadherin (KSC) are considered specific markers for RCC but are expressed preferentially in specific subtypes of RCC of lower grades. This study was aimed at evaluating the usefulness of PAX-2 in the diagnosis of renal tumors and comparing it with that of RCCM and KSC. Immunostaining for PAX-2, RCCM, and KSC was performed on consecutive tissue sections of 130 renal tumors.
PAX-2 was successfully detected in routine tissue specimens. Although PAX-2 seems to be more sensitive than RCCM and KSC, there is significant staining overlap in relation to histologic subtypes, justifying the use of all 3 markers, which helps detect the vast majority of renal neoplasms. PAX-2 seems to have a significant role in renal neogenesis and may represent a novel therapeutic target.
Cryptic seedling herbivory by nocturnal introduced generalists impacts survival, performance of native and exotic plants
Authors: Strauss Sharon Y. , Stanton Maureen L. , Emery Nancy C. , Bradley Carrie A. , Carleton Alexandra , Dittrich-Reed Dylan R. , Ervin Olivia A. , Gray Levi N. , Hamilton Andrew M. , Rogge Jennifer Harrington , Harper Skye D. , Law Kimberley Cook , Pham Vinh Q. , Putnam Matthew E. , Roth Tara M. , Theil Jacob H. , Wells Lara M. , Yoshizuka Eric M. 
Published: February 2009

Although much of the theory on the success of invasive species has been geared at escape from specialist enemies, the impact of introduced generalist invertebrate herbivores on both native and introduced plant species has been underappreciated. The role of nocturnal invertebrate herbivores in structuring plant communities has been examined extensively in Europe, but less so in North America. Many nocturnal generalists (slugs, snails, and earwigs) have been introduced to North America, and 96% of herbivores found during a night census at our California Central Valley site were introduced generalists. We explored the role of these herbivores in the distribution, survivorship, and growth of 12 native and introduced plant species from six families. We predicted that introduced species sharing an evolutionary history with these generalists might be less vulnerable than native plant species.We quantified plant and herbivore abundances within our heterogeneous site and also established herbivore removal experiments in 160 plots spanning the gamut of microhabitats. As 18 collaborators, we checked 2000 seedling sites every day for three weeks to assess nocturnal seedling predation. Laboratory feeding trials allowed us to quantify the palatability of plant species to the two dominant nocturnal herbivores at the site (slugs and earwigs) and allowed us to account for herbivore microhabitat preferences when analyzing attack rates on seedlings.The relationship between local slug abundance and percent cover of five common plant taxa at the field site was significantly negatively associated with the mean palatability of these taxa to slugs in laboratory trials. Moreover, seedling mortality of 12 species in open‐field plots was positively correlated with mean palatability of these taxa to both slugs and earwigs in laboratory trials.Counter to expectations, seedlings of native species were neither more vulnerable nor more palatable to nocturnal generalists than those of introduced species. Growth comparison of plants within and outside herbivore exclosures also revealed no differences between native and introduced plant species, despite large impacts of herbivores on growth.Cryptic nocturnal predation on seedlings was common and had large effects on plant establishment at our site. Without intensive monitoring, such predation could easily be misconstrued as poor seedling emergence.
Time asymmetry in the palaeobiogeographic history of species
Authors: Lopez-Martinez Nieves 
Published: February 2009

AbstractThe difficulties and hindrances of palaeobiogeography and historical biogeography in its long, sterile search for centres of origin or ancestral areas of species, leading some authors to withdraw the centre-of-origin as a non-scientific concept, are here considered as signals and not artefacts for the recognition of patterns in the biogeographic history of lineages. The time-symmetric model, which assumes gradual origination and extinction processes of a species, is here questioned and an alternative time-asymmetric model is proposed. The origination and expansion processes of a species history would be much faster and more unpredictable than the often gradual, long, predictable extinction process marked by previous signals of geographic area contraction. Monitored biological invasions, plankton blooms and episodes of coordinated migrations illustrate the fast expansion of novel species behaving as dissipative structures. The asymmetric biogeographic model is tested through palaeobiogeographic data on Old World mammal species and by the consistent preference of biostratigraphers for species appearance against species extinction as time-marker bioevents. Time-asymmetry is a common phenomenon of nature, indicating that asymmetry could well be a general property of Time itself.