bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of stromal cell‐derived factor 1 expression in patients with gastric cancer after surgical resection
Authors: Wang Xuefei , Zhang Heng , He Hongyong , Shen Zhenbin , Tang Zhaoqing , Xu Jiejie , Sun Yihong 
Published: September 2014

Aberrant chemokine stromal cell‐derived factor 1 (SDF‐1) expression has been shown to be involved in the development and progression of various malignancies. Our present study aims to investigate the clinical and prognostic value of SDF‐1 expression and improve risk stratification in patients with gastric cancer. Peritumoral and intratumoral SDF‐1 levels were assessed in 220 retrospectively enrolled gastric cancer patients, and their relations with clinicopathological features and clinical outcomes were evaluated. A predictive nomogram was created to refine risk stratification for overall survival of gastric cancer patients. Compared with peritumor tissues, tumor tissues showed decreased SDF‐1 expression levels according to TNM stage progression in gastric cancer specimens. Peritumoral SDF‐1 expression correlated positively with tumor invasion depth and lymph node metastasis, whereas intratumoral SDF‐1 expression associated negatively with tumor size, tumor differentiation, tumor invasion depth, lymph node metastasis, and clinical TNM stage. Moreover, both low peritumoral SDF‐1 expression and high intratumoral SDF‐1 expression indicated favorable overall survival, and SDF‐1 risk derived from the peritumoral/intratumoral SDF‐1 expression signature could stratify prognosis of patients with gastric cancer. After backward elimination, SDF‐1 risk was identified as an independent prognostic factor for survival. Finally, a predictive nomogram was generated with identified independent prognosticators to assess patient survival at 3 and 5 years following surgery. Conclusively, SDF‐1 risk, an identified independent prognostic factor, could be developed into a nomogram with tumor invasion depth, lymph node involvement, and distant metastasis to refine predictive accuracy for survival in patients with gastric cancer after surgical resection.
Serum chromogranin A is a useful marker for Japanese patients with pancreatic neuroendocrine tumors
Authors: Hijioka Masayuki , Ito Tetsuhide , Igarashi Hisato , Fujimori Nao , Lee Lingaku , Nakamura Taichi , Jensen Robert T. , Takayanagi Ryoichi 
Published: September 2014

Although chromogranin A (CGA) is a useful marker for pancreatic neuroendocrine tumors (pNET) in the West, its usefulness in Japanese populations is unclear. To assess this, we evaluated the serum CGA levels in 189 patients with various pancreatic diseases, including proven pNET (n = 69), pancreatic cancer (PC) (n = 50), chronic pancreatitis (CP) (n = 50) and autoimmune pancreatitis (AIP) (n = 20), and 112 normal controls (controls) using an ELISA kit. The mean CGA level of patients with pNET was significantly higher than any of the other groups (407.8 ± 984.6 ng/mL [pNET] vs 91.8 ± 101.8 ng/mL [PC], 93.6 ± 57.5 ng/mL [CP], 69.9 ± 52.4 ng/mL [AIP] and 62.5 ± 48.3 ng/mL [controls]). Limiting the analysis to patients not using proton pump inhibitors (PPI), the CGA level of patients with PC or CP was not significantly different compared with the controls. Discriminant analysis revealed that the best cut‐off value of CGA to distinguish patients with pNET from the controls was 78.7 ng/mL, with a sensitivity and specificity of 53.6% and 78.6%, respectively. In patients with pNET, significant factors associating with elevated CGA levels were tumor classification, tumor size, and the presence of liver metastases in univariate analysis as well as PPI use and the presence of liver metastases in multivariate analysis. We show that CGA is a useful marker for diagnosing pNET in Japanese populations and for distinguishing patients with pNET from patients with other pancreatic diseases. The increased use of CGA in Japan will likely be a helpful tool in managing these patients, as found in the West.
The ins and outs of the evolutionary origin of teeth
Authors: Donoghue Philip C. J. , Rücklin Martin 
Published: September 2014

SUMMARYThe role of teeth and jaws, as innovations that underpinned the evolutionary success of living jawed vertebrates, is well understood, but their evolutionary origins are less clear. The origin of teeth, in particular, is mired in controversy with competing hypotheses advocating their origin in external dermal denticles (“outside‐in”) versus a de novo independent origin (“inside‐out”). No evidence has ever been presented demonstrating materially the traditional “outside‐in” theory of teeth evolving from dermal denticles, besides circumstantial evidence of a commonality of structure and organogenesis, and phylogenetic evidence that dermal denticles appear earlier in vertebrate phylogeny that do teeth. Meanwhile, evidence has mounted in support of “inside‐out” theory, through developmental studies that have indicated that endoderm is required for tooth development, and fossil studies that have shown that tooth‐like structures evolved before dermal denticles (conodont dental elements), that tooth replacement evolving before teeth (thelodont pharyngeal denticles), and that teeth evolved many times independently through co‐option of such structures. However, the foundations of “inside‐out” theory have been undermined fatally by critical reanalysis of the evidence on which it was based. Specifically, it has been shown that teeth develop from dermal, endodermal or mixed epithelia and, therefore, developmental distinctions between teeth and dermal denticles are diminished. Furthermore the odontode‐like structure of conodont elements has been shown to have evolved independently of dermal and internal odontodes. The tooth‐like replacement encountered in thelodont pharyngeal odontodes has been shown to have evolved independently of teeth and tooth replacement and teeth have been shown to have evolved late within the gnathostome stem lineage indicating that it is probable, if not definitive, that teeth evolved just once in gnathostome evolution. Thus, the “inside‐out” hypothesis must be rejected. The phylogenetic distribution of teeth and dermal denticles shows that these odontodes were expressed first in the dermal skeleton, but their topological distribution extended internally in association with oral, nasal and pharyngeal orifices, in a number of distinct evolutionary lineages. This suggests that teeth and oral and pharyngeal denticles emerged phylogenetically through extension of odontogenic competence from the external dermis to internal epithelia. Ultimately, internal and external odontodes appear to be distinct developmental modules in living jawed vertebrates, however, the evidence suggests that this distinction was not established until the evolution of jawed vertebrates, not merely gnathostomes.
Early‐life‐stress affects the homeostasis of glutamatergic synapses
Authors: Toya Syutaro , Takatsuru Yusuke , Kokubo Michifumi , Amano Izuki , Shimokawa Noriaki , Koibuchi Noriyuki 
Published: September 2014

AbstractEarly‐life stress induces several neuropsychological disorders in adulthood, including depression. Such disorders may be induced by functional alteration of the glutamatergic system. However, their underlying mechanisms have not yet been fully clarified. Furthermore, the involvement of glucocorticoids, which are representative stress hormones, has not yet been fully clarified. In this study, we used maternal deprivation (MD) mice as an early‐life‐stress model, and studied the changes in the glutamatergic system in adulthood. The glutamate concentration and neuronal activity in the somatosensory cortex (SSC) increased under basal conditions in MD mice. Stressful physical stimulation (SPS) increased the concentration of corticosterone, but not of glutamate, in the control mouse SSC. On the other hand, in the MD mice, although the basal concentration of corticosterone in the SSC increased, no SPS‐induced increase was observed. In contrast, the concentration of glutamate increased greatly during SPS. It was significantly high for 30 min after stimulation. The expression level of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid/N‐methyl‐d‐aspartate receptors in the MD mice was also changed compared with that in the control mice after stimulation. These findings indicate that early‐life stress disrupts the homeostasis of glutamatergic synapses.
Dementia and severity of parkinsonism determines the handicap of patients in late‐stage Parkinson's disease: the Barcelona−Lisbon cohort
Authors: Coelho M. , Marti M. J. , Sampaio C. , Ferreira J. J. , Valldeoriola F. , Rosa M. M. , Tolosa E. 
Published: September 2014

Background and purposeHandicap has not been explored as a patient‐centred outcome measure in Parkinson's disease (PD). The clinical features and medication use in late stages of PD (LS‐PD) were reported previously.MethodsHandicap, medical conditions, use of healthcare resources and the impact of LS‐PD upon caregivers were characterized in a cross‐sectional study of LS‐PD stages 4 or 5 of Hoehn and Yahr (H&Y). Handicap was measured using the London Handicap Scale (LHS: 0, maximal handicap; 1, no handicap).ResultsThe mean LHS score in 50 patients was 0.33 (SD ±0.15). The presence of dementia, the Unified Parkinson's Disease Rating Scale part I score and the H&Y stage in ‘off’ independently predicted the LHS score (adjusted R2 = 0.62; P = 0.000). Comorbidities and past medical conditions were frequent. Thirty‐five patients lived at their house. Forty‐five received unpaid care. Mean visits to the family doctor in the preceding 6 months were 2.2 (SD ±3.0) and to a neurologist 1.7 (SD ±1.0). Use of other health resources was low. Unpaid caregivers spent much time with patients and reported a high burden.ConclusionHandicap could be measured in LS‐PD and the LHS was easily completed by patients and caregivers. The high handicap in our cohort was mostly driven by the presence of dementia, behavioural complaints and the severity of non‐dopaminergic motor features. Patients visited doctors infrequently and made low use of health resources, whilst unpaid caregivers reported a high burden.
Bacterial soft tissue infection in psoriasis despite induction of epidermal antimicrobial peptides
Authors: Steinz Kirsten , Schubert Sabine , Harder Jürgen , Gerdes Sascha , Mrowietz Ulrich , Gläser Regine 
Published: September 2014

AbstractAntimicrobial peptides and proteins (AMP) are highly active molecules with a broad‐spectrum of microbicidal activity. Human beta‐defensins (hBD)‐2 and hBD‐3 were initially isolated from psoriatic‐scale extracts, and other AMP have been identified in high concentrations in psoriatic skin explaining the uncommonness of skin infections in these patients. When a 71‐year‐old male patient suffering from a mild form of psoriasis (Psoriasis Area Severity Index PASI 4.4) presented a soft tissue infection (erysipelas) surrounding a psoriatic plaque of the elbow, we asked whether a local deficiency of AMP could be the reason for this infection. A detailed analysis of the expression and secretion levels of different classes of AMP was conducted. Induction of AMP was clearly shown by immunohistochemistry as well as by ELISA performed using skin‐washing fluids. Therefore, other factors, for example deep penetrating injuries bypassing the keratinocyte innate defense system, must have caused the soft tissue infection.
Overexpression of Wnt5a in mouse epidermis causes no psoriasis phenotype but an impairment of hair follicle anagen development
Authors: Zhu Xuming , Wu Yumei , Huang Sixia , Chen Yingwei , Tao Yixin , Wang Yushu , He Shigang , Shen Sanbing , Wu Ji , Guo Xizhi , Li Baojie , He Lin , Ma Gang 
Published: September 2014

AbstractIncreased Wnt5a expression has been observed in psoriatic plaques. However, whether Wnt5a overexpression directly causes psoriasis is unknown. In this study, we generated transgenic (TG) mice with epidermal Wnt5a overexpression under the control of the human K14 promoter. The skin of Wnt5a TG mice was not psoriatic, but characterized with normal proliferation and homeostasis of epidermis. Instead, these TG mice displayed impaired hair follicle transition from telogen to anagen, most likely due to impaired canonical Wnt signalling. These results suggest that increased Wnt5a expression alone is inadequate to induce psoriasis in the skin and possible involvement of Wnt5a in hair follicle cycling.
Combining confocal Raman microscopy and freeze‐drying for quantification of substance penetration into human skin
Authors: Franzen Lutz , Anderski Juliane , Planz Viktoria , Kostka Karl‐Heinz , Windbergs Maike 
Published: September 2014

AbstractIn the area of dermatological research, the knowledge of rate and extent of substance penetration into the human skin is essential not only for evaluation of therapeutics, but also for risk assessment of chemicals and cosmetic ingredients. Recently, confocal Raman microscopy emerged as a novel analytical technique for analysis of substance skin penetration. In contrast to destructive drug extraction and quantification, the technique is non‐destructive and provides high spatial resolution in three dimensions. However, the generation of time‐resolved concentration depth profiles is restrained by ongoing diffusion of the penetrating substance during analysis. To prevent that, substance diffusion in excised human skin can instantly be stopped at defined time points by freeze‐drying the sample. Thus, combining sample preparation by freeze‐drying with drug quantification by confocal Raman microscopy yields a novel analytical platform for non‐invasive and quantitative in vitro analysis of substance skin penetration. This work presents the first proof‐of‐concept study for non‐invasive quantitative substance depth profiling in freeze‐dried excised human stratum corneum by confocal Raman microscopy.
A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium‐activated chloride secretion in human sweat gland epithelial cells
Authors: Ertongur‐Fauth Torsten , Hochheimer Andreas , Buescher Joerg Martin , Rapprich Stefan , Krohn Michael 
Published: September 2014

AbstractSweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca2+‐activated Cl− channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL‐SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A‐dimerization domain. Chloride flux assays using halide‐sensitive YFP revealed that TMEM16A is functionally involved in Ca2+‐dependent Cl− secretion in NCL‐SG3 cells. Recombinant expression in NCL‐SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca2+‐activated Cl− permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland‐specific Cl− secretion providing opportunities to develop sweat gland‐specific therapeutics for treatment of sweating disorders.
Gains of DNA methylation in myeloid terminal differentiation are dispensable for gene silencing but influence the differentiated phenotype
Authors: Vento‐Tormo Roser , Álvarez‐Errico Damiana , Rodríguez‐Ubreva Javier , Ballestar Esteban 
Published: September 2014

DNA methylation‐mediated regulation drives and stabilizes transcription states throughout development. In myeloid differentiation, DNA methylation changes occur predominantly in the direction towards hypomethylation. Also, in vitro differentiation of monocytes to dendritic cells and macrophages is characterized by DNA demethylation. In this study, we identified the existence of methylation changes in the direction of hypermethylation among genes that become repressed during monocyte‐to‐dendritic cell differentiation. We identified the acquisition of DNA methylation in genes such as CSF3R, FYN, and CX3CR1, but not in others, such as CD14. Analysis of the dynamics of methylation and expression changes of these genes revealed that loss of expression was rapid and was associated with the loss of H3K4me3 and H3K36me3, whereas gains of DNA methylation were progressive and partially concomitant with increases in H3K9me3 and H3K27me3. Inhibition of DNA methyltransferases, with the DNA replication‐independent drug nanaomycin A, revealed that there were no effects on expression and H3K4me3 changes, despite the partial impairment of DNA methylation and H3K27me3 acquisition. However, cells treated with the DNA methyltransferase inhibitor showed lower levels of dendritic cell surface markers, suggesting a potential effect on the stability of the differentiated phenotype. Our data give rise to a novel perspective on the functional relevance and mechanisms of the acquisition of DNA methylation in myeloid cell differentiation.
Evolutionary analysis of multidrug resistance genes in fungi – impact of gene duplication and family conservation
Authors: Gossani Cristiani , Bellieny‐Rabelo Daniel , Venancio Thiago M. 
Published: September 2014

Although the emergence of bacterial drug resistance is of great concern to the scientific community, few studies have evaluated this phenomenon systematically in fungi by using genome‐wide datasets. In the present study, we assembled a large compendium of Saccharomyces cerevisiae chemical genetic data to study the evolution of multidrug resistance genes (MDRs) in the fungal lineage. We found that MDRs typically emerge in widely conserved families, most of which containing homologs from pathogenic fungi, such as Candida albicans and Coccidioides immitis, which could favor the evolution of drug resistance in those species. By integrating data from chemical genetics with protein family conservation, genetic and protein interactions, we found that gene families rarely have more than one MDR, indicating that paralogs evolve asymmetrically with regard to multidrug resistance roles. Furthermore, MDRs have more genetic and protein interaction partners than non‐MDRs, supporting their participation in complex biochemical systems underlying the tolerance to multiple bioactive molecules. MDRs share more chemical genetic interactions with other MDRs than with non‐MDRs, regardless of their evolutionary affinity. These results suggest the existence of an intricate system involved in the global drug tolerance phenotypes. Finally, MDRs are more likely to be hit repeatedly by mutations in laboratory evolution experiments, indicating that they have great adaptive potential. The results presented here not only reveal the main genomic features underlying the evolution of MDRs, but also shed light on the gene families from which drug resistance is more likely to emerge in fungi.
X‐box binding protein 1 is a novel key regulator of peroxisome proliferator‐activated receptor γ2
Authors: Cho Yoon Mi , Kwak Su‐Nam , Joo Nam‐Seok , Kim Dae Hun , Lee Ann‐Hwee , Kim Kyung‐Soo , Seo Jong Bae , Jeong Seong‐Whan , Kwon Oh‐Joo 
Published: September 2014

X‐box binding protein 1 (XBP1), a transcription factor of the unfolded protein response, plays various roles in many biological processes. We examined its pro‐adipogenic activity and target genes during adipogenic differentiation in wild‐type and genetically modified 3T3‐L1 cells. Signalling pathways that contribute to Xbp1 mRNA splicing, and the correlation of the transcriptionally active XBP1 isoform (XBP1s) level with body mass index and the level of peroxisome proliferator‐activated receptor γ2 (PPARγ2) in human adipose tissues were also examined. The mRNA and nuclear protein expression levels of XBP1s increased immediately following hormonal induction of adipogenesis, reaching a peak at 6 h. Results from cDNA microarray and gene expression analyses using genetically modified cells indicated that PPARγ2 was a principal target of XBP1s. The XBP1s‐specific binding motif, which is distinct from the CCAAT/enhancer‐binding protein α binding site, was identified in the PPARγ2 promoter by site‐directed mutagenesis. Fetal bovine serum, insulin, 3‐isobutyl‐1‐methylxanthine and dexamethasone contributed independently to Xbp1 mRNA splicing. In human subcutaneous adipose tissues, the levels of both Xbp1s and Pparγ2 mRNA increased proportionally with body mass index, and there was a significant positive correlation between the two genes. These data suggest for the first time that positive regulation of PPARγ2 is a principal mechanism of XBP1s‐mediated adipogenesis in 3T3‐L1 cells.
Spawning distribution and abundance of a northern Chinook salmon population
Authors: Sethi S. A. , Tanner T. 
Published: September 2014

AbstractChinook salmon, Oncorhynchus tshawytscha (Walbaum), is an important biological and cultural resource in Alaska, but knowledge about Chinook salmon ecology is limited in many regions. From 2009 to 2012, spawning distribution and abundance of a northern Chinook salmon population on the Togiak River in south‐west Alaska were assessed. Chinook salmon preferred deeper mainstem channel spawning habitat, with 12% (14 of 118 tags in 2009) to 21% (22 of 106 tags in 2012) of radio‐tagged fish spawning in smaller order tributaries. Tributary spawners tended to have earlier run timing than mainstem spawners. Chinook salmon exhibited extended holding and backout (entering freshwater but returning to saltwater before completing anadromous migration) behaviours near the mouth of Togiak River, potentially prolonging their exposure to fishery harvest. Mark–recapture total annual run estimates (2010–2012) ranged from 11 240 (2011) to 18 299 (2012) fish. Exploitation of Chinook salmon ranged from 36% (2012) to 55% (2011) during the study period, with incidental fishery catches near the mouth of the river comprising the largest source of harvest.
Declines in the energy content of yearling non‐native alewife associated with lower food web changes in Lake Michigan
Authors: Pothoven S. A. , Fahnenstiel G. L. 
Published: September 2014

AbstractJuveniles of non‐native alewife, Alosa pseudoharengus (Wilson), were collected in Lake Michigan in 1998, 1999, 2010, 2011 and 2013 to evaluate changes in energy content during a period of major ecosystem changes. Consistent with historical data, energy content of yearling alewife declined from late winter into late spring and was at its lowest point in June. Energy density and length‐adjusted, entire‐body energy were lower in 2010, 2011 and 2013 than in 1998 and 1999. Energy losses over the first winter in the lake were more severe for the 2010 year class (56% decrease) than for the 1998 year class (28% decrease). Alewife diets in late spring of 2010–2013 reflected the loss of major prey such as Diporeia spp. and a shift towards lower energy prey. The recent decline in energy content of yearling alewife can be linked to recent changes in productivity and abundance of key components of the lower food web of Lake Michigan following the dreissenid invasion.