bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Acetylcholinesterase (AChE): A Potential Therapeutic Target to Treat Alzheimer's Disease
Authors: Li Yong , Zhang Xiao‐xiao , Jiang Li‐juan , Yuan Li , Cao Ting‐ting , Li Xia , Dong Lin , Li Ying , Yin Shu‐Fan 
Published: March 2015

A new series of icariin derivatives were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. Most of the tested compounds exhibited high AChE inhibition and low toxicity, and among which compounds 1, 2, and 10 were the most potent (IC50 = 71.52 ± 22.43, 8.28 ± 1.45, 5.830 ± 1.78 nm, respectively).
T cell anergy and activation are associated with suboptimal humoral responses to measles revaccination in HIV-infected children on anti-retroviral therapy in Nairobi, Kenya
Authors: Buechler M B , Newman L P , Chohan B H , Njoroge A , Wamalwa D , Farquhar C 
Published: March 2015

Summary
HIV-infected children are less capable of mounting and maintaining protective humoral responses to vaccination against measles compared to HIV-uninfected children. This poses a public health challenge in countries with high HIV burdens. Administration of anti-retroviral therapy (ART) and revaccinating children against measles is one approach to increase measles immunity in HIV-infected children, yet it is not effective in all cases. Immune anergy and activation during HIV infection are factors that could influence responses to measles revaccination. We utilized a flow cytometry-based approach to examine whether T cell anergy and activation were associated with the maintenance of measles-specific immunoglobulin (Ig)G antibodies generated in response to measles revaccination in a cohort of HIV-infected children on ART in Nairobi, Kenya. Children who sustained measles-specific IgG for at least 1 year after revaccination displayed significantly lower programmed cell death 1 (PD-1) surface expression on CD8+ T cells on a per-cell basis and exhibited less activated CD4+ T cells compared to those unable to maintain detectable measles-specific antibodies. Children in both groups were similar in age and sex, CD4+ T cell frequency, duration of ART treatment and HIV viral load at enrolment. These data suggest that aberrant T cell anergy and activation are associated with the impaired ability to sustain an antibody response to measles revaccination in HIV-infected children on ART.
Metabolic profiling in Prader–Willi syndrome and nonsyndromic obesity: sex differences and the role of growth hormone
Authors: Irizarry Krystal A. , Bain James , Butler Merlin G. , Ilkayeva Olga , Muehlbauer Michael , Haqq Andrea M. , Freemark Michael 
Published: March 2015

SummaryObjectivesTo identify metabolic factors controlling appetite and insulin sensitivity in PWS and assess effects of GH treatment.MethodsWe compared amino acids, fatty acids and acylcarnitines in GH‐treated and untreated PWS children and obese and lean controls to identify biomarkers associated with ghrelin, peptide YY and markers of insulin sensitivity (adiponectin and HOMA‐IR).ResultsCompared with obese controls (OC), children with PWS had fasting hyperghrelinaemia, hyperadiponectinaemia, hypoinsulinaemia and increased ghrelin/PYY. Hyperghrelinaemia, hyperadiponectinaemia and hypoinsulinaemia were more striking in PWS females than males, and decreases in BCAA were detected only in PWS females. GH‐treated PWS subjects had lower leptin and higher IGF‐1 and adiponectin than untreated subjects; fasting ghrelin, PYY and insulin levels were comparable. Ghrelin correlated inversely with BCAA in PWS but not OC. Adiponectin correlated negatively with BMIz and HOMA‐IR in PWS; in contrast, adiponectin correlated more strongly with BCAA than BMIz or HOMA‐IR in OC.ConclusionsBCAA levels were lower in PWS females than OC females and correlated inversely with ghrelin. Low BCAA in PWS females may promote hyperghrelinaemia and hyperphagia, while hyperadiponectinaemia may maintain insulin sensitivity despite excess weight gain. GH treatment may reduce leptin and increase adiponectin, but does not affect fasting ghrelin or PYY.
Mortality after acute primary mesenteric infarction: a systematic review and meta‐analysis of observational studies
Authors: Adaba F. , Askari A. , Dastur J. , Patel A. , Gabe S. M. , Vaizey C. J. , Faiz O. , Nightingale J. M. D. , Warusavitarne J. 
Published: March 2015

AbstractAimThe primary aim of this study was to determine whether the in‐hospital mortality for acute mesenteric infarction has reduced in the last decade. The secondary aim was to determine if there was a statistical difference in mortality between patients having acute primary mesenteric infarction due to different causes.MethodA literature search was performed of PubMed, Ovid (Embase) and Google Scholar databases. Studies on acute mesenteric infarction of primary vascular pathology were included for pooled analyses while studies that had reported comparative mortality between arterial, venous and non‐occlusive mesenteric infarction (NOMI) were included in meta‐analyses. Their quality was assessed using the National Institute for Health and Care Excellence assessment scale. Odds ratios (ORs) of mortality were calculated using a Mantel−Haenszel random effect model.ResultsThe total number of patients was 4527 and the male/female ratio was 1912/2247. The pooled in‐hospital mortality was 63%. There was no significant reduction of in‐hospital mortality rate in the last decade (P = 0.78). There was a significant difference in in‐hospital mortality between acute arterial mesenteric infarction (73.9%) compared with acute venous mesenteric infarction (41.7%) [OR 3.47, confidence interval (CI) 2.43−4.96, P < 0.001] and NOMI (68.5%) compared with acute venous mesenteric infarction (44.2%) (OR 3.2, CI 1.83−5.6, P < 0.001). There was no difference in mortality between acute arterial mesenteric infarction and NOMI (OR 1.08, CI 0.57−2.03, P = 0.82).ConclusionIn‐hospital mortality rate has not changed in the last decade. Patients with arterial mesenteric infarction or with NOMI are over three times more likely to die during the first hospital admission compared with those with venous mesenteric infarction.
Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody‐mediated rejection: a pilot study
Authors: Bachelet Thomas , Nodimar Celine , Taupin Jean‐Luc , Lepreux Sebastien , Moreau Karine , Morel Delphine , Guidicelli Gwendaline , Couzi Lionel , Merville Pierre 
Published: March 2015

AbstractOutcome of patients with transplant glomerulopathy (TG) is poor. Using B‐cell targeting molecules represent a rational strategy to treat TG during chronic antibody‐mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post‐biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24‐month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor‐specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody‐mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events.
Causal path analyses of the association of protein intake with risk of mortality and graft failure in renal transplant recipients
Authors: Said M. Yusof , Deetman Petronella E. , de Vries Aiko P. J. , Zelle Dorien M. , Gans Rijk O. B. , Navis Gerjan , Joosten Michel M. , Bakker Stephan J. L. 
Published: March 2015

AbstractThe effect of a low protein intake on survival in renal transplant recipients (RTR) is unknown. A low protein intake may increase risks of malnutrition, low muscle mass, and death. We aimed to study associations of protein intake with mortality and graft failure and to identify potential intermediate factors. Protein intake was estimated from 24‐h urinary urea excretion (24‐h UUE). Graft failure was defined as return to dialysis or retransplantation. We used Cox regression analyses to analyze associations with outcome and potential intermediate factors in the causal path. In 604 RTR, mean ± SD 24‐h UUE was 380 ± 114 mmol/24‐h. During median follow‐up for 7.0 yr (interquartile range: 6.2–7.5 yr), 133 RTR died and 53 developed graft failure. In univariate analyses, 24‐h UUE was associated with lower risk of mortality (HR [95% CI] = 0.80 [0.69–0.94]) and graft failure (HR [95% CI] = 0.72 [0.56–0.92]). These associations were independent of potential confounders. In causal path analyses, the association of 24‐h UUE with mortality disappeared after adjustment for muscle mass. Low protein intake is associated with increased risk of mortality and graft failure in RTR. Causal path analyses reveal that the association with mortality is explained by low muscle mass. These findings suggest that protein intake restriction should not be advised to RTR.
Donor kidney microthrombi and outcomes of kidney transplant: a single‐center experience
Authors: Sood Puneet , Randhawa Parmjeet S. , Mehta Rajil , Hariharan Sundaram , Tevar Amit D. 
Published: March 2015

AbstractThe kidney wait list has outgrown the supply of available organs every year. Efforts are being made to minimize discard rate of organs. One such area is the use of kidneys with glomerular microthrombi (MT). We retrospectively examined graft/patient outcomes in 28 cases with MT in pre‐implantation biopsies. All patients had follow‐up of at least 36 months, or until graft loss or death. In total, 17 of the 18 patients who underwent follow‐up biopsy within 90 days of transplantation had cleared all MT. Most patients had excellent long‐term graft function. On a closer review of the biopsies included in our study, we found that even in the organs with the most widespread thrombosis, the median percentage of glomeruli with more than 50 percentage of the capillary loops occluded was 8% (range 0–17%). The current practice of mentioning the % of glomeruli with thrombi cannot adequately capture the extent of donor organ pathology, as the actual % glomerular area involved can vary greatly from case to case. Future studies should attempt to quantify donor thrombi by a more robust method and revisit the issue of using clinico‐pathologic parameters to predict allograft function in the setting of MT.
In ovo gene manipulation of melanocytes and their adjacent keratinocytes during skin pigmentation of chicken embryos
Authors: Murai Hidetaka , Tadokoro Ryosuke , Sakai Ken‐Ichiro , Takahashi Yoshiko 
Published: March 2015

During skin pigmentation in avians and mammalians, melanin is synthesized in the melanocytes, and subsequently transferred to adjacently located keratinocytes, leading to a wide coverage of the body surface by melanin‐containing cells. The behavior of melanocytes is influenced by keratinocytes shown mostly by in vitro studies. However, it has poorly been investigated how such intercellular cross‐talk is regulated in vivo because of a lack of suitable experimental models. Using chicken embryos, we developed a method that enables in vivo gene manipulations of melanocytes and keratinocytes, where these cells are separately labeled by different genes. Two types of gene transfer techniques were combined: one was a retrovirus‐mediated gene infection into the skin/keratinocytes, and the other was the in ovo DNA electroporation into neural crest cells, the origin of melanocytes. Since the Replication‐Competent Avian sarcoma‐leukosis virus long terminal repeat with Splice acceptor (RCAS) infection was available only for the White leghorn strain showing little pigmentation, melanocytes prepared from the Hypeco nera (pigmented) were back‐transplanted into embryos of White leghorn. Prior to the transplantation, enhanced green fluorescent protein (EGFP)+Neor+‐electroporated melanocytes from Hypeco nera were selectively grown in G418‐supplemented medium. In the skin of recipient White leghorn embryos infected with RCAS‐mOrange, mOrange+ keratinocytes and transplanted EGFP+ melanocytes were frequently juxtaposed each other. High‐resolution confocal microscopy also revealed that transplanted melanocytes exhibited normal behaviors regarding distribution patterns of melanocytes, dendrite morphology, and melanosome transfer. The method described in this study will serve as a useful tool to understand the mechanisms underlying intercellular regulations during skin pigmentation in vivo.
Postponing Passage: Doorways, Distinctions, and the Thresholds of Personhood among Older Chicagoans
Authors: Buch Elana D. 
Published: March 2015

AbstractThis article analyzes the quotidian ways that older Chicagoans remade and traversed physical boundaries between their homes and the city beyond. In so doing, it explores how changing engagements with the environment impact social personhood in later life. In a context in which personhood is equated with independence, elders relying on paid care workers to remain in their homes found themselves at the threshold of social death. To sustain their independence and personhood, older Chicagoans sought to prevent spatial and social transitions using a range of everyday tactics and material practices located around the doorways of their homes. These liminal practices simultaneously reasserted racial, class, and other social distinctions between elders, home care workers and others, helping elders continue to occupy familiar subject positions. For these older adults, homes and their thresholds became resources with which they resisted profound changes to their daily lives, subjectivities, and social personhood.
Laparoscopic‐assisted tube cystotomy for urethral rupture in a foal
Authors: Oreff G. L. , Tatz A. J. , Ranen E. , Dahan R. , Kelmer G. 
Published: March 2015

SummaryA 10‐day‐old Tennessee Walking Horse colt was hospitalised due to a pelvic urethral tear. After 2 unsuccessful attempts to repair the tear by primary closure, the colt underwent perineal urethroplasty and laparoscopic‐assisted tube cystotomy which permitted complete urine diversion and allowed the urethral tear to heal completely.
Crystal structure of LptH, the periplasmic component of the lipopolysaccharide transport machinery from Pseudomonas aeruginosa
Authors: Bollati Michela , Villa Riccardo , Gourlay Louise J. , Benedet Mattia , Dehò Gianni , Polissi Alessandra , Barbiroli Alberto , Martorana Alessandra M. , Sperandeo Paola , Bolognesi Martino , Nardini Marco 
Published: March 2015

Lipopolysaccharide (LPS) is the main glycolipid present in the outer leaflet of the outer membrane (OM) of Gram‐negative bacteria, where it modulates OM permeability, therefore preventing many toxic compounds from entering the cell. LPS biogenesis is an essential process in Gram‐negative bacteria and thus is an ideal target pathway for the development of novel specific antimicrobials. The lipopolysaccharide transport (Lpt) system is responsible for transporting LPS from the periplasmic surface of the inner membrane, where it is assembled, to the cell surface where it is then inserted in the OM. The Lpt system has been widely studied in Escherichia coli, where it consists of seven essential proteins located in the inner membrane (LptBCFG), in the periplasm (LptA) and in the OM (LptDE). In the present study, we focus our attention on the Pseudomonas aeruginosa PAO1 Lpt system. We identified an LptA orthologue, named LptH, and solved its crystal structure at a resolution of 2.75 Å. Using interspecies complementation and site‐directed mutagenesis of a conserved glycine residue, we demonstrate that P. aeruginosa LptH is the genetic and functional homologue of E. coli LptA, with whom it shares the β‐jellyroll fold identified also in other members of the canonical E. coli Lpt model system. Furthermore, we modeled the N‐terminal β‐jellyroll domain of P. aeruginosa LptD, based on the crystal structure of its homologue from Shigella flexneri, aiming to provide more general insight into the mechanism of LPS binding and transport in P. aeruginosa. Both LptH and LptD may represent new targets for the discovery of next generation antibacterial drugs, targeting specific opportunistic pathogens such as P. aeruginosa.DatabaseCoordinates and structure factors have been deposited in the Protein Data Bank under accession number PDB 4uu4.
Plasticity Region Genes jhp0940, jhp0945, jhp0947, and jhp0949 of Helicobacter pylori in Isolates from Mexican Children
Authors: Romo‐González Carolina , Consuelo‐Sánchez Alejandra , Camorlinga‐Ponce Margarita , Velázquez‐Guadarrama Norma , García‐Zúñiga Magdalena , Burgueño‐Ferreira Juan , Coria‐Jiménez Rafael 
Published: March 2015

AbstractBackgroundThe genes jhp0940, jhp0945, jhp0947, and jhp0949 belong to the plasticity region of the Helicobacter pylori genome. Due to their prevalence in isolates from patients with gastritis, duodenal ulcer, and gastric cancer, they have been proposed as markers of gastroduodenal diseases. These genes are associated with pro‐inflammatory cytokine induction through the NF‐κB activation pathway. Nevertheless, the status of these genes is unknown in H. pylori isolates from children. The aim of the present work was to determine the frequency of the jhp0940‐jhp0945‐jhp0947‐jhp0949 genes in H. pylori isolates from children.Materials and MethodsWe identified the jhp0940, jhp0945, jhp0947, and jhp0949 genes and the relationship of each with the virulence factors cagA, cagPAI, and dupA by PCR in 49 isolates of H. pylori from children. The results were corroborated using dot blots. In addition, we compared the prevalence of these genes with the prevalence in adults.ResultsThe prevalence of jhp0940 (53.1%), jhp0945 (44.9%), jhp0947 (77.6%), and jhp0949 (83.7%) was determined in the isolates from children, as was the prevalence of the virulence genes cagA (63.3%), cagPAI (71.4%), and dupA (37.5%). No association was found between the four genes of the plasticity region and the virulence genes. The presence of the intact locus integrated by jhp0940‐jhp0945‐jhp0947‐jhp0949 was very common among the isolates from children.ConclusionThe genes jhp0940, jhp0947, and jhp0949 were present in more than 50% of the H. pylori isolates, and the joint presence of jhp0940‐jhp0945‐jhp0947‐jhp0949 was very frequent. The frequency of these genes in isolates from children could contribute to the virulence of H. pylori and the evolution of the infection.
Helicobacter pylori Might Induce TGF‐β1‐Mediated EMT by Means of cagE
Authors: Chang Hyun , Kim Nayoung , Park Ji Hyun , Nam Ryoung Hee , Choi Yoon Jeong , Park Seon Mee , Choi Yoon Jin , Yoon Hyuk , Shin Cheol Min , Lee Dong Ho 
Published: March 2015

AbstractBackgroundEpithelial–mesenchymal transition (EMT), in which polarized epithelial cells have mesenchymal cell phenotypes, is thought to be a key process of invasion and metastasis of cancer. Transforming growth factor beta‐1 (TGF‐β1) is known to be carcinogenic and Helicobacter pylori is a predominant carcinogen of gastric cancer. Our study aimed to determine whether TGF‐β1 or H. pylori infection enhances EMT process and cytotoxin‐associated gene E (CagE) is associated with EMT.Materials and MethodsHuman gastric cancer cell AGS and MKN45 were treated with recombinant TGF‐β1 or H. pylori including cagE‐negative (ΔcagE) mutant. Besides the assessment of EMT‐related markers expression levels by means of RT‐qPCR, Western blot, and immunofluorescence assay, the induction of in vitro EMT on gastric cancer cells (AGS and MKN cell lines) was confirmed by wound‐healing assay and invasion assay.ResultsWhen gastric cancer cells were treated with TGF‐β1 or various strains of cagE‐positive H. pylori, EMT‐related marker altered significantly. However, the ΔcagE mutant did not. Wound‐healing assay and invasion assay showed enhanced migration ability of the cells treated with cagE‐positive H. pylori but not in ΔcagE mutant.ConclusionsEMT induction in gastric cancer cells by TGF‐β1 was confirmed. Only infection with cagE‐positive H. pylori upregulated the TGF‐β1‐mediated EMT pathway and consequently promotes EMT. Therefore, H. pylori might induce TGF‐β1‐mediated EMT associated with the cagE.
Intracellular Osteopontin Induced by CagA‐positive Helicobacter pylori Promotes Beta‐catenin Accumulation and Interleukin‐8 Secretion in Gastric Epithelial cells
Authors: Chang Wei‐Lun , Yang Hsiao‐Bai , Cheng Hsiu‐Chi , Yeh Yi‐Chun , Kao Cheng‐Yen , Wu Jiunn‐Jong , Lu Cheng‐Chan , Sheu Bor‐Shyang 
Published: March 2015

AbstractBackgroundOsteopontin, an important immune modulator and oncogenic promoter, is upregulated in H. pylori‐infected gastric mucosa. However, the underlying mechanisms and biological significance are poorly understood. We investigated whether osteopontin was upregulated in gastric epithelial cells by H. pylori and the virulence factors involved. Moreover, cellular component changes caused by osteopontin were also investigated.Materials and MethodsThe gastric epithelial cell line MKN45 was cocultured with wild‐type and mutant H. pylori to analyze osteopontin expression. Beta‐catenin levels in cell lysate and interleukin‐8 levels in supernatant were analyzed. The difference in osteopontin expression levels in both gastric epithelium and plasma was compared between H. pylori‐infected patients and uninfected controls.ResultsH. pylori induced intracellular, but not secretory, osteopontin expression in MKN45 cells. Accordingly, osteopontin expression intensity in gastric epithelium was higher in H. pylori‐infected patients than in controls, but osteopontin levels in plasma were similar between both patient groups. H. pylori virulence factor CagA delivered via the type IV secretion system was essential for intracellular osteopontin upregulation. H. pylori induced β‐catenin accumulation and interleukin‐8 secretion, whereas osteopontin knockdown completely abrogated these effects, in MKN45 cells. TLR2 antagonist abolished iOPN expression induced by H. pylori gastritis strain, but not by H. pylori cancer strain.ConclusionsH. pylori is dependent on CagA translocation via the type IV secretion system to induce intracellular osteopontin expression in gastric epithelial cells. Upregulated intracellular osteopontin may promote gastric carcinogenesis via increased β‐catenin accumulation and interleukin‐8 secretion.