Literature Watch
Point of Care Technologies for the Evaluation and Management of Obstetrics, Neonatal, and Pediatric Critical Care Patients, and for Patients with Disorders of Reproductive Tract and Infertility (R43)
Notice of Intent to Publish a Funding Opportunity Announcement for Exploratory Clinical Trial Grants in Arthritis and Musculoskeletal and Skin Diseases (R21)
Identification of Reproductive-Tract Specific Proteins/Transcripts for the Development of Male and Female Non-Hormonal Contraceptives (R01)
Notice of Intent to Publish a Funding Opportunity Announcement for Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Centers Research Centers (P50)
"systems biology"; +15 new citations
15 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/04/13
PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions.
The logic of transcriptional regulator recruitment architecture at cis-regulatory modules controlling liver functions.
Genome Res. 2017 Apr 11;:
Authors: Dubois-Chevalier J, Dubois V, Dehondt H, Mazrooei P, Mazuy C, Sérandour AA, Gheeraert C, Penderia G, Baugé E, Derudas B, Hennuyer N, Paumelle R, Marot G, Carroll JS, Lupien M, Staels B, Lefebvre P, Eeckhoute J
Abstract
Control of gene transcription relies on concomitant regulation by multiple transcriptional regulators (TR). However, how recruitment of a myriad of TR is orchestrated at cis-regulatory modules (CRM) to account for co-regulation of specific biological pathways is only partially understood. Here, we have used mouse liver CRM involved in regulatory activities of the hepatic TR, NR1H4 (FXR; farnesoid X receptor), as our model system to tackle this question. Using integrative cistromic, epigenomic, transcriptomic and interactomic analyses, we reveal a logical organization where trans-regulatory modules (TRM), which consist of subsets of preferentially and co-ordinately co-recruited TR, assemble into hierarchical combinations at hepatic CRM. Different combinations of TRM add to a core TRM, broadly found across the whole landscape of CRM, to discriminate promoters from enhancers. These combinations also specify distinct sets of CRM differentially organized along the genome and involved in regulation of either housekeeping/cellular maintenance genes or liver-specific functions. In addition to these TRM which we define as obligatory, we show that facultative TRM, such as one comprising core circadian TR, are further recruited to selective subsets of CRM to modulate their activities. TRM transcend TR classification into ubiquitous versus liver-identity factors, as well as TR grouping into functional families. Hence, hierarchical superimpositions of obligatory and facultative TRM bring about independent transcriptional regulatory inputs defining different sets of CRM with logical connection to regulation of specific gene sets and biological pathways. Altogether, our study reveals novel principles of concerted transcriptional regulation by multiple TR at CRM.
PMID: 28400425 [PubMed - as supplied by publisher]
The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans.
The Anti-helminthic Compound Mebendazole Has Multiple Antifungal Effects against Cryptococcus neoformans.
Front Microbiol. 2017;8:535
Authors: Joffe LS, Schneider R, Lopes W, Azevedo R, Staats CC, Kmetzsch L, Schrank A, Del Poeta M, Vainstein MH, Rodrigues ML
Abstract
Cryptococcus neoformans is the most lethal pathogen of the central nervous system. The gold standard treatment of cryptococcosis, a combination of amphotericin B with 5-fluorocytosine, involves broad toxicity, high costs, low efficacy, and limited worldwide availability. Although the need for new antifungals is clear, drug research and development (R&D) is costly and time-consuming. Thus, drug repurposing is an alternative to R&D and to the currently available tools for treating fungal diseases. Here we screened a collection of compounds approved for use in humans seeking for those with anti-cryptococcal activity. We found that benzimidazoles consist of a broad class of chemicals inhibiting C. neoformans growth. Mebendazole and fenbendazole were the most efficient antifungals showing in vitro fungicidal activity. Since previous studies showed that mebendazole reaches the brain in biologically active concentrations, this compound was selected for further studies. Mebendazole showed antifungal activity against phagocytized C. neoformans, affected cryptococcal biofilms profoundly and caused marked morphological alterations in C. neoformans, including reduction of capsular dimensions. Amphotericin B and mebendazole had additive anti-cryptococcal effects. Mebendazole was also active against the C. neoformans sibling species, C. gattii. To further characterize the effects of the drug a random C. gattii mutant library was screened and indicated that the antifungal activity of mebendazole requires previously unknown cryptococcal targets. Our results indicate that mebendazole is as a promising prototype for the future development of anti-cryptococcal drugs.
PMID: 28400768 [PubMed - in process]
Rare primary mucosal melanoma of the larynx.
Rare primary mucosal melanoma of the larynx.
Ear Nose Throat J. 2016 Dec;95(12):E28-E31
Authors: Blanchard A, Nguyen JB, Daroca P, Friedlander P, Lewin E, Vu J, Palacios E
Abstract
Few cases of primary mucosal melanoma of the larynx have been documented in the literature, so only a limited amount of data exists regarding its diagnosis and treatment. The prognosis is poor, as patients often present at a late stage with regional or distant metastases. We describe the case of a 66-year-old man who presented with hoarseness and dysphagia. Laryngoscopy identified a dark discoloration of the supraglottic larynx and incomplete mobility of the right vocal fold; an excisional biopsy confirmed the diagnosis. We discuss the epidemiology, clinical features, diagnosis, interpretation of imaging findings, and management of this rare malignant melanoma.
PMID: 27929604 [PubMed - indexed for MEDLINE]
Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis).
Thoracic involvement in generalised lymphatic anomaly (or lymphangiomatosis).
Eur Respir Rev. 2016 Jun;25(140):170-7
Authors: Luisi F, Torre O, Harari S
Abstract
Generalised lymphatic anomaly (GLA), also known as lymphangiomatosis, is a rare disease caused by congenital abnormalities of lymphatic development. It usually presents in childhood but can also be diagnosed in adults. GLA encompasses a wide spectrum of clinical manifestations ranging from single-organ involvement to generalised disease. Given the rarity of the disease, most of the information regarding it comes from case reports. To date, no clinical trials concerning treatment are available. This review focuses on thoracic GLA and summarises possible diagnostic and therapeutic approaches.
PMID: 27246594 [PubMed - indexed for MEDLINE]
Why we should care about ultra-rare disease.
Why we should care about ultra-rare disease.
Eur Respir Rev. 2016 Jun;25(140):101-3
Authors: Harari S
PMID: 27246584 [PubMed - indexed for MEDLINE]
[Breast implant-associated anaplastic large cell lymphoma. Case report of an undiagnosed form, management and reconstruction (ALCL)].
[Breast implant-associated anaplastic large cell lymphoma. Case report of an undiagnosed form, management and reconstruction (ALCL)].
Ann Chir Plast Esthet. 2016 Jun;61(3):223-30
Authors: Alhamad S, Guerid S, El Fakir EH, Biron P, Tourasse C, Delay E
Abstract
Breast implant-associated anaplastic large cell lymphoma (ALCL) is an extremely rare disease. Is a new nosologic entity with a multifactorial origin and a wide occurrence delay after breast implantation. This article reports the case of a 60 years old patient with a progressive swelling of the right breast after aesthetic breast implants. Diagnostic was delayed because first surgeon was not familiar with the disease. Patient was then referred to us for management. We performed an implant removal and a complete capsulectomy. Pathologic report confirms the diagnostic. After one year and normal ultrasound evaluation, we reconstructed the breast with lipomodeling and mastopexy. Contralateral implant was also removed at time of reconstruction. Vast majority of breast implant-associated ALCL occurs at a time lapse of 11 to 15 years after implant augmentation, with a mean age of 63 years. Among the worldwide 173 cases reported in March 2015, smooth implants seem not to be at risk but 80% of cases were associated with macrotexturized implants. Clinical presentation and diagnostic tools are more and more published but there is to date no recommendation concerning reconstruction delay after implant removal for this pathology. We advise the realization of a breast ultrasound every three months during the first year and wait for a one-year period before reconstruction. In case of aesthetic surgery, mastopexia can be done to allow for glandular shaping. Lipomodeling is an excellent technique to correct the lack of volume due to implant removal. In case of reconstructive setting, implant can be replaced by flap procedure with lipomodeling if needed or lipomodeling alone if recipient site is favorable and patient has enough fat tissue. Contralateral implant should be removed during reconstruction time.
PMID: 27107559 [PubMed - indexed for MEDLINE]
AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling.
AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling.
Oncotarget. 2017 Mar 28;:
Authors: Li J, Guo Y, Duan L, Hu X, Zhang X, Hu J, Huang L, He R, Hu Z, Luo W, Tan T, Huang R, Liao D, Zhu YS, Luo DX
Abstract
BACKGROUND: Aldo-keto reductase family 1, member B10 (AKR1B10), is known to be significantly induced in the cells of various cancers such as breast cancer. However, the mechanisms of AKR1B10 promoting tumorigenesis in breast cancer remain unclear. In the present study, we demonstrated the potential role and mechanism of AKR1B10 in the invasion and migration of breast cancer cells.
METHODS: The expression level of AKR1B10 in breast carcinoma, para-carcinoma and cancer tissues were detected by immunohistochemical evaluation and real-time polymerase chain reaction (RT-PCR), and the correlationships between AKR1B10 expression and clinicopathological features in breast cancer patients (n=131) were investigated. AKR1B10 was ectopically expressed in MCF-7 cells or silenced in BT-20 cells. The roles of AKR1B10 expression in the migration and invasion of MCF-7 cells and BT-20 cells were explored by wound healing assay, transwell migration assay and transwell matrigel invasion assay, and finally the activation level of extracellular signal-regulated kinase 1/2 (EKR1/2) activation and the expression level of matrix metalloproteinase-2 (MMP2) and vimentin in MCF-7 and BT-20 cells were measured by western blot.
RESULTS: We found that AKR1B10 expression was increased in malignant tissues, which was correlated positively with tumor size, lymph node metastasis (p<0.05). MCF-7/AKR1B10 cells displayed a higher ability of migration (43.57±1.04%) compared with MCF-7/vector cells (29.12±1.34%) in wound healing assay, and the migrated cell number of MCF-7/AKR1B10 was more (418.43±9.62) than that of MCF-7/vector (222.43±17.75) in transwell migration assay without matrigel. We furtherly confirmed MCF-7/AKR1B10 cells invaded faster compared with MCF-7/vector cells by transwell matrigel invasion assay. Finally, we found AKR1B10 induced the migration and invasion of MCF-7 and BT-20 cells by activating EKR signaling, which promoted the expressions of MMP2 and vimentin. PD98059, a specific inhibitor of the activation of MEK, blocked the migration and invasion by inhibiting the expression of MMP2 and vimentin.
CONCLUSIONS: AKR1B10 is overexpressed in breast cancer, and promotes the migration and invasion of MCF-7 and BT-20 cells by activating ERK signaling pathway.
PMID: 28402270 [PubMed - as supplied by publisher]
Association of CKIP-1 P21A polymorphism with risk of chronic heart failure in a Chinese population.
Association of CKIP-1 P21A polymorphism with risk of chronic heart failure in a Chinese population.
Oncotarget. 2017 Mar 28;:
Authors: Li MP, Zhang YJ, Hu XL, Zhou JP, Yang YL, Peng LM, Qi H, Yang TL, Chen XP
Abstract
Pathological cardiac hypertrophy is an independent risk factor for chronic heart failure. Casein kinase-2 interacting protein-1 (CKIP-1) can inhibit pathological cardiac hypertrophy. Therefore, we investigated whether CKIP-1 nonsynonymous polymorphism rs2306235 (Pro21Ala) contributes to risk and prognosis of chronic heart failure in a Chinese population. A total of 923 adult patients with chronic heart failure and 1020 age- and gender-matched healthy controls were recruited. CKIP-1 rs2306235 polymorphism was genotyped using PCR-restriction fragment length polymorphism. Additional follow-up data for 140 chronic heart failure patients was evaluated. The rs2306235 G allele was associated with an increased risk of chronic heart failure (OR = 1.38, 95% CI = 1.09-1.75, p = 0.007), especially in patients with hypertension (OR = 1.45, 95% CI = 1.09-1.75, p = 0.006) and coronary heart disease (OR = 1.41, 95% CI = 1.09-1.83, p = 0.010) after adjustment for multiple cardiovascular risk factors. However, rs2306235 polymorphism was not associated with cardiovascular mortality in chronic heart failure (p = 0.875). CKIP-1 rs2306235 polymorphism may be a risk factor for chronic heart failure in a Chinese Han population.
PMID: 28402261 [PubMed - as supplied by publisher]
Association between VEGF-A and VEGFR-2 polymorphisms and response to treatment of neovascular AMD with anti-VEGF agents: a meta-analysis.
Association between VEGF-A and VEGFR-2 polymorphisms and response to treatment of neovascular AMD with anti-VEGF agents: a meta-analysis.
Br J Ophthalmol. 2016 Oct 21;:
Authors: Wu M, Xiong H, Xu Y, Xiong X, Zou H, Zheng M, Wang X, Zhou X
Abstract
AIMS: The purpose of this study is to investigate whether gene polymorphisms of the vascular endothelial growth factor A (VEGF-A) and its receptor (VEGFR-2) have a pharmacogenetics effect on the anti-VEGF treatment for neovascular age-related macular degeneration (nAMD).
METHODS: We carried out a meta-analysis focusing on the relationship between VEGF-related gene polymorphisms and treatment response of nAMD.
RESULTS: For the single nucleotide polymorphisms (SNPs) within VEGF-A and VEGFR-2, anti-VEGF treatment was much more effective in patients with nAMD having rs833061 (CC vs TT:OR=2.222, 95% CI 1.252 to 3.944, p=0.006; CT vs TT: OR=2.537,95% CI 1.478 to 4.356, p=0.001 and CC vs CT+TT: OR=2.362, 95% CI 1.414 to 3.946, p=0.001), particularly for Asians (CC vs TT: OR=2.903, 95% CI 1.150 to 7.330, p=0.024; CT vs TT: OR=3.849, 95% CI 1.522 to 9.733, p=0.004 and CC vs CT+TT: OR=3.339, 95% CI 1.369 to 8.145, p=0.008, respectively). In subgroup analysis, rs833061 was more likely to be a predictor of response to anti-VEGF therapy specifically when ranibizumab (RBZ) only regime was adopted or visual acuity (VA) was taken as the standardised assessment of outcome. No association with response to anti-VEGF treatment was detected for the other eight polymorphisms.
CONCLUSIONS: Pharmacogenetics of VEGF-A polymorphism rs833061 may play a positive role in response to anti-VEGF therapy for nAMD.
PMID: 28400373 [PubMed - as supplied by publisher]
Genetic variation in Kruppel like factor 15 is associated with left ventricular hypertrophy in patients with type 2 diabetes: Discovery and replication cohorts.
Genetic variation in Kruppel like factor 15 is associated with left ventricular hypertrophy in patients with type 2 diabetes: Discovery and replication cohorts.
EBioMedicine. 2017 Mar 30;:
Authors: Patel SK, Wai B, Lang CC, Levin D, Palmer CN, Parry HM, Velkoska E, Harrap SB, Srivastava PM, Burrell LM
Abstract
Left ventricular (LV) hypertrophy (LVH) is a heritable trait that is common in type 2 diabetes and is associated with the development of heart failure. The transcriptional factor Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy in experimental models. This study investigated if KLF15 gene variants were associated with LVH in type 2 diabetes. In stage 1 of a 2-stage approach, patients with type 2 diabetes and no known cardiac disease were prospectively recruited for a transthoracic echocardiographic assessment (Melbourne Diabetes Heart Cohort) (n=318) and genotyping of two KLF15 single nucleotide polymorphisms (SNPs) (rs9838915, rs6796325). In stage 2, the association of KLF15 SNPs with LVH was investigated in the Genetics of Diabetes Audit and Research in Tayside Scotland (Go-DARTS) type 2 diabetes cohort (n=5631). The KLF15 SNP rs9838915 A allele was associated in a dominant manner with LV mass before (P=0.003) and after (P=0.001) adjustment for age, gender, body mass index (BMI) and hypertension, and with adjusted septal (P<0.0001) and posterior (P=0.004) wall thickness. LVH was present in 35% of patients. Over a median follow up of 5.6years, there were 22 (7%) first heart failure hospitalizations. The adjusted risk of heart failure hospitalization was 5.5-fold greater in those with LVH and the rs9838915 A allele compared to those without LVH and the GG genotype (hazard ratio (HR) 5.5 (1.6-18.6), P=0.006). The association of rs9838915 A allele with LVH was replicated in the Go-DARTS cohort. We have identified the KLF15 SNP rs9838915 A allele as a marker of LVH in patients with type 2 diabetes, and replicated these findings in a large independent cohort. Studies are needed to characterize the functional importance of these results, and to determine if the SNP rs9838915 A allele is associated with LVH in other high risk patient cohorts.
PMID: 28400202 [PubMed - as supplied by publisher]
Pharmacogenetic Tests in Psychiatry: From Fear to Failure to Hype.
Pharmacogenetic Tests in Psychiatry: From Fear to Failure to Hype.
J Clin Psychopharmacol. 2016 Aug;36(4):299-304
Authors: de Leon J
PMID: 27269957 [PubMed - indexed for MEDLINE]
Genes affecting warfarin response-interactive or additive?
Genes affecting warfarin response-interactive or additive?
J Clin Pharmacol. 2015 03;55(3):258-60
Authors: Cavallari LH, Duarte JD
Abstract
Genotypes for cytochrome P450 (CYP) 2C9 and vitamin K epoxide reductase complex 1 (VKORC1) contribute significantly to the inter-patient variability in warfarin dose requirements. These genotypes in addition to clinical factors explain approximately 50% of the dose variability in Europeans, but less in other populations. Thus, a large portion of the variability remains unexplained and has been the focus of on-going research. Trials evaluating the clinical utility of genotype-guided warfarin dosing have shown a benefit in Europeans, but not in an ethnically diverse cohort. Identifying and accounting for variants important in non-European populations will likely be necessary before a benefit with genotype-guided dosing will be realized in these populations.
PMID: 25385663 [PubMed - indexed for MEDLINE]
Patient-derived Airway Secretion Dissociation Technique to Isolate and Concentrate Immune cells using Closed-loop Inertial Microfluidics.
Patient-derived Airway Secretion Dissociation Technique to Isolate and Concentrate Immune cells using Closed-loop Inertial Microfluidics.
Anal Chem. 2017 Apr 12;:
Authors: Ryu H, Choi K, Qu Y, Kwon T, Lee JS, Han J
Abstract
Assessment of airway secretion cells, both for research and clinical purposes, is a highly desired goal in patients with acute and chronic pulmonary diseases. However, lack of proper cell isolation and enrichment techniques hinder downstream evaluation and characterization of cells found in airway secretions. Here, we demonstrate a novel enrichment method to capture immune-related cells from clinical airway secretions using closed-loop separation of spiral inertial microfluidics (C-sep). By recirculating the output focusing stream back to the input reservoir, and running continuously with a high flow processing rate, one can achieve optimal concentration, recovery and purity of airway immune cells from a large volume of diluent, which was not readily possible in the single-pass operation. Our method reproducibly recovers 94.0% of polymorphonuclear leukocytes (PMNs), with up to 105 PMNs in clear diluted buffer from 50 µl of airway secretions obtained from mechanically ventilated patients. We show that C-sep isolated PMNs show higher neutrophil elastase (NE) release following activation by phorbol 12-myristate 13-acetate (PMA) than cells isolated by conventional mucolytic method. By capturing cells without chemically disrupting their potential function, our method is expected to expand the possibility of clinical in-vitro cell based biological assays for various pulmonary diseases such as acute respiratory distress syndrome, pneumonia, cystic fibrosis and bronchiectasis.
PMID: 28402103 [PubMed - as supplied by publisher]
SANI-Severe Asthma Network in Italy: a way forward to monitor severe asthma.
SANI-Severe Asthma Network in Italy: a way forward to monitor severe asthma.
Clin Mol Allergy. 2017;15:9
Authors: Senna G, Guerriero M, Paggiaro PL, Blasi F, Caminati M, Heffler E, Latorre M, Canonica GW, SANI
Abstract
Even if severe asthma (SA) accounts for 5-10% of all cases of the disease, it is currently a crucial unmet need, owing its difficult clinical management and its high social costs. For this reason several networks, focused on SA have been organized in some countries, in order to select these patients, to recognize their clinical features, to evaluate their adherence, to classify their biological/clinical phenotypes, to identify their eligibility to the new biologic therapies and to quantify the costs of the disease. Aim of the present paper is to describe the ongoing Italian Severe Asthma Network (SANI). Up today 49 centres have been selected, widespread on the national territory. Sharing the same diagnostic protocol, data regarding patients with SA will be collected and processed in a web platform. After their recruitment, SA patients will be followed in the long term in order to investigate the natural history of the disease. Besides clinical data, the cost/benefit evaluation of the new biologics will be verified as well as the search of peculiar biomarker(s) of the disease.
PMID: 28400707 [PubMed - in process]
Within-Host Evolution of Burkholderia pseudomallei during Chronic Infection of Seven Australasian Cystic Fibrosis Patients.
Within-Host Evolution of Burkholderia pseudomallei during Chronic Infection of Seven Australasian Cystic Fibrosis Patients.
MBio. 2017 Apr 11;8(2):
Authors: Viberg LT, Sarovich DS, Kidd TJ, Geake JB, Bell SC, Currie BJ, Price EP
Abstract
Cystic fibrosis (CF) is a genetic disorder characterized by progressive lung function decline. CF patients are at an increased risk of respiratory infections, including those by the environmental bacterium Burkholderia pseudomallei, the causative agent of melioidosis. Here, we compared the genomes of B. pseudomallei isolates collected between ~4 and 55 months apart from seven chronically infected CF patients. Overall, the B. pseudomallei strains showed evolutionary patterns similar to those of other chronic infections, including emergence of antibiotic resistance, genome reduction, and deleterious mutations in genes involved in virulence, metabolism, environmental survival, and cell wall components. We documented the first reported B. pseudomallei hypermutators, which were likely caused by defective MutS. Further, our study identified both known and novel molecular mechanisms conferring resistance to three of the five clinically important antibiotics for melioidosis treatment. Our report highlights the exquisite adaptability of microorganisms to long-term persistence in their environment and the ongoing challenges of antibiotic treatment in eradicating pathogens in the CF lung. Convergent evolution with other CF pathogens hints at a degree of predictability in bacterial evolution in the CF lung and potential targeted eradication of chronic CF infections in the future.IMPORTANCEBurkholderia pseudomallei, the causative agent of melioidosis, is an environmental opportunistic bacterium that typically infects immunocompromised people and those with certain risk factors such as cystic fibrosis (CF). Patients with CF tend to develop chronic melioidosis infections, for reasons that are not well understood. This report is the first to describe B. pseudomallei evolution within the CF lung during chronic infection. We show that the pathways by which B. pseudomallei adapts to the CF lung are similar to those seen in better-studied CF pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia complex species. Adaptations include the accumulation of antibiotic resistance, loss of nonessential genes, metabolic alterations, and virulence factor attenuation. Known and novel mechanisms of resistance to three of the five antibiotics used in melioidosis treatment were identified. Similar pathways of evolution in CF pathogens, including B. pseudomallei, provide exciting avenues for more-targeted treatment of chronic, recalcitrant infections.
PMID: 28400528 [PubMed - in process]
Pages
