bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative analysis of nasal transcripts reveals potential biomarkers for Parkinson’s disease
Authors: Kim Hyojung , Kang Seok-Jae , Jo Young Mi , Kim Min Song , Lee Yunjong , Cho Seok-Hyun , Kim Hee-Tae 
Published: July 2019

AbstractPatients with Parkinson’s disease (PD) oftentimes develop olfactory dysfunction in their early stages, converting the nasal environment into a useful source of potential biomarkers. Here we determined the possible application of nasal fluid cells for PD biomarker identification. Thirty PD patients and 13 age-matched healthy controls were enrolled in this study. Messenger RNA levels of selected PD-related genes were monitored through real-time quantitative PCR. Target gene transcripts can be efficiently amplified from the cDNA library from human nasal fluid cell pellets. And subsequent analysis showed both a marked downregulation of parkin transcripts and an upregulation of AIMP2 in PD patients when compared to controls (cutoff value = 1.753 for with 84.2% sensitivity and 84.6% specificity; 0.359 for parkin with 76.7% sensitivity and 76.9 specificity). Moreover, alteration pattern of parkin and AIMP2 in PD was distinct from another neurodegenerative disease, multiple system atrophy. Analysis in both the early and late stages of PD cases reported that parkin levels inversely correlated with PD stages. Our results validate the practical value of easily accessible nasal fluid cells and the utility of both AIMP2 and parkin as potential biomarkers for PD diagnosis.
Water uptake by indoor surface films
Authors: Schwartz-Narbonne Heather , Donaldson D. James 
Published: July 2019

AbstractIndoor surfaces provide a plentiful and varied substrate on which multiphase reactions can occur which can be important to the chemical makeup of the indoor environment. Here, we attempt to characterise real indoor surface films via water uptake behaviour and ionic composition. We show that water uptake by indoor films is different than that observed outdoors, and can vary according to room use, building characteristics, and season. Similarly, preliminary investigation into the ionic composition of the films showed that they varied according to the room in which they were collected. This study highlights the importance of different types of soiling to multiphase chemistry, especially those reactions controlled by relative humidity or adsorbed water.
Structural basis for broad substrate specificity of UDP-glucose 4-epimerase in the human milk oligosaccharide catabolic pathway of Bifidobacterium longum
Authors: Nam Young-Woo , Nishimoto Mamoru , Arakawa Takatoshi , Kitaoka Motomitsu , Fushinobu Shinya 
Published: July 2019

AbstractInfant gut-associated bifidobacteria has a metabolic pathway that specifically utilizes lacto-N-biose I (Gal-β1,3-GlcNAc) and galacto-N-biose (Gal-β1,3-GalNAc) from human milk and mucin glycans. UDP-glucose 4-epimerase (GalE) from Bifidobacterium longum (bGalE) catalyzes epimerization reactions of UDP-Gal into UDP-Glc and UDP-GalNAc into UDP-GlcNAc with the same level of activity that is required to send galacto-hexoses into glycolysis. Here, we determined the crystal structures of bGalE in three ternary complex forms: NAD+/UDP, NAD+/UDP-GlcNAc, and NAD+/UDP-Glc. The broad specificity of bGalE was explained by structural features of the binding pocket for the N-acetyl or C2 hydroxy group of the substrate. Asn200 is located in a pocket of the C2 group, and its side chain adopts different conformations in the complex structures with UDP-Glc and UDP-GlcNAc. On the other side, Cys299 forms a large pocket for the C5 sugar ring atom. The flexible C2 pocket and the large C5 pocket of bGalE are suitable for accommodating both the hydroxy and N-acetyl groups of the substrate during sugar ring rotation in the catalytic cycle. The substrate specificity and active site structure of bGalE were distinct from those of Esherichia coli GalE but similar to those of human GalE.
Differential homotypic and heterotypic interactions of antigen 43 (Ag43) variants in autotransporter-mediated bacterial autoaggregation
Authors: Ageorges Valentin , Schiavone Marion , Jubelin Grégory , Caccia Nelly , Ruiz Philippe , Chafsey Ingrid , Bailly Xavier , Dague Etienne , Leroy Sabine , Paxman Jason , Heras Begoña , Chaucheyras-Durand Frédérique , Rossiter Amanda E. , Henderson Ian R. , Desvaux Mickaël 
Published: July 2019

AbstractAntigen 43 (Ag43) is a cell-surface exposed protein of Escherichia coli secreted by the Type V, subtype a, secretion system (T5aSS) and belonging to the family of self-associating autotransporters (SAATs). These modular proteins, comprising a cleavable N-terminal signal peptide, a surface-exposed central passenger and an outer membrane C-terminal translocator, self-recognise in a Velcro-like handshake mechanism. A phylogenetic network analysis focusing on the passenger revealed for the first time that they actually distribute into four distinct classes, namely C1, C2, C3 and C4. Structural alignment and modelling analyses demonstrated these classes arose from shuffling of two different subdomains within the Ag43 passengers. Functional analyses revealed that homotypic interactions occur for all Ag43 classes but significant differences in the sedimentation kinetics and aggregation state were present when Ag43C3 was expressed. In contrast, heterotypic interaction occurred in a very limited number of cases. Single cell-force spectroscopy demonstrated the importance of specific as well as nonspecific interactions in mediating Ag43-Ag43 recognition. We propose that structural differences in the subdomains of the Ag43 classes account for different autoaggregation dynamics and propensities to co-interact.
A Tri-fusion Reporter Mouse Reveals Tissue-Specific FGF1B Promoter Activity in vivo
Authors: Liu Shan-Wen , Hsu Ching-Han , Chen Mei-Ru , Chiu Ing-Ming , Lin Kurt M. 
Published: July 2019

AbstractTransgenic mice harboring imaging reporters take full advantage of imaging technologies in studies using living mice. Here, we established a tri-fusion multimodal reporter gene containing fragments from firefly luciferase, enhanced green fluorescent protein, and herpes simplex virus type 1 thymidine kinase and generated tri-fusion reporter Tg mice. Fibroblast growth factor type 1 (FGF1), a multifunctional mitogen to a wide range of tissues, regulates proliferation of neural stem cells of the brain, where FGF1 expression is initiated through activation of the FGF1B (F1B) promoter. The reporter mouse under the control of the human F1B promoter enables visualization in vivo where F1B activity is elevated, including tissues not only in the brain but also in the nasopharynx, skull, spine, and testes, particularly in Leydig cells. Treating Tg mice with the alkylating agent busulfan, which is known to eradicate Leydig cells and disrupt spermatogenesis in mice, eliminated the reporter signals. Restoring Leydig cells recovered reporter expression, indicating that the reporter can be used as a surrogate marker for Leydig cells. The F1B tri-fusion reporter mouse model can be utilized in longitudinal monitoring of the health status of the male reproductive system, such as in studies exploring the toxicity of chemicals to spermatogenesis.
Potential population level impact on tuberculosis incidence of using an mRNA expression signature correlate-of-risk test to target tuberculosis preventive therapy
Authors: Sumner Tom , Scriba Thomas J. , Penn-Nicholson Adam , Hatherill Mark , White Richard G. 
Published: July 2019

AbstractAchieving the WHO End-Tuberculosis (TB) targets requires approaches to prevent progression to TB among individuals with Mycobacterium tuberculosis (M.tb) infection. Effective preventive therapy (PT) exists, but current tests have low specificity for identifying who, among those infected, is at risk of developing TB. Using mathematical models, we assessed the potential population-level impact on TB incidence of using a new more specific mRNA expression signature (COR) to target PT among HIV-uninfected adults in South Africa. We compared the results to the use of the existing interferon-γ release assay (IGRA). With annual screening coverage of 30% COR-targeted PT could reduce TB incidence in 2035 by 20% (95% CI 15–27). With the same coverage, IGRA-targeted PT could reduce TB incidence by 39% (31–48) but would require greater use of PT resulting in a higher number needed to treat per TB case averted (COR: 49 (29–77); IGRA: 84 (59–123)). The relative differences between COR and IGRA were not sensitive to screening coverage. COR-targeted PT could contribute to reducing total TB burden in high incidence countries like South Africa by allowing more efficient targeting of treatment. To maximise impact, COR-like tests may be best utilised in the highest burden regions, or sub-populations, within these countries.
Association between interleukin-21 gene rs6822844 polymorphism and rheumatoid arthritis susceptibility
Authors: Ren Kewei , Tang Jilei , Nong Luming , Shen Nan , Li Xiaolong 
Published: July 2019

Abstract
Controversial results concerning the association between a polymorphism rs6822844 in the interleukin (IL) 21 (IL-21) gene and rheumatoid arthritis (RA) have existed. A meta-analysis to confirm above relationships is necessary to be performed immediately. We conducted a search in the PubMed database, covering all papers published up to 20 October 2018. Overall, six case–control studies with 3244 cases and 3431 healthy controls were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed with both Egger’s and Begg’s tests. After calculation, we found that IL-21 rs6822844 polymorphism could decrease RA risk in overall genetic models (allelic contrast: OR = 0.77, 95% CI = 0.62–0.97, P=0.024; TG versus GG: OR = 0.68, 95% CI = 0.50–0.92, P=0.013, and dominant genetic model: OR = 0.72, 95% CI = 0.55–0.94, P=0.016). Similarly, stratified analysis by race, source of control, significantly decreased association was found in Asians, Caucasians and hospital-based (HB) control source. Finally, in the subgroup analysis of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status, poorly decreased relationship was detected between IL-21 rs6822844 polymorphism and RF negative and ACPA positive RA risk, respectively. No obvious evidence of publication bias was detected in overall analysis. In summary, our study indicated that IL-21 rs6822844 polymorphism was significantly associated with decreased RA susceptibility.
Long noncoding RNA-MEG3 contributes to myocardial ischemia–reperfusion injury through suppression of miR-7-5p expression
Authors: Zou Liyuan , Ma Xiaokun , Lin Shuo , Wu Bingyuan , Chen Yang , Peng Chaoquan 
Published: July 2019

Abstract
Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) plays an important role in protection of ischemia–reperfusion (I/R) injury in brain and liver. However, role of MEG3 in myocardial I/R injury remains unclear. Here, the role of MEG3 in protection of myocardial I/R injury and its association with microRNA-7-5p (miR-7-5p) was investigated using rat cardiac I/R model and myocardial I/R cell model. Our results showed that MEG3 was significantly up-regulated and miR-7-5p was significantly down-regulated after I/R. Following I/R, the levels of intact PARP and intact caspase-3 were reduced, while the cleaved fragments of PARP and caspase-3 were increased. TUNEL assay showed an increase in cardiomyocyte apoptosis after I/R. The levels of I/R-induced creatine kinase (CK) and lactate dehydrogenase (LDH) were inhibited by knockdown of MEG3 (siMEG3). SiMEG3 increased cell proliferation and inhibited cell apoptosis after I/R. In contrast, overexpression of MEG3 increased the I/R-induced CK and LDH activities and cell apoptosis and decreased cell proliferation. The dual-luciferase reporter system showed a direct binding of MEG3 to miR-7-5p. The level of miR-7-5p was negatively associated with the change in levels of MEG3 in H9c2 cells. The levels of intact RARP1 and caspase-3 were significantly increased by knockdown of MEG3. Co-transfection of miR-7-5p inhibitor with siMEG3 activates CK and LDH, significantly decreased cell proliferation, increased cell apoptosis, and decreased intact poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3. In summary, down-regulation of MEG3 protects myocardial cells against I/R-induced apoptosis through miR-7-5p/PARP1 pathway, which might provide a new therapeutic target for treatment of myocardial I/R injury.
Genetic polymorphism and transcriptional regulation of CREBBP gene in patient with diffuse large B-cell lymphoma
Authors: Zhao Haifeng , Kan Yutian , Wang Xinyuan , Chen Leiyuan , Ge Peng , Qian Zhengzi 
Published: July 2019

Abstract
In the present study, we aim to examine the relationship between genetic polymorphism and transcriptional expression of cyclic AMP response element binding protein (CREBBP) and the risk of diffuse large B-cell lymphoma (DLBCL). Two hundred and fifty healthy individuals and 248 DLBCL patients participated in the present study. The CREBBP rs3025684 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mRNA expression of CREBBP was tested by the real-time quantitative PCR (RT-qPCR). The allele A frequency of CREBBP rs3025684 in DLBCL patients was obviously higher than that of controls (P=0.01). No significant difference was detected between CREBBP rs3025684 polymorphism and clinical characteristics of DLBCL patients when subgrouped according to different parameters. The results demonstrated that the allele A of CREBBP rs3025684 increased the susceptibility to DLBCL (P=0.004), with a worse overall survival (OS) rate (P=0.002), a worse progression-free survival (PFS) rate (P=0.033) and poor prognosis (P=0.003) in DLCBL patients. Furthermore, the expression of CREBBP mRNA was considerably decreased in DLBCL patients as compared with controls (P&lt;0.001), and the expression in patients with GG genotype was up-regulated in comparison with patients with GA and AA genotype (P=0.016 and P=0.001, respectively). However, no statistical differences were found in OS (P=0.201) and PFS (P=0.353) between the lower CREBBP mRNA level subgroup and higher CREBBP mRNA level subgroup. These data suggested that the CREBBP gene may be an important prognostic factor in DLBCL patients and perform an essential function in the development of DLBCL.
Endoscopic Endonasal Reconstruction of High-Flow Cerebrospinal Fluid Leak with Fascia Lata “Button” Graft and Nasoseptal Flap: Surgical Technique and Case Series
Authors: Khatiwala Roshni V. , Shastri Karthik S. , Peris-Celda Maria , Kenning Tyler , Pinheiro-Neto Carlos D. 
Published: July 2019

AbstractBackground The endoscopic endonasal approach (EEA) has become increasingly used for resection of skull base tumors in the sellar and suprasellar regions. A nasoseptal flap (NSF) is routinely used for anterior skull base reconstruction; however, there are numerous additional allografts and autografts being used in conjunction with the NSF. The role of perioperative cerebrospinal fluid (CSF) diversion is also unclear.Objective This study was aimed to analyze success of high-flow CSF leak repair during EEA procedures without use of CSF diversion through lumbar drainage.Methods A retrospective chart review of patients who had intraoperative high-flow CSF leak during EEA procedures at our institution between January 2013 and December 2017 was performed. CSF leaks were repaired with use of a fascia lata button graft and nasoseptal flap, without use of perioperative lumbar drains.Results A total of 38 patients were identified (10 male, 28 female). Patient BMIs ranged from 19.7 to 49 kg/m2 (median = 31 kg/m2), with 18 patients meeting criteria for obesity (BMI > 30 kg/m2) and 12 patients overweight (25 kg/m2 < BMI < 29.9 kg/m2). There was no incidence of postoperative CSF leak.Conclusion In our experience, the nasoseptal flap used in conjunction with the fascia lata button graft is a safe, effective and robust combination for cranial base reconstruction with high-flow intraoperative CSF leaks, without need for lumbar drains.
Patient Outcomes after Reirradiation of Small Skull Base Tumors using Stereotactic Body Radiotherapy, Intensity Modulated Radiotherapy, or Proton Therapy
Authors: Ng Sweet Ping , Wang He , Pollard Courtney , Nguyen Theresa , Bahig Houda , Fuller Clifton D. , Gunn G. Brandon , Garden Adam S. , Reddy Jay P. , Morrison William H. , Shah Shalin , Rosenthal David I. , Frank Steven J. , Guha-Thakurta Nandita , Ferrarotto Renata , Hanna Ehab Y. , Su Shirley Y. , Phan Jack 
Published: July 2019

Abstract
Purpose The aim of this study was to evaluate outcomes of patients who received reirradiation for small skull base tumors utilizing either intensity modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and proton radiotherapy (PRT).
Methods Patients who received IMRT, SBRT or PRT reirradiation for recurrent or new small skull base tumors (< 60 cc) between April 2000 and July 2016 were identified. Those with < 3 months follow-up were excluded. Clinical outcomes and treatment toxicity were assessed. The Kaplan–Meier method was used to estimate the local control (LC), regional control (RC), distant control (DC), progression free survival (PFS), and overall survival (OS).
Results Of the 75 patients eligible, 30 (40%) received SBRT, 30 (40%) received IMRT, and 15 (20%) received PRT. The median retreatment volume was 28 cc. The median reirradiation dose was 66 Gy in 33 fractions for IMRT/PRT, and 45 Gy in 5 fractions for SBRT. The median time to reirradiation was 41 months. With a median follow-up of 24 months, the LC, RC, DC, PFS, and OS rates were 84%, 79%, 82%, 60%, and 87% at 1 year, and 75%, 72%, 80%, 49%, and 74% at 2 years. There was no difference in OS between radiation modalities. The 1- and 2-year late Grade 3 toxicity rates were 3% and 11% respectively..
Conclusions Reirradiation of small skull base tumors utilizing IMRT, PRT, or SBRT provided good local tumor control and low rates of Grade 3 late toxicity. A prospective clinical trial is needed to guide selection of radiation treatment modalities.
Voluntary Wheel Running Attenuates Salt-Induced Vascular Stiffness Independent of Blood Pressure
Authors: Guers John J , Farquhar William B , Edwards David G , Lennon Shannon L 
Published: July 2019

Abstract

BACKGROUND
Excess dietary salt can lead to the development of arterial stiffness and high blood pressure (BP). Regular physical activity can protect against arterial stiffening and lower BP. Less is known regarding the role of exercise on the vasculature independent of BP under high salt (HS) conditions. The aim of the study was to determine whether wheel running protects against the development of dietary salt-induced arterial stiffness independent of BP.

METHODS
Rats were maintained on either normal salt (NS; 0.49% NaCl) or HS (4.0% NaCl) diet for 6 weeks and further divided into a voluntary wheel running (NS-VWR, HS-VWR) or cage control group (NS, HS). Carotid–femoral pulse wave velocity (PWV) was measured using applanation tonometry at baseline (BSL) and 6 weeks.

RESULTS
BP was measured weekly and remained unchanged among groups throughout the 6 weeks (P &gt; 0.05). PWV was elevated at 6 weeks in HS compared to baseline (HS-BSL, 3.27 ± 0.17 vs. HS-6 week, 4.13 ± 0.26 m/s; P &lt; 0.05) and was lower at 6 weeks in both VWR groups (NS-VWR, 2.98 ± 0.29, HS-VWR, 3.11 ± 0.23 m/s) when compared to HS at 6 weeks (P &lt; 0.05). This was supported by a significant increase in aortic collagen I in the HS group alone and transforming growth factor beta (TGF-β) was greater in the HS group compared to both NS groups (P &lt; 0.05). Wheel running resulted in a greater aortic phosphorylated eNOS and SOD-2 in HS-WVR (P &lt; 0.05) compared to HS.

CONCLUSIONS
These data suggest that VWR may protect against collagen accumulation through a TGF-β-mediated pathway by improving nitric oxide bioavailability and redox balance in rats.
Myocardial MMP-2 contributes to SERCA2a proteolysis during cardiac ischaemia–reperfusion injury
Authors: Roczkowsky Andrej , Chan Brandon Y H , Lee Tim Y T , Mahmud Zabed , Hartley Bridgette , Julien Olivier , Armanious Gareth , Young Howard S , Schulz Richard 
Published: July 2019

Abstract

Aims
Matrix metalloproteinase-2 (MMP-2) is a zinc-dependent protease which contributes to cardiac contractile dysfunction when activated during myocardial ischaemia–reperfusion (IR) injury. MMP-2 is localized to several subcellular sites inside cardiac myocytes; however, its role in the sarcoplasmic reticulum (SR) is unknown. The Ca2+ ATPase SERCA2a, which pumps cytosolic Ca2+ into the SR to facilitate muscle relaxation, is degraded in cardiac IR injury; however, the protease responsible for this is unclear. We hypothesized that MMP-2 contributes to cardiac contractile dysfunction by proteolyzing SERCA2a, thereby impairing its activity in IR injury.

Methods and results
Isolated rat hearts were subjected to IR injury in the presence or absence of the selective MMP inhibitor ARP-100, or perfused aerobically as a control. Inhibition of MMP activity with ARP-100 significantly improved the recovery of cardiac mechanical function and prevented the increase of a 70 kDa SERCA2a degradation fragment following IR injury, although 110 kDa SERCA2a and phospholamban levels appeared unchanged. Electrophoresis of IR heart samples followed by LC-MS/MS confirmed the presence of a SERCA2a fragment of ∼70 kDa. MMP-2 activity co-purified with SR-enriched microsomes prepared from the isolated rat hearts. Endogenous SERCA2a in SR-enriched microsomes was proteolyzed to ∼70 kDa products when incubated in vitro with exogenous MMP-2. MMP-2 also cleaved purified porcine SERCA2a in vitro. SERCA activity in SR-enriched microsomes was decreased by IR injury; however, this was not prevented with ARP-100.

Conclusion
This study shows that MMP-2 activity is found in SR-enriched microsomes from heart muscle and that SERCA2a is proteolyzed by MMP-2. The cardioprotective actions of MMP inhibition in myocardial IR injury may include the prevention of SERCA2a degradation.
Aging With Vision Loss: A Framework for Assessing the Impact of Visual Impairment on Older Adults
Authors: Swenor Bonnielin K , Lee Moon J , Varadaraj Varshini , Whitson Heather E , Ramulu Pradeep Y 
Published: July 2019

Abstract
There is limited research examining the impact of visual impairment (VI) on older adults while considering the complexities of aging, leaving gaps in our understanding of how health consequences of VI might be averted. We created a framework integrating concepts from disability, geriatrics, and ophthalmology that conceptualizes how VI challenges successful aging. Here, VI influences multiple functional domains, and increases the risk of negative health outcomes. This model acknowledges that common causes, such as risk factors that affect eyes and other systems simultaneously, may also drive the relationship between VI and health outcomes. Finally, the model highlights how the impact of VI on aging outcomes can be addressed at multiple intervention points.