bluuebunny/crossref_metadata_2025_split huggingface dataset:
The involvement of thrombin in the pathogenesis of glioblastoma
Authors: Krenzlin Harald , Lorenz Viola , Alessandri Beat 
Published: March 2017

AbstractProthrombin and its active derivative thrombin are key members of the coagulation system. The only site of extra‐hepatic thrombin expression is the central nervous system (CNS), where it is involved in brain development, protection, and regeneration. Thrombin affects various degenerative and ischemic CNS diseases like Alzheimer's, multiple sclerosis, cerebral ischemia, and hemorrhage in a dose dependent manner. Additionally, the association of thrombin with various malignancies has recently become evident. Thrombin facilitates the interaction between tumor cells with platelets, endothelial cells, and the adhesion to matrix proteins in various tumor types. Consequently, thrombin enables tumor cell seeding and metastasis, resulting in increased tumor cell growth and angiogenesis. Despite the exceptional position of thrombin in the CNS, its involvement in brain tumor course and development has so far been largely neglected. Over the last decade, several studies found a detrimental effect of thrombin in the most devastating of all primary brain tumors, glioblastomas (GBM). This review highlights the current knowledge on the involvement of thrombin in the pathophysiology and clinical course of GBMs. © 2017 Wiley Periodicals, Inc.
Opportunities for pharmacists to optimise quality use of medicines in a Sri Lankan hospital: an observational, prospective, cohort study
Authors: Perera Dhineli Michelle Patricia , Coombes Judith Ann , Shanika Lelwala Guruge Thushani , Dawson Andrew , Lynch Catherine , Mohamed Fahim , De Silva Hithanadura Asita , Jayamanne Shaluka Francis , Peters Nimali Buddhima , Myers Brooke , Coombes Ian David 
Published: March 2017

AbstractBackgroundQuality use of medicines (QUM) has been identified as a priority in Sri Lanka.AimTo identify opportunities to optimise QUM, and evaluate medication appropriateness and medication information exchanged with patients and carers on discharge in a Sri Lankan tertiary care hospital.MethodsAn observational, prospective, cohort study of patients systematically sampled from two medical wards. A research pharmacist determined their pre‐admission medication regimen via interview at time of discharge. Issues of poor adherence and discrepancies between the pre‐ and post‐admission medication regimens were recorded. Drug‐related problems were categorised into opportunities to optimise drug therapy. The appropriateness of discharge medications was evaluated using a validated tool. The patient or carer was interviewed after discharge regarding the quality of medicine information exchanged in hospital.ResultsThe 578 recruited patients were taking 1756 medications prior to admission, and 657 (37.4%) of these medications were not continued during admission. Opportunities to optimise drug therapy were identified on 1496 occasions during admission (median, 2.0 opportunities/patient), 215 opportunities, (14.4%) were resolved spontaneously by the medical team prior to discharge. The median score for appropriateness of medications on discharge was 1.5 per patient (interquartile range, 0.0–3.5). Of 427 patients surveyed after discharge, 52% recalled being asked about their medications on admission to hospital, 75% about previous adverse medication reactions and 39% recalled being informed about changes to their medications on discharge.ConclusionSignificant opportunities exist for pharmacists to enhance quality use of medicines for patients in the current hospital‐based healthcare system in Sri Lanka.
Biometric Differentiation of Wild Philippine Pigs from Introduced Sus scrofa in Modern and Archaeological Assemblages
Authors: Ingicco T. , Piper P. J. , Amano N. , Paz V. J. , Pawlik A. F. 
Published: March 2017

AbstractIn many parts of Eurasia, the Middle East and Southeast Asia where native wild suids occur, it is notoriously difficult to differentiate these from introduced domestic pigs in the prehistoric archaeological record. Yet, correct identification of the initial appearance or introduction of domestic pigs (Sus scrofa) is essential for determining the timing for the transition from purely hunting to the adoption of managed animal populations within different regions across the globe. In a recent review of techniques used by zooarchaeologists to distinguish between domestic and wild pig populations, the analysts concluded that the most reliable method was metrical analyses, when the data produce a clear two‐population pattern, one domestic, the other wild. In this study, we demonstrate how linear metrics are an effective tool, albeit at different levels of confidence, for differentiating the native and endemic species of Philippine pig from S. scrofa, both within modern contemporary assemblages, and the archaeological record. Copyright © 2017 John Wiley & Sons, Ltd.
Taphonomy and Paleoichnology of Olduvai Hominid 1 (OH1), Tanzania
Authors: Matu M. , Crevecoeur I. , Huchet J.‐B. 
Published: March 2017

AbstractThis paper presents a case study of the Late Pleistocene skeletal remains of Olduvai Hominid 1, which were unearthed in Tanzania. Excavated in 1913, this fossil shows severe damage due to subterranean termites (Insecta: Isoptera). By combining methods to quantify and locate traces on the skeleton with the study of the different taphonomic processes that altered the deposit, we demonstrate a non‐arbitrary pattern of termite alteration of the skeletal remains. These results shed new light on the possibility to reconstruct the original position of a skeleton in a deposit and the potential to infer the space of decomposition and past funerary practices. Copyright © 2017 John Wiley & Sons, Ltd.
Influence of ABCC2, CYP2C8, and CYP2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients
Authors: Genvigir Fabiana D. V. , Nishikawa Alvaro M. , Felipe Claudia R. , Tedesco‐Silva Helio , Oliveira Nagilla , Salazar Antony B. C. , Medina‐Pestana Jose O. , Doi Sonia Q. , Hirata Mario H. , Hirata Rosario D. C. 
Published: March 2017

Study ObjectiveTo investigate the influence of single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP2C8, CYP2J2, and UGT2B7) and transporters (ABCC2 and ABCG2) on dose and dose‐adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients.DesignPharmacogenetic analysis of patients enrolled in a previously published study.PatientsOne hundred forty‐eight adult kidney transplant recipients treated with tacrolimus, enteric‐coated mycophenolate sodium, and prednisone for 90 days posttransplantation.Measurements and Main ResultsABCC2 c.−24C>T and c.3972C>T, ABCG2 c.421C>A, CYP2C8*3, CYP2J2 c.−76G>T, and UGT2B7 c.372A>G SNPs were determined by real‐time polymerase chain reaction. The CYP3A5*3C SNP data were used to eliminate the confounding effect of this variant on the results. ABCC2 c.3972T allele carriers showed higher tacrolimus C:D values than did carriers of the c.3972CC genotype. The CYP2C8*3 variant was also associated with slightly higher tacrolimus C:D values and higher estimated glomerular filtration rate but only in CYP3A5‐nonexpressing patients (CYP3A5*3C/*3C carriers). None of the SNPs were associated with mycophenolate sodium dose or episodes of biopsy‐confirmed acute rejection or delayed graft function. The CYP2J2 c.−76T allele was associated with increased risk for treatment‐induced nausea and/or vomiting (OR: 5.30, 95% confidence interval 1.49‐18.79, p<0.05).ConclusionThe ABCC2 c.3972C >T polymorphism affected tacrolimus C:D in Brazilian kidney transplant recipients. Further, CYP2C8*3 and CYP2J2 c.−76G>T SNPs influenced the renal function of these patients and the occurrence of adverse events during treatment with tacrolimus and mycophenolate sodium.
Cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy: A longitudinal cohort study
Authors: Libert Yves , Borghgraef Cindy , Beguin Yves , Delvaux Nicole , Devos Martine , Doyen Chantal , Dubruille Stéphanie , Etienne Anne‐Marie , Liénard Aurore , Merckaert Isabelle , Reynaert Christine , Slachmuylder Jean‐Louis , Straetmans Nicole , Van Den Neste Eric , Bron Dominique , Razavi Darius 
Published: March 2017

AbstractObjectiveDespite the well‐known negative impacts of cancer and anticancer therapies on cognitive performance, little is known about the cognitive compensatory processes of older patients with cancer. This study was designed to investigate the cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy.MethodsWe assessed 89 consecutive patients (age ≥ 65 y) without severe cognitive impairment and 89 age‐, sex‐, and education level‐matched healthy controls. Cognitive compensatory processes were investigated by (1) comparing cognitive performance of patients and healthy controls in novel (first exposure to cognitive tasks) and non‐novel (second exposure to the same cognitive tasks) contexts, and (2) assessing psychological factors that may facilitate or inhibit cognitive performance, such as motivation, psychological distress, and perceived cognitive performance. We assessed cognitive performance with the Trail‐Making, Digit Span and FCSR‐IR tests, psychological distress with the Hospital Anxiety and Depression Scale, and perceived cognitive performance with the FACT‐Cog questionnaire.ResultsIn novel and non‐novel contexts, average cognitive performances of healthy controls were higher than those of patients and were associated with motivation. Cognitive performance of patients was not associated with investigated psychological factors in the novel context but was associated with motivation and psychological distress in the non‐novel context.ConclusionsOlder, clinically fit patients with hematologic malignancies undergoing chemotherapy demonstrated lower cognitive compensatory processes compared to healthy controls. Reducing distress and increasing motivation may improve cognitive compensatory processes of patients in non‐novel contexts.
Structural and mechanistic insights into homocysteine degradation by a mutant of methionine γ‐lyase based on substrate‐assisted catalysis
Authors: Sato Dan , Shiba Tomoo , Yunoto Shunsuke , Furutani Kazuo , Fukumoto Mitsuki , Kudou Daizou , Tamura Takashi , Inagaki Kenji , Harada Shigeharu 
Published: March 2017

AbstractMethionine γ‐lyse (MGL) catalyzes the α, γ‐elimination of l‐methionine and its derivatives as well as the α, β‐elimination of l‐cysteine and its derivatives to produce α‐keto acids, volatile thiols, and ammonia. The reaction mechanism of MGL has been characterized by enzymological studies using several site‐directed mutants. The Pseudomonas putida MGL C116H mutant showed drastically reduced degradation activity toward methionine while retaining activity toward homocysteine. To understand the underlying mechanism and to discern the subtle differences between these substrates, we analyzed the crystal structures of the reaction intermediates. The complex formed between the C116H mutant and methionine demonstrated that a loop structure (Ala51–Asn64) in the adjacent subunit of the catalytic dimer cannot approach the cofactor pyridoxal 5′‐phosphate (PLP) because His116 disrupts the interaction of Asp241 with Lys240, and the liberated side chain of Lys240 causes steric hindrance with this loop. Conversely, in the complex formed between C116H mutant and homocysteine, the thiol moiety of the substrate conjugated with PLP offsets the imidazole ring of His116 via a water molecule, disrupting the interaction of His116 and Asp241 and restoring the interaction of Asp241 with Lys240. These structural data suggest that the Cys116 to His mutation renders the enzyme inactive toward the original substrate, but activity is restored when the substrate is homocysteine due to substrate‐assisted catalysis.
Biochemical characterization and structural insight into aliphatic β‐amino acid adenylation enzymes IdnL1 and CmiS6
Authors: Cieślak Jolanta , Miyanaga Akimasa , Takaku Ryoma , Takaishi Makoto , Amagai Keita , Kudo Fumitaka , Eguchi Tadashi 
Published: March 2017

ABSTRACTMacrolactam antibiotics such as incednine and cremimycin possess an aliphatic β‐amino acid as a starter unit of their polyketide chain. In the biosynthesis of incednine and cremimycin, unique stand‐alone adenylation enzymes IdnL1 and CmiS6 select and activate the proper aliphatic β‐amino acid as a starter unit. In this study, we describe the enzymatic characterization and the structural basis of substrate specificity of IdnL1 and CmiS6. Functional analysis revealed that IdnL1 and CmiS6 recognize 3‐aminobutanoic acid and 3‐aminononanoic acid, respectively. We solved the X‐ray crystal structures of IdnL1 and CmiS6 to understand the recognition mechanism of these aliphatic β‐amino acids. These structures revealed that IdnL1 and CmiS6 share a common recognition motif that interacts with the β‐amino group of the substrates. However, the hydrophobic side‐chains of the substrates are accommodated differently in the two enzymes. IdnL1 has a bulky Leu220 located close to the terminal methyl group of 3‐aminobutanoate of the trapped acyl‐adenylate intermediate to construct a shallow substrate‐binding pocket. In contrast, CmiS6 possesses Gly220 at the corresponding position to accommodate 3‐aminononanoic acid. This structural observation was supported by a mutational study. Thus, the size of amino acid residue at the 220 position is critical for the selection of an aliphatic β‐amino acid substrate in these adenylation enzymes. Proteins 2017; 85:1238–1247. © 2017 Wiley Periodicals, Inc.
Thermodynamics of an aminoglycoside modifying enzyme with low substrate promiscuity: The aminoglycoside N3 acetyltransferase‐VIa
Authors: Kumar Prashasti , Serpersu Engin H. 
Published: March 2017

ABSTRACTKinetic, thermodynamic, and structural properties of the aminoglycoside N3‐acetyltransferase‐VIa (AAC‐VIa) are determined. Among the aminoglycoside N3‐acetyltransferases, AAC‐VIa has one of the most limited substrate profiles. Kinetic studies showed that only five aminoglycosides are substrates for this enzyme with a range of fourfold difference in kcat values. Larger differences in KM (∼40‐fold) resulted in ∼30‐fold variation in kcat/KM. Binding of aminoglycosides to AAC‐VIa was enthalpically favored and entropically disfavored with a net result of favorable Gibbs energy (ΔG < 0). A net deprotonation of the enzyme, ligand, or both accompanied the formation of binary and ternary complexes. This is opposite of what was observed with several other aminoglycoside N3‐acetyltransferases, where ligand binding causes more protonation. The change in heat capacity (ΔCp) was different in H2O and D2O for the binary enzyme–sisomicin complex but remained the same in both solvents for the ternary enzyme–CoASH–sisomicin complex. Unlike, most other aminoglycoside‐modifying enzymes, the values of ΔCp were within the expected range of protein‐carbohydrate interactions. Solution behavior of AAC‐VIa was also different from the more promiscuous aminoglycoside N3‐acetyltransferases and showed a monomer‐dimer equilibrium as detected by analytical ultracentrifugation (AUC). Binding of ligands shifted the enzyme to monomeric state. Data also showed that polar interactions were the most dominant factor in dimer formation. Overall, thermodynamics of ligand‐protein interactions and differences in protein behavior in solution provide few clues on the limited substrate profile of this enzyme despite its >55% sequence similarity to the highly promiscuous aminoglycoside N3‐acetyltransferase. Proteins 2017; 85:1258–1265. © 2017 Wiley Periodicals, Inc.
Bi‐centric view of the isostructural phase transitions in α‐Bi2Se3 and α‐Bi2Te3
Authors: Zhu Hailiang , Dong Juncai , Li Pengshan , Wang Yan , Guo Zhiying , Shan Xuemei , Gong Yu , An Pengfei , Li Xiaodong , Zhang Jing , Chen Dongliang 
Published: March 2017

Most of A2B3‐type 3D topological insulators (e.g., Bi2Se3, Bi2Te3, Sb2Te3) have been reported to exhibit a pressure‐induced isostructural phase transition (IPT) in the low‐pressure region (<5 GPa); however, the underlying mechanism is not fully understood yet. Here, we comparatively investigated the IPTs in α‐Bi2Se3 and α‐Bi2Te3 using high‐pressure Bi L3‐edge X‐ray absorption fine structure spectroscopy, complemented with density functional theory (DFT) calculation. Near the IPT, the slope of the Bi L3‐edge absorption energy shows a sudden decrease. In contrast to the monotonous shortening of the Bi–Bi bond‐distance under compression, it is moreover rather surprising that the Bi–Se2 (Te2) and Bi–Se1 (Te1) bond‐distances exhibit abnormal elongations around the IPT, which is synchronized with abrupt increases for their Debye–Waller factor. DFT calculation results show that near the IPT a structural distortion may appear for extremely small energy barrier. Those results indicate that each quintuple layer unit shrinks along the layer direction but elongates perpendicular to the layers at the onset of the IPT, which would be associated with a remarkable increase for the local structural disorder. Therefore, our findings suggest that the IPTs in α‐Bi2Se3 and α‐Bi2Te3 are coupled with a simultaneous charge redistribution and structural distortion accompanied with a static structural disorder increase.Sketch of the changes of local structure of centric Bi and lattice structure around the IPT.
Extractives fom Cedar Deodara and Alnus Cordata in the Presence of Molybdenum Catalysts
Authors: Mecca Marisabel , Todaro Luigi , D'Auria Maurizio 
Published: March 2017

AbstractSoxhlet extraction of cedar wood with ethanol/toluene mixture in the presence of molybdenum catalysts can increase the amount of extracts. The treatment of cedar wood in the presence of H3PMo12O40 gave 7.9 % extractives. In the presence of silica supported MoO3, the amount of extractives was 17.0 %. The extractives were partially soluble in chloroform (76.5 % with silica supported MoO3 and 33 % by using H3PMo12O40). The extracts of cedar can be a source of fatty acids for biodiesel production and simple carbohydrates. The analysis of the chloroform soluble fraction showed that cedar wood gave a mixture of 2‐hydroxy‐1‐(hydroxymethyl)ethyl hexadecanoate and 2,3‐dihydroxypropyl octadecanoate. GC‐MS of water soluble fraction showed the presence of some simple carbohydrates. The treatment of alder in the same conditions gave 3.5 % (37.6 % soluble in chloroform) extractives when silica supported MoO3 was used and 15.5 % (6.1 % soluble in chloroform) extractives when H3PMo12O40 was the catalyst. The soluble fraction is a source of fatty acid derivatives, while in the insoluble fraction ribose, glucose and myo‐inositol were recovered.
Acid Catalyzed Synthesis of Spiroindolone Scaffolds by Iso‐Pictet‐Spengler Spirocyclisation and Evaluation of their Antibacterial Activity
Authors: Dawange Monali A. , Urmode Tukaram D. , Khan Ayesha , Kusurkar Radhika S. 
Published: March 2017

AbstractAcetic acid catalyzed synthesis of new spiroindolones (tetrahydrospiro‐γ‐carbolines) was achieved in good yield by iso‐Pictet Spengler spirocyclisation of substituted isotryptamines with isatins. All the compounds were characterized by spectral and analytical data and were screened for antibacterial activities against S. aureus, E. coli, P. aeruginosa and S. typhi bacteria. The preliminary antibacterial study indicated that compounds bearing halo substituent are showing potent inhibitory activity towards S. typhi and P. aeruginosa and moderate activities towards S. aureus and E. coli.
5‐Amino‐6,7,8,9‐Tetrahydrobenzo[b][1,8]Naphthyridin‐2(1H)‐One: The first Example of a new Family of HuperTacrines for Alzheimer's Disease Therapy
Authors: Balmori Alba , Chioua Mourad , de la Bellacasa Raimon Puig , Estrada‐Tejedor Roger , Ismaili Lhassane , Marco‐Contelles José , Borrell José I. 
Published: March 2017

AbstractIn this communication we have described the synthesis of 2‐amino‐6‐oxo‐1,6‐dihydropyridine‐3‐carbonitrile (4), and the preparation of 5‐amino‐6,7,8,9‐tetrahydrobenzo[b][1,8]naphthyridin‐2(1H)‐one (3 a), a non‐hepatotoxic, antioxidant agent, showing moderate, but selective human acetylcholinesterase inhibition.
Concise Review: MSC Adhesion Cascade—Insights into Homing and Transendothelial Migration
Authors: Nitzsche Franziska , Müller Claudia , Lukomska Barbara , Jolkkonen Jukka , Deten Alexander , Boltze Johannes 
Published: March 2017

AbstractMesenchymal stem cells (MSCs) are promising candidates for adult cell therapies in regenerative medicine. To fully exert their potential, efficient homing and migration toward lesion sites play an important role. Local transplantation deposits MSC in spatial proximity to the lesion, but often requires invasive procedures. Systemic administration routes are favored, but require the targeted extravasation of the circulating MSC at the site of injury. Transplanted MSC can indeed leave the blood flow and transmigrate through the endothelial barrier, and reach the lesion site. However, the underlying processes are not completely dissolved yet. Recent in vitro and in vivo research identified some key molecules scattered light on the extravasation mechanism. This review provides a detailed overview over the current knowledge of MSC transendothelial migration. We use the leukocyte extravasation process as a role model to build a comprehensive concept of MSC egress mechanisms from the blood stream and identified relevant similarities as well as important differences between the extravasation mechanisms.
GABAA and GABAB receptor dysregulation in superior frontal cortex of subjects with schizophrenia and bipolar disorder
Authors: Fatemi S. Hossein , Folsom Timothy D. , Thuras Paul D. 
Published: March 2017

AbstractSchizophrenia and bipolar disorder are complex psychiatric disorders that affect millions of people worldwide. Evidence from gene association and postmortem studies has identified abnormalities of the gamma‐aminobutyric acid (GABA) signaling system in both disorders. Abnormal GABAergic signaling and transmission could contribute to the symptomatology of these disorders, potentially through impaired gamma oscillations which normally occur during cognitive processing. In the current study, we examined the protein expression of 14 GABAA and two GABAB receptor subunits in the superior frontal cortex of subjects with schizophrenia, bipolar disorder, and healthy controls. Analyses of Variance (ANOVAs) identified significant group effects for protein levels for the α1, α6, β1, β3, δ, ɛ, and π GABAA receptor subunits and R1 and R2 GABAB receptor subunits. Follow‐up t tests confirmed changes for these subunits in subjects with schizophrenia, subjects with bipolar disorder, or both groups. Alterations in stoichiometry of GABA receptor subunits could result in altered ligand binding, transmission, and pharmacology of GABA receptors in superior frontal cortex. Thus, impaired GABAergic transmission may negatively contribute to symptoms such as anxiety or panic as well as impaired learning and information processing, all of which are disrupted in schizophrenia and bipolar disorder. Taken together, these results provide additional evidence of GABAergic receptor abnormalities in these disorders.