bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth of Bacillus methanolicus in 2 M methanol at 50 °C: the effect of high methanol concentration on gene regulation of enzymes involved in formaldehyde detoxification by the ribulose monophosphate pathway
Authors: Bozdag Ahmet , Komives Claire , Flickinger Michael C 
Published: May 2015

Abstract
Bacillus methanolicus MGA3 is a Gram-positive aerobic methylotroph growing optimally at 50–53 °C. Methylotrophy in B. methanolicus is encoded on pBM19 and by two chromosomal copies of the methanol dehydrogenase (mdh), hexulose phosphate synthase (hps) and phosphohexuloisomerase (phi) genes. However, there are no published studies on the regulation of methylotrophy or the dominant mechanism of detoxification of intracellular formaldehyde in response to high methanol concentration. The µ max of B. methanolicus MGA3 was assessed on methanol, mannitol and glucose. B. methanolicus achieved a µ max at 25 mM initial methanol of 0.65 ± 0.007 h−1, which decreased to 0.231 ± 0.004 h−1 at 2 M initial methanol. Slow growth was also observed with initial methanol concentrations of &gt;2 M. The µ max on mannitol and glucose are 0.532 ± 0.002 and 0.336 ± 0.003 h−1, respectively. Spiking cultures with additional methanol (100 mM) did not disturb the growth rate of methanol-grown cells, whereas, a 50 mM methanol spike halted the growth in mannitol. Surprisingly, growth in methanol was inhibited by 1 mM formaldehyde, while mannitol-grown cells tolerated 2 mM. Moreover, mannitol-grown cells removed formaldehyde faster than methanol-grown cells. Further, we show that methanol oxidation in B. methanolicus MGA3 is mainly carried out by the pBM19-encoded mdh. Formaldehyde and formate addition down-regulate the mdh and hps genes in methanol-grown cells. Similarly, they down-regulate mdh genes in mannitol-grown cells, but up-regulate hps. Phosphofructokinase (pfk) is up-regulated in both methanol and mannitol-grown cells, which suggests that pfk may be a possible synthetic methylotrophy target to reduce formaldehyde growth toxicity at high methanol concentrations.
Enhanced production of l-sorbose in an industrial Gluconobacter oxydans strain by identification of a strong promoter based on proteomics analysis
Authors: Hu Yudong , Wan Hui , Li Jianghua , Zhou Jingwen 
Published: May 2015

Abstract
Gluconobacter oxydans is capable of rapidly incomplete oxidation of many sugars and alcohols, which means the strain has great potential for industrial purposes. Strong promoters are one of the essential factors that can improve strain performance by overexpression of specific genes. In this study, a pipeline for screening strong promoters by proteomics analysis was established. Based on the procedure, a new strong promoter designated as PB932_2000 was identified in G. oxydans WSH-003. The promoter region was characterized based on known genome sequence information using BPROM. The strength of PB932_2000 was further assessed by analysis of enhanced green fluorescent protein (egfp) expression and comparison with egfp expression by two commonly used strong promoters, PE. coli_tufB and PG. oxydans_tufB. Both quantitative real-time PCR and fluorescence intensities for egfp gene expression showed that PB932_2000 promoter is stronger than the other two. Overexpression of d-sorbitol dehydrogenase (sldh) by PB932_2000 in G. oxydans WSH-003 enhanced the titer and productivity of l-sorbose synthesis from d-sorbitol by 12.0 % and 33.3 %, respectively. These results showed that proteomics analysis is an efficient way to identify strong promoters. The isolated promoter PB932_2000 could further facilitate the metabolic engineering of G. oxydans.
Increasing succinic acid production using the PTS-independent glucose transport system in a Corynebacterium glutamicum PTS-defective mutant
Authors: Zhou Zhihui , Wang Chen , Xu Hongtao , Chen Zhongjun , Cai Heng 
Published: May 2015

Abstract
Succinic acid synthesized from glucose shows potential as a bio-based platform chemical. However, the need for a high glucose concentration, and the accompanying low yields, limit its industrial applications. Despite efficient glucose uptake by the phosphotransferase system (PTS), 1 mol of phosphoenolpyruvate is required for each mole of internalized glucose. Therefore, a PTS-defective Corynebacterium glutamicum mutant was constructed to increase phosphoenolpyruvate availability for succinic acid synthesis, resulting in a lower glucose utilization rate and slower growth. The transcriptional regulator iolR was also deleted to enable the PTS-defective mutant to utilize glucose via iolT-mediated glucose transport. Deletion of iolR and overexpression of iolT1 and ppgk (polyphosphate glucokinase) in the PTS-deficient C. glutamicum strain completely restored glucose utilization, increasing production by 11.6 % and yield by 32.4 % compared with the control. This study revealed for the first time that iolR represses the expression of the two glucokinase genes (glk and ppgk).
Aboveground carbon dynamics following strip clear‐cutting in the Peruvian Amazon
Authors: Rondon Xanic J. , Gorchov David L. , Noble Robert B. , Cornejo Fernando 
Published: May 2015

AbstractAboveground carbon dynamics were estimated in two strips (30 m × 150 m) clear‐cut in the Peruvian Amazon following 15 years after clearing. While strip 1 recovered 50 % (64 Mg C ha−1) of its pre‐clearing carbon stocks, the clear‐cut portion of strip 2 recovered 39 % (53 Mg C ha−1). During this period, there were high carbon sequestration rates (>6 Mg C ha−1 year−1) from tree growth and low carbon emission rates from tree mortality (up to 3 Mg C ha−1 year−1) in both strip 1 and the clear‐cut portion of strip 2. Recruits make up most of the tree composition in both strips, and therefore play an important role in carbon sequestration. However, there were high carbon emission rates from timber harvesting and processing (>20 Mg C ha−1 year−1). A thinning treatment, applied 7 years after clearing, did not affect carbon dynamics. In the 15‐year period total carbon emissions (+) were greater than sequestration (−). Net carbon fluxes for strip 1 and the clear‐cut portion of strip 2 were +26 and +68 Mg C ha−1. Comparable carbon dynamics were found in the deferment‐cut treatment, applied to the south half of strip 2. To conclude, the 15 year‐old clear‐cut strips are not carbon sinks yet, and will require >140 years to reach old‐growth carbon stocks.
Cervical fractures with associated spinal cord injury in children and adolescents: Epidemiology, costs, and in-hospital mortality rates in 4418 patients
Authors: Jain Amit , Brooks Jaysson T. , Rao Sandesh S. , Ain Michael C. , Sponseller Paul D. 
Published: May 2015

Background Cervical spine fractures with spinal cord injury (CFSCI) can be devastating. We describe the epidemiology of children and adolescents with CFSCI. Methods Using the Nationwide Inpatient Sample (NIS) database, we identified 4418 patients (≤18 years old) who had CFSCI from 2000 through 2010. Outcomes of interest were patient characteristics (age, sex), injury characteristics [fracture location, spinal cord injury (SCI) pattern], economic variables (duration of hospital stay, total hospital charges), and mortality. Results Upper cervical fractures (UCFs) occurred half as often (31.4 %) as lower cervical fractures (LCFs; 68.8 %). Among patients <8 years old, 73.6 % had UCFs; among patients ≥8 years old, 72.3 % had LCFs. Overall, 68.7 % had incomplete SCI, 22.4 % had complete SCI, 6.6 % had central cord syndrome, and 2.3 % had anterior cord syndrome. Patients with complete SCI had the longest hospital stays and highest hospital charges. The overall in-hospital mortality rate was 7.3 %, with a sixfold higher rate in patients <8 (30.6 %) vs. those ≥8 (5.1 %) years old ( p < 0.001). There was a threefold higher mortality rate in patients with upper (13.5 %) vs. lower (4.3 %) cervical fractures ( p < 0.001). Patients with complete SCI had a 1.85-fold higher mortality rate than patients with other cord syndromes ( p < 0.001). Conclusions Patients <8 years old were more likely than older patients to sustain UCFs. Patients with UCFs had a significantly higher mortality rate than those with LCFs. Patients with complete SCI had the longest duration of hospital stay and highest hospital charges and in-hospital mortality rate.
APOE effect on Alzheimer's disease biomarkers in older adults with significant memory concern
Authors: Risacher Shannon L. , Kim Sungeun , Nho Kwangsik , Foroud Tatiana , Shen Li , Petersen Ronald C. , Jack Clifford R. , Beckett Laurel A. , Aisen Paul S. , Koeppe Robert A. , Jagust William J. , Shaw Leslie M. , Trojanowski John Q. , Weiner Michael W. , Saykin Andrew J. ,   Alzheimer's Disease Neuroimaging Initiative (ADNI)
Published: May 2015

AbstractIntroductionThis study assessed apolipoprotein E (APOE) ε4 carrier status effects on Alzheimer's disease imaging and cerebrospinal fluid (CSF) biomarkers in cognitively normal older adults with significant memory concerns (SMC).MethodsCognitively normal, SMC, and early mild cognitive impairment participants from Alzheimer's Disease Neuroimaging Initiative were divided by APOE ε4 carrier status. Diagnostic and APOE effects were evaluated with emphasis on SMC. Additional analyses in SMC evaluated the effect of the interaction between APOE and [18F]Florbetapir amyloid positivity on CSF biomarkers.ResultsSMC ε4+ showed greater amyloid deposition than SMC ε4−, but no hypometabolism or medial temporal lobe (MTL) atrophy. SMC ε4+ showed lower amyloid beta 1–42 and higher tau/p‐tau than ε4−, which was most abnormal in APOE ε4+ and cerebral amyloid positive SMC.DiscussionSMC APOE ε4+ show abnormal changes in amyloid and tau biomarkers, but no hypometabolism or MTL neurodegeneration, reflecting the at‐risk nature of the SMC group and the importance of APOE in mediating this risk.
PREFERENCES VS. DESIRES: DEBATING THE FUNDAMENTAL STRUCTURE OF CONATIVE STATES
Authors: Schulz Armin W. 
Published: May 2015

Abstract:I address an overlooked question about the structure of the cognitive/conative model of the mind that underlies much of the work in economics, psychology and philosophy: namely, whether conative states are fundamentally monistic (desire-like) or comparative (preference-like). I argue that two seemingly promising sets of theoretical considerations – namely, the structure of Rational Choice Theory, and considerations of computational efficiency – are unable to resolve this debate. Given this, I suggest that a consideration that speaks in favour of the preference-based view is the fact that it makes it easier to explain certain empirically observed patterns in decision making.
IAPT: Improving Access to Psychiatric Training. CBT delivery by junior psychiatrists in primary care is good for the service, good for training and good for patients
Authors: Moorhead Steve 
Published: May 2015

AbstractThe feasibility and effectiveness of trainee psychiatrists providing CBT in primary care was assessed by a triangulated procedure of service overview, trainee feedback and assessment of clinical measures. Hitherto trainees sought ‘suitable’ cases by individual request. In the primary-care setting: 82% of 11 trainees (50% previously) completed a ‘short case’ treatment within a 6-month attachment; 86% of trainees found the level of supervision ‘about right’; depression and anxiety scores for patients (n= 16) achieved statistically significant gains and showed moderate to large effect sizes. Although there was no comparator group, findings were just above the IAPT aim of a 50% recovery. Conclusions are that completion of their ‘short case’ experience within a 6-month attachment is feasible in a primary-care setting. Evidence that patients and the service also benefited demonstrates this to be good and ethical ‘business’ for the service provider. Integrating these skills into routine medical psychiatric practice may remain a later supervision need. Other training experiences including psychological treatments could initially be best met in less testing clinical encounters than those experienced in secondary care. Locally agreed formal arrangements would facilitate this and there is potential for the development of greater cross-service understanding in the longer term.
The use of CBT in dementia care: a rationale for Communication and Interaction Therapy (CAIT) and therapeutic lies
Authors: James Ian A. 
Published: May 2015

AbstractAt the very beginning of our lives we have similar needs, but as we get older the ways of maintaining our wellbeing will vary greatly. Quite simply, we get more different and complex as we age! Hence, attempts to both meet older people's needs and treat their psychological difficulties often require comprehensive assessments and biopsychosocial formulations. It is relevant to note that many of the latter formulations are informed by CBT theory, even when dealing with people presenting with dementia and challenging behaviour. Despite the conceptual complexities, there is increasing evidence to suggest that the most effective interventions for this ‘challenging’ population are basic communication strategies. This paper outlines the key principles of effective communication under the heading of Communication and Interaction Therapy (CAIT). The concepts underpinning CAIT are illustrated via a number of case studies of people living in 24-hour care. It will be argued that an implication of this approach is the judicious use of therapeutic lies, but only as a last resort.
Peptides derived from the dependence receptor ALK are proapoptotic for ALK-positive tumors
Authors: Aubry A , Galiacy S , Ceccato L , Marchand C , Tricoire C , Lopez F , Bremner R , Racaud-Sultan C , Monsarrat B , Malecaze F , Allouche M 
Published: May 2015

AbstractALK is a receptor tyrosine kinase with an oncogenic role in various types of human malignancies. Despite constitutive activation of the kinase through gene alterations, such as chromosomal translocation, gene amplification or mutation, treatments with kinase inhibitors invariably lead to the development of resistance. Aiming to develop new tools for ALK targeting, we took advantage of our previous demonstration identifying ALK as a dependence receptor, implying that in the absence of ligand the kinase-inactive ALK triggers or enhances apoptosis. Here, we synthesized peptides mimicking the proapoptotic domain of ALK and investigated their biological effects on tumor cells. We found that an ALK-derived peptide of 36 amino acids (P36) was cytotoxic for ALK-positive anaplastic large-cell lymphoma and neuroblastoma cell lines. In contrast, ALK-negative tumor cells and normal peripheral blood mononuclear cells were insensitive to P36. The cytotoxic effect was due to caspase-dependent apoptosis and required N-myristoylation of the peptide. Two P36-derived shorter peptides as well as a cyclic peptide also induced apoptosis. Surface plasmon resonance and mass spectrometry analysis of P36-interacting proteins from two responsive cell lines, Cost lymphoma and SH-SY5Y neuroblastoma, uncovered partners that could involve p53-dependent signaling and pre-mRNA splicing. Furthermore, siRNA-mediated knockdown of p53 rescued these cells from P36-induced apoptosis. Finally, we observed that a treatment combining P36 with the ALK-specific inhibitor crizotinib resulted in additive cytotoxicity. Therefore, ALK-derived peptides could represent a novel targeted therapy for ALK-positive tumors.
Uncoupling Neogenin association with lipid rafts promotes neuronal survival and functional recovery after stroke
Authors: Shabanzadeh A P , Tassew N G , Szydlowska K , Tymianski M , Banerjee P , Vigouroux R J , Eubanks J H , Huang L , Geraerts M , Koeberle P D , Mueller B K , Monnier P P 
Published: May 2015

AbstractThe dependence receptor Neogenin and its ligand, the repulsive guidance molecule a (RGMa), regulate apoptosis and axonal growth in the developing and the adult central nervous system (CNS). Here, we show that this pathway has also a critical role in neuronal death following stroke, and that providing RGMa to neurons blocks Neogenin-induced death. Interestingly, the Neogenin pro-death function following ischemic insult depends on Neogenin association with lipid rafts. Thus, a peptide that prevents Neogenin association with lipid rafts increased neuronal survival in several in vitro stroke models. In rats, a pro-survival effect was also observed in a model of ocular ischemia, as well as after middle cerebral artery occlusion (MCAO). Treatments that prevented Neogenin association with lipid rafts improved neuronal survival and the complexity of the neuronal network following occlusion of the middle artery. Toward the development of a treatment for stroke, we developed a human anti-RGMa antibody that also prevents Neogenin association with lipid rafts. We show that this antibody also protected CNS tissue from ischemic damage and that its application resulted in a significant functional improvement even when administrated 6 h after artery occlusion. Thus, our results draw attention to the role of Neogenin and lipid rafts as potential targets following stroke.
Arachidonic acid promotes skin wound healing through induction of human MSC migration by MT3-MMP-mediated fibronectin degradation
Authors: Oh S Y , Lee S-J , Jung Y H , Lee H J , Han H J 
Published: May 2015

AbstractArachidonic acid (AA) is largely released during injury, but it has not been fully studied yet how AA modulates wound repair with stem cells. Therefore, we investigated skin wound-healing effect of AA-stimulated human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) in vivo and its molecular mechanism in vitro. We found that transplantation of hUCB-MSCs pre-treated with AA enhanced wound filling, re-epithelization, and angiogenesis in a mouse skin excisional wound model. AA significantly promoted hUCB-MSCs migration after a 24 h incubation, which was inhibited by the knockdown of G-protein-coupled receptor 40 (GPR40). AA activated mammalian target of rapamycin complex 2 (mTORC2) and Aktser473 through the GPR40/phosphoinositide 3-kinase (PI3K) signaling, which was responsible for the stimulation of an atypical protein kinase C (PKC) isoform, PKCζ. Subsequently, AA stimulated phosphorylation of p38 MAPK and transcription factor Sp1, and induced membrane type 3-matrix metalloproteinase (MT3-MMP)-dependent fibronectin degradation in promoting hUCB-MSCs motility. Finally, the silencing of MT3-MMP in AA-stimulated hUCB-MSCs failed to promote the repair of skin wounds owing to impaired cell motility. In conclusion, AA enhances skin wound healing through induction of hUCB-MSCs motility by MT3-MMP-mediated fibronectin degradation, which relies on GPR40-dependent mTORC2 signaling pathways.
Platelet-activating factor induces cell cycle arrest and disrupts the DNA damage response in mast cells
Authors: Puebla-Osorio N , Damiani E , Bover L , Ullrich S E 
Published: May 2015

AbstractPlatelet-activating factor (PAF) is a potent phospholipid modulator of inflammation that has diverse physiological and pathological functions. Previously, we demonstrated that PAF has an essential role in ultraviolet (UV)-induced immunosuppression and reduces the repair of damaged DNA, suggesting that UV-induced PAF is contributing to skin cancer initiation by inducing immune suppression and also affecting a proper DNA damage response. The exact role of PAF in modulating cell proliferation, differentiation or transformation is unclear. Here, we investigated the mechanism(s) by which PAF affects the cell cycle and impairs early DNA damage response. PAF arrests proliferation in transformed and nontransformed human mast cells by reducing the expression of cyclin-B1 and promoting the expression of p21. PAF-treated cells show a dose-dependent cell cycle arrest mainly at G2–M, and a decrease in the DNA damage response elements MCPH1/BRIT-1 and ataxia telangiectasia and rad related (ATR). In addition, PAF disrupts the localization of p-ataxia telangiectasia mutated (p-ATM), and phosphorylated-ataxia telangiectasia and rad related (p-ATR) at the site of DNA damage. Whereas the potent effect on cell cycle arrest may imply a tumor suppressor activity for PAF, the impairment of proper DNA damage response might implicate PAF as a tumor promoter. The outcome of these diverse effects may be dependent on specific cues in the microenvironment.
The p38α mitogen-activated protein kinase is a key regulator of myelination and remyelination in the CNS
Authors: Chung S-H , Biswas S , Selvaraj V , Liu X-B , Sohn J , Jiang P , Chen C , Chmilewsky F , Marzban H , Horiuchi M , Pleasure D E , Deng W 
Published: May 2015

AbstractThe p38α mitogen-activated protein kinase (MAPK) is one of the serine/threonine kinases regulating a variety of biological processes, including cell-type specification, differentiation and migration. Previous in vitro studies using pharmacological inhibitors suggested that p38 MAPK is essential for oligodendrocyte (OL) differentiation and myelination. To investigate the specific roles of p38α MAPK in OL development and myelination in vivo, we generated p38α conditional knockout (CKO) mice under the PLP and nerve/glial antigen 2 (NG2) gene promoters, as these genes are specifically expressed in OL progenitor cells (OPCs). Our data revealed that myelin synthesis was completely inhibited in OLs differentiated from primary OPC cultures derived from the NG2 Cre-p38α CKO mouse brains. Although an in vivo myelination defect was not obvious after gross examination of these mice, electron microscopic analysis showed that the ultrastructure of myelin bundles was severely impaired. Moreover, the onset of myelination in the corpus callosum was delayed in the knockout mice compared with p38α fl/fl control mice. A delay in OL differentiation in the central nervous system was observed with concomitant downregulation in the expression of OPC- and OL-specific genes such as Olig1 and Zfp488 during early postnatal development. OPC proliferation was not affected during this time. These data indicate that p38α is a positive regulator of OL differentiation and myelination. Unexpectedly, we observed an opposite effect of p38α on remyelination in the cuprizone-induced demyelination model. The p38α CKO mice exhibited better remyelination capability compared with p38α fl/fl mice following demyelination. The opposing roles of p38α in myelination and remyelination could be due to a strong anti-inflammatory effect of p38α or a dual reciprocal regulatory action of p38α on myelin formation during development and on remyelination after demyelination.
IPS-1 differentially induces TRAIL, BCL2, BIRC3 and PRKCE in type I interferons-dependent and -independent anticancer activity
Authors: Kumar S , Ingle H , Mishra S , Mahla R S , Kumar A , Kawai T , Akira S , Takaoka A , Raut A A , Kumar H 
Published: May 2015

AbstractRIG-I-like receptors are the key cytosolic sensors for RNA viruses and induce the production of type I interferons (IFN) and pro-inflammatory cytokines through a sole adaptor IFN-β promoter stimulator-1 (IPS-1) (also known as Cardif, MAVS and VISA) in antiviral innate immunity. These sensors also have a pivotal role in anticancer activity through induction of apoptosis. However, the mechanism for their anticancer activity is poorly understood. Here, we show that anticancer vaccine adjuvant, PolyIC (primarily sensed by MDA5) and the oncolytic virus, Newcastle disease virus (NDV) (sensed by RIG-I), induce anticancer activity. The ectopic expression of IPS-1 into type I IFN-responsive and non-responsive cancer cells induces anticancer activity. PolyIC transfection and NDV infection upregulate pro-apoptotic gene TRAIL and downregulate the anti-apoptotic genes BCL2, BIRC3 and PRKCE. Furthermore, stable knockdown of IPS-1, IRF3 or IRF7 in IFN-non-responsive cancer cells show reduced anticancer activity by suppressing apoptosis via TRAIL and anti-apoptotic genes. Collectively, our study shows that IPS-1 induces anticancer activity through upregulation of pro-apoptotic gene TRAIL and downregulation of the anti-apoptotic genes BCL2, BIRC3 and PRKCE via IRF3 and IRF7 in type I IFN-dependent and -independent manners.