bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct immunological activation profiles of dSLIM® and ProMune® depend on their different structural context
Authors: Kapp Kerstin , Schneider Jacqueline , Schneider Lisa , Gollinge Nadine , Jänsch Stefanie , Schroff Matthias , Wittig Burghardt , Kleuss Christiane 
Published: October 2016

AbstractIntroductionDNA‐based TLR9 agonists are potent activators of the immune system. ProMune® and dSLIM® belong to different families of TLR9 agonists and both have been established as cancer immunotherapeutics in clinical proof‐of‐concept studies. Unfortunately, ProMune® failed in pivotal oncological trials. dSLIM®, the active ingredient of Lefitolimod (MGN1703), successfully finished a double‐blinded, placebo‐controlled phase II study in patients with advanced colorectal cancer, exhibiting improved progression‐free survival and durable disease control.MethodsTo explain the different systemic efficacies of dSLIM® and ProMune®, both TLR9 agonists and chimeric molecules thereof are analyzed side‐by‐side in a panel of in vitro assays for immune activation.Results and conclusionsIndeed, dSLIM® exposure results in an IFN‐α dependent broad activation of immune cells whereas ProMune® strongly stimulates B cells. Moreover, all functional effects of dSLIM® strictly depend on the presence of CG‐motifs within its dumbbell‐shaped, covalently closed structural context. Conversely, several immunological effects of ProMune® like IL‐8 secretion are independent of CG‐motifs and could be ascribed to the phosphorothioate‐modifications of its DNA backbone, which may have caused the side effects of ProMune® in clinical trials. Finally, we showed that the implementation of ProMune® (ODN2006) base sequence into the characteristic dSLIM® dumbbell form resulted in dSLIM2006 with all beneficial effects for immunostimulation combined from both TLR9 classes without any CG‐independent effects.
CREATING A “NEST” OF EMOTIONAL SAFETY: REFLECTIVE SUPERVISION IN A CHILD–PARENT PSYCHOTHERAPY CASE
Authors: Many Michele M. , Kronenberg Mindy E. , Dickson Amy B. 
Published: October 2016

ABSTRACTReflective supervision is considered a key practice component for any infant mental health provider to work effectively with young children and their families. This article will provide a brief history and discussion of reflective supervision followed by a case study demonstrating the importance of reflective supervision in the context of child–parent psychotherapy (CPP; A.F. Lieberman, C. Ghosh Ippen, & P. Van Horn, ; A.F. Lieberman & P. Van Horn, , 2008). Given that CPP leverages the caregiver–child relationship as the mechanism for change in young children who have been impacted by stressors and traumas, primary objectives of CPP include assisting caregivers as they understand the meaning of their child's distress and improving the caregiver–child relationship to make it a safe and supportive space in which the child can heal. As this case will demonstrate, when a clinician is emotionally triggered by a family's negative intergenerational patterns of relating, reflective supervision supports a parallel process in which the psychotherapist feels understood and contained by the supervisor so that she or he is able to support the caregiver's efforts to understand and contain the child.
Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling
Authors: Balenga Nariman , Azimzadeh Pedram , Hogue Joyce A , Staats Paul N , Shi Yuhong , Koh James , Dressman Holly , Olson John A 
Published: October 2016

ABSTRACT

Abnormal feedback of serum calcium to parathyroid hormone (PTH) secretion is the hallmark of primary hyperparathyroidism (PHPT). Although the molecular pathogenesis of parathyroid neoplasia in PHPT has been linked to abnormal expression of genes involved in cell growth (e.g., cyclin D1, retinoblastoma, and β-catenin), the molecular basis of abnormal calcium sensing by calcium-sensing receptor (CaSR) and PTH hypersecretion in PHPT are incompletely understood. Through gene expression profiling, we discovered that an orphan adhesion G protein-coupled receptor (GPCR), GPR64/ADGRG2, is expressed in human normal parathyroid glands and is overexpressed in parathyroid tumors from patients with PHPT. Using immunohistochemistry, Western blotting, and coimmunoprecipitation, we found that GPR64 is expressed on the cell surface of parathyroid cells, is overexpressed in parathyroid tumors, and physically interacts with the CaSR. By using reporter gene assay and GPCR second messenger readouts we identified Gαs, 3′,5′-cyclic adenosine monophosphate (cAMP), protein kinase A, and cAMP response element binding protein (CREB) as the signaling cascade downstream of GPR64. Furthermore, we found that an N-terminally truncated human GPR64 is constitutively active and a 15–amino acid–long peptide C-terminal to the GPCR proteolysis site (GPS) of GPR64 activates this receptor. Functional characterization of GPR64 demonstrated its ability to increase PTH release from human parathyroid cells at a range of calcium concentrations. We discovered that the truncated constitutively active, but not the full-length GPR64 physically interacts with CaSR and attenuates the CaSR-mediated intracellular Ca2+ signaling and cAMP suppression in HEK293 cells. Our results indicate that GPR64 may be a physiologic regulator of PTH release that is dysregulated in parathyroid tumors, and suggest a role for GPR64 in pathologic calcium sensing in PHPT. © 2016 American Society for Bone and Mineral Research.
Simple and Rapid Bioink Jet Printing for Multiscale Cell Adhesion Islands
Authors: Mecozzi Laura , Gennari Oriella , Rega Romina , Battista Luigi , Ferraro Pietro , Grilli Simonetta 
Published: October 2016

A simple and rapid process for multiscale printing of bioinks with dot widths ranging from hundreds of microns down to 0.5 μm is presented. The process makes use of spontaneous surface charges generated pyroelectrically that are able to draw little daughter droplets directly from the free meniscus of a mother drop through jetting (“p‐jet”), thus avoiding time‐consuming and expensive fabrication of microstructured nozzles. Multiscale can be easily achieved by modulating the parameters of the p‐jet process. Here, it is shown that the p‐jet allows us to print well‐defined adhesion islands where NIH‐3T3 fibroblasts are constrained to live into cluster configurations ranging from 20 down to single cell level. The proposed fabrication approach can be useful for high‐throughput studies on cell adhesion, cytoskeleton organization, and stem cell differentiation.
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Microwave‐Induced Poly(ionic liquid)/Poly(vinyl alcohol) Shape Memory Composites
Authors: Du Haiyan , Liu Xiaoxiao , Yu Yulong , Xu Yuyu , Wang Yonghong , Liang Zhenhai 
Published: October 2016

Recently, different stimuli triggered shape memory polymer composites (SMPC) have received much research interest. However, most shape memory effects (SME) in polymer composites are mainly caused by introducing different functional inorganic fillers into polymer matrix. In the present work, the special structure of poly(ionic liquids), the heating effect of microwaves (MW), and the mechanism of SMPs are combined to design MW induced SMPC completely based on polymers, poly(ionic liquid)/poly(vinyl alcohol) (PIL/PVA) polymer networks. PILs contain anion cation pairs, which have strong MW absorption capability due to their dielectric properties. Polymer composites absorb MW energy under irradiation and generate MW heating, which could provide the required energy for shape recovery. The functional ionic liquid monomer (MIL) styrene imidazole ([VBBI][BF4]) is synthesized and polymerized. Then, PIL is mixed into PVA solution, which is crosslinked with glutaraldehyde to form P[VBBI][BF4]/PVA polymer networks. 1H NMR is used to characterize the structure of the synthesized styrene imidazole ILM and PIL. A bending test is applied to quantitatively characterize SMEs, which are affected by the PIL content in the composites and the applied MW power output. The present work combines the advantages of microwaves with PILs, opening up an efficient and environmentally friendly field for SMPs.
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Does change in neuromuscular jitter predict or correlate with clinical change in MG?
Authors: Sanders Donald B. , Massey Janice M. 
Published: October 2016

ABSTRACTIntroductionThe objective of this study was to determine if single‐fiber electromyography (SFEMG) jitter accurately reflects change in severity in myasthenia gravis (MG).MethodsWe reviewed jitter and outcome data from all MG patients in our clinic who had at least 2 jitter measurements in the extensor digitorum or frontalis muscle.ResultsChange in all parameters of jitter measured with SFEMG electrodes predicted clinical change with acceptable accuracy. Absolute and percentage change in mean value of consecutive interval differences were equally accurate in predicting clinical change and were more accurate than change in the proportion of fiber pairs with blocking or normal jitter.ConclusionsJitter is a sensitive measure of severity in MG and has a potential role as a biomarker in clinical trials and the clinic. Absolute or percentage change in mean jitter is the best jitter parameter to follow. The accuracy of change in jitter measured with other electrodes has yet to be determined. Muscle Nerve 56: 45–50, 2017.
Optimizing muscle selection for electromyography in amyotrophic lateral sclerosis
Authors: Babu Suma , Pioro Erik P , Li Jianbo , Li Yuebing 
Published: October 2016

ABSTRACTIntroductionWe compared the yield of limb and thoracic paraspinal muscle examination for revealing lower motor neuron (LMN) dysfunction on electromyography (EMG) in amyotrophic lateral sclerosis (ALS).MethodsA retrospective review of 354 patients with clinically definite or probable ALS was performed. Seventeen limb muscles and thoracic paraspinal muscles were evaluated for the presence of both active and chronic denervation.ResultsDistal limb muscles showed the highest electrodiagnostic sensitivities of LMN dysfunction in ALS regardless of onset region and diagnostic certainty at the time of diagnosis. Electrodiagnostic yield is higher in muscles from the onset limb. Noncontiguous spread of lower motor neuron degeneration is present in ALS. Optimally selected 6 upper and 5 lower extremity muscles yielded >98% of potential positive cervical or lumbosacral segments.ConclusionsAn algorithmic approach to needle EMG in ALS based on pretest probability of individual muscles optimizes electrodiagnostic yield, thus possibly minimizing test duration and patient discomfort. Muscle Nerve 56: 36–44, 2017.
The Cost of a Commute: A Multidisciplinary Approach to Osteoarthritis in New Kingdom Egypt
Authors: Austin A. E. 
Published: October 2016

AbstractThis article evaluates rates of osteoarthritis of the lower limb in human remains from Deir el‐Medina in order to compare the health of the residents of Deir el‐Medina with previous studies on other ancient Egyptian and Nubian populations. This study focuses on osteological observations from the commingled New Kingdom human remains documented during the 2012–2014 field seasons of the Institut Français d'Archéologie Orientale. This is the first publication of osteoarthritis for the human remains at Deir el‐Medina, a dataset which complements comparable populations at sites such as Amarna, Giza, and Tombos. It demonstrates that men in the village of Deir el‐Medina experienced significantly higher rates of osteoarthritis in the ankle and knee in comparison to women at Deir el‐Medina. Rates of osteoarthritis in the lower limb at Deir el‐Medina generally fall between workers' cemeteries and middle‐class or elite cemeteries.This study also includes data from Deir el‐Medina's detailed textual record and intact landscape in order to determine how occupation influenced these higher rates of osteoarthritis. The duration, intensity, and frequency of the workmen's hikes are reconstructed based on the surrounding landscape and 42 texts recording work days. This study compares rates of osteoarthritis with these datasets in order to document how the strain, duration, and frequency of the workmen's hikes may have impacted overall rates of osteoarthritis. Consequently, data from the texts and landscape surrounding Deir el‐Medina not only corroborate osteoarthritis patterns, but offer detailed daily life activity which can be used as a comparison for broader studies on osteoarthritis in ancient and modern populations. Copyright © 2016 John Wiley & Sons, Ltd.
Effect of circular permutation on the structure and function of type 1 blue copper center in azurin
Authors: Yu Yang , Petrik Igor D. , Chacón Kelly N. , Hosseinzadeh Parisa , Chen Honghui , Blackburn Ninian J. , Lu Yi 
Published: October 2016

AbstractType 1 copper (T1Cu) proteins are electron transfer (ET) proteins involved in many important biological processes. While the effects of changing primary and secondary coordination spheres in the T1Cu ET function have been extensively studied, few report has explored the effect of the overall protein structural perturbation on active site configuration or reduction potential of the protein, even though the protein scaffold has been proposed to play a critical role in enforcing the entatic or “rack‐induced” state for ET functions. We herein report circular permutation of azurin by linking the N‐ and C‐termini and creating new termini in the loops between 1st and 2nd β strands or between 3rd and 4th β strands. Characterization by electronic absorption, electron paramagnetic spectroscopies, as well as crystallography and cyclic voltammetry revealed that, while the overall structure and the primary coordination sphere of the circular permutated azurins remain the same as those of native azurin, their reduction potentials increased by 18 and 124 mV over that of WTAz. Such increases in reduction potentials can be attributed to subtle differences in the hydrogen‐bonding network in secondary coordination sphere around the T1Cu center.
A variational formulation of geophysical fluid motion in non‐Eulerian coordinates
Authors: Dubos Thomas 
Published: October 2016

Systematic methods to derive geophysical equations of motion possessing conservation laws for energy, momentum and potential vorticity have recently been developed. One approach is based on Hamilton's least action principle in Eulerian curvilinear coordinates and the other is based on the covariance upon time‐dependent changes of spatial coordinates. The variational approach unifies, facilitates and generalizes the formulation of a wide range of approximations. The covariant approach makes it straightforward to rewrite approximate equations of motion derived in a particular coordinate system in another coordinate system.The variational approach encompasses models that, like the β‐plane and non‐traditional shallow‐atmosphere approximations, lack a global inertial frame, so that the resulting motion cannot be interpreted as Newtonian motion observed in a non‐inertial frame. It has been previously suggested that such models are not covariant.In this work a covariant variational formulation is developed. As a consequence, it is shown that all models previously obtained by the variational approach are covariant upon time‐dependent changes of spatial coordinates.
A systematic review of cetothere baleen whales (Cetacea, Cetotheriidae) from the Late Miocene of Crimea and Caucasus, with a new genus
Authors: Gol'din Pavel , Startsev Dmitry 
Published: October 2016

AbstractNine taxa of Miocene baleen whales were described from the Black Sea region under the name Cetotherium before 1951, and a further four closely related species representing three genera have been added in recent years. This rich diversity requires taxonomic revision and ordering. Here, a new genus, Mithridatocetus, is described from the Tortonian of Crimea and Caucasus, with two species, M. eichwaldi and M. adygeicus (originally Kurdalagonus adygeicus); ‘Cetotherium’ mayeri (a nomen dubium) is also a member of this genus. In comparison with other Cetotheriinae, Mithridatocetus is distinguished by the autapomorphic shape of the tympanic bulla with the swollen main ridge, the lowered anterior portion of the involucrum and the oblique anterolateral margin; such synapomorphies, as a transversely narrow squamosal with the ventromedially oriented postglenoid process (shared with Eucetotherium), a squamosal cleft (shared with Kurdalagonus) and an oval surface of the compound posterior process of the tympanoperiotic on the posterolateral skull wall (shared with Brandtocetus); and a unique combination of a high neurocranium and a long and robust paroccipital process. The genus Kurdalagonus is redefined here as containing only one described species, K. mchedlidzei. Therefore, the group Cetotheriinae is now restricted to the latest Serravallian and Tortonian of the Eastern Paratethys and includes at least five genera: Cetotherium, Brandtocetus, Kurdalagonus, Mithridatocetus and Zygiocetus. In addition, ?Cetotherium priscum and C. incertum are considered to be nomina dubia; ‘Cetotherium’ klinderi and ‘Cetotherium’ pusillum require more complete specimens for reassessment; ‘Cetotherium’ maicopicum and Eucetotherium helmersenii require further research to identify their taxonomical affinities.
Multicompartment analysis of protein‐restricted phenylketonuric mice reveals amino acid imbalances in brain
Authors: Vogel Kara R. , Arning Erland , Bottiglieri Teodoro , Gibson K. Michael 
Published: October 2016

AbstractBackgroundThe mainstay of therapy for phenylketonuria (PKU) remains dietary protein restriction. Developmental and neurocognitive outcomes for patients, however, remain suboptimal. We tested the hypothesis that mice with PKU receiving protein‐restricted diets would reveal disruptions of brain amino acids that shed light on these neurocognitive deficits.MethodPhenylalanine hydroxylase‐deficient (PKU) mice and parallel controls (both wild‐type and heterozygous) were fed custom diets containing 18, 6, and 4 % protein for 3 weeks, after which tissues (brain, liver, sera) were collected for amino acid analysis profiling.ResultsPhenylalanine (phe) was increased in all tissues (p < 0.0001) of PKU mice and improved with protein restriction. In sera, decreased tyrosine (p < 0.01) was corrected (defined as not significantly different from the level in control mice receiving 18 % chow) with protein restriction, whereas protein restriction significantly increased many other amino acids. A similar trend for increased amino acid levels with protein restriction was also observed in liver. In brain, the effects of protein restriction on large neutral amino acids (LNAAs) were variable, with some deficit correction (threonine, methionine, glutamine) and no correction of tyrosine under any dietary paradigm. Protein restriction (4 % diet) in PKU mice significantly decreased lysine, arginine, taurine, glutamate, asparagine, and serine which had been comparable to control mice under 18 % protein intake.ConclusionDepletion of taurine, glutamate, and serine in the brain of PKU mice with dietary protein restriction may provide new insight into neurocognitive deficits of PKU.
A Relational Approach to Genetic Counseling for Hereditary Breast and Ovarian Cancer
Authors: Forbes Shepherd Rowan , Browne Tamara Kayali , Warwick Linda 
Published: October 2016

AbstractEthical issues arise for genetic counselors when a client fails to disclose a genetic diagnosis of hereditary disease to family: they must consider the rights of the individual client to privacy and confidentiality as well as the rights of the family to know their genetic risk. Although considerable work has addressed issues of non‐disclosure from the client's perspective, there is a lack of qualitative research into how genetic counselors address this issue in practice. In this study, a qualitative approach was taken to investigate whether genetic counselors in Australia use a relational approach to encourage the disclosure of genetic information from hereditary breast and ovarian cancer (HBOC) clients among family members; and if so, how they use it. Semi‐structured qualitative interviews were conducted with 16 genetic counselors from selected states across Australia. Data collection and analysis were guided by a basic iterative approach incorporating a hybrid methodology to thematic analysis. The findings provide indicative evidence of genetic counselors employing a relational approach in three escalating stages––covert, overt and authoritative––to encourage the disclosure of genetic information. The findings lend credence to the notion that genetic counselors envision a form of relational autonomy for their clients in the context of sharing genetic information, and they depart from individualistic conceptions of care/solely client‐centered counseling when addressing the needs of other family members to know their genetic status.
Surface Dilational Rheology, Foam, and Core Flow Properties of Alpha Olefin Sulfonate
Authors: Liu Hongsheng , Han Peihui , Sun Gang , Pan Feng , Li Bo , Wang Jingqin , Lv Changsen 
Published: October 2016

AbstractThe surface tension, surface dilational rheology, foaming and displacement flow properties of alpha olefin sulfonate (AOS) with inorganic salts were studied. The foam composite index (FCI), which reflects foaming capacity and foam stability, is used to evaluate foam properties. It is found that sodium and calcium salts can lead to decreases in AOS surface tension, critical micelle concentration, and molecular area at the gas–liquid interface. Sodium ions reduce the surface dilational viscoelasticity (E) and FCI of AOS, while calcium ions can enhance theEof AOS and make the FCI of AOS reach a maximum. In the solution containing calcium and sodium ions, the FCI of AOS is improved. Crude oil reduces the FCI of AOS. Injection pressure and displacing efficiency of AOS alternating carbon dioxide (CO2) injection are higher than injections of water alternating with CO2or CO2alone in low permeability cores.
Neuronal exosomes reveal Alzheimer's disease biomarkers in Down syndrome
Authors: Hamlett Eric D. , Goetzl Edward J. , Ledreux Aurélie , Vasilevko Vitaly , Boger Heather A. , LaRosa Angela , Clark David , Carroll Steven L. , Carmona‐Iragui María , Fortea Juan , Mufson Elliott J. , Sabbagh Marwan , Mohammed Abdul H. , Hartley Dean , Doran Eric , Lott Ira T. , Granholm Ann‐Charlotte 
Published: October 2016

AbstractIntroductionIndividuals with Down syndrome (DS) exhibit Alzheimer's disease (AD) neuropathology and dementia early in life. Blood biomarkers of AD neuropathology would be valuable, as non‐AD intellectual disabilities of DS and AD dementia overlap clinically. We hypothesized that elevations of amyloid β (Aβ) peptides and phosphorylated‐tau in neuronal exosomes may document preclinical AD.MethodsAD neuropathogenic proteins Aβ1–42, P‐T181‐tau, and P‐S396‐tau were quantified by enzyme‐linked immunosorbent assays in extracts of neuronal exosomes purified from blood of individuals with DS and age‐matched controls.ResultsNeuronal exosome levels of Aβ1–42, P‐T181‐tau, and P‐S396‐tau were significantly elevated in individuals with DS compared with age‐matched controls at all ages beginning in childhood. No significant gender differences were observed.DiscussionThese early increases in Aβ1–42, P‐T181‐tau, and P‐S396‐tau in individuals with DS may provide a basis for early intervention as targeted treatments become available.