bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Genetics of Metastasis
Authors: Weber Georg F 
Published: July 2017

Abstract

Representing the least understood aspect of carcinogenesis, metastasis – the spread of cancer cells throughout the body – is frequently the cause of death from malignant growths. The underlying process of cancer cell dissemination is controlled by gene regulation programs in the tumour cells and in the host. The tumour cell intrinsic genetic programs of metastasis confer invasiveness and anchorage independence. The responsible genes are typically deregulated by aberrant expression or splicing. Metastasis suppressor genes, when expressed, can negatively regulate dissemination, and their loss of function may support tumour spread. Organ preference of metastasis depends on more complex tumour–host interactions. It is mediated by site‐specific molecular signals and formation of a premetastatic niche. The molecular genetics of metastasis has led to the development of diagnostic tests, based on gene expression profiles that help predict metastatic potential. Further, it has opened prospects for the targeting of the main culprits in antimetastasis therapy.

Key Concepts

Similar to other functions within cancer cells, the ability to metastasise is under positive and negative genetic controls.

Cancer metastasis is guided by two intrinsic characteristics of cancer cells, invasiveness and anchorage‐independent survival.

Cancer cell invasiveness constitutes the breaking of tumour cells through tissue barriers and represents the earliest manifestation of metastasis.

Invasiveness is mediated by aberrant expression or splicing of stress response genes, comprising secreted proteases, homing receptors, cytokine ligands and associated signalling molecules.

The acquisition of invasiveness by tumour cells is accompanied by a characteristic and reversible remodelling, called the epithelial–mesenchymal transition.

Cancers shed their tumour cells into the blood or lymph stream from the earliest stages of growth on; most cells die in the circulation.

Fully transformed cells can survive without anchorage for extended periods of time. They escape anoikis due to an upregulation in their energy metabolism.

The biologic activity of metastasis‐mediating gene products is extensively regulated by posttranscriptional mechanisms.

Besides the positive regulators of dissemination, there are gene regulation programs that antagonise cancer spread. Metastasis suppressor genes can curb dissemination and need to be inactivated for cancers to spread.

Gene expression programs of metastasis and specific tumour–host interactions encode consistent patterns of organ preference by individual malignancies. Circulating cancer cells can recognise target organs through the use of tissue markers and through establishing a premetastatic niche.
Superresolution Microscopy
Authors: Zimmermann Timo 
Published: July 2017

AbstractMore than a century after Ernst Abbe defined the optical diffraction limit and thus seemed to rule out the accurate visualisation of subcellular details below its threshold forever, several approaches now achieve resolutions significantly below it. Structured illumination microscopy, stimulated emission depletion microscopy and single‐molecule localisation‐based methods use different strategies to separate and visualise the cellular and molecular details that until now were lost in the blur of diffraction. This opens up new possibilities in the observation of biological processes at the smallest scales. The new field is only developing and still poses exciting challenges that require new instrumentation and new labeling strategies.Key ConceptsResolution in light microscopy is not limited anymore by diffraction even though the optical diffraction limit still exists.Superresolution microscopy requires local contrast between structures that can be achieved through different mechanisms.All superresolution concepts are based on the control of ‘on’ and ‘off’ states of fluorescence.Label properties contribute to the achievable resolution gain, and labelling is an essential part of the superresolution result.Most superresolution images require postprocessing, and care needs to be taken to avoid image artefacts.
Genotype–Phenotype Relationship in Inherited Disorders of Hearing Impairment
Authors: Hoefsloot Lies H , Roux Anne‐Francoise 
Published: July 2017

Abstract

Hearing impairment is a genetically heterogeneous disorder. Many causative genes have been described, and the number is still expanding. Nonsyndromic hearing impairment has several clinical characteristics that may point into the direction of a certain gene, but this is not often the case. Syndromic hearing impairment is characterised by additional clinical symptoms, which may direct diagnostics towards the analysis of specific genes. However, the distinction between nonsyndromic hearing impairment and the syndromic forms of the disorder is becoming blurred when looking at the causative genes. The spectrum of mutations from mild to severe in one gene can lead to completely different clinical symptoms, and the phenotype–genotype relation is ever expanding. The molecular diagnosis of hearing impairment is challenging but has benefited tremendously from the introduction of massive parallel sequencing techniques.

Key Concepts

Hearing impairment can be syndromic or nonsyndromic, but extensive overlap exists in the genes involved.

Specific clinical characteristics of nonsyndromic hearing impairment have limited value in determining which gene is involved.

Syndromic hearing impairment is caused by a plethora of genes, and severe versus mild mutations in the same gene can lead to very different phenotypes.

Molecular diagnosis of hearing impairment is preferably done using massive parallel sequencing techniques.

In the coming years more genes will be discovered to be involved in hearing impairment.
Molecular Genetics of Salivary Gland Cancer
Authors: Clair Jon Mallen‐St. , Ha Patrick 
Published: July 2017

AbstractMalignant salivary gland tumours are rare cancers of the head and neck with varied histopathology and clinical behaviour. The most common forms of salivary gland malignancies include mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC) and a number of rare disease entities. Novel sequencing techniques and chromosomal analysis have led to an increased understanding of the genetics of these tumours. A characteristic molecular profile of many of these tumours is emerging and involves balanced chromosomal translocations that result in the expression of unique fusion proteins, as well as mutations in a limited subset of genes. Further elucidation of the molecular mechanisms of this heterogeneous group of tumours will be essential to design effective targeted therapies for salivary gland malignancies.Key ConceptsMalignant salivary gland tumors are rare tumors with varied clinical behavior and histopathology.Advances in genetic sequencings has enabled improved insight into the genetics of salivary gland tumors.The majority of salivary gland malignancies result from well-defined chromosomal translocations.The chromosomal translocations found in salivary gland malignancies result in the expression of fusion genes that are important in the etiology of these tumors.Salivary gland tumors result from the deregulation of a limited number of pathways and genes – which may be enable the development of targeted therapeutics for these rare tumors.
Genetics of Mevalonate Kinase Deficiency
Authors: Schulert Grant S 
Published: July 2017

AbstractMevalonate kinase deficiency (MKD) represents a spectrum of clinical phenotypes that result from genetic variants in theMVKgene encoding mevalonate kinase. This spectrum ranges from the autoinflammatory disorder hyper‐IgD and periodic fever syndrome (HIDS) on the mild to the severe metabolic disorder mevalonic aciduria (MA). Homozygous variants inMVKlead to loss of enzyme function, and severity of clinical phenotype is linked to degree of residual enzyme activity. However, the disease has variable genotype/phenotype correlation, and additional modifier genes may exist to alter the clinical presentation. In addition,MVKvariants have recently been associated with expanded phenotypes including retinitis pigmentosa, disseminated superficial actinic porokeratosis and inflammatory bowel disease. Further genetic and pathophysiological understanding of MKD is needed to better predict clinical course and direct management.Key ConceptsMKD is a metabolic autoinflammatory disorder linked to variants inMVK, encoding mevalonate kinase.MKD is an autosomal recessive condition with variants leading to loss of enzyme function.Severely affected MKD patients have minimal mevalonate kinase activity and present with MA.Patients with some residual enzyme activity lack metabolic and central nervous system features and manifest HIDS.While there is significant genotype–phenotype association in MKD, there is a broad range of clinical features.In addition, there are reports of asymptomatic patients despite biallelic variants and patients with heterozygous variants and HIDS.There may exist modifier genes which impact the clinical features of MKD such as risk for complications including macrophage activation syndrome.MVK variants have recently been linked to additional disorders including retinitis pigmentosa (RP) and disseminated superficial actinic porokeratosis (DSAP).Further genetic and pathophysiologic understanding of MKD is needed to improve patient diagnosis and management.
Molecular Genetics of
M
enkes Disease
Authors: Comstra Heather S , Faundez Victor 
Published: July 2017

Abstract

Menkes disease is a recessive childhood disorder that results from systemic copper deficiency. This deficiency leads to loss of cuproenzyme function and subsequent defects in the hair, skin and vasculature. Patients also display severe neurodegeneration linked to copper deficiency in the brain. Menkes disease is monogenic and caused by loss‐of‐function mutations in the copper transporter ATP7A. ATP7A is responsible for the provision of copper to secretory cuproenzymes and for exporting excess copper out of the cell. Mutations in ATP7A associated with Menkes disease are heterogenous in both type and primary structure location, and no specific mutations are observed more frequently than others. Allelic variants that do not lead to complete loss of ATP7A function produce occipital horn syndrome and a form of spinal muscular atrophy.

Key Concepts

Menkes disease is an X‐linked recessive disorder with an occurrence of 1/40 000–1/360 000.

Menkes disease presents 2–12 months after birth as hair, skin and joint abnormalities and later progresses to severe neurodegeneration.

Loss‐of‐function mutations in the copper transporter ATP7A produce Menkes disease, and milder mutations produce occipital horn syndrome, characterised predominantly by connective tissue abnormalities, and a variant of spinal muscular atrophy.

ATP7A is a Golgi‐localised protein that provides copper to secretory cuproenzymes. Under conditions of excess intracellular copper, ATP7A localises to the plasma membrane where it pumps excess copper out of the cell.

Over 350 mutations have been identified in ATP7A that lead to Menkes disease. These mutations do not cluster to particular sequences in the gene and include a range of mutation types such as missense mutations, deletions and nonsense mutations, among others.

Loss of ATP7A‐dependent cuproenzyme function accounts for many of the phenotypes associated with Menkes disease. For example, lack of copper incorporation into the melanin‐producing enzyme tyrosinase leads to hypopigmentation in patients.

The pathogenesis of the severe neurodegeneration observed in Menkes patients is not well understood and is an active area of investigation.
Executive Functions in School‐age Children: Influence of Age, Gender, School Type and Parental Education
Authors: Jacobsen Geise Machado , de Mello Clarissa Martins , Kochhann Renata , Fonseca Rochele Paz 
Published: July 2017

Summary: This study aimed to evaluate whether age, gender, type of school and parental education could predict executive performance in school‐age children. Unconstrained, phonemic and semantic verbal fluency tasks (n = 402), as well as the Hayling Sentence Completion Test (n = 275) and the Random Number Generation task (n = 274) were administered to typically developing 6‐to‐12‐year‐old children. A hierarchical regression analysis was performed (p ≤ 0.05). The most significant explanatory models involved child age and parental education, as well as these two variables in addition to the type of school attended by the child. The main individual predictors of executive performance were age and school type. These results may be related to structural and functional alterations in the brain, an increased repertoire of cognitive strategies, the effects of education and the intensity of environmental cognitive stimulation. These findings may contribute to the development of stimulation and intervention programs for EF in clinical and educational settings.Copyright © 2017 John Wiley & Sons, Ltd.
Perceptions of Credibility for a Memory Report of a Single Versus Repeated Event
Authors: Weinsheimer Camille C. , Coburn Patricia I. , Chong Kristin , MacLean Carla L. , Connolly Deborah A. 
Published: July 2017

Summary: When a person experiences an event that has multiple similar instances (i.e., a repeated event), memories for details that change across instances are challenging to recall. We expected that third parties would perceive memory reports of instances of repeated events as less credible than they would unique (i.e., single) events. Undergraduates participated in a single or repeated event, during which critical details were presented. Participants were asked to recall the session 2 days later, and memory reports were video recorded. New participants then viewed one video and evaluated the credibility of the speaker's memory report. Overall, repeated‐event reports were seen as less credible than were single‐event reports, despite the reports being equally accurate. Although credibility research in the context of repeated events has focused exclusively on child populations, a range of applications exists for adults (e.g., criminal and industrial eyewitnesses, and asylum seekers); we discussed our findings in these areas.Copyright © 2017 John Wiley & Sons, Ltd.
Synthesis of 1,2‐Dihydrocyclobuta[b]quinoline Derivatives from Isocyanophenyl‐Substituted Methylenecyclopropanes
Authors: Liu Hou‐Lu , Yuan Yu‐Chao , Wei Yin , Shi Min 
Published: July 2017

AbstractA new protocol to synthesize 1,2‐dihydrocyclobuta[b]quinoline derivatives from isocyanophenyl‐substituted methylenecyclopropanes via a formal insertion of isocyanide carbon into a C−C bond has been developed. The reaction proceeds smoothly in the presence of silver carbonate (5 mol%) upon heating in a highly atom economic manner and exhibits broad substrate scope, giving the desired products in moderate to excellent yields. Furthermore, several transformations of the obtained products have been also demonstrated.magnified image
Secondary Phosphine Oxide Preligands for Palladium‐Catalyzed C–H (Hetero)Arylations: Efficient Access to Pybox Ligands
Authors: Ghorai Debasish , Müller Valentin , Keil Helena , Stalke Dietmar , Zanoni Giuseppe , Tkachenko Boryslav A. , Schreiner Peter R. , Ackermann Lutz 
Published: July 2017

AbstractC–H arylations of oxazolines were accomplished with a well‐defined palladium catalyst derived from a secondary bisdiamantyl phosphine oxide. The single‐component secondary phosphine oxide (SPO)‐palladium complex enabled C–H activations with aryl bromides and challenging aryl chlorides in the absence of directing groups, setting the stage for the step‐economical synthesis of pybox ligands under racemization‐free reaction conditions.magnified image
Enhanced Light Harvesting in Perovskite Solar Cells by a Bioinspired Nanostructured Back Electrode
Authors: Wei Jian , Xu Rui‐Peng , Li Yan‐Qing , Li Chi , Chen Jing‐De , Zhao Xin‐Dong , Xie Zhong‐Zhi , Lee Chun‐Sing , Zhang Wen‐Jun , Tang Jian‐Xin 
Published: July 2017

AbstractLight management holds great promise of realizing high‐performance perovskite solar cells by improving the sunlight absorption with lower recombination current and thus higher power conversion efficiency (PCE). Here, a convenient and scalable light trapping scheme is demonstrated by incorporating bioinspired moth‐eye nanostructures into the metal back electrode via soft imprinting technique to enhance the light harvesting in organic–inorganic lead halide perovskite solar cells. Compared to the flat reference cell with a methylammonium lead halide perovskite (CH3NH3PbI3−xClx) absorber, 14.3% of short‐circuit current improvement is achieved for the patterned devices with moth‐eye nanostructures, yielding an increased PCE up to 16.31% without sacrificing the open‐circuit voltage and fill factor. The experimental and theoretical characterizations verify that the cell performance enhancement is mainly ascribed by the broadband polarization‐insensitive light scattering and surface plasmonic effects due to the patterned metal back electrode. It is noteworthy that this light trapping strategy is fully compatible with solution‐processed perovskite solar cells and opens up many opportunities toward the future photovoltaic applications.
Mantle cell lymphoma: 2017 update on diagnosis, risk‐stratification, and clinical management
Authors: Vose Julie M. 
Published: July 2017

AbstractDisease OverviewMantle cell lymphoma (MCL) is a non‐Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard therapies and a median overall survival (OS) of 4‐5 years.DiagnosisDiagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX‐11 or a low Ki‐67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma.Risk StratificationThe MCL International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki‐67 proliferative index if available. The median OS for the low‐risk group was not reached (5‐year OS of 60%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group.Risk‐Adapted TherapyFor selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytotoxicRegimen followed by autologous stem cell transplantation should be considered. Rituximab maintenance after autologous stem cell transplantation has also improved the progression‐free and overall survival. For older symptomatic MCL patients with intermediate or high risk MIPI, combination chemotherapy with R‐CHOP, R‐Bendamustine, or a clinical trial should be considered. In addition, rituximab maintenance therapy may prolong the progression‐free survival. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), lenalidamide (anti‐angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase [BTK] inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Clinical trials with novel agents are always a consideration for MCL patients.
Modelling Spatial Variations of the Speed of Light
Authors: Balcerzak Adam , Da̧browski Mariusz P. , Salzano Vincenzo 
Published: July 2017

AbstractWe extend a new method to measure possible variation of the speed of light by using Baryon Acoustic Oscillations and the Hubble function onto an inhomogeneous pressure model of the universe. The method relies on the fact that there is a simple relation between the angular diameter distance maximum and the Hubble function (H) evaluated at the same maximum‐condition redshift, which includes the speed of light c. One limit of such a method was the assumption of the vanishing of spatial curvature (though, as it has been shown, a non‐zero curvature has negligible effect). In this paper, apart from taking into account an inhomogeneity, we consider non‐zero spatial curvature and calculate an exact relation between and H. Our main result is the evaluation if current or future missions such as Square Kilometer Array (SKA) can be sensitive enough to detect any spatial variation of c which can in principle be related to the recently observed spatial variation of the fine structure constant (an effect known as α‐dipole).
Invariant‐Based Pulse Design for Three‐Level Systems Without the Rotating‐Wave Approximation
Authors: Kang Yi‐Hao , Chen Ye‐Hong , Huang Bi‐Hua , Song Jie , Xia Yan 
Published: July 2017

AbstractIn this paper, a scheme is put forward to design pulses which drive a three‐level system based on the reverse engineering with Lewis‐Riesenfeld invariant theory. The scheme can be applied to a three‐level system even when the rotating‐wave approximation (RWA) can not be used. The amplitudes of pulses and the maximal values of detunings in the system could be easily controlled by adjusting control parameters. We analyze the dynamics of the system by an invariant operator, so additional couplings are unnecessary. Moreover, the approaches to avoid singularity of pulses are studied and several useful results are obtained. We hope the scheme could contribute to fast quantum information processing without RWA.
Copper–Alkyne Complexation Responsible for the Nucleolar Localization of Quadruplex Nucleic Acid Drugs Labeled by Click Reactions
Authors: Lefebvre Joël , Guetta Corinne , Poyer Florent , Mahuteau‐Betzer Florence , Teulade‐Fichou Marie‐Paule 
Published: July 2017

AbstractG‐Quadruplex(es) (G4) are noncanonical nucleic‐acid structures found in guanine‐rich sequences. They can be targeted with small molecules (G4 ligands) acting as reporters, for tracking both in vitro and in cells. We explored the cellular localization of PhenDC3, one of the most powerful G4 ligands, by synthesizing two clickable azide and alkyne derivatives (PhenDC3‐alk, PhenDC3‐az) and labeling them in situ with the corresponding Cy5 click partners. A careful comparison of the results obtained for the copper‐based CuAAC and copper‐free SPAAC methodologies in fixed cells implicated CuI/alkyne intermediates in the nonspecific localization of ligands (and fluorophores) to the nucleoli. By contrast, SPAAC yielded similar nucleoplasmic labeling patterns in fixed and live cells. Our findings demonstrate the need for great care when using CuAAC to localize drugs in cells, and show that SPAAC gives results that are more consistent between fixed and live cells.
Catalytic Intermolecular Dicarbofunctionalization of Styrenes with CO2 and Radical Precursors
Authors: Yatham Veera Reddy , Shen Yangyang , Martin Ruben 
Published: July 2017

AbstractA redox‐neutral intermolecular dicarbofunctionalization of styrenes with CO2 at atmospheric pressure and carbon‐centered radicals is described. This mild protocol results in multiple C−C bond‐forming reactions from simple precursors in the absence of stoichiometric reductants, thus exploiting a previously unrecognized opportunity that complements existing catalytic carboxylation events.