bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteosarcoma: Genetics of Inherited Susceptibility
Authors: Mirabello Lisa 
Published: November 2013

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumour that typically occurs in adolescents and young adults. OS incidence has been related to growth and height, age, gender, ethnicity, certain inherited cancer predisposition syndromes, abnormal bone growth and therapeutic radiation. However, most cases are sporadic (not associated with an inherited syndrome) and no specific genetic or environmental predisposing factor has been identified. A common genetic susceptibility locus has not been found.

Germline genetics refers to
deoxyribonucleic acid (DNA)
sequence changes that are inherited and present in all cells of the body versus an acquired or somatic mutation. Germline candidate gene association studies have identified several common single nucleotide polymorphisms (SNPs) associated with risk of OS, including genes important in growth, cell cycle checkpoint control and tumour immunity. Recently, the first genome‐wide association study was conducted and further expands our understanding of the germline genetics of OS.

Key Concepts:

Epidemiologic studies have provided many important clues about the aetiology of OS, including an association with bone growth, which have directed much of the search for candidate genes associated with risk of OS.

OS is associated with several rare inherited cancer predisposition syndromes (Li–Fraumeni syndrome, hereditary bilateral retinoblastoma, Bloom, Werner, Rothmund Thomson syndromes, and Diamond–Blackfan anemia) that are caused by highly penetrant germline mutations. These syndromes are not a common cause of OS.

Candidate gene association studies have suggested several polymorphisms associated with risk of OS; SNP associations in the following candidate genes have been replicated in two or more studies:
IGF2R
,
FGFR3
,
MDM2
,
TGFBR1
and
CTLA‐4
.

An agnostic genome‐wide association study has found two novel loci associated with risk of OS:
GRM4
gene and the 2p25.2 chromosomal region.

Studies are needed to expand these genetic association findings to more ethnic groups and in larger samples sizes to determine if these are stable associations.
Genetics of Human Social Behaviour
Authors: Ebstein Richard P , Melman Rachel‐Bachner , Lai Poh San , Monakhov Mikhail , Chew Soo Hong 
Published: November 2013

Abstract

Our species,

Homo sapiens

, displays the most multifaceted social behaviour ever to evolve, far exceeding all other social species from eusocial insects to our nearest primate relatives. This intricate social behaviour underpins our remarkable success in evolving from cooperation in small bands of hunter gatherers ∼100 000 years ago to the apex of globalisation that characterises the twenty‐first century political and economic institutions. Although our social brains are remarkably flexible, a significant part of our social behaviour is hardwired and embedded in our deoxyribonucleic acid (DNA) code. The human mind is not a
tabula rasa
, and our behaviour is constrained to a significant extent by our genes. That is not to say that environment is unimportant; along with the genetic code, the interaction between environment and genes makes us who we are. The overall role of genes and environment is revealed firstly by twin studies and then by leveraging the human genome project. The latter enables the identification of specific genes that, together with the environment, contribute to individual differences in human social behaviour.

Key Concepts:

Twin studies demonstrate that both genes and environment more or less equally contribute to individual differences in almost all human behaviour.

Diverse social phenotypes such as pair bonding, parenting, fairness, altruism, trust, economic behaviour, political attitudes and others are partially hardwired.

Two nonapeptide hormones, oxytocin (OT) and arginine vasopressin (AVP), are paramount human social hormones and have been the focus of attention of studies based on translational evidence from rodents, especially the vole.

Candidate gene association studies have provisionally shown that genes in the AVP and OT neural pathways also contribute to human social behaviour.

Other neural pathways and their associated genes, especially dopamine and serotonin, have also been identified and linked to human social behaviour.

Neuroeconomics, which employs the principles and techniques of behavioural economic games, paves the way towards finding common polymorphisms by employing economic games as phenotypes in molecular genetic studies.

Genome‐wide association studies (GWAS), which are agnostic and hypothesis free, offer the opportunity to identify many novel genes contributing to human social behaviour.

To leverage the power of GWAS and discover new ‘social’ genes, sharpened phenotypes such as incentivised laboratory ‘games’ need to be employed. Such laboratory‐based phenotypes strategically go beyond pencil and paper questionnaires ideally employed in panel studies and surveys.
Gene Therapy for Parkinson Disease
Authors: Choong Chi‐Jing , Mochizuki Hideki 
Published: November 2013

AbstractParkinson disease (PD) presents several features including the relative selective localisation of pathology to the substantia nigra and well‐defined motor symptoms caused by dopaminergic degeneration that make it an ideal target for gene therapy. Parallel progress in viral vector systems has made it possible to deliver therapeutic genes directly into the brain with reasonable safety. To date, gene therapy for PD is mainly based on symptomatic approaches that involve enzyme‐replacement strategies to restore dopamine (DA) levels or correct the functional perturbation of the basal ganglia caused by DA loss and disease‐modifying approaches that depend on delivery of neurotrophic factors and alteration of genetic causes of PD to protect neuronal functions and slow down or even halt disease progression. As supported by the increasing preclinical and clinical evidence, gene therapy may be a promising treatment to relieve the disabling nature of PD.Key Concepts:Gene therapy for PD focusses on symptomatic approach that involves enzyme‐replacement strategy and disease‐modifying approach that depends on addition of neurotrophic factors.Intrastriatal expression of genes TH, AADC and GCH, the three key enzymes for DA biosynthesis, can compensate for the decreased levels of DA in PD patients.An approach aiming at modulating STN activity is done by delivering gene GAD, the rate‐limiting enzyme for GABA synthesis.Neurotrophic factors including GDNF and NTN have potent trophic activity on dopaminergic neurons and play essential roles in the protection and restoration of neuronal cells.Novel viral vectors are capable of delivering genetic materials to target cells and inducing sustained transgene expression.Four candidates for PD gene therapy including EIAV‐AADC‐TH‐GCH, AAV2‐AADC, AAV2‐GAD and AAV2‐NTN are currently under clinical trial evaluation.
Personalised Cancer Medicine: Fulfilling the Promise
Authors: Olzscha Heidi , New Maria , La Thangue Nicholas B 
Published: November 2013

Abstract

The continual increase in global cancer incidence has created a huge need for new and more effective cancer drugs. However, success is often limited by the heterogeneity among patients, which frequently leads to the failure of patients to respond to a drug together with toxic side effects. Personalised medicine uses our advancing molecular understanding of disease to provide the most efficient medical care for individual patients, depending on their unique clinical, genetic and environmental state. Various types of biomarkers assist this process by enabling prediction of clinical outcome on treatment, or measuring effect of treatment which is then correlated with a clinical endpoint. Omics technologies such as genomics, transcriptomics and proteomics are crucially important in the personalised medicine approach as they enable the analysis of multiple and large datasets to stratify patients into responder subgroups.

Key Concepts:

The increase in global cancer incidence calls for more effective therapies.

Personalised medicine identifies patients who respond differently to treatment.

Genetic and molecular heterogeneity in tumours contributes to variable treatment response.

Biomarker development is crucial for personalised cancer medicine.

Biomarkers can be prognostic, predictive and pharmacodynamic.

Molecular imaging enables the response to treatment to be visualised.

High‐throughput omics technologies allow analysis of large amounts of information on the healthy and diseased states.
X Chromosome and Spermatogenesis Defects
Authors: Stouffs Katrien , Lissens Willy 
Published: November 2013

Abstract

Spermatogenesis, the process through which mature spermatozoa are formed, is a complex process requiring a very strict regulation. More than 2000 genes are involved in spermatogenesis. Part of these genes has a unique function during spermatogenesis. The X chromosome is special because only one copy is present in men, whereas women have two X copies. Moreover, the mammalian X chromosome is enriched for testis‐specific genes. This makes the X chromosome particularly interesting in view of male infertility. Although multiple studies have tried to identify mutations in X‐linked spermatogenesis genes, the number of causative mutations detected so far remains low. Nowadays, new techniques allow the analysis of the complete X chromosome in a single experiment. Within the next few years, the knowledge on the role of the X chromosome in male infertility (and consequently also in spermatogenesis) will increase.

Key Concepts:

Men are hemizygous for X‐chromosomal genes: men only have one X chromosome; mutations in X‐linked genes (might) have an immediate impact on spermatogenesis.

Spermatogenic failure can be caused by genetic defects.

The X chromosome is enriched for spermatogenesis genes.

Many multi‐copy genes involved in spermatogenesis are also expressed in cancer cell lines. Therefore, these are often described as cancer‐testis (CT) genes.

Many X‐linked genes that are preferentially expressed in testis have not (yet) been evaluated in view of male infertility.

The study of individual genes in view of male infertility has been disappointing because it is a time‐consuming process and often no differences with normal controls have been detected.
Electron‐Deficient Alloxazinium Salts: Efficient Organocatalysts of Mild and Chemoselective Sulfoxidations with Hydrogen Peroxide
Authors: Ménová Petra , Dvořáková Hana , Eigner Václav , Ludvík Jiří , Cibulka Radek 
Published: November 2013

AbstractA series of substituted alloxazinium perchlorates has been prepared and tested as catalysts for the oxidation of sulfides to sulfoxides with hydrogen peroxide. The logarithms of the observed rate constants of thioanisole oxidation correlate with the Hammett σ constants of the substituents on the alloxazinium catalysts, as well as with their reduction potentials E0′ and their pKR+ values, representing the alloxazinium salt/pseudobase equilibrium. The stronger the electron‐withdrawing substituent, the more efficient is the alloxazinium catalyst. The alloxazinium salts with a cyano or trifluoromethyl group in position 8 proved to be the most efficient, operating at room temperature at small loadings, down to 0.1 mol%, achieving turnover number values of up to 640 and acceleration by a factor of 350 relative to the non‐catalyzed oxidation. The 8‐cyanoalloxazinium perchlorate was evaluated as the best catalyst; however, due to its relatively good accessibility, the 8‐(trifluoromethyl)alloxazinium perchlorate seems to be the catalyst of choice for sulfoxidations with hydrogen peroxide. It was successfully tested for the sulfoxidation of a series of aliphatic and aromatic sulfides on a preparative scale. It produced the corresponding sulfoxides in quantitative conversions and with high isolated yields (87–98%). No over‐oxidation to sulfone was ever observed.magnified image
A large‐scale nationwide newborn screening program for pompe disease in Taiwan: Towards effective diagnosis and treatment
Authors: Yang Chia‐Feng , Liu Hao‐Chuan , Hsu Ting‐Rong , Tsai Fang‐Chih , Chiang Sheng‐Fong , Chiang Chuan‐Chi , Ho Hui‐Chen , Lai Chih‐Jou , Yang Tsui‐Feng , Chuang Sung‐Yin , Lin Ching‐Yuang , Niu Dau‐Ming 
Published: November 2013

AbstractThe aim of this study was to: (a) analyze the results of a large‐scale newborn screening program for Pompe disease, and (b) establish an effective diagnostic protocol to obtain immediate, valid diagnosis of infantile‐onset Pompe disease (IOPD) to promote earlier treatment and better outcomes. In this study, 402,281 newborns were screened for Pompe disease from January 1, 2008 to May 1, 2012. Infants with low acid α‐glucosidase (GAA) activity were referred to Taipei Veterans General Hospital for diagnostic confirmation. Physical examination, biochemical parameter (creatine kinase [CK], alanine transaminase, aspartate aminotransferase, and lactate dehydrogenase), and echocardiogram assessments were performed immediately to effectively differentiate IOPD from suspected late‐onset Pompe disease (LOPD) or false‐positive cases with pseudodeficiency mutation. Six infants with IOPD all presented with hypotonia, extremely low GAA enzyme activity (≤0.5 µmol/L/hr) in initial dried blood spot analysis, high CK (≥250 U/L), and high left ventricular mass index (LVMI, ≥80 g/m2). By analyzing these parameters, IOPD was distinguished effectively and immediately from suspected LOPD and false‐positive cases. Except for the first referred case, five of the infants with IOPD received first‐time enzyme replacement therapy (ERT) within 4 hr of admission and exhibited marked improvement. Our findings indicate that certain clinical manifestations (hypotonia, high CK, enlarged LVMI, and extremely low GAA enzyme activity in initial dried blood spot analysis) can help in the rapid and effective differentiation of patients with IOPD from other patient with low GAA activity. Such differentiation allows for the early application of first‐time ERT and leads to better outcomes. © 2013 Wiley Periodicals, Inc.
Phenotypic and molecular characterization of 19q12q13.1 deletions: A report of five patients
Authors: Chowdhury Shimul , Bandholz Anne M. , Parkash Sandhya , Dyack Sarah , Rideout Andrea L. , Leppig Kathleen A. , Thiese Heidi , Wheeler Patricia G. , Tsang Marilyn , Ballif Blake C. , Shaffer Lisa G. , Torchia Beth S. , Ellison Jay W. , Rosenfeld Jill A. 
Published: November 2013

AbstractA syndrome associated with 19q13.11 microdeletions has been proposed based on seven previous cases that displayed developmental delay, intellectual disability, speech disturbances, pre‐ and post‐natal growth retardation, microcephaly, ectodermal dysplasia, and genital malformations in males. A 324‐kb critical region was previously identified as the smallest region of overlap (SRO) for this syndrome. To further characterize this microdeletion syndrome, we present five patients with deletions within 19q12q13.12 identified using a whole‐genome oligonucleotide microarray. Patients 1 and 2 possess deletions overlapping the SRO, and Patients 3–5 have deletions proximal to the SRO. Patients 1 and 2 share significant phenotypic overlap with previously reported cases, providing further definition of the 19q13.11 microdeletion syndrome phenotype, including the first presentation of ectrodactyly in the syndrome. Patients 3–5, whose features include developmental delay, growth retardation, and feeding problems, support the presence of dosage‐sensitive genes outside the SRO that may contribute to the abnormal phenotypes observed in this syndrome. Multiple genotype–phenotype correlations outside the SRO are explored, including further validation of the deletion of WTIP as a candidate for male hypospadias observed in this syndrome. We postulate that unique patient‐specific deletions within 19q12q13.1 may explain the phenotypic variability observed in this emerging contiguous gene deletion syndrome. © 2013 Wiley Periodicals, Inc.
A Palladium‐Nanoparticle and Silicon‐Nanowire‐Array Hybrid: A Platform for Catalytic Heterogeneous Reactions
Authors: Yamada Yoichi M. A. , Yuyama Yoshinari , Sato Takuma , Fujikawa Shigenori , Uozumi Yasuhiro 
Published: November 2013

AbstractWe report the development of a silicon nanowire array‐stabilized palladium nanoparticle catalyst, SiNA‐Pd. Its use in the palladium‐catalyzed Mizoroki‐Heck reaction, the hydrogenation of an alkene, the hydrogenolysis of nitrobenzene, the hydrosilylation of an α,β‐unsaturated ketone, and the C‐H bond functionalization reactions of thiophenes and indoles achieved a quantitative production with high reusability. The catalytic activity reached several hundred‐mol ppb of palladium, reaching a TON of 2 000 000.
Hybrid Surfactant Systems with Inorganic Constituents
Authors: Polarz Sebastian , Landsmann Steve , Klaiber Alexander 
Published: November 2013

AbstractSurfactants are molecules of enormous scientific and technological importance, which are widely used as detergents, emulsifiers, and for the preparation of diverse nanostructures. Their fascinating ability to form self‐organized structures, such as micelles or liquid crystals, originate from their amphiphilic architecture—a polar head group linked to a hydrophobic chain. While almost all known surfactants are organic, a new family of surfactants is now emerging, which combines amphiphilic properties with the advanced functionality of transition‐metal building blocks, for example, redox or catalytic activity and magnetism. These hybrid surfactants exhibit novel self‐organization features because of the unique size and electronic properties of the metal‐containing entities.
Effect of Growth Stage on Essential‐Oil Yield and Composition of Daucus sahariensis
Authors: Flamini Guido , Smaili Tahar , Zellagui Amar , Gherraf Noureddine , Cioni Pier Luigi 
Published: November 2013

AbstractThe essential oils obtained by hydrodistillation from Daucus sahariensis Murb. harvested at three different growth stages were characterized by GC/MS analysis. In total, 88 compounds were identified, with myristicin (29.8–51.7%), myrcene (6.7–31.1%), α‐pinene (11.6–14.8%), and limonene (5.3–11.5%) as main constituents. Monoterpene hydrocarbons were the most represented compounds in the oils of the plant samples collected during the flower‐budding and full‐flowering periods. On the contrary, during the fruiting stage, the oils were dominated by phenylpropanoids. The essential oils were subject of considerable variation in their composition during the various developmental stages, particularly concerning the content of myrcene that decreased significantly passing from the vegetative to the fruiting stage. Conversely, for myristicin, the opposite trend was observed. Furthermore, the essential‐oil yields were quite low during the flower‐budding phase (0.27%), but rapidly increased during plant development (0.63 and 0.68% for the flowering and fruiting phases, resp.).
Using annexin V‐coated magnetic beads to capture active tissue factor‐bearing microparticles from body fluids
Authors: Gieseler Frank , Gamperl Hans , Theophil Frederike , Stenzel Inga , Quecke Tabea , Ungefroren Hendrik , Lehnert Hendrik 
Published: November 2013

AbstractMicroparticles, found in all body fluids including peripheral blood, are important elements that regulate cellular interactions under both physiological and pathological conditions. They play an important role in blood clot formation and increased cell aggregation. However, little is known about the components of the microparticles and their mechanism of action. A method to quantify and assess the underlying mechanism of action of microparticles in pathologies is therefore desirable. We present a specific method to isolate cell‐derived microparticles from malignant effusions using annexin V‐coated magnetic microbeads. The microparticles can be detected by flow cytometry. Our results show that the microparticles can be isolated with >80% specificity when bound to annexin V‐coated magnetic beads, which was originally developed for the detection of apoptotic cells. We also show that the isolated microparticles were still functionally active and can be used for further analysis. Thus, our method enables isolation as well as structural and functional characterisation of the microparticles which are produced in numerous patho‐physiological situations. This should help gain a deeper insight into various disease situations, which in turn should pave the way for the development of novel drugs and specific therapy strategies.
The Series of Rare Earth Complexes [Ln2Cl6(μ‐4,4′‐bipy)(py)6], Ln=Y, Pr, Nd, Sm‐Yb: A Molecular Model System for Luminescence Properties in MOFs Based on LnCl3 and 4,4′‐Bipyridine
Authors: Matthes Philipp R. , Nitsch Jörn , Kuzmanoski Ana , Feldmann Claus , Steffen Andreas , Marder Todd B. , Müller‐Buschbaum Klaus 
Published: November 2013

AbstractA series of 12 dinuclear complexes [Ln2Cl6(μ‐4,4′‐bipy)(py)6], Ln=Y, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, (1–12, respectively) was synthesized by an anhydrous solvothermal reaction in pyridine. The complexes contain a 4,4′‐bipyridine bridge and exhibit a coordination sphere closely related to luminescent lanthanide MOFs based on LnCl3 and 4,4‐bipyridine. The dinuclear complexes therefore function as a molecular model system to provide a better understanding of the luminescence mechanisms in the Ln‐N‐MOFs [Ln2Cl6(4,4′‐bipy)3]⋅2(4,4′‐bipy). Accordingly, the luminescence properties of the complexes with Ln=Y, Sm, Eu, Gd, Tb, Dy, (1, 4–8) were determined, showing an antenna effect through a ligand–metal energy transfer. The highest efficiency of luminescence is observed for the terbium‐based compound 7 displaying a high quantum yield (QY of 86 %). Excitation with UV light reveals typical emission colors of lanthanide‐dependent intra 4f–4f‐transition emissions in the visible range (TbIII: green, EuIII: red, SmIII: salmon red, DyIII: yellow). For the GdIII‐ and YIII‐containing compounds 6 and 1, blue emission based on triplet phosphorescence is observed. Furthermore, ligand‐to‐metal charge‐transfer (LMCT) states, based on the interaction of Cl− with EuIII, were observed for the EuIII compound 5 including energy‐transfer processes to the EuIII ion. Altogether, the model complexes give further insights into the luminescence of the related MOFs, for example, rationalization of Ln‐independent quantum yields in the related MOFs.
Self‐Association of an Enantiopure β‐Pentapeptide in Nematic Liquid Crystals
Authors: Bortolus Marco , Wright Karen , Toffoletti Antonio , Toniolo Claudio , Maniero Anna Lisa 
Published: November 2013

AbstractHerein, we report for the first time that nematic liquid‐crystalline environments drive the reversible self‐aggregation of an enantiopure β‐pentapeptide into oligomers with a well‐defined structure. The peptide contains four (1S,2S)‐2‐aminocyclopentane carboxylic acid (ACPC) residues and the paramagnetic β‐amino acid (3R,4R)‐4‐amino‐1‐oxyl‐2,2,5,5‐tetramethylpyrrolidine‐3‐carboxylic acid (POAC). The structure of the oligomers was investigated by electron paramagnetic resonance (EPR) spectroscopy, which allowed us to obtain the intermonomer distance distribution in the aggregates as a function of peptide concentration in two nematic liquid crystals, E7 and ZLI‐4792. The aggregates were modeled on the basis of the EPR data, and their orientation and order in the nematic phase were studied by the surface tensor method.