bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sigma Factors in Gene Expression
Authors: Chandrangsu Pete , Helmann John D 
Published: March 2014

Abstract

Sigma (σ) factors control the promoter selectivity of bacterial RNA polymerase (RNAP). On binding to RNAP, σ factors allow efficient promoter recognition and transcription initiation. Bacterial promoters are typically comprised of two hexameric
deoxyribonucleic acid (DNA)
sequences located approximately 10 and 35 bases upstream of the transcription start site (the −10 and −35 element, respectively). All bacteria contain a primary σ factor that is responsible for transcription of housekeeping genes necessary for growth and survival. In addition, many bacteria encode multiple alternative σ factors. The level and activity of the alternative σ factors are highly regulated and can vary depending on environmental or developmental signals. The synthesis of alternative σ factors allows the coordinated activation of discrete sets of genes through the recognition of distinct promoter sequences and thereby contributes to stress responses, motility, endospore formation and numerous other adaptive responses.

Key Concepts:

σ Factors are necessary for promoter recognition by RNA polymerase and efficient transcription initiation.

Transcription initiation is a highly regulated, multistep process.

σ Factors can be grouped into two families on the basis of their similarity to the housekeeping σ factor, σ
70
, or the nitrogen‐responsive σ factor, σ
54
.

Members of the σ
70
family generally contain four conserved domains (regions 1–4).

Most bacteria encode multiple alternative σ factors that direct transcription of genes in response to environmental cues and developmental transitions. Alternative σ
70
family proteins often lack region 1 and sometimes region 3 (minimally containing conserved regions 2 and 4).

σ Factor activity can be regulated at many levels, such as through sequestration by anti‐σ factors or by protolytic activation.
Poliovirus
Authors: Minor Philip D 
Published: March 2014

Abstract

Poliovirus is a member of the Picornavirus family, positive strand
ribonucleic acid (RNA)
viruses responsible for many human and animal diseases. The atomic structure of poliovirus was solved in the 1980s. Classification is now based on genomic sequences. The growth cycle of polio involves attachment to a specific receptor found only in the Old World monkeys and the higher primates. The viral proteins are translated as a single large precursor that is then cleaved by virus‐encoded proteases; initiation of translation is from an internal ribosomal entry site in the 5' noncoding region. The pathogenesis of poliovirus has been intensively studied, although many aspects remain poorly understood. The disease is most likely to be eradicated in the near future through use of vaccines. Of the three serotypes found in nature, wild‐type 2 has not been isolated since 1999 and no wild‐type 3 has been isolated since November 2012.

Key Concepts:

Picornaviruses are now classified on the basis of sequence comparisons.

Poliomyelitis was rare before the twentieth century when improving hygiene meant that infants were exposed to the virus after maternal antibody had declined.

Picornaviruses are classified into different species on the basis of their sequence, and recombination within a species is common.

High‐resolution molecular structures of the picornaviruses were obtained by X‐ray crystallography in the mid‐1980s.

Polio replication requires a specific receptor site found only in the Old World monkeys and the higher primates. It causes disease only in the higher primates, mostly humans.

Poliovirus initiates translation of its genome into protein through an internal ribosome entry site in contrast to most other eukaryotic messenger RNAs where initiation requires a free capped and methylated 5′ terminus.

Poliovirus replicates primarily in the gut; however, it also replicates in unidentified tissue types, in addition to the motor neurones of the central nervous system.

Live attenuated and killed virus vaccines are both used in controlling and eradicating polio depending on the circumstances.

The Global Polio Eradication Initiative is the largest public health initiative aimed at a single human disease in history.
Protist Evolution and Phylogeny
Authors: Pawlowski Jan 
Published: March 2014

AbstractThe beginning of this century brought spectacular changes in our understanding of eukaryote phylogeny, especially the early evolution of microeukaryotic lineages commonly called protists. Phylogenomic studies based on analysis of more than 200 genes produced a relatively well‐resolved tree of eukaryotes. Metagenetic studies usingenvironmental deoxyribonucleic acid (eDNA)revealed an extraordinary diversity of protist lineages, highlighting their great ecological and evolutionary importance. A new higher level classification of eukaryotes combining the results of microscopic and various ‘omics’ studies has been proposed. In this classification, the majority of eukaryotes are placed in seven monophyletic supergroups: Amoebozoa, Opisthokonta, Archaeplastida, Alveolata, Stramenopiles, Rhizaria and Excavata. Phylogenetic relationships between these supergroups and 11 independent eukaryotic lineages are relatively well established. However, there is no consensus concerning the position of the root of eukaryotic tree. Further single‐cell microscopic and genomic studies are also necessary for exploring the extraordinary diversity of protistan phyla revealed by the eDNA surveys.Key Concepts:Molecular phylogenies drastically changed our understanding of eukaryotes evolution.Phylogenomic data are essential for reconstructing the deep relationships of eukaryotes.Ribosomal phylogenies are useful for inferring relationships within protistan phyla and for species identification.Current protist classification comprises 4–7 supergroups and a few independent lineages.Important part of protist diversity has been uncovered by environmental DNA study.
DNA
Structure: Sequence Effects
Authors: Frank‐Kamenetskii Maxim D 
Published: March 2014

Abstract

Deoxyribonucleic acid (DNA)
sequence significantly affects the local stability of the DNA double helix. Two types of stability of the DNA duplex must be distinguished: thermodynamic stability and kinetic stability. Although stability of the DNA region depends mostly on its G•C content, it is stacking interaction between adjacent base pairs which have dominating contribution into the overall region stability. Sequence effects play especially important role in the stability of DNA helices different from B‐ and A‐forms such as Z‐DNA, parallel duplex, triplexes and quadruplexes. Depending on their particular sequence, different DNA sites are capable of adopting various unusual structures, among them: the cruciform, the triplex H form, the Z form and quadruplexes. These sequence‐dependent structures are stabilized by DNA negative supercoiling. They attract more and more attention in recent years because of their potential as targets for anticancer drugs and as tools in bio‐ and nanotechnology.

Key Concepts:

DNA thermodynamic stability determines equilibrium properties of the double helix but equilibrium is not always achievable.

DNA kinetic stability governs DNA behaviour at the characteristic time of experiment.

Stacking interactions, rather than base pairing, play the decisive role in determining the stability of the DNA double helix.

Highly sequence‐dependent DNA unusual structures dramatically affect DNA structural variability.

Unusual structures are thermodynamically unfavourable in linear DNA but their formation becomes possible in negatively supercoiled DNA.
Developmental Syndromes of Ras/
MAPK
Pathway Dysregulation
Authors: Malaquias Alexsandra C , Jorge Alexander AL 
Published: March 2014

Abstract

The term RASopathies designates a group of developmental syndromes caused by germline mutations in genes that encode proteins of the Ras/mitogen‐activated protein kinase (MAPK) signalling pathway. Ras/MAPK pathway controls several biological functions, such as cell proliferation, migration, differentiation and apoptosis. Similar molecular mechanisms disturbing the Ras/MAPK pathway were described in the RASopathies, including Noonan syndrome, Noonan syndrome with multiple lentigines, Noonan syndrome‐like disorder with loose anagen hair,
CBL
mutation‐associated syndrome, Costello syndrome, cardiofaciocutaneous syndrome, neurofibromatosis type 1 and Legius syndrome. Even though these syndromes share some overlapping features, genotype–phenotype correlations are well established for each of these, supporting the idea that they represent clinically distinct disorders. Owing to the similar mechanism encompassing Ras/MAPK germline and somatic mutations, Ras/MAPK pathway components have been considered a potential therapeutic target for RASopathies by promoting pathway modulation or small‐molecule inhibition.

Key Concepts:

Ras/MAPK is one of the most well‐known signalling pathways and plays an important role in critical cellular functions to normal development.

RASopathies are a group of medical genetic disorders caused by gain‐of‐function germline mutations in components of the Ras/MAPK signalling pathway.

Although the RASopathies may share clinically overlapping features, they also exhibit some individual ones that support the concept that they are distinct disorders.

Ras/MAPK germline mutations are similar to somatic mutations when associated with cancer, but they tend to be weakly activating.

Noonan syndrome is a frequent autosomal dominant disorder characterised by facial dysmorphisms, heart defects, short stature and learning disabilities.

The best clinical practice for each RASopathy could be defined if its genotype–phenotype correlation is understood.
Genetics and Genomics of Malignant Rhabdoid Tumours
Authors: Wei Darmood , Weissman Bernard E 
Published: March 2014

Abstract

Malignant rhabdoid tumours (MRTs) represent an aggressive paediatric cancer with limited treatment options. Although MRTs mainly arise in the kidney and brain of patients under the age of 8 years, they may appear in other major organs as well as in soft tissues. Remarkably, these tumours possess few mutations other than the ones that inactivate the SNF5/INI1 gene, the smallest member of the SWI/SNF chromatin‐remodelling complex. In addition, these cancers lack other hallmarks of adult malignancies including genomic instability, aberrant karyotypes and abnormal regulation of cellular stress‐response pathways. Their major defect appears to arise from epigenetic instability, presumably through changes in nucleosome positioning due to defective chromatin‐remodelling activity. Recent reports have shown that SNF5 loss affects key signalling pathways such as cell cycle regulation,
deoxyribonucleic acid (DNA)
damage repair and gene transcription. Thus, MRTs offer a unique model for studying the role of epigenetics in driving tumourigenesis and for the development of novel treatment approaches.

Key Concepts:

Malignant rhabdoid tumours are rare and aggressive paediatric cancers.

MRT was the first tumour in which mutations in the SWI/SNF chromatin‐remodelling complex were identified.

Inactivation of the SNF5/INI1 tumour suppressor gene drives MRT development.

MRTs often show no changes in copy number or karyotype.

The key mechanisms by which SNF5/INI1 loss induces MRT development remain unclear.

MRTs offer a unique model for epigenetic‐driven tumourigenesis.
Interpreting Disease Relevance of Amino Acid Substitutions
Authors: Vihinen Mauno 
Published: March 2014

Abstract

High‐throughput sequencing methods can generate large amounts of information about genetic variations; however, interpretation of this data has become a severe bottleneck for efficient use of genomic data, for example, in diagnostics. Identification of variations responsible for phenotypes is laborious and many times difficult task. Amino acid substitutions are among most common disease‐causing variants. Human genome codes for, on an average, approximately 11 000 such variants. Computational tools are needed to filter and rank raw variation datasets for further studies. Amino acid substitutions can have numerous effects, and mechanisms behind them are diverse. Therefore, different kinds of methods have been developed. Tolerance predictors aim at finding out likely harmful variants. Mechanism‐ and effect‐specific tools are dedicated for specific outcomes of variants.

Key Concepts:

Amino acid substitution is a change in protein sequence where a single residue is changed.

Benchmark dataset contains cases with known effect. It serves as the gold standard, for example, for method performance assessment and training machine learning‐based methods.

Human variome project (HVP) is an international organisation coordinating research and standards for variation research.

Next generation sequencing methods are fast nucleotide sequencing methods taking benefit of multiplexing and able of sequencing complete genomes very fast.

Performance measures are used to indicate performance of prediction methods. For full picture of performance, a number of measures should be reported.

Tolerance predictors are methods to predict whether amino acid substitutions are tolerated or not in a sequence.

Variation is a change in nucleotide or amino acid sequence in comparison with the reference sequence.
Palladium‐Catalyzed Intermolecular C‐2 Alkenylation of Indoles Using Oxygen as the Oxidant
Authors: Yan Zhao‐Lei , Chen Wen‐Liang , Gao Ya‐Ru , Mao Shuai , Zhang Yan‐Lei , Wang Yong‐Qiang 
Published: March 2014

AbstractA general and efficient palladium‐catalyzed intermolecular direct C‐2 alkenylation of indoles using oxygen as the oxidant has been developed. The reaction is of complete regio‐ and stereoselectivity. All products are E‐isomers at the C‐2‐position with no Z‐isomers and 3‐substituted products were detected.magnified image
Copper‐Catalyzed Diversity‐Oriented Three‐ and Five‐ Component Synthesis of Mono‐ and Dipropargylic Amines via Coupling of Alkynes, α‐Amino Esters and Aldehydes
Authors: Sharma Nandini , Sharma Upendra K. , Mishra Nigam M. , Van der Eycken Erik V. 
Published: March 2014

AbstractMono‐ as well as dipropargylic amines were synthesized using α‐amino esters as inexpensive building blocks under a single catalytic system (copper bromide, 100 °C, 4 h, toluene) where the reactant ratio (1a/2a/3a) acted as product specific switch. Both secondary (mono) as well as tertiary (di) propargylic amines formed via three‐ and five‐component coupling exhibited wide substrate scope with moderate to good yields and satisfactory diastereoselectivity in a few cases. The practical utility of the method is enhanced by providing a facile access to enantiopure propargylic amines via lipase‐catalyzed resolution along with synthesis of unsymmetrical dipropargylic amines, secondary propargylic amines bearing quaternary carbon centers and imidazolidin‐2‐ones.magnified image
Gp120 in the pathogenesis of human immunodeficiency virus–associated pain
Authors: Yuan Su‐Bo , Shi Yuqiang , Chen Jinghong , Zhou Xiangfu , Li Guangyu , Gelman Benjamin B. , Lisinicchia Joshua G. , Carlton Susan M. , Ferguson Monique R. , Tan Alai , Sarna Sushil K. , Tang Shao‐Jun 
Published: March 2014

ObjectiveChronic pain is a common neurological comorbidity of human immunodeficiency virus (HIV)‐1 infection, but the etiological cause remains elusive. The objective of this study was to identify the HIV‐1 causal factor that critically contributes to the pathogenesis of HIV‐associated pain.MethodsWe first compared the levels of HIV‐1 proteins in postmortem tissues of the spinal cord dorsal horn (SDH) from HIV‐1/acquired immunodeficiency syndrome patients who developed chronic pain (pain‐positive HIV‐1 patients) and HIV‐1 patients who did not develop chronic pain (pain‐negative HIV‐1 patients). Then we used the HIV‐1 protein that was specifically increased in the pain‐positive patients to generate mouse models. Finally, we performed comparative analyses on the pathological changes in the models and the HIV‐1 patients.ResultsWe found that HIV‐1 gp120 was significantly higher in pain‐positive HIV‐1 patients (vs pain‐negative HIV‐1 patients). This finding suggested that gp120 was a potential causal factor of the HIV‐associated pain. To test this hypothesis, we used a mouse model generated by intrathecal injection of gp120 and compared the pathologies of the model and the pain‐positive human HIV‐1 patients. The results showed that the mouse model and pain‐positive human HIV‐1 patients developed extensive similarities in their pathological phenotypes, including pain behaviors, peripheral neuropathy, glial reactivation, synapse degeneration, and aberrant activation of pain‐related signaling pathways in the SDH.InterpretationOur findings suggest that gp120 may critically contribute to the pathogenesis of HIV‐associated pain. Ann Neurol 2014;75:837–850
Crystalline structure and morphology of poly(L‐lactide) formed under high pressure
Authors: Yuan Chaosheng , Cheng Xuerui , Zhu Xiang , Wang Yongqiang , Yang Kun , Wang Zheng , Su Lei 
Published: March 2014

ABSTRACTThe poly(l‐lactide) (PLLA) samples were prepared by the annealing under 100 MPa at 75–145°C and 200 MPa at 105–145°C for 6 h, respectively. The crystalline structures, thermal properties and morphology were investigated using differential scanning calorimetry (DSC), wide‐angle X‐ray diffraction (WAXD), and scanning electron microscopy (SEM). On the basis of the DSC and WAXD results, it can be seen that the α′ form was formed by the annealing under 100 MPa at 85–95°C but not found under 200 MPa at 105–145°C. A phase diagram of PLLA crystal form under high pressure was constructed under the given experimental conditions, which displayed the α′ form was formed at limited temperature and pressure range. Besides, SEM suggested that the PLLA samples annealed under 100 MPa crystallize to form lamellar‐like crystals due to the low growth rate and the confined crystallization behavior under high pressure. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40637.
Cascade Control System‐Based Cost Effective Combination of Tensor Product Model Transformation and Fuzzy Control
Authors: Precup Radu‐Emil , Petriu Emil M. , Rădac Mircea‐Bogdan , Preitl Stefan , Fedorovici Lucian‐Ovidiu , Dragoş Claudia‐Adina 
Published: March 2014

AbstractThis paper proposes the combination of tensor product (TP)‐based model transformation and of fuzzy control as a cost effective cascade control system (CS) structure. A novel two‐step design approach is suggested. A parallel distributed compensation technique is used in the first step in the TP‐based design of the inner state feedback control loops which is next characterized by simple models using equivalent state feedback matrices. The modulus optimum method and the modal equivalent principle are used in the second step to design the Mamdani PI‐fuzzy controller in the outer control loops. The cost effective feature of the original cascade CS combination concerns the simplicity of the CS structure, of the controllers and of the design approach. The presentation is focused on the level control in horizontal three tank systems where two cascade CS structures are separately designed to control two water levels. The efficiency of the cascade CS structure is proved by real‐time experimental results for a laboratory three tank system. Comparisons with the Mamdani PI‐fuzzy CS and with the cascade combination of TP and PI CS are included.
Microscopic monitoring provides information on structure and properties during biocatalyst immobilization
Authors: Bidmanova Sarka , Hrdlickova Eva , Jaros Josef , Ilkovics Ladislav , Hampl Ales , Damborsky Jiri , Prokop Zbynek 
Published: March 2014

AbstractEnzymes have a wide range of applications in different industries owing to their high specificity and efficiency. Immobilization is often used to improve biocatalyst properties, operational stability, and reusability. However, changes in the structure of biocatalysts during immobilization and under process conditions are still largely uncertain. Here, three microscopy techniques – bright‐field, confocal and electron microscopy – were applied to determine the distribution and structure of an immobilized biocatalyst. Free enzyme (haloalkane dehalogenase), cross‐linked enzyme aggregates (CLEAs) and CLEAs entrapped in polyvinyl alcohol lenses (lentikats) were used as model systems. Electron microscopy revealed that sonicated CLEAs underwent morphological changes that strongly correlated with increased catalytic activity compared to less structured, non‐treated CLEAs. Confocal microscopy confirmed that loading of the biocatalyst was not the only factor affecting the catalytic activity of the lentikats. Confocal microscopy also showed a significant reduction in the pore size of lentikats exposed to 25% tetrahydrofuran and 50% dioxane. Narrow pores appeared to provide protection to CLEAs from the detrimental action of cosolvents, which significantly correlated with higher activity of CLEAs compared to free enzyme. The results showed that microscopy can provide valuable information about the structure and properties of a biocatalyst during immobilization and under process conditions.
A Sustainable Concept for the Supply of Pure CO2 as a C‐Source for Solar Fuels – Synergies of Biochar and Biogas
Authors: Liebeck Miriam , Dörr Timo , Vogel G. Herbert 
Published: March 2014

AbstractIn times of the German energy transition (“Energiewende”) chemical storage technologies achieve an increasing interest because only with their help can the energy of the excess electricity from wind and solar plants be stored in huge quantities in the form of hydrocarbons. The hydrogen generated by water electrolysis can be converted with carbon dioxide into hydrocarbons. In addition, pure CO2 must be available at a reasonable price. A sustainable concept is presented to meet this demand in CO2.
Hyperacute ischemic stroke without lesions on diffusion‐weighted imaging in a patient treated with rtPA thrombolysis
Authors: Jing Zhen , Zhang Shijun , Tang Jingjing , Xu Anding , Ruan Yiwen , Huang Li'an 
Published: March 2014

Key Clinical MessageWe report a comatose patient with severe neurological deficits who was without spontaneous language or movement. He had a good response to recombinant tissue plasminogen activator (rtPA) thrombolysis even though there were no detectable lesions on diffusion‐weighted imaging (DWI). DWI is very sensitive for diagnosing hyperacute ischemic stroke, and rtPA thrombolysis is the best treatment. However, rtPA thrombolysis in ischemic stroke patients without lesions on DWI has rarely been reported.