bluuebunny/crossref_metadata_2025_split huggingface dataset:
High Dose Rate Brachytherapy in the Treatment of Cervical Cancer: Preliminary Experience with Cobalt 60 Radionuclide Source—A Prospective Study
Authors: Ntekim Atara , Adenipekun Adeniyi , Akinlade Bidemi , Campbell Oladapo 
Published: December 2010

Iridium-192 is widely used for high-dose rate brachytherapy. Co-60 source with similar geometric and dosimetric properties are now available. It has a longer half life but higher energy than Iridium-192. If Co-60 source can produce similar results, it will be more economical for low resource settings. Objective To evaluate the acute gastrointestinal and genitourinary toxicity associated with Co-60 source in the brachytherapy of cervical cancer. Methods Seventy patients with cervical cancer received 45 Gy in 22 fractions of pelvic external beam radiotherapy and 19.5 Gy in 3 fractions of HDR with Co-60 source using tandem and ring applicators with 6 courses of cisplatin 50 mg/m2 and 5 fluorouracil 1000 mg/m2 every 3 weeks Toxicity was scored using NCI-CTC version 4.0. Results The median total BED (Gy10) for tumor was 86.2 (84.4–88.8) while that for rectum (BED Gy3) was 124.4 (120–133). Two patients (3%) had grade 3 gastrointestinal toxicity while all others had ≤grade 2 toxicity and this is comparable with previous results. Conclusion Co-60 as HDR brachytherapy source is tolerable and is economical for low resource settings.
Puberty Onset among Boys in Riyadh, Saudi Arabia
Authors: Alwan Ibrahim Al , Felimban Naila , Altwaijri Yasmin , Tamim Hani , Mutair Angham Al , Shoukh Mohamed , Tamimi Waleed 
Published: December 2010

Background The ages of onset of pubertal characteristics are influenced by genetic, geographic, dietary and socioeconomic factors; however, due to lack of country-specific norms, clinicians in Saudi Arabia use Western estimates as standards of reference for local children. Aims The aim of the Riyadh Puberty Study was to provide data on pubertal development to determine the average age of onset of pubertal characteristics among Saudi boys. Methods Cross-sectional study among male school children in Riyadh, Saudi Arabia, in 2006, 542 schoolboys, aged 6 to 16 years old, from diverse socioeconomic levels were selected into the sample using a cluster sample design. Tanner stages were ascertained during physical examination by pediatric endocrine consultants, and also trained pediatric residents and fellows. Results The mean age (standard deviation) at Tanner Stages 2, 3, 4, and 5 for pubic hair development of Saudi boys was 11.4 (1.6), 13.3 (1.3), 14.4 (1.0) and 15.1 (0.8) years old, respectively. For gonadal development, the mean age (standard deviation) at stages 2, 3, 4, and 5 were 11.4 (1.5), 13.3 (1.2), 14.3 (1.1) and 15.0 (0.9) years old, respectively. Conclusion The ages of onset of pubertal characteristics, based on gonadal development, among Saudi boys are comparable to those reported in Western populations.
Anti-annexin V Antibodies in Women with Recurrent Miscarriage
Authors: EL-Gharib M.N. , Elhawary T.M. , Elshourbagy S.H. , Morad M.A. 
Published: December 2010

Objective To determine the role of anti-annexin V antibodies (a-A5) as an etiologic factor in recurrent pregnancy failure. Study design Prospective observational study. Material and methods The study included ninety first trimester pregnant women who had a history of unexplained recurrent miscarriage (group I) with ninety well-matched pregnant women with a history of normal reproductive outcome allocated as control group (GII) and another ninety nonpregnant women (GIII). Sera from all women controls were analyzed for anti-annexin antibody measured by Elisa. Results The mean value of a-A5 was 11.37 ± 6.78, 7.7 ± 1.40 and 6.20 ± 0.95 ng/ml in groups I, II and III respectively. There was a significant increase in the mean value a-A5 among women with a history of recurrent miscarriage, compared with controls. The mean value was 13.92 ± 2.42 ng/ml among patients with unfavourable outcome, compared with a corresponding value of 6.95 V 0.58 ng/ml among women with favourable outcome. The receiver operator characteristic curve revealed that the cutoff value of a-A5 was 8.61 ng/ml. Conclusion This study emphasizes the relationship between anti-annexin V antibodies and recurrent miscarriage.
Dissimilatory Sulfite Reductase
Authors: Parey Kristian , Schiffer Alexander , Steuber Julia , Fritz Günter , Ermler Ulrich , Kroneck Peter MH 
Published: December 2010

AbstractDissimilatory sulfite reductase (dSiR) belongs to the group of oxidoreductases and is a key enzyme of the biogeochemical sulfur cycle. The enzyme is organized as a heterotetrameric α2β2, or a heterohexameric α2β2γ2complex, and catalyzes the reduction of sulfite (SO32−) to hydrogen sulfide (H2S) in a six‐electron transfer process as the final step of dissimilatory sulfate reduction. Thiosulfate (S2O32−) and trithionate (S3O62−) have been postulated as potential intermediates in this energy conserving process, which evolved in an early stage of prokaryotic life in an anoxic environment. Like assimilatory sulfite reductase (aSiR), dSiR also reduces nitrite to ammonia. Sulfite reductases and related nitrite reductases are the only known class of enzymes that couple a siroheme (an iron‐tetrahydroporphyrin of the isobacteriochlorin class) to an iron–sulfur cluster to construct a catalytically active redox center.
Calmodulin Interactions withCav1 andCav2 Voltage‐Gated Calcium ChannelIQDomains
Authors: Kim Eun Young , Findeisen Felix , Minor Daniel L 
Published: December 2010

AbstractHigh‐voltage‐activated calcium channels (CaV1s and CaV2s) are transmembrane protein complexes that couple membrane depolarization to cellular calcium entry. Because calcium is an intracellular messenger and CaVs are important calcium sources, CaVs have a key role in the conversion of electrical signals into the chemical signaling cascades that drive a variety of vital physiological processes in nerve and muscle. These include excitation‐contraction coupling, hormone release, gene regulation, and synaptic transmission. CaVs are regulated by a diverse set of feedback mechanisms. Two important forms of activity‐dependent feedback modulation involve interactions between calcium‐calmodulin (Ca2+/CaM) and the CaVα1pore‐forming subunit of CaV1s and CaV2s: calcium‐dependent inactivation (CDI) in which calcium influx promotes channel closing following activation, and calcium‐dependent facilitation (CDF), a process that enhances channel opening in response to elevated cytoplasmic calcium. The main site of action for Ca2+/CaM is a motif, known as anIQ domain, located on the C‐terminal cytoplasmic tail of the CaVα1pore‐forming subunit. Strikingly, different Ca2+/CaM lobes are responsible for CDI and CDF in CaV1 and CaV2 channels. Crystallographic studies have indicated a structural basis for the apparent inversion of lobe‐specific roles in CDI and CDF in which Ca2+/CaM binds CaV1 and CaV2 IQ domains in opposite orientations.
Medicinal Inorganic Chemistry: Continuum of Dose versus Response—From Deficiency through Optimal Intake to Toxicity
Authors: Thompson Katherine H. 
Published: December 2010

AbstractMetal‐ion essentiality is not a static concept. Over the course of the last several decades, essentiality has been redefined to broaden the definition beyond “necessary to support human life” to include “having a defined biochemical function.” The main effect of this redefinition has been to restrain the addition of additional ultratrace elements, present in the human body, but not clearly required in a specific amount in the daily nutrient intake, to the ever‐expanding list of known essential elements. Essential metal ions are associated not only with recognizable deficiency symptoms under conditions of inadequate intake but also with existing homeostatic mechanisms that regulate absorption, distribution, storage, and excretion of the metal‐ion in vivo. The Bertrand diagram is a schematic representation of the range of essential metal‐ion intake consistent with optimal nutrient intake, bounded on the lower intake range by deficiency symptoms and on the upper intake end, by increasingly severe toxicity symptoms. The continuum of dose versus response includes both tails of this spectrum for all essential metal ions. Not all metal ions are the same: each has an appropriate “window of optimal intake” whose width and concentration ranges vary widely from one metal ion to the other.
Medicinal Inorganic Chemistry: Ligand Design Objectives and Principles
Authors: Thompson Katherine H. 
Published: December 2010

AbstractMetal‐based pharmaceutical agents are composed of one or more metal ions and at least one ligand. Additional molecular substituents may include targeting moieties, linking groups, antioxidants, or pendant carbohydrates, or some combination of these. There are two main applications of metal‐based pharmaceutical agents: diagnostic and therapeutic. Ligand requirements for the two streams of development differ in some important ways, but are still based on the same basic principles for molecular design, including consideration of thermodynamic and hydrolytic stability, pharmacokinetics, molecular weight and charge, lipophilicity and hydrophilicity, aqueous solubility, functional groups, and ligand nontoxicity (sometimes achieved by using naturally occurring binding groups). Examples of the principles that are discussed in this article include Gd(III)‐based magnetic resonance imaging (MRI) contrast agents, Cu(II)‐clotrimazole, proposed as an antiparasitic agent,67Ga‐citrate for tumor imaging, and99 mTc(I)‐sestamibi for cardiac imaging.
Archaeal Ribosomes
Authors: Londei Paola 
Published: December 2010

Abstract

Ribosomes, the essential cellular organelles carrying out protein synthesis, have a basic design that is fundamentally conserved in all three kingdoms of life (Archaea, Bacteria and Eukarya). Nevertheless, there are ribosomal features specific of each kingdom. Archaeal ribosomes have a size and composition similar to those of their bacterial counterparts: they contain three
ribonucleic acid
(RNA) molecules, 16S, 23S and 5S RNA and 50–70 proteins depending on the species. However, the primary structures of both archaeal ribosomal RNA and r‐proteins are closer to those of eukaryotes. As many Archaea have adapted to function under conditions of extreme salt or temperature, their ribosomal components are highly resistant to such adverse conditions, and the overall ribosome structure often has an higher rigidity than that of mesophilic microorganisms. This makes archaeal ribosomes optimally suited for crystallographic studies, and in fact, high‐resolution three‐dimensional structures have been obtained with ribosomal crystals from halophilic and thermophilic Archaea. These studies pioneered the resolution at the atomic level of ribosome architecture, a feat that won the 2009 Nobel Prize in Chemistry to Ada Yonath, Thomas Steitz and Venki Ramakrishnan.

Key Concepts:

Ribosome structure is very well conserved in all cells. In Archaea, the small ribosomal subunits have certain structural features (‘bill’ and ‘lobes’) also seen in Eukarya but not in Bacteria.

Archaeal ribosomes are composed of 30S and 50S subunits that join to make a 70S particle. They contain 3 rRNA molecules (16S, 23S and 5S) and up to 68 ribosomal proteins.

The primary sequences of both archaeal rRNA and r‐proteins are closer to those of eukaryotes than to those of bacteria. All of the archaeal r‐proteins are represented in eukaryotes, whereas no r‐proteins are shared by Archaea and Bacteria only.

Archaeal ribosomes have a heterogeneous protein composition. Early branching Archaea (Crenarchaeota) tend to have protein‐richer ribosomes, whereas late‐branching species (halobacteriales, Thermoplasmatales) tend to have protein‐poorer ribosomes.

The ribosomes of the extremophilic Archaea show specific adaptations to harsh environmental conditions. In general, they have a more rigid structure than mesophilic ribosomes. Halophilic ribosomes increase their hydration capacity by having acidic instead of basic ribosomal proteins.
Histocompatibility Antigen Complex of Man
Authors: Mehra Narinder K , Kaur Gurvinder 
Published: December 2010

Abstract

The histocompatibility antigens are cell surface glycoproteins expressed on nucleated cells whose major function is to bind peptides within the cell or from outside and present them at the cell surface for inspection by T cells of the immune system. These antigens are a part of the major histocompatibility complex (MHC), which exists in most vertebrate species and whose products were originally defined as the most crucial elements controlling graft rejection. Human MHC research has revealed human leucocyte antigen (HLA) to be the most polymorphic genetic system in the mammalian genome, and this unique diversity parallels the need for diverse peptide sites within the MHC to combat a fast‐evolving range of pathogens. Clinical screening of HLA polymorphism is now an important prophylactic biomarker system for various diseases and a useful tool for development of peptide‐based vaccination approaches.

Key Concepts:

HLA is the most polymorphic component of the human genome. It is a part of the major histocompatibility complex that exists in many animal species.

The major function of HLA molecules is antigen presentation.

High degree of molecular diversity of classical HLA class I and class II molecules is a reflection of their direct role as antigen presenting molecules against a wide range of pathogens

MHC region is characterised by strong linkage disequilibrium between its loci such that conserved ancestral haplotypes can be identified.

There are population‐based differences in allelic distribution of MHC molecules primarily due to historical human migration patterns and varying microbial pressures in different geographical regions

An individual heterozygous at a particular HLA locus has an added advantage than homozygous as the two different HLA molecules can bind and present large number of peptides.

The function of the ubiquitous HLA class I gene products (HLA‐A, HLA‐B and HLA‐C) is to present endogenous peptides to responding CD8+ T cells, whereas the class II coded molecules (HLA‐DR, HLA‐DQ and HLA‐DP) have restricted tissue distribution and process exogenous peptides for presentation to CD4+ helper T cells

The antigen‐binding cleft of HLA class I molecules can bind peptides that are usually nonamers, whereas the HLA class II antigen‐binding cleft can bind longer peptides of 11–18 mers.

Polymorphisms in the MHC have been associated with disease susceptibility and varying rates of disease progression.

MHC matching is crucial in donor selection for haematopoietic stem cell and organ transplantation.
Rabies: Virus and Disease
Authors: Nadin‐Davis Susan A 
Published: December 2010

Abstract

Rabies is an acute encephalomyelitis, caused by a group of genetically related lyssaviruses. The primary sources of rabies are major animal reservoirs in the orders Chiroptera and Carnivora, although this deadly zoonosis may affect all mammals, including humans. Despite the availability of biologicals that are efficacious in preventing the disease, once clinical signs develop, the disease is almost invariably fatal and kills over 50 000 people annually. The most effective control measures involve parenteral dog vaccination and oral vaccination of wildlife. Genetic analysis of lyssaviruses is extending our understanding of their diversity and evolution. The mechanisms that contribute to viral pathogenesis are being explored by studying the molecular interactions of the viral components with host cell factors. Such knowledge may provide for new less costly vaccines and effective therapeutic interventions in the future.

Key Concepts:

Rabies is a neurological disease that can affect almost all mammals and is almost invariably fatal once clinical signs develop.

Rabies is caused by all members of the
Lyssavirus
genus, bullet‐shaped neurotropic viruses with small RNA genomes, which are normally transmitted in virus‐laden saliva through bites.

Humans rarely transmit the disease to other humans but are exposed through contact with rabid animals.

Prevention of human disease is undertaken by a regimen of timely post‐exposure prophylaxis.

Distinct
Lyssavirus
species and variants thereof are maintained in dogs in the developing world and by several wildlife species including foxes, skunks, raccoons, raccoon dogs, mongooses, jackals and many species of bats.

Through a series of viral–host interactions, rabies virus has evolved mechanisms that maintain the neural network required for its propagation and spread within the infected host while avoiding clearance by the host's immune system.

Knowledge of the diversity of the
Lyssavirus
genus is steadily expanding with increased surveillance and development of molecular tools to enable rapid characterisation of new isolates.

Current vaccines and biologicals are ineffective against the more diverse members of the genus thereby indicating that additional novel reagents may be required in the future.

Ultimately, control and eradication of rabies will require elimination of the disease from animal reservoirs through the application of efficacious and cost‐effective methods of animal vaccination.
Duisberg, Carl
Authors: Parascandola John 
Published: December 2010

Abstract

Carl Dusiberg (1861–1935) was a German chemist and industrial executive. He began working in the German dyestuffs industry in the late nineteenth century, when it was a rapidly expanding field. He and his colleagues produced many new dyestuffs and intermediates. His real strength, however, was in the area of management. Along with Carl Bosch, he was responsible for the merger of several German chemical companies into a large conglomerate, IG Farbenindustrie. It was the largest firm in Europe and dominated the chemical market. The company was ostracised after World War II for its collaboration with the Nazi regime (e.g. in the production of poison gas for the death camps) and its use of slave labour, but Duisberg died before these excesses took place.

Key Concepts:

Carl Dusiberg was involved in the rapid expansion of the German dye industry in the late nineteenth century.

Carl Duisberg was a cofounder of the German chemical conglomerate IG Farbenindustrie.

IG Farben collaborated with the Nazi regime during World War II.

He was (1861–1935) a German chemist and industry executive, a principal founder of the German firm I. G. Farbenindustrie AG.
Cystathionine β‐synthase (CBS) Deficiency: Genetics
Authors: Kožich Viktor , Kruger Warren D , Kraus Jan Peter 
Published: December 2010

AbstractCystathionine β‐synthase(CBS) is an enzyme that catalyses condensation of homocysteine and serine to cystathionine. CBS deficiency, an autosomal recessive trait with estimated population frequency of around 1:10 000–1:20 000, resembles in the most severe forms Marfan syndrome with thromboembolism and neurological impairment, whereas milder forms may manifest with only thromboembolism or may remain asymptomatic. Laboratory findings include grossly elevated plasma total homocysteine and in part of patients also elevated blood methionine; the latter feature is utilised in neonatal screening. CBS binds three cofactors: pyridoxal 5′‐phosphate, an allosteric activatorS‐adenosylmethionine and haem with as yet unresolved function. In theCBSgene, more than 150 different mutations have been described to date, almost 90% of them are missense variants. Although some of the mutations affectribonucleic acidprocessing and its stability, the majority of mutations lead to enzyme misfolding and misassembly, which may be in part rescued by chemical or molecular chaperones.Key Concepts:Cystathionine β‐synthase catalyses the first step in homocysteinetrans‐sulfuration.Cystathionine β‐synthase is a modular enzyme composed of a haem‐bindingN‐terminal domain, the catalytically active core and theC‐terminal autoinhibitory domain.More than 150 different pathogenic mutations have been described in theCBSgene, almost 90% of all mutantCBSalleles carry missense mutations.Misfolding and misassembly of mutant CBS subunits is a common pathogenic mechanism leading to CBS deficiency.Mutation topology predicts in part the behaviour of mutant CBS enzymes, solvent accessible mutations have less severe effect than those buried in the enzyme globule.Deficient CBS activity leads to gross elevation of plasma total homocysteine and often to elevated blood methionine levels.Phenotypic consequences of mutations in theCBSgene include thromboembolism and vascular occlusion, which is accompanied in some patients by lens dislocation, marfanoid features and varying degree of neurological involvement.Population frequency of clinically ascertained patients with CBS deficiency is one to two orders of magnitude lower than the frequency calculated from the prevalence of heterozygotes for pathogenic mutations; this observation indicates an ascertainment bias or lack of symptoms in many CBS‐deficient individuals.Murine models of CBS deficiency recapitulate in part the pathophysiology and organ involvement observed in human patients.
Sex Differences in Brain Function
Authors: McCarthy Margaret M 
Published: December 2010

Abstract

Sex differences in the brain come in many sizes, shapes and forms. The most robust differences between males and females are not surprisingly those directly relevant to reproduction. The neural underpinnings controlling sex behaviour and control of gonadal function are establishing during a developmental sensitive period by the differential hormonal milieu found in males versus females. Considerable advances have been made in identifying the cellular mechanisms of early organizational effects of testosterone and its metabolite estradiol, which then determine adult physiology and behaviour. These mechanisms are highly region‐specific and impact on cell death, axonal projections and synaptogenesis, resulting in a brain that combines varying degrees of maleness and femaleness. The study of reproductive endpoints is not only valid in its own right but also provides insight into the more subtle sex differences associated with cognition, emotionality, social behaviour and relative risk of neurological disorders and diseases of mental health.

Key Concepts:

During development sex‐specific hormones organize the brain into a male or female phenotype which is then activated by hormones in adulthood.

The largest magnitude sex differences in the brain are in areas associated with control of reproduction.

Hormones regulate growth factors, cell death, cell genesis and synaptogenesis to build sexually dimorphic neural circuits.

There are multiple cellular mechanisms of hormonally mediated sexual differentiation which vary by brain region and endpoint.

Because of the myriad of mechanisms and the impact of environment and experience, ultimately every brain is a moasic of masculine and feminine in varying degrees.