bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐cycle‐regulatory elements and the control of cell differentiation in the budding yeast
Authors: Wittenberg Curt , La Valle Roberto 
Published: August 2003

AbstractThe stable differentiation of cells into other cell types typically involves dramatic reorganization of cellular structures and functions. This often includes remodeling of the cell cycle and the apparatus that controls it. Here we review our understanding of the role and regulation of cell cycle control elements during cell differentiation in the yeast, Saccharomyces cerevisiae. Although the process of differentiation may be more overtly obvious in metazoan organisms, those systems are by nature more difficult to study at a mechanistic level. We consider the relatively well‐understood mechanisms by which mating‐type switching and the pheromone‐induced differentiation of gametes are coupled to the cell cycle as well as the more obscure mechanisms that govern the remodeling of the cell cycle during meiosis and filamentous growth. In some cases, the cell cycle is a primary stimulus for differentiation whereas, in other cases, the signals that promote differentiation alter the cell cycle. Thus, despite relative simplicity of these processes in yeast, the nature of the interplay between the cell cycle and differentiation is diverse. BioEssays 25:856–867, 2003. © 2003 Wiley Periodicals, Inc.
Collective specification of cellular development
Authors: Sachs Tsvi 
Published: August 2003

AbstractStudies of chimeras and in vivo development demonstrate that cell lineages are often quite variable, apparently in response to chance perturbations. This points to an apparent contradiction: although individual cells are the units of genetic information and differentiation, not all cellular events need be precise for the development of functional organisms. The social organization of ants can serve as a metaphor that helps understand the mechanisms that underlie such development. Ants suggest that continued cellular interactions and environmental conditions could specify the proportion and general location of specialized units. Leaf venation is used as a concrete example of this general principle. A signal produced continuously by all cells specifies a requirement for vein differentiation. The cells that respond by differentiation then transport the signal away from the leaf; this removal acting as a feedback indicating that the requirement is being met. Because transport increases during vein differentiation, early initiation occurs in excess and vein ‘competition’ for the signal assures an acceptable outcome. Such specification would be robust since it does not depend on events in any single cell, and chance events, rather than being corrected or reversed, may be built upon in reaching an expected, collective phenotype. The absence of detailed information preceding development distinguishes this hypothesis from the common alternatives of a program or blueprint. Collective specification would have important implications for developmental plasticity and evolution. BioEssays 25:897–903, 2003. © 2003 Wiley Periodicals, Inc.
Apoptosis—an introduction
Authors: Lawen Alfons 
Published: August 2003

AbstractApoptosis has become a major research area in the biomedical sciences. As there are more than 13,000 papers published annually on the topic, it is impossible to keep track on all developments in the area. The individual aspects of molecular control of apoptosis are well reviewed, but more general, introductory recent reviews into the field are lacking. This review aims to give a brief overview of the field, providing an introduction into the literature for students and newcomers; as it is written for the un‐initiated, wherever possible, review articles will be cited rather than original papers. BioEssays 25:888–896, 2003. © 2003 Wiley Periodicals, Inc.
Evolution of flowering in response to day length: Flipping the CONSTANS switch
Authors: Simpson Gordon G. 
Published: August 2003

AbstractDay length provides an important environmental cue by signalling conditions favourable for flowering. While Arabidopsis promotes flowering in response to long days, rice promotes flowering in response to short days. Despite this difference, a recent paper reveals that the network controlling this response is highly conserved in these distantly related plants, only the activity of one component is reversed.1 This reveals how an important developmental process can be diversified for adaptation by using the same set of genes, but regulating them differently. BioEssays 25:829–832, 2003. © 2003 Wiley Periodicals, Inc.
Mum, this bud's for you: Where do you want it? roles for Cdc42 in controlling bud site selection in Saccharomyces cerevisiae
Authors: Nelson W. James 
Published: August 2003

AbstractThe generation of asymmetric cell shapes is a recurring theme in biology. In budding yeast, one form of cell asymmetry occurs for division and is generated by anisotropic growth of the mother cell to form a daughter cell bud. Previous genetic studies uncovered key roles for the small GTPase Cdc42 in organizing the actin cytoskeleton and vesicle delivery to the site of bud growth,1,2 but a recent paper has also raised questions about how control of Cdc42 activity is integrated into a proposed hierarchical regulatory pathway that specifies a unique site of bud formation.3 BioEssays 25:833–836, 2003. © 2003 Wiley Periodicals, Inc.
From genes to therapeutics: Educating the government and the public on biomedical sciences—a Singapore experience
Authors: Phon Too Heng 
Published: August 2003

AbstractSingapore has a highly developed economy and has been recognized to have one of the best business environments in Asia. Her success is based largely on focused developments of key industries in traded services and manufacturing sectors. The challenge for Singapore is to utilize her small human resource to transform the present economy to a more knowledge‐intensive economy. Singapore has recently embarked on the ambitious goal of developing Biomedical Sciences as an industry. Educating the government and the public on various aspects of this new industry was identified as one of the essential steps towards this goal. The challenge was to inspire non‐biologists to embrace the life sciences. This review describes how a series of workshops were developed to address the needs and the challenges of educating the public and the government. BioEssays 25:913–917, 2003. © 2003 Wiley Periodicals, Inc.
Chemical and functional diversity of small molecule ligands for RNA
Authors: Hermann Thomas 
Published: August 2003

AbstractFunctional RNAs such as ribosomal RNA and structured domains of mRNA are targets for small molecule ligands that can act as modulators of the RNA biological activity. Natural ligands for RNA display a bewildering structural and chemical complexity that has yet to be matched by synthetic RNA binders. Comparison of natural and artificial ligands for RNA may help to direct future approaches to design and synthesize potent novel scaffolds for specific recognition of RNA targets. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Thermodynamics of aminoglycoside–rRNA recognition
Authors: Pilch Daniel S. , Kaul Malvika , Barbieri Christopher M. , Kerrigan John E. 
Published: August 2003

Abstract2‐Deoxystreptamine (2‐DOS) aminoglycosides are a family of structurally related broad‐spectrum antibiotics that are used widely in the treatment of infections caused by aerobic Gram‐negative bacilli. Their antibiotic activities are ascribed to their abilities to bind a highly conserved A site in the 16 S rRNA of the 30 S ribosomal subunit and interfere with protein synthesis. The abilities of the 2‐DOS aminoglycosides to recognize a specific subdomain of a large RNA molecule make these compounds archetypical models for RNA‐targeting drugs. This article presents a series of calorimetric, spectroscopic, osmotic stress, and computational studies designed to evaluate the thermodynamics (ΔG, ΔH, ΔS, ΔCp) of aminoglycoside–rRNA interactions, as well as the hydration changes that accompany these interactions. In conjunction with the current structural database, the results of these studies provide important insights into the molecular forces that dictate and control the rRNA binding affinities and specificities of the aminoglycosides. Significantly, identification of these molecular driving forces [which include binding‐linked drug protonation reactions, polyelectrolyte contributions from counterion release, conformational changes, hydration effects, and molecular interactions (e.g., hydrogen bonds and van der Waals interactions)], as well as the relative magnitudes of their contributions to the binding free energy, could not be achieved by consideration of structural data alone, highlighting the importance of acquiring both thermodynamic and structural information for developing a complete understanding of the drug–RNA binding process. The results presented here begin to establish a database that can be used to predict, over a range of conditions, the relative affinity of a given aminoglycoside or aminoglycoside mimetic for a targeted RNA site vs binding to potential competing secondary sites. This type of predictive capability is essential for establishment of a rational design approach to the development of new RNA‐targeted drugs. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Ribosomal crystallography: Peptide bond formation and its inhibition
Authors: Bashan Anat , Zarivach Raz , Schluenzen Frank , Agmon Ilana , Harms Joerg , Auerbach Tamar , Baram David , Berisio Rita , Bartels Heike , Hansen Harly A. S. , Fucini Paola , Wilson Daniel , Peretz Moshe , Kessler Maggie , Yonath Ada 
Published: August 2003

AbstractRibosomes, the universal cellular organelles catalyzing the translation of genetic code into proteins, are protein/RNA assemblies, of a molecular weight 2.5 mega Daltons or higher. They are built of two subunits that associate for performing protein biosynthesis. The large subunit creates the peptide bond and provides the path for emerging proteins. The small has key roles in initiating the process and controlling its fidelity.Crystallographic studies on complexes of the small and the large eubacterial ribosomal subunits with substrate analogs, antibiotics, and inhibitors confirmed that the ribosomal RNA governs most of its activities, and indicated that the main catalytic contribution of the ribosome is the precise positioning and alignment of its substrates, the tRNA molecules.A symmetry‐related region of a significant size, containing about two hundred nucleotides, was revealed in all known structures of the large ribosomal subunit, despite the asymmetric nature of the ribosome. The symmetry rotation axis, identified in the middle of the peptide‐bond formation site, coincides with the bond connecting the tRNA double‐helical features with its single‐stranded 3′ end, which is the moiety carrying the amino acids. This thus implies sovereign movements of tRNA features and suggests that tRNA translocation involves a rotatory motion within the ribosomal active site.This motion is guided and anchored by ribosomal nucleotides belonging to the active site walls, and results in geometry suitable for peptide‐bond formation with no significant rearrangements. The sole geometrical requirement for this proposed mechanism is that the initial P‐site tRNA adopts the flipped orientation.The rotatory motion is the major component of unified machinery for peptide‐bond formation, translocation, and nascent protein progression, since its spiral nature ensures the entrance of the nascent peptide into the ribosomal exit tunnel. This tunnel, assumed to be a passive path for the growing chains, was found to be involved dynamically in gating and discrimination. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Recognition of double‐stranded RNA by proteins and small molecules
Authors: Carlson Coby B. , Stephens Olen M. , Beal Peter A. 
Published: August 2003

AbstractMolecular recognition of double‐stranded RNA (dsRNA) is a key event for numerous biological pathways including the trafficking, editing, and maturation of cellular RNA, the interferon antiviral response, and RNA interference. Over the past several years, our laboratory has studied proteins and small molecules that bind dsRNA with the goal of understanding and controlling the binding selectivity. In this review, we discuss members of the dsRBM class of proteins that bind dsRNA. The dsRBM is a ∼70 amino acid sequence motif found in a variety of dsRNA‐binding proteins. Recent results have led to a new appreciation of the ability of these proteins to bind selectivity to certain sites on dsRNA. This property is discussed in light of the RNA selectivity observed in the function of two proteins that contain dsRBMs, the RNA‐dependent protein kinase (PKR) and an adenosine deaminase that acts on dsRNA (ADAR2). In addition, we introduce peptide–acridine conjugates (PACs), small molecules designed to control dsRBM–RNA interactions. These intercalating molecules bear variable peptide appendages at opposite edges of an acridine heterocycle. This design imparts the potential to exploit differences in groove characteristics and/or base‐pair dynamics at binding sites to achieve selective binding. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: An analysis of x‐ray crystal structures
Authors: Vicens Quentin , Westhof Eric 
Published: August 2003

AbstractThe potential of RNA molecules to be used as therapeutic targets by small inhibitors is now well established. In this fascinating wide‐open field, aminoglycoside antibiotics constitute the most studied family of RNA binding drugs. Within the last three years, several x‐ray crystal structures were solved for aminoglycosides complexed to one of their main natural targets in the bacterial cell, the decoding aminoacyl–tRNA site (A site). Other crystallographic structures have revealed the binding modes of aminoglycosides to the three existing types of resistance‐associated enzymes. The present review summarizes the various aspects of the molecular recognition of aminoglycosides by these natural RNA or protein receptors. The analysis and the comparisons of the detailed interactions offer insights that are helpful in designing new generations of antibiotics. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Fluorescence‐based methods for evaluating the RNA affinity and specificity of HIV‐1 Rev–RRE inhibitors
Authors: Luedtke Nathan W. , Tor Yitzhak 
Published: August 2003

AbstractRNA plays a pivotal role in the replication of all organisms, including viral and bacterial pathogens. The development of small molecules that selectively interfere with undesired RNA activity is a promising new direction for drug design. Currently, there are no anti‐HIV treatments that target nucleic acids. This article presents the HIV‐1 Rev response element (RRE) as an important focus for the development of antiviral agents that target RNA. The Rev binding site on the RRE is highly conserved, even between different groups of HIV‐1 isolates. Compounds that inhibit HIV replication by binding to the RRE and displacing Rev are therefore expected to retain activity across groups of genetically diverse HIV infections. Systematic evaluations of both the RRE affinity and specificity of numerous small molecule inhibitors are essential for deciphering the parameters that govern effective RRE recognition. This article discusses fluorescence‐based techniques that are useful for probing a small molecule's RRE affinity and its ability to inhibit Rev–RRE binding. Rev displacement experiments can be conducted by observing the fluorescence anisotropy of a fluorescein‐labeled Rev peptide, or by quantifying its displacement from a solid‐phase immobilized RRE. Experiments conducted in the presence of competing nucleic acids are useful for evaluating the RRE specificity of Rev‐RRE inhibitors. The discovery and characterization of new RRE ligands are described. Eilatin is a polycyclic aromatic heterocycle that has at least one binding site on the RRE (apparent Kd ≈ 0.13 μM), but it does not displace Rev upon binding the RRE (IC50 > 3 μM). In contrast, ethidium bromide and two eilatin‐containing metal complexes show better consistency between their RRE affinity and their ability to displace a fluorescent Rev peptide from the RRE. These results highlight the importance of conducting orthogonal binding assays that establish both the RNA affinity of a small molecule and its ability to inhibit the function of the RNA target. Some Rev–RRE inhibitors, including ethidium bromide, Λ‐[Ru(bpy)2eilatin]2+, and Δ‐[Ru(bpy)2eilatin]2+ also inhibit HIV‐1 gene expression in cell cultures (IC50 = 0.2–3 μM). These (and similar) results should facilitate the future discovery and implementation of anti‐HIV drugs that are targeted to viral RNA sites. In addition, a deeper general understanding of RNA–small molecule recognition will assist in the effective targeting of other therapeutically important RNA sites. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Sequence and structure space of RNA‐binding peptides
Authors: Das Chandreyee , Frankel Alan D. 
Published: August 2003

AbstractStudies of RNA‐binding peptides, and recent combinatorial library experiments in particular, have demonstrated that diverse peptide sequences and structures can be used to recognize specific RNA sites. The identification of large numbers of sequences capable of binding to a particular site has provided extensive phylogenetic information used to deduce basic principles of recognition. The high frequency at which RNA‐binding peptides are found in large sequence libraries suggests plausible routes to evolve sequence‐specific binders, facilitating the design of new binding molecules and perhaps reflecting characteristics of natural evolution. © 2003 Wiley Periodicals, Inc. Biopolymers, 2003
Differences between endocrine surgeons and endocrinologists in the management of non-toxic multinodular goitre
Authors: Bhagat M C , Dhaliwal S S , Bonnema S J , Hegedüs L , Walsh J P 
Published: August 2003

Abstract

Background
It is not known whether the management of multinodular goitre differs between endocrinologists and endocrine surgeons.

Methods
A questionnaire containing a hypothetical case (a 42-year-old euthyroid woman with a 50–80-g multinodular goitre) and 11 variations on the case was sent to endocrinologists and endocrine surgeons in Australia.

Results
The response rate was 55 per cent, including 45 endocrine surgeons and 127 endocrinologists. For the index case, serum thyroid-stimulating hormone (TSH), fine-needle aspiration biopsy and ultrasonography were widely used by both groups. Thyroid antibodies and scintigraphy were ordered by a greater proportion of endocrinologists than surgeons, and computed tomography more frequently by surgeons than endocrinologists. Treatment recommendations differed significantly between specialties for the index case (endocrinologists: no treatment 65 per cent, thyroxine 22 per cent, surgery 10 per cent, radioiodine 3 per cent; surgeons: no treatment 67 per cent, thyroxine 2 per cent, surgery 31 per cent; P &lt; 0·001) and for seven of the variations. In particular, for a patient with suppressed TSH, most endocrinologists (60 per cent) recommended radioiodine treatment, whereas there was no consensus among surgeons (surgery 40 per cent, no treatment 36 per cent, radioiodine 21 per cent). For a patient with a partly intrathoracic goitre, most surgeons (88 per cent) recommended surgery, whereas there was no consensus among endocrinologists (surgery 45 per cent, no treatment 34 per cent, thyroxine treatment 13 per cent, radioiodine 8 per cent).

Conclusion
There are clinically significant differences between endocrine surgeons and endocrinologists in the management of multinodular goitre.
Laparoscopic compared with conventional treatment of acute adhesive small bowel obstruction
Authors: Wullstein C , Gross E 
Published: August 2003

AbstractBackgroundAlthough laparoscopy may be associated with fewer intra-abdominal adhesions and quicker recovery of bowel function, it remains unclear whether patients with acute small bowel obstruction (SBO) might benefit from laparoscopic techniques.MethodThe results of patients with acute SBO treated laparoscopically (LAP; n = 52) and conventionally (CONV; n = 52) were compared in a retrospective matched-pair analysis. Conversions were included in the laparoscopic group.ResultsComplete laparoscopic treatment was performed in 25 patients (48·1 per cent). Major intraoperative complications occurred in 15 patients in the LAP group and eight in the CONV group (P = 0·156). Intraoperative perforations were more frequent in patients who had undergone more than one previous laparotomy (P = 0·066). Postoperative complications occurred in ten patients (19·2 per cent) in the LAP group and in 21 patients (40·4 per cent) who had conventional surgery (P = 0·032). Bowel movements started 3·5 days after operation in the LAP group and 4·4 days after conventional operation (P = 0·001). The length of hospital stay was 11·3 and 18·1 days respectively (P &lt; 0·001).ConclusionLaparoscopic treatment of acute SBO was feasible in about half of these patients. Postoperative recovery was improved after laparoscopic procedures but the risk of intraoperative complications increased. A laparoscopic approach seems justified in a subset of patients.
Cold provocation testing and hand–arm vibration syndrome—an audit of the results of the Department of Trade and Industry scheme for the evaluation of miners
Authors:   Members of the Medical Reference Panel of the Department of Trade and Industry (UK) HAVS Compensation Scheme, Proud G , Burke F , Lawson I J , McGeoch K L , Miles J N V 
Published: August 2003

Abstract

Background
Hand–arm vibration syndrome (HAVS) is a major industrial disease that causes considerable morbidity among workers exposed to vibration. Compensation is paid to those affected in civil claims against employers and (in the UK) in claims made under Social Security legislation rules for Prescribed Disease A11. Diagnostic tests have been proposed but most are not objective. The cold provocation test (CPT), which is objective, is often included in the evaluation of HAVS.

Methods
A continuous audit was made of the findings recorded at the 18 HAVS test centres in the UK established to evaluate miners. The audit, and its outcome, were monitored by the Medical Reference Panel who advise the Department of Trade and Industry. This audit report constitutes the second analysis of the findings relating to the CPT.

Results
The CPT, with measurement of digital rewarming times, is of no value in assessing vibration-induced damage to the hands.

Conclusion
In its present format, the CPT should not be used for evaluating the vascular component of HAVS.