bluuebunny/crossref_metadata_2025_split huggingface dataset:
Models of intracellular transport and evolution of the Golgi complex
Authors: Beznoussenko Galina V. , Mironov Alexander A. 
Published: October 2002

AbstractWe have performed a systematic analysis of models explaining the mechanisms of the intracellular biosecretory transport. The models assessed include not only those based on one mechanism (the dissociation model (and its individual case, the vesicular model), the progression model (and its individual cases, the cisterna maturation/progression and the carrier maturation models), and the lateral diffusion model (and its individual case, the bolus model), but also combined models of transport (the percolating‐vesicles model and the synthetic model), including several transport mechanisms. Most of these models are not able to explain recent data on the evolution of genes involved in intracellular transport and Golgi evolution. The carrier maturation model proposing that fusion of the large cargo domain with the distal (closer to the plasmalemma) compartment precedes fission of the domain from the proximal compartment exhibits the best performance in correlation with the available information on evolution of the biosecretory pathway. Anat Rec 268:226–238, 2002. © 2002 Wiley‐Liss, Inc.
Living well through chronic illness: The relevance of virtue theory to patients with chronic osteoarthritis
Authors: Swift Teresa L. , Ashcroft Richard E. , Tadd Win , Campbell Alastair V. , Dieppe Paul A. 
Published: October 2002

AbstractObjectiveVirtues and vices possessed by patients may affect their quality of life and how well they cope with disease. The objective of this study is to assess the relevance of the concept of virtue and vice to patients with chronic arthritis.MethodsAristotle's theory of virtue and vice was used to construct a guide for in‐depth interviews, carried out with 5 patients with chronic osteoarthritis. Interviews were tape recorded, transcribed, and analyzed (using Interpretative Phenomenological Analysis) for information on personal qualities or intellectual approaches that participants thought necessary to thrive in the face of chronic disease.ResultsFive main themes emerged: strength, prudence, gratitude, self‐worth, and insight into flourishing. The data on each of these is compared with Aristotle's definitions of virtues and vices.ConclusionsAristotle's virtue theory can be applied to the narratives of these patients with chronic osteoarthritis, and may help in understanding their coping strategies and quality of life.
Bcl‐2 rescues motoneurons from early cell death in the cervical spinal cord of the chicken embryo
Authors: Sato Noboru , Sakuma Chie , Kato Hiromi , Milligan Carolanne E. , Oppenheim Ronald W. , Yaginuma Hiroyuki 
Published: October 2002

AbstractMotoneurons (MNs) in the cervical spinal cord of the chicken embryo undergo programmed cell death (PCD) between embryonic day (E) 4 and E5. The intracellular molecules regulating this early phase of PCD remain unknown. Here we show that introduction of Bcl‐2 by a replication‐competent avian retroviral vector prevented MN degeneration at E4.5, whereas the expression of the green fluorescent protein (GFP) was ineffective. Bcl‐2 expression did not affect the number of Islet‐1/2‐positive MNs at the onset of cell death (E4). However, when examined at the end of the cell death period (E5.5), the number of Islet‐1/2‐positive MNs was clearly increased in Bcl‐2‐transfected embryos compared with control and GFP‐transfected embryos. Activation of caspase‐3, which is normally observed in this early MN death, was also prevented by Bcl‐2. Thus, MNs in the cervical spinal cord appear to use intracellular pathway(s) for early PCD that is responsive to Bcl‐2. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 381–390, 2002
Planar cell polarity in the inner ear: How do hair cells acquire their oriented structure?
Authors: Lewis Julian , Davies Alex 
Published: October 2002

AbstractSensory hair cells in the ear and lateral line have an asymmetrical hair‐bundle structure, essential for their function as directional mechanotransducers. We examine four questions: (1) how does the planar asymmetry of the individual hair cell originate? (2) How are the orientations of neighboring hair cells coordinated? (3) How is the orientation of a group of hair cells controlled in relation to the ear as a whole? (4) How does the initial cell asymmetry lead to creation of the asymmetrical hair bundle? Studies of the development of hairs and bristles in Drosophila, combined with genetic data from vertebrates, suggest that the answer to questions (1) and (2) lies in asymmetries that develop at the cell cortex and at cell–cell junctions, generated by products of a set of primary planar cell polarity genes, including the transmembrane receptor Frizzled. A separate and largely independent mechanism controls asymmmetric allocation of cell fate determinants such as Numb at mitosis, in Drosophila and possibly in the ear also. Little is known about long‐range signals that might orient hair cells globally in the ear, but progress has been made in identifying a set of genes responsible for read‐out of the primary polarity specification. These genes, in flies and vertebrates, provide a link to assembly of the polarized cytoskeleton; myosin VIIA appears to belong in this group. The mechanism creating the staircase pattern of stereocilium lengths is unknown, but could involve regulation of stereocilium growth by Ca2+ ions entering via transduction channels. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 190–201, 2002
Understanding inner ear development with gene expression profiling
Authors: Chen Zheng‐Yi , Corey David P. 
Published: October 2002

AbstractUnderstanding the development of the inner ear requires knowing the spatial and temporal pattern of gene expression, and the functions of those gene products. In the last decade, hearing research has benefited tremendously from the progress of the human and mouse genome projects, as amply illustrated by the identification of many deafness genes in both human and mouse. However, the sheer amount of information generated from the genome project has far outpaced the rate at which it is utilized. Microarray technology offers a means to quantify the expression level of transcripts at a whole‐genome scale. Cross‐tissue comparisons will identify genes unique to the inner ear, which will expedite the identification of new deafness genes. Microdissection and subtraction after ablation of cell types can reveal genes expressed in certain cells, such as hair cells. Expression profiling of both inner ear and other tissues, under a variety of conditions (such as during development, with drug treatment or in knock‐out animals), can be used for cluster analysis to group genes of similar expression. Coexpression can suggest functional pathways and interactions between known genes, and can identify new genes in a structure or pathway. In this review we give examples for both transcription factors and cochlear structures. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 276–285, 2002
A review of inner ear fate maps and cell lineage studies
Authors: Kil Sung‐Hee , Collazo Andres 
Published: October 2002

AbstractA renewed interest in the development of the inner ear has provided more data on the fate and cell lineage relationships of the tissues making up this complex structure. The inner ear develops from a simple ectodermal thickening of the head called the otic placode, which undergoes a great deal of growth and differentiation to form a multichambered nonsensory epithelium that houses the six to nine sensory organs of the inner ear. Despite a large number of studies examining otic development, there have been surprisingly few fate maps generated. The published fate maps encompass four species and range from preotic to otocyst stages. Although some of these studies were consistent with a compartment and boundary model, other studies reveal extensive cell mixing during development. Cell lineage studies have been done in fewer species. At the single cell level the resulting clones in both chicks and frogs appear somewhat restricted in terms of distribution. We conclude that up until late placode stages there are no clear lineage restriction boundaries, meaning that cells seem to mix extensively at these early stages. At late placode stages, when the otic cup has formed, there are at least two boundaries located dorsally in the forming otocyst but none ventrally. These conclusions are consistent with all the fate maps and reconciles the chick and frog data. These results suggest that genes involved in patterning the inner ear may have dynamic and complex expression patterns. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 129–142, 2002
Mycothiol-Deficient
Mycobacterium smegmatis
Mutants Are Hypersensitive to Alkylating Agents, Free Radicals, and Antibiotics
Authors: Rawat Mamta , Newton Gerald L. , Ko Mary , Martinez Gladys J. , Fahey Robert C. , Av-Gay Yossef 
Published: October 2002

ABSTRACT

Mycothiol (MSH; 1
d
-
myo
-inosityl 2-[
N
-acetyl-
l
-cysteinyl]amido-2-deoxy-α-
d
-glucopyranoside) is the major low-molecular-weight thiol produced by mycobacteria. Mutants of
Mycobacterium smegmatis
mc
2
155 deficient in MSH production were produced by chemical mutagenesis as well as by transposon mutagenesis. One chemical mutant (mutant I64) and two transposon mutants (mutants Tn1 and Tn2) stably deficient in MSH production were isolated by screening for reduced levels of MSH content. The MSH contents of transposon mutants Tn1 and Tn2 were found to be less than 0.1% that of the parent strain, and the MSH content of I64 was found to be 1 to 5% that of the parent strain. All three strains accumulated 1
d
-
myo
-inosityl 2-deoxy-α-
d
-glucopyranoside to levels 20- to 25-fold the level found in the parent strain. The cysteine:1
d
-
myo
-inosityl 2-amino-2-deoxy-α-
d
-glucopyranoside ligase (MshC) activities of the three mutant strains were ≤2% that of the parent strain. Phenotypic analysis revealed that these MSH-deficient mutants possess increased susceptibilities to free radicals and alkylating agents and to a wide range of antibiotics including erythromycin, azithromycin, vancomycin, penicillin G, rifamycin, and rifampin. Conversely, the mutants possess at least 200-fold higher levels of resistance to isoniazid than the wild type. We mapped the mutation in the chemical mutant by sequencing the
mshC
gene and showed that a single amino acid substitution (L205P) is responsible for reduced MSH production and its associated phenotype. Our results demonstrate that there is a direct correlation between MSH depletion and enhanced sensitivity to toxins and antibiotics.
Biological Cost of Rifampin Resistance from the Perspective of
Staphylococcus aureus
Authors: Wichelhaus Thomas A. , Böddinghaus Boris , Besier Silke , Schäfer Volker , Brade Volker , Ludwig Albrecht 
Published: October 2002

ABSTRACT

Resistance determinants that interfere with normal physiological processes in the bacterial cell usually cause a reduction in biological fitness. Fitness assays revealed that 17 of 18 in vitro-selected chromosomal mutations within the
rpoB
gene accounting for rifampin resistance in
Staphylococcus aureus
were associated with a reduction in the level of fitness. There was no obvious correlation between the level of resistance to rifampin and the level of fitness loss caused by
rpoB
mutations. Among 23 clinical rifampin-resistant
S. aureus
isolates from six countries, only seven different
rpoB
genotypes could be identified, whereby the mutation 481His→Asn was present in 21 (91%) of these 23 isolates. The mutation 481His→Asn, in turn, which confers low-level rifampin resistance on its own, was not shown to be associated with a cost of resistance in vitro. The restriction to distinct mutations that confer rifampin resistance in vivo, as demonstrated here, appears to be determined by the Darwinian fitness of the organisms.
Proinflammatory and Cytotoxic Effects of Hexadecylphosphocholine (Miltefosine) against Drug-Resistant Strains of
Trypanosoma cruzi
Authors: Saraiva Victor B. , Gibaldi Daniel , Previato José O. , Mendonça-Previato Lucia , Bozza Marcelo T. , Freire-de-Lima Célio G. , Heise Norton 
Published: October 2002

ABSTRACT

The increased resistance of the protozoan parasite
Trypanosoma cruzi
to nitro derivatives is one of the major problems for the successful treatment of Chagas' disease. In the present study, we have tested the effects of 1-
O
-hexadecylphosphocholine (miltefosine) against strains of
T. cruzi
that are partially resistant (strain Y) and highly resistant (strain Colombiana) to the drugs in clinical use. As expected, epimastigotes of strain Colombiana showed higher levels of resistance to benznidazole than those of strain Y. However, the level of resistance to miltefosine was the same for both strains. This alkylphospholipid was also extremely toxic against intracellular amastigotes of both strains. This ether-lipid analogue induced in a dose-dependent manner the production of tumor necrosis factor alpha and nitric oxide (NO) radicals by infected and noninfected macrophages, suggesting that miltefosine may activate macrophages in vitro. Nevertheless, the cytotoxic effect of miltefosine against intracellular amastigotes was independent of the amount of NO produced by the infected macrophages since the same dose-response curves for miltefosine were observed when the NO production was blocked by the NO synthase inhibitor
N
G
-monomethyl-
l
-arginine monoacetate. Preliminary in vivo studies with BALB/c mice infected with strain Y indicated that oral miltefosine promoted survival and reduced the parasitemia to levels comparable to those observed when benznidazole was used. Four months after treatment, no parasites were detected in the blood or spleen tissue sections maintained in culture. Together, these results support the hypothesis that miltefosine may be used for the treatment of Chagas' disease, including cases caused by resistant strains of
T. cruzi
.
Histone Deacetylase Inhibitors Enhance
Candida albicans
Sensitivity to Azoles and Related Antifungals: Correlation with Reduction in
CDR
and
ERG
Upregulation
Authors: Smith W. Lamar , Edlind Thomas D. 
Published: October 2002

ABSTRACT

Histone acetylation and deacetylation play important roles in eukaryotic gene regulation. Several histone deacetylase (HDA) inhibitors have been characterized, including trichostatin A (TSA), apicidin, and sodium butyrate. We tested their effects on
Candida albicans
in vitro growth, heat sensitivity, and germ tube formation; minimal effects were observed. However, there was a dramatic effect of TSA on
C. albicans
sensitivity to the azoles fluconazole, itraconazole, and miconazole. Similar effects were observed with other HDA inhibitors and with the antifungals terbinafine and fenpropimorph, which target, as do azoles, enzymes in the ergosterol biosynthetic pathway. In contrast, HDA inhibitors had minimal effect on the activities of amphotericin B, flucytosine, and echinocandin, which have unrelated targets. Specifically, addition of 3 μg of TSA/ml lowered the itraconazole MIC for five susceptible
C. albicans
isolates an average of 2.7-fold at 24 h, but this increased to >200-fold at 48 h. Thus, the primary effect of TSA was a reduction in azole trailing. TSA also enhanced itraconazole activity against
Candida parapsilosis
and
Candida tropicalis
but had no effect with four less related yeast species. To examine the molecular basis for these effects, we studied expression of
ERG
genes (encoding azole and terbinafine targets) and
CDR/MDR1
genes (encoding multidrug transporters) in
C. albicans
cells treated with fluconazole or terbinafine with or without TSA. Both antifungals induced to various levels the expression of
ERG1
,
ERG11
,
CDR1
, and
CDR2
; addition of TSA reduced this upregulation 50 to 100%. This most likely explains the inhibition of azole and terbinafine trailing by TSA and, more generally, provides evidence that trailing is mediated by upregulation of target enzymes and multidrug transporters.
Erythromycin Resistance in
Borrelia burgdorferi
Authors: Terekhova Darya , Sartakova Marina L. , Wormser Gary P. , Schwartz Ira , Cabello Felipe C. 
Published: October 2002

ABSTRACT

Susceptibility testing of laboratory strains and clinical isolates of
Borrelia burgdorferi
indicates that resistance to erythromycin is present in them. Evaluation of the MICs, minimal bactericidal concentrations, and kinetics of bacterial killing of erythromycin suggests that this resistance is increased by preexposure to the antibiotic, is dependent on inoculum size, and may be the result of selection of subpopulations of bacterial cells with increased resistance.
Prognostic value of enhanced bone marrow angiogenesis in early B-cell chronic lymphocytic leukemia
Authors: Molica Stefano , Vacca Angelo , Ribatti Domenico , Cuneo Antonio , Cavazzini Francesco , Levato Domenico , Vitelli Gaetano , Tucci Luigi , Roccaro Aldo M. , Dammacco Franco 
Published: October 2002

Abstract
Because tumor progression is angiogenesis-dependent, angiogenesis density was investigated by immunohistochemistry and computed image analysis in bone marrow (BM) biopsies of 45 newly diagnosed patients with Binet stage A B-cell chronic lymphocytic leukemia (BCLL) and correlated to upstaging and progression-free survival during a 40-month follow-up period. Their microvessel areas and counts were significantly higher than those of patients with anemia due to iron or vitamin B12deficiencies. A cutoff value of 0.90 mm2 × 10−2 or greater of the microvessel area identified patients with earlier upstaging and shorter progression-free survival. When the cutoff was applied to the Rai subclassification, both Rai 0 and Rai I-II patients who upstaged and shortened the progression-free survival were classified correctly. Information of this type was not given by the microvessel counts. The cutoff did not correlate with other predictors representative of tumor mass or disease progression. The microvessel area correlated with the expression of angiogenic vascular endothelial growth factor (VEGF) by tumor tissue, and serum levels of VEGF were found to be of prognostic value. A causal relationship between risk of progression and BM angiogenesis in BCLL is suggested. A risk stratification inside Rai is proposed. The prognostic usefulness of BM angiogenesis in patients with BCLL is envisaged.
Regulation of thymic epithelium by keratinocyte growth factor
Authors: Erickson Matthew , Morkowski Stanislaw , Lehar Sophie , Gillard Geoffrey , Beers Courtney , Dooley James , Rubin Jeffrey S. , Rudensky Alexander , Farr Andrew G. 
Published: October 2002

AbstractHere we demonstrate that keratinocyte growth factor (KGF) and FGFR2IIIb signaling can affect development and function of thymic epithelium (TE) and that αβ-lineage thymocytes contribute to intrathymic levels of KGF. Thymocyte expression of KGF is developmentally regulated, being undetectable in CD3−4−8− thymocytes and expressed at highest levels by mature CD4 or CD8 thymocytes. Exposure of thymocyte-depleted fetal thymic lobes to KGF resulted in reduced thymic epithelial expression of class II major histocompatibility complex (MHC), invariant chain (Ii), and cathepsin L (CatL) molecules involved in thymocyte-positive selection and also stimulated expression of the cytokines interleukin 6 (IL-6) and thymic stromal-derived lymphopoietin (TSLP), while having little effect on IL-7 or stem cell factor expression. Within intact fetal thymic organ culture (FTOC), exogenous KGF impairs the generation of CD4 thymocytes. Two lines of evidence point to responsiveness of the medullary TE compartment to KGF and FGFR2IIIb signaling. First, the medullary compartment is expanded in intact FTOC exposed to KGF in vitro. Second, in the RAG-deficient thymus, where the thymocytes do not express detectable levels of KGF message, the hypoplastic medullary TE compartment can be expanded by administration of recombinant KGF in vivo. This expansion is accompanied by restoration of the normal profile of medullary TE–associated chemokine expression in the RAG2−/−thymus. Collectively, these findings point to a role for KGF and FGFR signaling in the development and function of thymic epithelium.
Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors
Authors: Haynes Nicole M. , Trapani Joseph A. , Teng Michèle W. L. , Jackson Jacob T. , Cerruti Loretta , Jane Stephen M. , Kershaw Michael H. , Smyth Mark J. , Darcy Phillip K. 
Published: October 2002

AbstractTumor cells are usually weakly immunogenic as they largely express self-antigens and can down-regulate major histocompatability complex/peptide molecules and critical costimulatory ligands. The challenge for immunotherapies has been to provide vigorous immune effector cells that circumvent these tumor escape mechanisms and eradicate established tumors. One promising approach is to engineer T cells with single-chain antibody receptors, and since T cells require 2 distinct signals for optimal activation, we have compared the therapeutic efficacy of erbB2-reactive chimeric receptors that contain either T-cell receptor zeta (TCR-ζ) or CD28/TCR-ζ signaling domains. We have demonstrated that primary mouse CD8+ T lymphocytes expressing the single-chain Fv (scFv)–CD28-ζ receptor have a greater capacity to secrete Tc1 cytokines, induce T-cell proliferation, and inhibit established tumor growth and metastases in vivo. The suppression of established tumor burden by cytotoxic T cells expressing the CD28/TCR-ζ chimera was critically dependent upon their interferon gamma (IFN-γ) secretion. Our study has illustrated the practical advantage of engineering a T-cell signaling complex that codelivers CD28 activation, dependent only upon the tumor's expression of the appropriate tumor associated antigen.
Identification of the hemangioblast in postnatal life
Authors: Pelosi Elvira , Valtieri Mauro , Coppola Simona , Botta Rosanna , Gabbianelli Marco , Lulli Valentina , Marziali Giovanna , Masella Barbara , Müller Robert , Sgadari Cecilia , Testa Ugo , Bonanno Giuseppina , Peschle Cesare 
Published: October 2002

AbstractPostnatal CD34+ cells expressing vascular endothelial growth factor receptor 2 (KDR) generate hematopoietic or endothelial progeny in different in vitro and in vivo assays. Hypothetically, CD34+KDR+ cells may comprise hemangioblasts bipotent for both lineages. This hypothesis is consistent with 2 series of experiments. In the first series, in clonogenic culture permissive for hematopoietic and endothelial cell growth, CD34+KDR+ cells generate large hemato-endothelial (Hem-End) colonies (5% of seeded cells), whereas CD34+KDR− cells do not. Limiting-dilution analysis indicates that Hem-End colonies are clonally generated by single hemangioblasts. Sibling cells generated by a hemangioblast, replated in unicellular culture, produce either hematopoietic or Hem-End colonies, depending on the specific culture conditions. Identification of endothelial cells was based on the expression of VE-cadherin and endothelial markers and with lack of CD45 and hematopoietic molecules, as evaluated by immunofluorescence, immunocytochemistry, and reverse transcription–polymerase chain reaction. Furthermore, endothelial cells were functionally identified using low-density lipoprotein (LDL) uptake and tube-formation assays. In the second series, to evaluate the self-renewal capacity of hemangioblasts, single CD34+KDR+ cells were grown in 3-month extended long-term culture (ELTC) through 3 serial culture rounds—that is, blast cells generated in unicellular ELTC were reseeded for a subsequent round of unicellular ELTC. After 9 months, 10% blasts from tertiary ELTC functioned as hemangioblasts and generated macroscopic Hem-End colonies in clonogenic culture. These studies identified postnatal hemangioblasts in a CD34+KDR+ cell subset, endowed with long-term proliferative potential and bilineage differentiation capacity. Although exceedingly rare, hemangioblasts may represent the lifetime source/reservoir for primitive hematopoietic and endothelial progenitors.