bluuebunny/crossref_metadata_2025 huggingface dataset:
Poverty, underdevelopment and infant mental health*
Authors: Richter LM
Published: May 2003

Abstract:  Very great advances have occurred in disciplinary and professional knowledge of infant development and its influence on subsequent development. This expertise includes the ways in which early experiences affect the capacity of mature individuals for social adjustment and productive competence, and promising methods of intervention to promote infant mental health and prevent adverse sequelae of risk conditions. However, very little of this knowledge has been applied in work among infants and children living in conditions of poverty and underdevelopment. This lack of application continues despite the enormous threats to the well‐being of infants and young children brought about by the combined effects of poverty and the AIDS pandemic, especially in southern Africa. Protein−energy malnutrition, maternal depression, and institutional care of infants and small children are cited as illustrative of areas in which interventions, and their evaluation, are desperately needed in resource‐poor countries. An argument is made for the critical importance of considering and addressing psychological factors in care givers and children in conditions of extreme material need. An example is provided of a simple intervention model based on sound developmental principles that can be implemented by trained non‐professionals in conditions of poverty and underdevelopment.
Parents’ descriptions of development and problems associated with infants with Turner syndrome: A retrospective study
Authors: Starke M , Albertsson Wikland K , Möller A
Published: May 2003

Objective:  To describe parents’ experiences of having an infant diagnosed with Turner syndrome and to determine whether receiving the diagnosis influenced the parents’ perceptions of their child's development and/or problems during infancy. In addition, we set out to determine whether the late development of the infant and the perceived problems were related to genotype.

Methods:  In this retrospective study, 54 parents (39 mothers and 15 fathers) from different families, each containing a girl with Turner syndrome, were interviewed in order to describe the development, feeding and overall well‐being of their daughter during infancy (defined as being before the age of 2 years).

Results:  Late development was reported to occur in the areas of motor activity (39%), fine motor control (59%), speech (37%) and language (37%). Feeding problems were frequent (74%) and screaming periods occurred in 41%. No differences were found between the responses of the parents whose children were diagnosed before 2 years of age and the responses of those whose children were diagnosed after 2 years of age. No differences were found concerning development and/or problems between the genotypes.

Conclusions:  Parents reported delayed development and problems to do with feeding and crying during infancy. These problems had an effect on their everyday life and that of their families, especially the problems relating to feeding. Parents reported that support and advice would have been of significant benefit in coping with the feeding difficulties. Parents were particularly concerned that the personnel at well‐baby clinics should be more knowledgeable about the difficulties that can occur in families with an infant with Turner syndrome.
Unethical practices in authorship of scientific papers
Authors: Bennett Dianne M , Taylor David McD
Published: May 2003

Over the past few decades, there has been an increase in the number of multi‐author papers within scientific journals. This increase, in combination with the pressure to publish within academia, has precipitated various unethical authorship practices within biomedical research. These include dilution of authorship responsibility, ‘guest’, ‘pressured’ and ‘ghost’ authorship, and obfuscation of authorship credit within by‐lines. Other authorship irregularities include divided and duplicate publication. This article discusses these problems and why the International Committee of Medical Journal Editors guidelines are failing to control them.
Reduced access block causes shorter emergency department waiting times: An historical control observational study
Authors: Dunn Robert
Published: May 2003

Objective:To study the effect of changes in hospital occupancy and ED occupancy on ED waiting times during a 13‐day period of improved bed access.

Methods:A comparative, observational study of 1133 ED attendances in the study period and 2332 attendances in a historical control period.

Results:During the study period, mean hospital occupancy decreased from 94.9% to 89.0% (P < 0.001), mean ED occupancy decreased from 19.1 to 14.8 patients (P < 0.001) and the mean ED waiting time decreased from 58.5 to 37.1 min (P < 0.001). There were statistically significant reductions in waiting times for patients in Australasian triage scale (ATS) categories 2–5. Departmental staffing levels, attendances and patient acuity were not significantly different during the study and control periods.

Conclusions:Modest decreases in hospital occupancy resulted in highly significant reductions in ED waiting times. Emergency department overcrowding due to large numbers of admitted patients awaiting hospital admission is a major cause of ED dysfunction.
Implications for urgent transfusion of uncrossmatched blood in the emergency department: The prevalence of clinically significant red cell antibodies within different patient groups
Authors: Saverimuttu Josobel , Greenfield Tony , Rotenko Irene , Crozier John , Jalaludin Bin , Harvey Michael
Published: May 2003

Objective: To define the prevalence of alloantibodies as a factor of age and underlying clinical disease, with particular relevance to the prediction of the safety of uncrossmatched blood in different demographic groups.

Methods: A retrospective review was conducted of all immunohaematological studies on blood samples submitted to the blood bank of a tertiary referral hospital between January 1998 and December 1999.

Results: A total of 27 968 antibody screens in 15 966 patients were analysed. When only clinically significant antibodies were considered, the total alloimmunization prevalence was 1.9% and the prevalence of antibodies capable of causing an immediate transfusion reaction was 0.6%. The prevalence of antibodies capable of causing an immediate transfusion reaction was 0.1% in the under 30 years of age group. Clinically significant antibodies were found in 5.1% in the haematology and oncology unit patients. The risk rises with age and female sex.

Conclusion: We conclude that uncrossmatched blood is associated with low risk in patients < 30 years of age. The knowledge that patients have not been exposed to previous transfusion or pregnancy will reduce the risk even further.
A Note on Cluster Headache in A Population-Based Twin Register
Authors: Svensson DA , Ekbom K , Pedersen NL , Träff H , Waldenlind E
Published: May 2003

Evidence of a familial risk factor in cluster headache is accumulating and studies of twin concordance may resolve family resemblance into genetic and environmental influences. The past literature on cluster headache in twins comprises a few case reports of concordant monozygotic pairs. Swedish twin pairs with a diagnosis of cluster headache were selected through a cross-match of national registers of twin births and hospitalizations. Seventeen discordant twin pairs were found, in which it was possible to verify cluster headache status in 11 complete pairs (two monozygotic, four dizygotic, and five unlike-sexed pairs). In both members of a female monozygotic pair, migraine without aura developed after birth of the first child and remitted by menopause, whereas post-menopausal development of chronic cluster headache occurred in only one of them. The importance of individual specific factors for cluster headache was demonstrated. However, to explain familial aggregation a larger sample of affected twin pairs is necessary.
Selective Decrease in Serotonin Synthesis Rate in Rat Brainstem Raphe Nuclei Following Chronic Administration of Low Doses of Amitriptyline: an Effect Compatible with an Anti-Migraine Effect
Authors: Pringsheim T , Diksic M , Dobson C , Nguyen K , Hamel E
Published: May 2003

The effects of chronic, low-dose amitriptyline on serotonin (5-HT) synthesis rate were measured in rat brain using autoradiography and the trapping of α-[14C]-methyl-L-tryptophan (α-[14C]-MTrp). Rats received amitriptyline (2 mg/kg per day) or saline via intraperitoneal osmotic minipumps for 21 days. Amitriptyline had no effect on any physiological parameters measured, or on free or total plasma tryptophan levels. However, amitriptyline exerted selective decreases of 15% and 17% ( P < 0.001) in serotonin synthesis rates in the dorsal and median raphe nuclei, respectively. There was no reduction in any of the projection areas studied, including the cerebral cortex, hippocampus, thalamus, hypothalamus or striatum. The data suggest that chronic low doses of amitriptyline can lead to sustained 5-HT re-uptake inhibition selectively in the raphe nuclei, an effect compatible with tonic activation of 5-HT1A autoreceptors and inhibition of 5-HT synthesis. The failure of chronic amitriptyline treatment to affect 5-HT synthesis rate in the projection areas may ensure an adequate regulation of pain pathways implicated in migraine headache, an effect possibly related to amitriptyline anti-migraine efficacy.
Caffeine-Induced Headache in Children and Adolescents
Authors: Hering-Hanit R , Gadoth N
Published: May 2003

Caffeine is the most widely used behaviourally active substance. Excessive caffeine consumption, mostly in the form of coffee and tea, is a well-recognized cause of headache or migraine, and withdrawal can cause headache. Nevertheless, caffeine abuse headache is not listed as a separate category in the International Headache Society classification, 1988. We report our experience with children and adolescents with daily or near-daily headache and excessive consumption of caffeine in the form of cola drinks. Over a period of 5 years we have encountered, in a tertiary headache clinic in a general hospital, 36 children and adolescents (17 girls and 19 boys) with daily or near-daily headache related to excessive caffeine intake in the form of cola drinks. The mean age of the subjects was 9.2 years (range 6-18) and mean headache duration was 1.8 years (range 0.6-5). All were heavy cola drinks consumers; at least 1.5 L of cola drinks per day (192.88 mg of caffeine daily), and an average of 11 (range 10.5-21) L of cola drinks a week, which amounts to 1414.5 mg of caffeine (range 1350.1-2700.3). Patients were encouraged to achieve gradual withdrawal from cola drinks, which led to complete cessation of all headaches in 33 subjects, whereas one boy and two adolescent girls continued to suffer from migraine without aura not frequent enough to justify prophylactic medication. Children and adolescents with high daily caffeine consumption in the form of cola drinks may suffer from caffeine-induced daily headache. Gradual withdrawal can be achieved without withdrawal headache and with complete disappearance of the induced chronic daily headache.
A qualitative evaluation of the ‘Trailblazers’ teaching the teachers programme in mental health
Authors: Brown Celia A. , Wakefield Sarah E. , Bullock Alison D. , Field Steve J.
Published: May 2003

This article aims to provide an evaluation of the ‘Trailblazers’ programme, and seeks to identify the factors affecting the impact of the programme. ‘Trailblazers’ is a learner‐centred ‘Teaching the Teachers’ programme in primary care mental health. In the first programme to be run in the West Midlands, seven pairs of participants attended three residential modules and developed an action plan that was cascaded to local colleagues. A primarily qualitative investigation, exploring the experiences of the first cohort of 14 Trailblazers in the West Midlands, demonstrated that the modules were well received and over 200 other professionals benefited from education sessions delivered by the participants. Most delegates were keen to be involved in future programmes and regional policy‐making. The Trailblazers programme demonstrated short‐term effectiveness in terms of participant reaction, knowledge and changes in professional practice.
Clinical learning environments: an evaluation of an innovative role to support preregistration nursing placements
Authors: Clarke Charlotte L. , Gibb Catherine E. , Ramprogus Vince
Published: May 2003

Contemporary nurse education places a high value on learning in the clinical environment. Combined with increasing numbers of students there are unprecedented demands on clinical areas and staff. One response to this problem has been the development of the practice placement facilitator (PPF) role. This study aimed to evaluate, over 12 months, the impact of the PPF role on the provision of practice placements, student support during placement and professional development needs of staff as clinical supervisors/assessors. The evaluation focused on three areas: capacity to accommodate students; quality of placements in relation to the role of the PPF; and the evolution of the role of the PPF. Data‐collection methods included interviews, focus groups, questionnaires and secondary data analysis. The findings of the study demonstrated that: many different groups of learners are present in clinical environments; students need to have continuity of support; clinical staff derive benefits from an enhanced understanding of the needs of learners through the work of the PPF; and that if the role and function of the PPF post is unclear and/or poorly maintained there will be detrimental effects.
Do Italian Mothers Prefer Cesarean Delivery?
Authors: Donati Serena , Grandolfo Michele E. , Andreozzi Silvia
Published: May 2003

ABSTRACT: Background: In Italy the proportion of births by cesarean section rose from 11.2 percent in 1980 to 27.9 percent in 1996 and 33.2 percent in 2000. The aim of this study was to identify factors, other than medical and obstetrical risk, that may influence the method of delivery and to analyze mother's preference for vaginal versus cesarean delivery among women after the birth of their first baby in university hospitals in Italy.

Methods: Primiparous women were selected from 100 consecutive deliveries in 23 university hospitals in 1999. To determine antenatal, delivery, and postnatal history, and women's preference for method of delivery, trained health personnel interviewed 1986 women.

Results: Of the 1986 women who were interviewed (response rate 95%), 1023 primiparas comprised the study sample. The cesarean section rate was 36 percent. Ninety‐one percent of the women who delivered spontaneously and 73 percent of those who underwent a cesarean section would have preferred a vaginal delivery.

Conclusions: Most of the interviewed women in this study preferred, or were satisfied with, vaginal birth. (BIRTH 30:2 June 2003)
Taking Antenatal Group B Streptococcus Seriously: Women's Experiences of Screening and Perceptions of Risk
Authors: Darbyshire Philip , Collins Carmel , McDonald Helen M. , Hiller Janet E.
Published: May 2003

ABSTRACT: Background: Early‐onset group B streptococcal disease is a serious cause of neonatal morbidity and mortality. Although screening protocols for group B streptococcus are common, little is known of women's perceptions of this screening and the disease itself. The purpose of this study was to gain an understanding of women's experiences, knowledge, and perceptions about this bacteria and its screening.

Methods: Nine focus group interviews with 35 women explored their experiences and understanding of group B streptococcus screening. Transcribed interview data were interpreted to identify and articulate the women's experiences.

Results: Most women had little knowledge or understanding of group B streptococcus, obtaining their information largely from the stories or experiences of friends or family. Women struggled to understand the meaning and implications, both physical and ‘‘moral,’’ of the disease for their baby and for themselves, clearly indicating both the subjective and statistical importance of the concept of risk for pregnant women.

Conclusions: Group B streptococcus continues to be poorly understood by pregnant women who try to understand and weigh up its risks and implications so as to make the best decisions about screening. The women participated in screening ultimately, however, since it was seen to be patently ‘‘best for baby,’’ relatively easy for them to undergo, and part of routine antenatal care. (BIRTH 30:2 June 2003)
PHOTOSYNTHETIC PIGMENT COMPOSITION IN THE PRIMITIVE GREEN ALGA MESOSTIGMA VIRIDE (PRASINOPHYCEAE): PHYLOGENETIC AND EVOLUTIONARY IMPLICATIONS1
Authors: Yoshii Yukie , Takaichi Shinichi , Maoka Takashi , Inouye Isao
Published: May 2003

The photosynthetic pigment composition of Mesostigma viride Lauterborn, a primitive green alga, was determined. This alga contained chl a and b, lycopene, lutein, siphonaxanthin, γ‐carotene, β‐carotene, antheraxanthin, violaxanthin, neoxanthin, and two novel carotenoid fatty acid esters, siphonaxanthin C12:0 ester and siphonaxanthin C14:0 ester. The esters were saturated, whereas all previously identified siphonaxanthin and loroxanthin esters have been mono‐unsaturated (trans‐Δ2). Neoxanthin was the all‐trans form. This is the first such case detected in the chloroplasts of green plants. The 9′‐cis form of neoxanthin is believed to be universally present in the chloroplasts of green plants (Streptophyta and Chlorophyta) and is a precursor of abscisic acid. However, the 9′‐cis form was not found in M. viride. Based on these results, we discuss the phylogenetic implications and early evolution of the antenna pigment system in green plants.
ENHANCEMENT OF INTRACELLULAR SAXITOXIN ACCUMULATION BY LIDOCAINE HYDROCHLORIDE IN THE CYANOBACTERIUM CYLINDROSPERMOPSIS RACIBORSKII T3 (NOSTOCALES)1
Authors: Pomati Francesco , Neilan Brett A. , Suzuki Takahiro , Manarolla Gianluca , Rossetti Carlo
Published: May 2003

The metabolic effect of three different concentrations of lidocaine hydrochloride (0.01, 0.1, and 1 μM) on growth and saxitoxin (STX) production of the freshwater cyanobacterium Cylindrospermopsis raciborskii (Wolosznska) T3 was analyzed. Lidocaine hydrochloride increased both the growth rate and the final growth yield in the toxic cyanobacterium, with a maximum of 25% and 18% for a 1‐μM dose, respectively. Moreover, C. raciborskii T3 samples harvested at the end of the growth phase and analyzed for STX content by HPLC showed an increase in STX intracellular concentration of 14.3% and 49.3% after exposure to 0.01 and 0.1 μM lidocaine hydrochloride, respectively, whereas 1 μM lidocaine hydrochloride resulted in a 114% incremental change in STX content. The time course of the 1‐μM lidocaine hydrochloride effect showed the highest rate of increase in mean STX intracellular concentration (298%) within the first 2 h after induction. The increase in STX content induced by lidocaine hydrochloride in C. raciborskii T3 was dependent on the concentration of Na+ ions in the culture medium and alkaline pH. The results suggest a possible action of lidocaine hydrochloride on membrane ion fluxes and the hypothesis of a potential linkage between cyanobacterial homeostasis and STX regulation.
INTERMEDIATE FEATURES OF CYANELLE DIVISION OF CYANOPHORA PARADOXA (GLAUCOCYSTOPHYTA) BETWEEN CYANOBACTERIAL AND PLASTID DIVISION1
Authors: Iino Masato , Hashimoto Haruki
Published: May 2003

Cyanelles of glaucocystophytes may be the most primitive of the known plastids based on their peptidoglycan content and the sequence phylogeny of cyanelle DNA. In this study, EM observations have been made to characterize the cyanelle division of Cyanophora paradoxa Korshikov and to gain insights into the evolution of plastid division. Constriction of cyanelles involves ingrowth of the septum at the cleavage site with the inner envelope membrane invaginating at the leading edge and the outer envelope membrane invaginating behind the septum. This means the inner and outer envelope membranes do not constrict simultaneously as they do in plastid division in other plants. The septum and the cyanelle envelope became stained after a silver‐methenamine staining was applied for in situ detection of polysaccharides. Septum formation was inhibited by β‐lactams and vancomycin, which are potent inhibitors of bacterial peptidoglycan biosynthesis. These results suggest the presence of peptidoglycan at the septum and the cyanelle envelope. In dividing cyanelles, a single electron‐dense ring (cyanelle ring) was observed on the stromal face of the inner envelope membrane at the isthmus, but no ring‐like structures were detected on the outer envelope membrane. Thus a single, stromal cyanelle ring such as this is quite unique and also distinct from FtsZ rings, which are not detectable by TEM. These features suggest that the cyanelle division of glaucocystophytes represents an intermediate stage between cyanobacterial and plastid division. If monophyly of all plastids is true, the cyanelle ring and the homologous inner plastid dividing ring might have evolved earlier than the outer plastid dividing ring.
PARMALES (CHRYSOPHYCEAE) FROM THE GULF OF TEHUANTEPEC, MEXICO, INCLUDING THE DESCRIPTION OF A NEW SPECIES, TETRAPARMA INSECTA SP. NOV., AND A PROPOSAL TO THE TAXONOMY OF THE GROUP1
Authors: Bravo‐Sierra Ernesto , Hernández‐Becerril David U.
Published: May 2003

There are few studies dedicated to species of the Order Parmales all over the world. All 12 taxa described are part of the marine ultraplankton (less than 5 μm). Analysis of filtered samples from the Gulf of Tehuantepec yielded specimens of two taxa of the group. One is a new species, belonging to the genus Tetraparma. Tetraparma insecta sp. nov. is solitary and spherical (2.8–3.8 μm diameter), and all plates lack ornamentations or knobs, the walls are smooth, and only the plate junctions are seen. The shield plates are convex and show a conspicuous rim, some of them with an indentation. This species shows superficial similarities with Tetraparma pelagica, the other species described of the genus, and is very similar to siliceous forms, previously found, with no formal name. The other species is the taxon Triparma laevis form mexicana (Kosman) stat. nov., earlier described for Mexican waters, which has an irregular ala, the shield plates have knobs at the center, the triradiate plates show a “Y”‐shaped keel, and the walls of plates and ala show minute granules. Tetraparma insecta was distributed widely in the study area and was relatively abundant, reaching a density of 4 × 104·L−1, with an evident preference for subsurface waters (10–20 m depth), whereas T. laevis form mexicana was rare and scarce. Both species seem to be restricted to tropical–subtropical waters. We discuss the taxonomy of Parmales, especially concerning the category of subspecies within the group. Parmales is a widespread group in cold and tropical waters.
Functional divergence within the
APETALA3/PISTILLATA
floral homeotic gene lineages
Authors: Lamb Rebecca S. , Irish Vivian F.
Published: May 2003

Changes in homeotic gene expression patterns or in the functions of the encoded proteins are thought to play a prominent role in the evolution of new morphologies. The floral homeotic
APETALA3
(
AP3
) and
PISTILLATA
(
PI
) genes encode MADS domain-containing transcription factors required to specify petal and stamen identities in
Arabidopsis
. We have previously shown that perianth expression of
AP3
and
PI
homologs varies in different groups of angiosperms with diverse floral structures, suggesting that changes in expression may contribute to changing morphology. We have investigated the possibility that changes in the functions of the encoded gene products may also have played a role in the evolution of different floral morphologies.
AP3
and
PI
are members of paralogous gene lineages and share extensive similarity along the length of the protein products. Genes within these lineages encode products with characteristic C-terminal motifs that we show are critical for functional specificity. In particular, the C terminus of AP3 is sufficient to confer AP3 functionality on the heterologous PI protein. Furthermore, we have shown that the evolution of the divergent AP3 C-terminal domain in the core eudicots is correlated with the acquisition of a role in specifying perianth structures. These results suggest that divergence in these sequence motifs has contributed to the evolution of distinct functions for these floral homeotic gene products.
Exo1: A new chemical inhibitor of the exocytic pathway
Authors: Feng Yan , Yu Sidney , Lasell Troy K. R. , Jadhav Ashutosh P. , Macia Eric , Chardin Pierre , Melancon Paul , Roth Michael , Mitchison Timothy , Kirchhausen Tomas
Published: May 2003

A phenotypic screen was used to search for drug-like molecules that can interfere with specific steps in membrane traffic. 2-(4-Fluorobenzoylamino)-benzoic acid methyl ester (Exo1), identified in this screen, induces a rapid collapse of the Golgi to the endoplasmic reticulum, thus acutely inhibiting the traffic emanating from the endoplasmic reticulum. Like Brefeldin A (BFA), Exo1 induces the rapid release of ADP-ribosylation factor (ARF) 1 from Golgi membranes but has less effect on the organization of the trans-Golgi network. Our data indicate that Exo1 acts by a different mechanism from BFA. Unlike BFA, Exo1 does not induce the ADP-ribosylation of CtBP/Bars50 and does not interfere with the activity of guanine nucleotide exchange factors specific for Golgi-based ARFs. Thus, Exo1 allows the fatty acid exchange activity of Bars50 to be distinguished from ARF1 activity in the control of Golgi tubulation.
Instability of GGL domain-containing RGS proteins in mice lacking the G protein β-subunit Gβ5
Authors: Chen Ching-Kang , Eversole-Cire Pamela , Zhang Haikun , Mancino Valeria , Chen Yu-Jiun , He Wei , Wensel Theodore G. , Simon Melvin I.
Published: May 2003

RGS (regulator of G protein signaling) proteins containing the G protein γ-like (GGL) domain (RGS6, RGS7, RGS9, and RGS11) interact with the fifth member of the G protein β-subunit family, Gβ5. This interaction is necessary for the stability of both the RGS protein and for Gβ5. Consistent with this notion, we have found that elevation of RGS9-1 mRNA levels by transgene expression does not increase RGS9-1 protein level in the retina, suggesting that Gβ5 levels may be limiting. To examine further the interactions of Gβ5 and the GGL domain-containing RGS proteins, we inactivated the Gβ5 gene. We found that the levels of GGL domain-containing RGS proteins in retinas and in striatum are eliminated or reduced drastically, whereas the levels of G
γ
2
and RGS4 proteins remain normal in the absence of Gβ5. The homozygous Gβ5 knockout (Gβ5
–
/
–
) mice derived from heterozygous knockout mating are runty and exhibit a high preweaning mortality rate. We concluded that complex formation between GGL domain-containing RGS proteins and the Gβ5 protein is necessary to maintain their mutual stability
in vivo
. Furthermore, in the absence of Gβ5 and all four RGS proteins that form protein complexes with Gβ5, the animals that survive into adulthood are viable and have no gross defects in brain or retinal morphology.
Global atmospheric black carbon inferred from AERONET
Authors: Sato Makiko , Hansen James , Koch Dorothy , Lacis Andrew , Ruedy Reto , Dubovik Oleg , Holben Brent , Chin Mian , Novakov Tica
Published: May 2003

AERONET, a network of well calibrated sunphotometers, provides data on aerosol optical depth and absorption optical depth at >250 sites around the world. The spectral range of AERONET allows discrimination between constituents that absorb most strongly in the UV region, such as soil dust and organic carbon, and the more ubiquitously absorbing black carbon (BC). AERONET locations, primarily continental, are not representative of the global mean, but they can be used to calibrate global aerosol climatologies produced by tracer transport models. We find that the amount of BC in current climatologies must be increased by a factor of 2–4 to yield best agreement with AERONET, in the approximation in which BC is externally mixed with other aerosols. The inferred climate forcing by BC, regardless of whether it is internally or externally mixed, is ≈1 W/m
2
, most of which is probably anthropogenic. This positive forcing (warming) by BC must substantially counterbalance cooling by anthropogenic reflective aerosols. Thus, especially if reflective aerosols such as sulfates are reduced, it is important to reduce BC to minimize global warming.
Spectra of random graphs with given expected degrees
Authors: Chung Fan , Lu Linyuan , Vu Van
Published: May 2003

In the study of the spectra of power-law graphs, there are basically two competing approaches. One is to prove analogues of Wigner's semicircle law, whereas the other predicts that the eigenvalues follow a power-law distribution. Although the semicircle law and the power law have nothing in common, we will show that both approaches are essentially correct if one considers the appropriate matrices. We will prove that (under certain mild conditions) the eigenvalues of the (normalized) Laplacian of a random power-law graph follow the semicircle law, whereas the spectrum of the adjacency matrix of a power-law graph obeys the power law. Our results are based on the analysis of random graphs with given expected degrees and their relations to several key invariants. Of interest are a number of (new) values for the exponent β, where phase transitions for eigenvalue distributions occur. The spectrum distributions have direct implications to numerous graph algorithms such as, for example, randomized algorithms that involve rapidly mixing Markov chains.
T lymphoid differentiation in human bone marrow
Authors: Klein Florian , Feldhahn Niklas , Lee Sanggyu , Wang Hui , Ciuffi Fiammetta , von Elstermann Mirko , Toribio María L. , Sauer Heinrich , Wartenberg Maria , Barath Varun Singh , Krönke Martin , Wernet Peter , Rowley Janet D. , Müschen Markus
Published: May 2003

The unique role of the thymus in the development of T cells was established >4 decades ago. To elucidate how uncommitted lymphoid progenitor cells are instructed to migrate from bone marrow to the thymus to undergo T lymphoid differentiation, we generated and analyzed a genome-wide gene expression profile of CD7+CD10+human bone marrow T cell lineage precursors (TLPs) by using the serial analysis of gene expression technique. Unexpectedly, the serial analysis of gene expression profile identified a high number of (pre-) T cell receptor antigen (TCR)-related transcripts in bone marrow TLPs. To determine the configuration of the TCRβ locus in these cells at a quantitative level, we sorted and analyzed bone marrow TLPs from five donors by single-cell PCR. Similar proportions of TLPs harbored TCRβ germ-line alleles, D-J, or V-DJ gene rearrangements. Thus, bone marrow TLPs are heterogenous with respect to TCRβ rearrangement status, suggesting an active recombination machinery that is consistent with the expression ofRAG1, RAG2, andTdTin this population. As a hallmark of ongoing TCRβ V-DJ rearrangement, we could amplify broken-ended recombination-signal sequence DNA intermediates from bone marrow TLPs, but not from mature T cells by ligation-mediated PCR. Approximately half of the TCRβ rearrangements were compatible with the expression of a functional pre-TCR, which is in agreement with surface expression ofpre-Tα on bone marrow TLPs as shown by confocal laser microscopy and flow cytometry. At a frequency <0.5% of mononucleated cells in human bone marrow, this population is rare, yet it exemplifies T lymphoid differentiation in the human already before immigration into the thymus.
Inhibition of p53-induced apoptosis without affecting expression of p53-regulated genes
Authors: Lotem Joseph , Gal Hilah , Kama Rachel , Amariglio Ninette , Rechavi Gideon , Domany Eytan , Sachs Leo , Givol David
Published: May 2003

Using DNA microarray and clustering of expressed genes we have analyzed the mechanism of inhibition of wild-type p53-induced apoptosis by the cytokine interleukin 6 (IL-6) and the calcium mobilizer thapsigargin (TG). Clustering analysis of 1,786 genes, the expression level of which changed after activation of wild-type p53 in the absence or presence of IL-6 or TG, showed that these compounds did not cause a general inhibition of the ability of p53 to up-regulate or down-regulate gene expression. Expression of various p53 targets implicated as mediators of p53-induced apoptosis was also not affected by IL-6 or TG. These compounds thus can bypass the effect of wild-type p53 on gene expression and inhibit apoptosis. IL-6 and TG activated different p53-independent pathways of gene expression that include up-regulation of antiapoptotic genes. IL-6 and TG also activated different differentiation-associated genes. The ability of compounds such as cytokines and calcium mobilizers to inhibit p53-mediated apoptosis without generally inhibiting gene expression regulated by p53 can facilitate tumor development and tumor resistance to radiation and chemotherapy in cells that retain wild-type p53.
PPARγ and PPARδ negatively regulate specific subsets of lipopolysaccharide and IFN-γ target genes in macrophages
Authors: Welch John S. , Ricote Mercedes , Akiyama Taro E. , Gonzalez Frank J. , Glass Christopher K.
Published: May 2003

Natural and synthetic agonists of the peroxisome proliferator-activated receptor γ (PPARγ) regulate adipocyte differentiation, glucose homeostasis, and inflammatory responses. Although effects on adipogenesis and glucose metabolism are genetically linked to PPARγ, the PPARγ dependence of antiinflammatory responses of these substances is less clear. Here, we have used a combination of mRNA expression profiling and conditional disruption of the PPARγ gene in mice to characterize programs of transcriptional activation and repression by PPARγ agonists in elicited peritoneal macrophages. Natural and synthetic PPARγ agonists, including the thiazolidinedione rosiglitazone (Ro), modestly induced the expression of a surprisingly small number of genes, several of which were also induced by a specific PPARδ agonist. The majority of these genes encode proteins involved in lipid homeostasis. In contrast, Ro inhibited induction of broad subsets of lipopolysaccharide and IFN-γ target genes in a gene-specific and PPARγ-dependent manner. At high concentrations, Ro inhibited induction of lipopolysaccharide target genes in PPARγ-deficient macrophages, at least in part by activating PPARδ. These studies establish overlapping transactivation and transrepression functions of PPARγ and PPARδ in macrophages and suggest that a major transcriptional role of PPARγ is negative regulation of specific subsets of genes that are activated by T helper 1 cytokines and pathogenic molecules that signal through pattern recognition receptors. These findings support a physiological role of PPARγ in regulating both native and acquired immune responses.
Rb
function in extraembryonic lineages suppresses apoptosis in the CNS of
Rb
-deficient mice
Authors: de Bruin Alain , Wu Lizhao , Saavedra Harold I. , Wilson Pamela , Yang Ying , Rosol Thomas J. , Weinstein Michael , Robinson Michael L. , Leone Gustavo
Published: May 2003

Retinoblastoma (
Rb
)-deficient embryos show severe defects in neurogenesis, erythropoiesis, and lens development and die at embryonic day 14.5. Our recent results demonstrated a drastic disorganization of the labyrinth layer in the placenta of
Rb
-deficient embryos, accompanied by reduced placental transport function. When these
Rb
-
/
-
embryos were supplied with a wild-type placenta by using either tetraploid aggregation or genetic approaches, animals survived until birth. Here we analyze the role of extraembryonic
Rb
in regulating proliferation, apoptosis, and differentiation in the rescued animals at different developmental stages. Many of the neurological and erythroid abnormalities thought to be responsible for the embryonic lethality of
Rb
-
/
-
animals, including the ectopic apoptosis in the CNS, were virtually absent in rescued
Rb
-
/
-
pups. However, rescued animals died at birth with severe skeletal muscle defects. Like in Rb knockout embryos, rescued animals showed a marked increase in DNA replication and cell division in the CNS. In sharp contrast, the typical widespread neuronal apoptosis was absent in Rb-deficient embryos reconstituted with a normal placenta. In lens fiber cells, however, the inappropriate proliferation and apoptosis that is normally observed in
Rb
-
/
-
embryos continued unabated in rescued animals. These results demonstrate that Rb function in extraembryonic lineages plays an important role in the survival of neuronal cells and in the differentiation of the erythroid lineage, providing mechanistic insight into the cell autonomous and nonautonomous functions of Rb during development.
Picosecond conformational transition and equilibration of a cyclic peptide
Authors: Bredenbeck Jens , Helbing Jan , Sieg Arne , Schrader Tobias , Zinth Wolfgang , Renner Christian , Behrendt Raymond , Moroder Luis , Wachtveitl Josef , Hamm Peter
Published: May 2003

Ultrafast IR spectroscopy is used to monitor the nonequilibrium backbone dynamics of a cyclic peptide in the amide I vibrational range with picosecond time resolution. A conformational change is induced by means of a photoswitch integrated into the peptide backbone. Although the main conformational change of the backbone is completed after only 20 ps, the subsequent equilibration in the new region of conformational space continues for times >16 ns. Relaxation and equilibration processes of the peptide backbone occur on a discrete hierarchy of time scales. Albeit possessing only a few conformational degrees of freedom compared with a protein, the peptide behaves highly nontrivially and provides insights into the complexity of fast protein folding.
Guanylate cyclase-activating protein (GCAP) 1 rescues cone recovery kinetics in GCAP1/GCAP2 knockout mice
Authors: Pennesi Mark E. , Howes Kim A. , Baehr Wolfgang , Wu Samuel M.
Published: May 2003

Mediated by guanylate cyclase-activating proteins (GCAPs), cytoplasmic Ca2+levels regulate the activity of photoreceptor guanylate cyclase (GC) and the synthesis of cGMP, the internal transmitter of phototransduction. When GCAP1 is expressed in transgenic mice on a GCAP null background, it restores the wild-type flash responses in rod photoreceptors. In this communication, we explored the role of GCAP1 in cone photoreceptors by using electroretinograms (ERGs). Under cone isolation conditions, ERGs recorded from mice lacking both GCAP1 and GCAP2 had normal amplitudes of the saturated a-wave and b-wave. However, recordings from these mice demonstrated a widened b-wave and increased sensitivity of both M- and UV-cone systems. Paired-flash ERGs revealed a delayed recovery of both the cone driven b-wave and a-wave and suggest that the delay originated from the photoreceptors. To test whether GCAP1 could restore normal cone response recovery, mice that expressed only transgenic GCAP1 in the absence of wild-type GCAP expression were tested. Immunohistochemical analysis demonstrated that cones of these mice expressed high levels of GCAP1. Paired-flash ERGs showed that the recovery of the cone-driven a-wave was restored to normal, whereas recovery of the cone-driven b-wave was slightly faster than that observed in wild-type mice. These studies reveal that, similar to rods, deletion of GCAP1 and GCAP2 delays the recovery of light responses in cones and GCAP1 restores the recovery of cone responses in the absence of GCAP2.
Chloride, not sodium, stimulates expression of the γ subunit of Na/K-ATPase and activates JNK in response to hypertonicity in mouse IMCD3 cells
Authors: Capasso Juan M. , Rivard Christopher J. , Enomoto Laura M. , Berl Tomas
Published: May 2003

Hypertonicity induced by NaCl, but not by urea or mannitol, up-regulates expression of the γ subunit of Na/K-ATPase in cells of the murine inner medullary collecting duct line (IMCD3) by activation of the Jun kinase 2 (JNK2) pathways. We examined the ionic mediators of the osmosensitive response. An increase in osmolality to 550 milliosmoles per kg of water (mosmol/kgH
2
O) for 48 h by replacement of NaCl with choline chloride did not prevent the up-regulation of the γ subunit. Neither Na
+
ionophores nor inhibitors of cellular Na
+
uptake altered the up-regulation of the γ subunit or JNK activation. Changes in cell cation concentrations driven by incubation in low-K
+
medium were effective in up-regulating the α
1
subunit of Na/K-ATPase but did not have any effect on the γ subunit. The replacement of NaCl with choline chloride did not down-regulate γ-subunit expression in cells adapted to hypertonicity. In contrast, the replacement of NaCl with sodium acetate, or pretreatment of cells with the Cl
-
channel inhibitor 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB) completely blocked γ-subunit up-regulation, inhibited JNK activation, and caused a significant decrement in cell survival in hypertonic but not isotonic conditions. In adapted cells, replacement of 300 mosmol/kgH
2
O NaCl with sodium acetate resulted in down-regulation of the γ subunit. In conclusion, we describe a Na
+
-independent, Cl
-
-dependent mechanism for hypertonicity-mediated activation of the JNK and the subsequent synthesis of the γ subunit of Na/K-ATPase, which are necessary for cellular survival in these anisotonic conditions.
Golgi-dependent transport of cholesterol to the
Chlamydia trachomatis
inclusion
Authors: Carabeo Reynaldo A. , Mead David J. , Hackstadt Ted
Published: May 2003

Cholesterol, a lipid not normally found in prokaryotes, was identified in purified
Chlamydia trachomatis
elementary bodies and in the chlamydial parasitophorous vacuole (inclusion) membrane of infected HeLa cells. Chlamydiae obtained eukaryotic host cell cholesterol both from
de novo
synthesis or low-density lipoprotein. Acquisition of either
de novo
-synthesized cholesterol or low-density lipoprotein-derived cholesterol was microtubule-dependent and brefeldin A-sensitive, indicating a requirement for the Golgi apparatus. Transport also required chlamydial protein synthesis, indicative of a pathogen-directed process. The cholesterol trafficking pathway appears to coincide with a previously characterized delivery of sphingomyelin to the inclusion in that similar pharmacological treatments inhibited transport of both sphingomyelin and cholesterol. These results support the hypothesis that sphingomyelin and cholesterol may be cotransported via a Golgi-dependent pathway and that the chlamydial inclusion receives cholesterol preferentially from a brefeldin A-sensitive pathway of cholesterol trafficking from the Golgi apparatus to the plasma membrane.
An actin–ribonucleoprotein interaction is involved in transcription by RNA polymerase II
Authors: Percipalle Piergiorgio , Fomproix Nathalie , Kylberg Karin , Miralles Francesc , Björkroth Birgitta , Daneholt Bertil , Visa Neus
Published: May 2003

To determine the function of actin in the cell nucleus, we sought to identify nuclear actin-binding proteins in the dipteran
Chironomus tentans
using DNase I-affinity chromatography. We identified the RNA-binding protein hrp65 as an actin-binding protein and showed that the C-terminal sequence of the hrp65-2 isoform is able to interact directly with actin
in vitro. In vivo
crosslinking and coimmunoprecipitation experiments indicated that hrp65 and actin are also associated in the living cell. Moreover,
in vivo
administration of a competing peptide corresponding to the C-terminal sequence of hrp65-2 disrupted the actin–hrp65-2 interaction and caused a specific and drastic reduction of transcription as judged by puff regression and diminished bromo-UTP incorporation. Our results indicate that an actin-based mechanism is implicated in the transcription of most if not all RNA polymerase II genes and suggest that an actin–hrp65-2 interaction is required to maintain the normal transcriptional activity of the cell. Furthermore, immunoelectron microscopy experiments and nuclear run-on assays suggest that the actin–hrp65-2 complex plays a role in transcription elongation.
Beta cell MHC class I is a late requirement for diabetes
Authors: Hamilton-Williams Emma E. , Palmer Stephanie E. , Charlton Brett , Slattery Robyn M.
Published: May 2003

Type 1 diabetes occurs as a result of an autoimmune attack on the insulin-producing beta cells. Although CD8 T cells have been implicated both early and late in this process, the requirement for direct interaction between these cells and MHC class I on the beta cells has not been demonstrated. By using nonobese diabetic mice lacking beta cell class I expression, we show that both initiation and progression of insulitis proceeds unperturbed. However, without beta cell class I expression, the vast majority of these mice do not develop hyperglycemia. These findings demonstrate that a direct interaction between CD8 T cells and beta cells is not required for initiation or early disease progression. The requirement for class I on beta cells is a relatively late checkpoint in the development of diabetes.
Specificity of short interfering RNA determined through gene expression signatures
Authors: Semizarov Dimitri , Frost Leigh , Sarthy Aparna , Kroeger Paul , Halbert Donald N. , Fesik Stephen W.
Published: May 2003

Short interfering RNA (siRNA) is widely used for studying gene function and holds great promise as a tool for validating drug targets and treating disease. A critical assumption in these applications is that the effect of siRNA on cells is specific, i.e., limited to the specific knockdown of the target gene. In this article, we characterize the specificity of siRNA by applying gene expression profiling. Several siRNAs were designed against different regions of the same target gene for three different targets. Their effects on cells were compared by using DNA microarrays to generate gene expression signatures. When the siRNA design and transfection conditions were optimized, the signatures for different siRNAs against the same target were shown to correlate very closely, whereas the signatures for different genes revealed no correlation. These results indicate that siRNA is a highly specific tool for targeted gene knockdown, establishing siRNA-mediated gene silencing as a reliable approach for large-scale screening of gene function and drug target validation.
Genomewide demarcation of RNA polymerase II transcription units revealed by physical fractionation of chromatin
Authors: Nagy Peter L. , Cleary Michael L. , Brown Patrick O. , Lieb Jason D.
Published: May 2003

Epigenetic modifications of chromatin serve an important role in regulating the expression and accessibility of genomic DNA. We report here a genomewide approach for fractionating yeast chromatin into two functionally distinct parts, one containing RNA polymerase II transcribed sequences, and the other comprising noncoding sequences and genes transcribed by RNA polymerases I and III. Noncoding regions could be further fractionated into promoters and segments lacking promoters. The observed separations were apparently based on differential crosslinking efficiency of chromatin in different genomic regions. The results reveal a genomewide molecular mechanism for marking promoters and genomic regions that have a license to be transcribed by RNA polymerase II, a previously unrecognized level of genomic complexity that may exist in all eukaryotes. Our approach has broad potential use as a tool for genome annotation and for the characterization of global changes in chromatin structure that accompany different genetic, environmental, and disease states.