bluuebunny/crossref_metadata_2025_split huggingface dataset:
Negative Osmoregulation of the
Salmonella ompS1
Porin Gene Independently of OmpR in an
hns
Background
Authors: Flores-Valdez Mario Alberto , Puente José Luis , Calva Edmundo 
Published: November 2003

ABSTRACT

The
ompS1
gene encodes a quiescent porin in
Salmonella enterica
serovars Typhi and Typhimurium. By using random
mariner
transposon mutagenesis, mutations that caused derepression of
ompS1
expression were isolated, one in
S. enterica
serovar Typhi and two in
S. enterica
serovar Typhimurium. All of them mapped in the
hns
gene in the region coding for the carboxy terminus of the H-NS nucleoid protein. The derepressed
ompS1
expression was subject to negative regulation at high osmolarity, both in the presence and in the absence of OmpR. This observation was possible due to the fact that there are two promoters: P1, which is OmpR dependent, and P2, which does not require OmpR for activation (rather, OmpR represses P2). The sequences upstream from position −88, a region previously shown to be involved in the negative regulation of
ompS1
, can form a static bend, and the integrity of this region was required for function and binding of H-NS and for osmoregulation, as determined with gene reporter fusions of different lengths and with a 31-bp deletion mutant. This is consistent with the notion that this region determines a structure required for repression. Hence,
ompS1
shares negative regulation by H-NS with other loci, such as the
bgl
operon and the
ade
gene.
Null Mutations in a Nudix Gene,
ygdP
, Implicate an Alarmone Response in a Novel Suppression of Hybrid Jamming
Authors: Hand Nicholas J. , Silhavy Thomas J. 
Published: November 2003

ABSTRACT

Induction of the toxic LamB-LacZ protein fusion, Hyb42-1, leads to a lethal generalized protein export defect. The
prlF1
suppressor causes hyperactivation of the cytoplasmic Lon protease and relieves the inducer sensitivity of Hyb42-1. Since
prlF1
does not cause a detectable change in the stability or level of the hybrid protein, we conducted a suppressor screen, seeking factors genetically downstream of
lon
with
prlF1
-like phenotypes. Two independent insertions in the
ygdP
open reading frame relieve the toxicity of the fusion protein and share two additional properties with
prlF1
: cold sensitivity and the ability to suppress the temperature sensitivity of a
degP
null mutation. Despite these similarities,
ygdP
does not appear to act in the same genetic pathway as
prlF1
and
lon
, suggesting a fundamental link between the phenotypes. We speculate that the common properties of the suppressors relate to secretion defects. The
ygdP
gene (also known as
nudH
) has been shown to encode a Nudix protein that acts as a dinucleotide oligophosphate (alarmone) hydrolase. Our results suggest that loss of
ygdP
function leads to the induction of an alarmone-mediated response that affects secretion. Using an epitope-tagged
ygdP
construct, we present evidence that this response is sensitive to secretion-related stress and is regulated by differential proteolysis of YgdP in a self-limiting manner.
Identification and Characterization of a Unique Adenosine Kinase from
Mycobacterium tuberculosis
Authors: Long Mary C. , Escuyer Vincent , Parker William B. 
Published: November 2003

ABSTRACT

Adenosine kinase (AK) is a purine salvage enzyme that catalyzes the phosphorylation of adenosine to AMP. In
Mycobacterium tuberculosis
, AK can also catalyze the phosphorylation of the adenosine analog 2-methyladenosine (methyl-Ado), the first step in the metabolism of this compound to an active form. Purification of AK from
M. tuberculosis
yielded a 35-kDa protein that existed as a dimer in its native form. Adenosine (Ado) was preferred as a substrate at least 30-fold (

K
m

= 0.8 ± 0.08 μM) over other natural nucleosides, and substrate inhibition was observed when Ado concentrations exceeded 5 μM.
M. tuberculosis
and human AKs exhibited different affinities for methyl-Ado, with

K
m

values of 79 and 960 μM, respectively, indicating that differences exist between the substrate binding sites of these enzymes. ATP was a good phosphate donor (

K
m

= 1100 ± 140 μM); however, the activity levels observed with dGTP and GTP were 4.7 and 2.5 times the levels observed with ATP, respectively.
M. tuberculosis
AK activity was dependent on Mg
2+
, and activity was stimulated by potassium, as reflected by a decrease in the

K
m

and an increase in
V
max
for both Ado and methyl-Ado. The N-terminal amino acid sequence of the purified enzyme revealed complete identity with Rv2202c, a protein currently classified as a hypothetical sugar kinase. When an AK-deficient strain of
M. tuberculosis
(SRICK1) was transformed with this gene, it exhibited a 5,000-fold increase in AK activity compared to extracts from the original mutants. These results verified that the protein that we identified as AK was coded for by
Rv2202c.
AK is not commonly found in bacteria, and to the best of our knowledge,
M. tuberculosis
AK is the first bacterial AK to be characterized. The enzyme shows greater sequence homology with ribokinase and fructokinase than it does with other AKs. The multiple differences that exist between
M. tuberculosis
and human AKs may provide the molecular basis for the development of nucleoside analog compounds with selective activity against
M. tuberculosis
.
Arginine-Agmatine Antiporter in Extreme Acid Resistance in
Escherichia coli
Authors: Iyer Ram , Williams Carole , Miller Christopher 
Published: November 2003

ABSTRACT

The process of arginine-dependent extreme acid resistance (XAR) is one of several decarboxylase-antiporter systems that protects
Escherichia coli
and possibly other enteric bacteria from exposure to the strong acid environment of the stomach. Arginine-dependent acid resistance depends on an intracellular proton-utilizing arginine α-decarboxylase and a membrane transport protein necessary for delivering arginine to and removing agmatine, its decarboxylation product, from the cytoplasm. The arginine system afforded significant protection to wild-type
E. coli
cells in our acid shock experiments. The gene coding for the transport protein is identified here as a putative membrane protein of unknown function, YjdE, which we now name
adiC
. Strains from which this gene is deleted fail to mount arginine-dependent XAR, and they cannot perform coupled transport of arginine and agmatine. Homologues of this gene are found in other bacteria in close proximity to homologues of the arginine decarboxylase in a gene arrangement pattern similar to that in
E coli
. Evidence for a lysine-dependent XAR system in
E. coli
is also presented. The protection by lysine, however, is milder than that by arginine.
A Novel Family of
Escherichia coli
Toxin-Antitoxin Gene Pairs
Authors: Brown Jason M. , Shaw Karen Joy 
Published: November 2003

ABSTRACT

Bacterial toxin-antitoxin protein pairs (TA pairs) encode a toxin protein, which poisons cells by binding and inhibiting an essential enzyme, and an antitoxin protein, which binds the toxin and restores viability. We took an approach that did not rely on sequence homology to search for unidentified TA pairs in the genome of
Escherichia coli
K-12. Of 32 candidate genes tested, ectopic expression of 6 caused growth inhibition. In this report, we focus on the initial characterization of
yeeV
,
ykfI
, and
ypjF
, a novel family of toxin proteins. Coexpression of the gene upstream of each toxin restored the growth rate to that of the uninduced strain. Unexpectedly, we could not detect in vivo protein-protein interactions between the new toxin and antitoxin pairs. Instead, the antitoxins appeared to function by causing a large reduction in the level of cellular toxin protein.
SoxRS-Regulated Expression and Genetic Analysis of theyggXGene ofEscherichia coli
Authors: Pomposiello Pablo J. , Koutsolioutsou Anastasia , Carrasco Daniel , Demple Bruce 
Published: November 2003

ABSTRACTGenomic studies with bacteria have identified redox-responsive genes without known roles in counteracting oxidative damage. Previous transcriptional profiling showed that expression of one such gene,yggX, was activated by superoxide stress inEscherichia coli. Here we show that this activation could be mimicked by artificial expression of the regulatory protein SoxS. Northern analysis confirmed the transcriptional activation ofyggXby oxidative stress or SoxS expression but not in response to the related MarA or Rob proteins. Northern analysis showed thatmltC, which codes for a peptidoglycan hydrolase and is positioned immediately downstream ofyggX, was also regulated by oxidative stress or ectopic expression of SoxS. Purified SoxS protein bound to the predictedyggXpromoter region, between positions 223 and 163 upstream from theyggXtranslational start site. Within this region, a 20-bp sequence was found to be necessary for oxidative stress-mediated activation ofyggXtranscription. AyggXdeletion strain was hypersensitive to the redox-cycling agent paraquat, and a plasmid expressing YggX complemented the sensitivity of the deletion strain. Under exposure to paraquat, theyggXdeletion strain showed a deficiency in aconitase activity compared to the isogenic wild-type strain, while expression of YggX from a multicopy plasmid increased the aconitase levels above those of the wild-type strain. These results demonstrate the direct regulation of theyggXgene by the redox-sensing SoxRS system and provide further evidence for the involvement ofyggXin protection of iron-sulfur proteins against oxidative damage.
The Product of a Developmental Gene,
crgA
, That Coordinates Reproductive Growth in
Streptomyces
Belongs to a Novel Family of Small Actinomycete-Specific Proteins
Authors: Del Sol Ricardo , Pitman Andrew , Herron Paul , Dyson Paul 
Published: November 2003

ABSTRACT

On solid media, the reproductive growth of
Streptomyces
involves antibiotic biosynthesis coincident with the erection of filamentous aerial hyphae. Following cessation of growth of an aerial hypha, multiple septation occurs at the tip to form a chain of unigenomic spores. A gene,
crgA
, that coordinates several aspects of this reproductive growth is described. The gene product is representative of a well-conserved family of small actinomycete proteins with two C-terminal hydrophobic-potential membrane-spanning segments. In
Streptomyces avermitilis
,
crgA
is required for sporulation, and inactivation of the gene abolished most sporulation septation in aerial hyphae. Disruption of the orthologous gene in
Streptomyces coelicolor
indicates that whereas CrgA is not essential for sporulation in this species, during growth on glucose-containing media, it influences the timing of the onset of reproductive growth, with precocious erection of aerial hyphae and antibiotic production by the mutant. Moreover, CrgA subsequently acts to inhibit sporulation septation prior to growth arrest of aerial hyphae. Overexpression of CrgA in
S. coelicolor
, uncoupling any nutritional and growth phase-dependent regulation, results in growth of nonseptated aerial hyphae on all media tested, consistent with a role for the protein in inhibiting sporulation septation.
Starvation Survival Response of
Mycobacterium tuberculosis
Authors: Parish Tanya 
Published: November 2003

ABSTRACT

The ability of
Mycobacterium tuberculosis
auxotrophs to survive long-term starvation was measured. Tryptophan and histidine auxotrophs did not survive single-amino-acid starvation, whereas a proline auxotroph did. All three auxotrophs survived complete starvation. THP-1 cells were also able to restrict the growth of the tryptophan and histidine auxotrophs.
Secretion Defects That Activate the Phage Shock Response of
Escherichia coli
Authors: Jones Susan E. , Lloyd Louise J. , Tan Kum K. , Buck Martin 
Published: November 2003

ABSTRACT

The phage shock protein (
psp
) operon of
Escherichia coli
is induced by membrane-damaging cues. Earlier studies linked defects in secretion across the inner membrane to induction of the
psp
response. Here we show that defects in
yidC
and
sec
secretion induce
psp
but that defects in
tat
and
srp
have no effect. We have also determined the cellular location of PspB and PspD proteins.
Translocon “Pulling” of Nascent SecM Controls the Duration of Its Translational Pause and Secretion-Responsive
secA
Regulation
Authors: Butkus Martha E. , Prundeanu Lucia B. , Oliver Donald B. 
Published: November 2003

ABSTRACT

SecA is an ATPase and motor protein that drives protein translocation across the bacterial plasma membrane. In
Escherichia coli
SecA levels are regulated by the secretion needs of the cell utilizing
secM
, which encodes a secreted protein. Previous studies demonstrated that this regulation requires a translational pause within
secM
, whose duration regulates the accessibility of the
secA
Shine-Dalgarno sequence on
secM secA
mRNA. Here we provide evidence that translocon “pulling” of nascent SecM is what regulates the duration of the
secM
translational pause, and thus
secA
expression levels, thereby providing direct support for this model.
aadAConfers Streptomycin Resistance inBorrelia burgdorferi
Authors: Frank Kristi L. , Bundle Sharyl F. , Kresge Michele E. , Eggers Christian H. , Samuels D. Scott 
Published: November 2003

ABSTRACTTo enhance genetic manipulation of the Lyme disease spirocheteBorrelia burgdorferi, we assayed theaadAgene for the ability to confer resistance to the antibiotics spectinomycin and streptomycin. Using the previously described pBSV2 as a backbone, a shuttle vector, termed pKFSS1, which carries theaadAopen reading frame fused to theB.burgdorferi flgBpromoter was constructed. The hybridflgBpromoter-aadAcassette confers resistance to spectinomycin and streptomycin in bothB.burgdorferiandEscherichia coli. pKFSS1 has a replication origin derived from the 9-kb circular plasmid and can be comaintained inB.burgdorferiwith extant shuttle vector pCE320, which has a replication origin derived from a 32-kb circular plasmid, or pBSV2, despite the fact that pKFSS1 and pBSV2 have the same replication origin. Our results demonstrate the availability of a new selectable marker and shuttle vector for genetically dissectingB.burgdorferiat the molecular level.
Recollecting Forms in the Phaedo
Authors: Dimas Panos 
Published: November 2003

AbstractAccording to an interpretation that has dominated the literature, the traditional interpretation as I call it, the recollection argument aims at establishing the thesis that our learning in this life consists in recollecting knowledge the soul acquired before being born into a body, or thesis R, by using the thesis that there exist forms, thesis F, as a premise. These entities, the forms, are incorporeal, immutable, and transcendent in the sense that they exist separately from material perceptibles, which in turn are related to them through participation and by being caused by them in some sense. But the properties of transcendence, immutability and incorporeality are sufficient to signal forms, and so the thesis that there exist forms claims that there exists entities with at least these three properties. In the first section of this paper, I argue that strong textual and more general exegetical reasons suggest that the traditional interpretation is mistaken. Furthermore, this interpretation, as I argue in the second section, fails to credit Plato with a proper argument for recollection. In section III, I present an alternative account of the argument for R in the Phaedo. At the same time I defend a more general interpretation according to which the metaphysical doctrine Plato offers in the Phaedo represents a natural continuation of the philosophical position that stands at the centre of the dialectical conversations we find in the shorter Socratic dialogues.
False Pleasures, Appearance and Imagination in the Philebus
Authors: Delcomminette Sylvain 
Published: November 2003

AbstractThis paper examines the discussion about false pleasures in the Philebus (36 c3-44 a11). After stressing the crucial importance of this discussion in the economy of the dialogue, it attempts to identify the problematic locus of the possibility of true or false pleasures. Socrates points to it by means of an analogy between pleasure and doxa. Against traditional interpretations, which reduce the distinction drawn in this passage to a distinction between doxa and pleasure on the one hand and their object on the other, it is argued that, rather, Socrates distinguishes between the mere fact of having a doxa or a pleasure, on the one hand, and the content of these acts, on the other hand. Consequently, the possibility for a pleasure to be false does not concern its relation to an object, but the affective content which defines it. In order to show how the affective content of a pleasure can be false, it is necessary to examine the three species of false pleasures described by Socrates in their relation to appearance and imagination. Appearance is not identical with perception for Plato: it consists in a mixture of perception and doxa. As for imagination, it consists in "illustrating" a doxa present in the soul by means of a "quasi-perception". It is the presence of a doxa in each of these processes which makes it possible for them to be true or false, while mere perception cannot be either true or false. It is then argued that according to the Philebus pleasure can be false precisely because its affective content is not a mere perception, but either an appearance or an imagination.
Paternal age and risk for schizophrenia
Authors: Zammit Stanley , Allebeck Peter , Dalman Christina , Lundberg Ingvar , Hemmingson Tomas , Owen Michael J. , Lewis Glyn 
Published: November 2003

BackgroundPreviously reported associations between advancing paternal age and schizophrenia could be due to an increase in paternal germ cell mutations or be confounded by heritable personality traits associated with schizophrenia that result in delayed parenthood.AimsTo investigate this association while adjusting for personality traits related to poor social integration in the subjects.MethodA cohort of 50 087 adolescent males was followed up by record linkage to determine hospital admissions for schizophrenia between 1970 and 1996.ResultsAdvancing paternal age was associated with an increased risk of developing schizophrenia in a ‘dose-dependent’ manner. The adjusted odds ratio for each 10-year increase in paternal age was 1.3 (95% Cl 1.0–1.5; P=0.015).ConclusionsAdvancing paternal age is an independent risk factor for schizophrenia. Adjusting for social integration in subjects made little difference to this association, consistent with the hypothesis that advancing paternal age may increase liability to schizophrenia owing to accumulating germ cell mutations.
Cost-effectiveness of current and optimal treatment for schizophrenia
Authors: Andrews Gavin , Sanderson Kristy , Corry Justine , Issakidis Cathy , Lapsley Helen 
Published: November 2003

BackgroundThis paper is part of a project to identify the proportion of the burden of each mental disorder averted by current and optimal interventions, and the cost-effectiveness of both.AimsTo use epidemiological data on schizophrenia to model the cost-effectiveness of current and optimal treatment.MethodCalculate the burden of schizophrenia in the years lived with disability (YLD) component of disability-adjusted life-years lost, the proportion averted by current interventions, the proportion that could be averted by optimal treatment and the cost-effectiveness of both.ResultsCurrent interventions avert some 13% of the burden, whereas 22% could be averted by optimal treatment. Current interventions cost about AUS$200 000 per YLD averted, whereas optimal treatment at a similar cost could increase the number of YLDs averted by two-thirds. Even so, the majority of the burden of schizophrenia remains unavertable.ConclusionsOptimal treatment is affordable within the present budget and should be implemented.
Choking deaths: the role of antipsychotic medication
Authors: Ruschena David , Mullen Paul E. , Palmer Simon , Burgess Philip , Cordner Stephen M. , Drummer Olaf H. , Wallace Cameron , Barry-Walsh Justin 
Published: November 2003

BackgroundAn increased risk of choking associated with antipsychotic medication has been repeatedly postulated.AimsTo examine this association in a large number of cases of choking deaths.MethodCases of individuals who had died because of choking were linked with a case register recording contacts with public mental health services. The actual and expected rates of psychiatric disorder and the presence of psychotropic medication in post-mortem blood samples were compared.ResultsThe 70 people who had choked to death were over 20 times more likely to have been treated previously for schizophrenia. They were also more likely to have had a prior organic psychiatric syndrome. The risk for those receiving thioridazine or lithium was, respectively, 92 times and 30 times greater than expected. Other antipsychotic and psychotropic drugs were not over-represented.ConclusionsThe increased risk of death in people with schizophrenia may be a combination of inherent predispositions and the use of specific antipsychotic drugs. The increased risk of choking in those with organic psychiatric syndromes is consistent with the consequences of compromised neurological competence.
Prescribing practices of community child and adolescent psychiatrists
Authors: Doerry Ursula , Kent Lindsey 
Published: November 2003

Aims and MethodA questionnaire was sent to all 55 community child and adolescent psychiatrists working in the West Midlands to examine the prescribing practices of community child psychiatrists, because most previous studies have included prescribing data from specialist (tier 4) services.ResultsThe survey had a good response rate (87%). The vast majority of child psychiatrists were prescribing stimulants and antidepressants, and over half were prescribing antipsychotics and melatonin. At least half of the consultants would consider prescribing an antipsychotic for the treatment of aggressive behaviour. One-third of consultants cited pressure on services as a reason for prescribing medication.Clinical ImplicationsCommunity child psychiatrists were prescribing more medication than expected, which may have a considerable impact on referral rates to adult services in the future. It is concerning that the increased use of medication may be a reflection of pressure on services.
Background stressors and deliberate self-harm
Authors: Keeley Helen S. , O'Sullivan Mary , Corcoran Paul 
Published: November 2003

Aims and MethodIn this study we aimed to identify negative life events, especially those associated with repetition, in the background histories of patients in a 2-year prospective monitoring study of hospital-treated deliberate self-harm (DSH). Thematic analysis of the narratives recorded during assessment was used to produce general categories of life events.ResultsIn 3031 DSH episodes (n=2287 individuals), women reported more life events than men. Family and interpersonal problems were most commonly reported. Reporting a dysfunctional family of origin, a history of sexual abuse and the imprisonment of self or other were associated with repetition retrospectively and prospectively.Clinical ImplicationsThe background history of patients who harm themselves should be explored routinely on assessment in order to help establish risk of repetition and to determine appropriate follow-up.