bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Evolution of Morphological Regulatory Functions in Candida Species
Authors: Lackey Erika , Vipulanandan Geethanjali , Childers Delma S. , Kadosh David 
Published: August 2013

ABSTRACT

Morphological transitions play an important role in virulence and virulence-related processes in a wide variety of pathogenic fungi, including the most commonly isolated human fungal pathogen
Candida albicans
. While environmental signals, transcriptional regulators, and target genes associated with
C. albicans
morphogenesis are well-characterized, considerably little is known about morphological regulatory mechanisms and the extent to which they are evolutionarily conserved in less pathogenic and less filamentous non-
albicans Candida
species (NACS). We have identified specific optimal filament-inducing conditions for three NACS (
C. tropicalis
,
C. parapsilosis
, and
C. guilliermondii
), which are very limited, suggesting that these species may be adapted for niche-specific filamentation in the host. Only a subset of evolutionarily conserved
C. albicans
filament-specific target genes were induced upon filamentation in
C. tropicalis
,
C. parapsilosis
, and
C. guilliermondii
. One of the genes showing conserved expression was
UME6
, a key filament-specific regulator of
C. albicans
hyphal development. Constitutive high-level expression of
UME6
was sufficient to drive increased filamentation as well as biofilm formation and partly restore conserved filament-specific gene expression in both
C. tropicalis
and
C. parapsilosis
, suggesting that evolutionary differences in filamentation ability among pathogenic
Candida
species may be partially attributed to alterations in the expression level of a conserved filamentous growth machinery. In contrast to
UME6
,
NRG1
, an important repressor of
C. albicans
filamentation, showed only a partly conserved role in controlling NACS filamentation. Overall, our results suggest that
C. albicans
morphological regulatory functions are partially conserved in NACS and have evolved to respond to more specific sets of host environmental cues.
Identification of the Set of Genes, Including Nonannotated
morA
, under the Direct Control of ModE in Escherichia coli
Authors: Kurata Tatsuaki , Katayama Akira , Hiramatsu Masakazu , Kiguchi Yuya , Takeuchi Masamitsu , Watanabe Tomoyuki , Ogasawara Hiroshi , Ishihama Akira , Yamamoto Kaneyoshi 
Published: August 2013

ABSTRACT

ModE is the molybdate-sensing transcription regulator that controls the expression of genes related to molybdate homeostasis in
Escherichia coli
. ModE is activated by binding molybdate and acts as both an activator and a repressor. By genomic systematic evolution of ligands by exponential enrichment (SELEX) screening and promoter reporter assays, we have identified a total of nine operons, including the hitherto identified
modA
,
moaA
,
dmsA
, and
napF
operons, of which six were activated by ModE and three were repressed. In addition, two promoters were newly identified and direct transcription of novel genes, referred to as
morA
and
morB
, located on antisense strands of
yghW
and
torY
, respectively. The
morA
gene encodes a short peptide, MorA, with an unusual initiation codon. Surprisingly, overexpression of the
morA
5′ untranslated region exhibited an inhibitory influence on colony formation of
E. coli
K-12.
Pilin and Sortase Residues Critical for Endocarditis- and Biofilm-Associated Pilus Biogenesis in Enterococcus faecalis
Authors: Nielsen Hailyn V. , Flores-Mireles Ana L. , Kau Andrew L. , Kline Kimberly A. , Pinkner Jerome S. , Neiers Fabrice , Normark Staffan , Henriques-Normark Birgitta , Caparon Michael G. , Hultgren Scott J. 
Published: August 2013

ABSTRACT

Enterococci commonly cause hospital-acquired infections, such as infective endocarditis and catheter-associated urinary tract infections. In animal models of these infections, a long hairlike extracellular protein fiber known as the endocarditis- and biofilm-associated (Ebp) pilus is an important virulence factor for
Enterococcus faecalis
. For Ebp and other sortase-assembled pili, the pilus-associated sortases are essential for fiber formation as they create covalent isopeptide bonds between the sortase recognition motif and the pilin-like motif of the pilus subunits. However, the molecular requirements governing the incorporation of the three pilus subunits (EbpA, EbpB, and EbpC) have not been investigated in
E. faecalis
. Here, we show that a Lys residue within the pilin-like motif of the EbpC subunit was necessary for EbpC polymerization. However, incorporation of EbpA into the pilus fiber only required its sortase recognition motif (LPXTG), while incorporation of EbpB only required its pilin-like motif. Only the sortase recognition motif would be required for incorporation of the pilus tip subunit, while incorporation of the base subunit would only require the pilin recognition motif. Thus, these data support a model with EbpA at the tip and EbpB at the base of an EbpC polymer. In addition, the housekeeping sortase, SrtA, was found to process EbpB and its predicted catalytic Cys residue was required for efficient cell wall anchoring of mature Ebp pili. Thus, we have defined molecular interactions involved in fiber polymerization, minor subunit organization, and pilus subcellular compartmentalization in the
E. faecalis
Ebp pilus system. These studies advance our understanding of unique molecular mechanisms of sortase-assembled pilus biogenesis.
Suppressor Analysis Reveals a Role for SecY in the SecA2-Dependent Protein Export Pathway of Mycobacteria
Authors: Ligon Lauren S. , Rigel Nathan W. , Romanchuk Artur , Jones Corbin D. , Braunstein Miriam 
Published: August 2013

ABSTRACT

All bacteria use the conserved Sec pathway to transport proteins across the cytoplasmic membrane, with the SecA ATPase playing a central role in the process. Mycobacteria are part of a small group of bacteria that have two SecA proteins: the canonical SecA (SecA1) and a second, specialized SecA (SecA2). The SecA2-dependent pathway exports a small subset of proteins and is required for
Mycobacterium tuberculosis
virulence. The mechanism by which SecA2 drives export of proteins across the cytoplasmic membrane remains poorly understood. Here we performed suppressor analysis on a dominant negative
secA2
mutant (
secA2 K129R
) of the model mycobacterium
Mycobacterium smegmatis
to better understand the pathway used by SecA2 to export proteins. Two extragenic suppressor mutations were identified as mapping to the promoter region of
secY
, which encodes the central component of the canonical Sec export channel. These suppressor mutations increased
secY
expression, and this effect was sufficient to alleviate the
secA2 K129R
phenotype. We also discovered that the level of SecY protein was greatly diminished in the
secA2 K129R
mutant, but at least partially restored in the suppressors. Furthermore, the level of SecY in a suppressor strongly correlated with the degree of suppression. Our findings reveal a detrimental effect of SecA2 K129R on SecY, arguing for an integrated system in which SecA2 works with SecY and the canonical Sec translocase to export proteins.
How Escherichia coli Tolerates Profuse Hydrogen Peroxide Formation by a Catabolic Pathway
Authors: Ravindra Kumar Sripriya , Imlay James A. 
Published: August 2013

ABSTRACT

When
Escherichia coli
grows on conventional substrates, it continuously generates 10 to 15 μM/s intracellular H
2
O
2
through the accidental autoxidation of redox enzymes. Dosimetric analyses indicate that scavenging enzymes barely keep this H
2
O
2
below toxic levels. Therefore, it seemed potentially problematic that
E. coli
can synthesize a catabolic phenylethylamine oxidase that stoichiometrically generates H
2
O
2
. This study was undertaken to understand how
E. coli
tolerates the oxidative stress that must ensue. Measurements indicated that phenylethylamine-fed cells generate H
2
O
2
at 30 times the rate of glucose-fed cells. Two tolerance mechanisms were identified. First, in enclosed laboratory cultures, growth on phenylethylamine triggered induction of the OxyR H
2
O
2
stress response. Null mutants (
ΔoxyR
) that could not induce that response were unable to grow. This is the first demonstration that OxyR plays a role in protecting cells against endogenous H
2
O
2
. The critical element of the OxyR response was the induction of H
2
O
2
scavenging enzymes, since mutants that lacked NADH peroxidase (Ahp) grew poorly, and those that additionally lacked catalase did not grow at all. Other OxyR-controlled genes were expendable. Second, phenylethylamine oxidase is an unusual catabolic enzyme in that it is localized in the periplasm. Calculations showed that when cells grow in an open environment, virtually all of the oxidase-generated H
2
O
2
will diffuse across the outer membrane and be lost to the external world, rather than enter the cytoplasm where H
2
O
2
-sensitive enzymes are located. In this respect, the periplasmic compartmentalization of phenylethylamine oxidase serves the same purpose as the peroxisomal compartmentalization of oxidases in eukaryotic cells.
Topoisomerase I (TopA) Is Recruited to ParB Complexes and Is Required for Proper Chromosome Organization during Streptomyces coelicolor Sporulation
Authors: Szafran Marcin , Skut Patrycja , Ditkowski Bartosz , Ginda Katarzyna , Chandra Govind , Zakrzewska-Czerwińska Jolanta , Jakimowicz Dagmara 
Published: August 2013

ABSTRACTStreptomycesspecies are bacteria that resemble filamentous fungi in their hyphal mode of growth and sporulation. InStreptomyces coelicolor, the conversion of multigenomic aerial hyphae into chains of unigenomic spores requires synchronized septation accompanied by segregation of tens of chromosomes into prespore compartments. The chromosome segregation is dependent on ParB protein, which assembles into an array of nucleoprotein complexes in the aerial hyphae. Here, we report that nucleoprotein ParB complexes are boundin vitroandin vivoby topoisomerase I, TopA, which is the only topoisomerase I homolog found inS. coelicolor. TopA cannot be eliminated, and its depletion inhibits growth and blocks sporulation. Surprisingly, sporulation in the TopA-depleted strain could be partially restored by deletion ofparB. Furthermore, the formation of regularly spaced ParB complexes, which is a prerequisite for proper chromosome segregation and septation during the development of aerial hyphae, has been found to depend on TopA. We hypothesize that TopA is recruited to ParB complexes during sporulation, and its activity is required to resolve segregating chromosomes.
TraG Encoded by the pIP501 Type IV Secretion System Is a Two-Domain Peptidoglycan-Degrading Enzyme Essential for Conjugative Transfer
Authors: Arends Karsten , Celik Ertugrul-Kaan , Probst Ines , Goessweiner-Mohr Nikolaus , Fercher Christian , Grumet Lukas , Soellue Cem , Abajy Mohammad Yaser , Sakinc Tuerkan , Broszat Melanie , Schiwon Katarzyna , Koraimann Guenther , Keller Walter , Grohmann Elisabeth 
Published: August 2013

ABSTRACT

pIP501 is a conjugative broad-host-range plasmid frequently present in nosocomial
Enterococcus faecalis
and
Enterococcus faecium
isolates. We focus here on the functional analysis of the type IV secretion gene
traG
, which was found to be essential for pIP501 conjugative transfer between Gram-positive bacteria. The TraG protein, which localizes to the cell envelope of
E. faecalis
harboring pIP501, was expressed and purified without its N-terminal transmembrane helix (TraGΔTMH) and shown to possess peptidoglycan-degrading activity. TraGΔTMH was inhibited by specific lytic transglycosylase inhibitors hexa-
N
-acetylchitohexaose and bulgecin A. Analysis of the TraG sequence suggested the presence of two domains which both could contribute to the observed cell wall-degrading activity: an N-terminal soluble lytic transglycosylase domain (SLT) and a C-terminal cysteine-, histidine-dependent amidohydrolases/peptidases (CHAP) domain. The protein domains were expressed separately, and both degraded peptidoglycan. A change of the conserved glutamate residue in the putative catalytic center of the SLT domain (E87) to glycine resulted in almost complete inactivity, which is consistent with this part of TraG being a predicted lytic transglycosylase. Based on our findings, we propose that TraG locally opens the peptidoglycan to facilitate insertion of the Gram-positive bacterial type IV secretion machinery into the cell envelope.
Second-generation surveillance for HIV/AIDS in Pakistan: results from the 4th round of Integrated Behavior and Biological Survey 2011–2012
Authors: Emmanuel Faran , Salim Momina , Akhtar Naeem , Arshad Salwa , Reza Tahira Ezra 
Published: August 2013

ObjectivesIn an effort to fully analyse and understand the HIV situation and its epidemiology in Pakistan, a bilateral collaboration between the National AIDS Control Program and the Canadian International Development Agency resulted in the establishment of an effective second-generation surveillance (SGS) system for HIV/AIDS between 2004 and 2012 in accordance with the published guidelines. This paper presents findings from the 4th round of SGS.MethodsA mapping exercise was initially conducted for size estimations of the key vulnerable populations: people who inject drugs (PWIDs), male sex workers (MSWs),hijrasex workers (HSWs), and female sex workers (FSWs), followed by an Integrated Behavioral and Biological Surveillance in 20 selected cities across Pakistan.ResultsThe estimated sizes of the four key populations mapped in the 20 cities were 89 178 FSWs, 46 351 PWIDs, 23 317 HSWs and 19 119 MSWs. The HIV sero-prevalence among PWIDs was the highest among all key populations surveyed at 37.8% (CI 37.3 to 38.3) nationally, followed by a prevalence of 7.2% (CI 6.8 to 7.5) among HSWs, 3.1% (CI 2.8 to 3.4) among MSWs and 0.8% (CI 0.4 to 1.0) for FSWs. Various key risk behaviours, that is, sharing of syringes by PWIDs and inconsistent use of condoms by sex workers, were documented.ConclusionsPakistan's HIV epidemic that once was characterised primarily by transmission among PWIDs is now increasingly characterised by significant sexual transmission, and all types of sex workers (male,hijraand female) exhibit epidemiological proportions of infection. There is a need to develop concrete strategic plans for each vulnerable subpopulation, initially focusing prevention resources on those with a higher risk or vulnerability.
TDP1 and PARP1 Deficiency Are Cytotoxic to Rhabdomyosarcoma Cells
Authors: Fam Hok Khim , Walton Cheryl , Mitra Sheetal A. , Chowdhury Miraj , Osborne Nichola , Choi Kunho , Sun Guobin , Wong Patrick C.W. , O'Sullivan Maureen J. , Turashvili Gulisa , Aparicio Samuel , Triche Timothy J. , Bond Mason , Pallen Catherine J. , Boerkoel Cornelius F. 
Published: August 2013

Abstract
Rhabdomyosarcoma is the most common soft tissue sarcoma in children. Metastatic rhabdomyosarcoma in children has a 5-year event-free survival rate of &lt;30%, and a recent clinical trial with irinotecan, a topoisomerase I inhibitor, failed to improve outcome. Therefore, it was surmised that failure of irinotecan may be the result of overexpression of the DNA repair enzyme tyrosyl-DNA phosphodiesterase (TDP1), which processes topoisomerase I-DNA complexes resulting from topoisomerase I inhibitor treatment. Using human tissue microarrays and gene expression arrays, a marked overexpression of TDP1 protein and mRNA in RMS tumors was observed. Critically, knockdown of TDP1 or inhibition of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme in the same complex as TDP1, sensitized rhabdomyosarcoma cell lines to analogues of irinotecan. Interestingly, BRCA1/2 mutations or altered expression was not detectable in rhabdomyosarcoma cells; however, TDP1 knockdown and PARP-1 inhibition alone were cytotoxic to a subset of rhabdomyosarcoma cells, suggesting that they harbor genetic lesions in DNA repair components that have synthetic lethal interactions with loss of TDP1 or PARP1 function. Furthermore, culturing embryonal rhabdomyosarcoma cells in serum/nutrient—restricted medium increased cellular cytotoxicity upon PARP-1 inhibition and was intrinsically cytotoxic to alveolar, though not embryonal rhabdomyosarcoma cells. The results of these studies suggest a compensatory role for TDP1 in rhabdomyosarcoma after topoisomerase-I based therapy and further demonstrate that TDP1 knockdown, PARP-1 inhibition, and dietary restriction have therapeutic validity.
Implications: Selective targeting of TDP1 and/or PARP-1 in rhabdomyosarcoma induces cytotoxicity and sensitizes to DNA damaging agents. Mol Cancer Res; 11(10); 1179–92. ©2013 AACR.
Ipilimumab Treatment Results in an Early Decrease in the Frequency of Circulating Granulocytic Myeloid-Derived Suppressor Cells as well as Their Arginase1 Production
Authors: de Coaña Yago Pico , Poschke Isabel , Gentilcore Giusy , Mao Yumeng , Nyström Maria , Hansson Johan , Masucci Giuseppe V. , Kiessling Rolf 
Published: August 2013

Abstract
Blocking the immune checkpoint molecule CTL antigen-4 (CTLA-4) with ipilimumab has proven to induce long-lasting clinical responses in patients with metastatic melanoma. To study the early response that takes place after CTLA-4 blockade, peripheral blood immune monitoring was conducted in five patients undergoing ipilimumab treatment at baseline, three and nine weeks after administration of the first dose. Along with T-cell population analysis, this work was primarily focused on an in-depth study of the myeloid-derived suppressor cell (MDSC) populations. Ipilimumab treatment resulted in lower frequencies of regulatory T cells along with reduced expression levels of PD-1 at the nine-week time point. Three weeks after the initial ipilimumab dose, the frequency of granulocytic MDSCs was significantly reduced and was followed by a reduction in the frequency of arginase1-producing CD3− cells, indicating an indirect in trans effect that should be taken into account for future evaluations of ipilimumab mechanisms of action. Cancer Immunol Res; 1(3); 158–62. ©2013 AACR.
The Emergence of Semantic Meaning in the Ventral Temporal Pathway
Authors: Carlson Thomas A. , Simmons Ryan A. , Kriegeskorte Nikolaus , Slevc L. Robert 
Published: August 2013

Abstract
In the ventral visual pathway, early visual areas encode light patterns on the retina in terms of image properties, for example, edges and color, whereas higher areas encode visual information in terms of objects and categories. At what point does semantic knowledge, as instantiated in human language, emerge? We examined this question by studying whether semantic similarity in language relates to the brain's organization of object representations in inferior temporal cortex (ITC), an area of the brain at the crux of several proposals describing how the brain might represent conceptual knowledge. Semantic relationships among words can be viewed as a geometrical structure with some pairs of words close in their meaning (e.g., man and boy) and other pairs more distant (e.g., man and tomato). ITC's representation of objects similarly can be viewed as a complex structure with some pairs of stimuli evoking similar patterns of activation (e.g., man and boy) and other pairs evoking very different patterns (e.g., man and tomato). In this study, we examined whether the geometry of visual object representations in ITC bears a correspondence to the geometry of semantic relationships between word labels used to describe the objects. We compared ITC's representation to semantic structure, evaluated by explicit ratings of semantic similarity and by five computational measures of semantic similarity. We show that the representational geometry of ITC—but not of earlier visual areas (V1)—is reflected both in explicit behavioral ratings of semantic similarity and also in measures of semantic similarity derived from word usage patterns in natural language. Our findings show that patterns of brain activity in ITC not only reflect the organization of visual information into objects but also represent objects in a format compatible with conceptual thought and language.
Moltmann’s Crucified God
Authors: Mostert Christiaan 
Published: August 2013

Abstract
Forty years ago Jürgen Moltmann published The Crucified God, which set the cat among a few theological pigeons. In the face of the history of suffering in the world, Moltmann argued that we must speak of God ‘within earshot of the dying Jesus’. In the process he argues against the understanding of God, the immanent Trinity, as impassible. Having been sympathetic to Moltmann’s view, the author now raises some questions against it. Apart from the lack of a clear agreed meaning of impassibility (apatheia), the protagonists on each side of the question disagree fundamentally on the meaning of God’s transcendence and the abundance of God’s eternal ‘life’.
Simply Impossible: A Case against Divine Simplicity
Authors: Mullins R. T. 
Published: August 2013

Abstract
Within contemporary philosophical theology the doctrine of divine simplicity has regained attention.1 The pertinent literature has increased by several new defenses of the doctrine.2 One of the more surprising, and troubling, aspects of the contemporary defenses amongst Christian philosophers and theologians is a seeming lack of understanding about how radical the doctrine of divine simplicity truly is. As such, I wish to do a few things in this paper. First, systematically articulate the doctrine of divine simplicity. Second, argue that divine simplicity is not a possible perfection. Third, offer some concluding remarks and highlight remaining issues that will need to be sorted out for the debate over simplicity to meaningfully continue.
Evangelicalism and Racial Exclusivism in Afrikaner History: An Ambiguous Relationship
Authors: Muller Retief 
Published: August 2013

Abstract
What was the relationship in South Africa between evangelicalism and policies of segregation and apartheid in Afrikaner reformed Christianity? This article critically engages this question in reference to the claim by David Bosch that the first internal voices of protest against apartheid came from the side of evangelicals who had been involved in crosscultural mission. This considers the background of the theory, some historical representatives of evangelicalism in South Africa, and the hybridization of evangelicalism in the lives of certain dissident Afrikaner theologians. The conclusion assesses possible ways in which the Bosch thesis may, or may not, pertain to evangelicalism more generally.
Indigenous Religion(s) as an Analytical Category
Authors: Tafjord Bjørn Ola 
Published: August 2013

Abstract
Today the most common uses of “indigenous religion(s)” as an analytical category and as a class in the study of religions are intimately linked to discourses on “indigenous peoples.” The article argues that this often creates problems for critical scholarship. It contributes to the reproduction of stereotypes about particular kinds of religions among particular kinds of peoples; it nurtures ideas about religious similarities across vast spans of time and space; and it blurs boundaries between scholarship and politics and religionising. A different analytical use of “indigenous religion(s)” that sometimes proves more rewarding is identified in some historical and anthropological case studies, where the category is employed contextually as a relational concept, as the opposite of “foreign religion(s),” and not restricted to indigenous peoples. To counter the biases produced by the current primacy of one taxonomic scheme, it is necessary to engage a greater variety of ways and orders of classification.