bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leptospiral Outer Membrane Protein LipL41 Is Not Essential for Acute Leptospirosis but Requires a Small Chaperone Protein, Lep, for Stable Expression
Authors: King Amy M. , Bartpho Thanatchaporn , Sermswan Rasana W. , Bulach Dieter M. , Eshghi Azad , Picardeau Mathieu , Adler Ben , Murray Gerald L. 
Published: May 2013

ABSTRACT

Leptospirosis is a worldwide zoonosis caused by pathogenic
Leptospira
spp., but knowledge of leptospiral pathogenesis remains limited. However, the development of mutagenesis systems has allowed the investigation of putative virulence factors and their involvement in leptospirosis. LipL41 is the third most abundant lipoprotein found in the outer membranes of pathogenic leptospires and has been considered a putative virulence factor. LipL41 is encoded on the large chromosome 28 bp upstream of a small open reading frame encoding a hypothetical protein of unknown function. This gene was named
lep
, for
L
ipL41
e
xpression
p
artner. In this study,
lipL41
was found to be cotranscribed with
lep
. Two transposon mutants were characterized: a
lipL41
mutant and a
lep
mutant. In the
lep
mutant, LipL41 protein levels were reduced by approximately 90%. Lep was shown through cross-linking and coexpression experiments to bind to LipL41. Lep is proposed to be a molecular chaperone essential for the stable expression of LipL41. The roles of LipL41 and Lep in the pathogenesis of
Leptospira interrogans
were investigated; surprisingly, neither of these two unique proteins was essential for acute leptospirosis.
Human Endothelial Cells Internalize Candida parapsilosis via N-WASP-Mediated Endocytosis
Authors: Shintaku Tatsushi , Glass Kyle A. , Hirakawa Matthew P. , Longley Sarah J. , Bennett Richard J. , Bliss Joseph M. , Shaw Sunil K. 
Published: May 2013

ABSTRACT

Candida parapsilosis
is a frequent cause of disseminated candidiasis and is associated with significant morbidity and mortality. Although important in pathogenesis, interactions of this organism with endothelial cells have received less attention than those of
Candida albicans
. Internalization of
C. parapsilosis
by monolayers of human endothelial cells was examined in an
in vitro
assay and compared to that of
C. albicans
. Both live and heat-killed yeast were efficiently internalized, with heat-killed yeast subsequently being detected in an acidic subcompartment. Internalization was marked by a process of engulfment by thin membrane extensions from the endothelium. Efficiency of internalization differed among different clinical isolates and species of yeast. Opsonization of
C. parapsilosis
by serum factors was not sufficient to cause endocytosis; instead, serum appeared to directly stimulate endothelial uptake. Colocalization of endothelial actin and N-WASP at sites of
C. parapsilosis
internalization was observed. A Förster-resonance energy transfer (FRET) probe for N-WASP activity showed active N-WASP at sites of internalization for both live and heat-killed
C. parapsilosis
and
C. albicans
. An actin nucleation inhibitor (cytochalasin D) and an N-WASP inhibitor (wiskostatin) both inhibited uptake of heat-killed
C. parapsilosis
, as did short interfering RNA-mediated ablation of N-WASP. Thus, endocytosis by endothelial cells may represent a means of traversal of the blood vessel wall by yeast during disseminated candidiasis, and N-WASP may play a key role in the process.
Cdc42 Promotes Host Defenses against Fatal Infection
Authors: Lee Keunwook , Boyd Kelli L. , Parekh Diptiben V. , Kehl-Fie Thomas E. , Baldwin H. Scott , Brakebusch Cord , Skaar Eric P. , Boothby Mark , Zent Roy 
Published: May 2013

ABSTRACTThe small Rho GTPase Cdc42 regulates key signaling pathways required for multiple cell functions, including maintenance of shape, polarity, proliferation, invasion, migration, differentiation, and morphogenesis. As the role of Cdc42-dependent signaling in fibroblastsin vivois unknown, we attempted to specifically delete it in these cells by crossing the Cdc42fl/flmouse with an fibroblast-specific protein 1 (FSP1)-Cre mouse, which is thought to mediate recombination exclusively in fibroblasts. Surprisingly, the FSP1-Cre;Cdc42fl/flmice died at 3 weeks of age due to overwhelming suppurative upper airway infections that were associated with neutrophilia and lymphopenia. Even though major aberrations in lymphoid tissue development were present in the mice, the principal cause of death was severe migration and killing abnormalities of the neutrophil population resulting in an inability to control infection. We also show that in addition to fibroblasts, FSP1-Cre deleted Cdc42 very efficiently in all leukocytes. Thus, by using this nonspecific Cre mouse, we inadvertently demonstrated the importance of Cdc42 in host protection from lethal infections and suggest a critical role for this small GTPase in innate immunity.
Upregulation of the Host SLC11A1 Gene by Clostridium difficile Toxin B Facilitates Glucosylation of Rho GTPases and Enhances Toxin Lethality
Authors: Feng Yanan , Cohen Stanley N. 
Published: May 2013

ABSTRACTPseudomembranous enterocolitis associated withClostridium difficileinfection is an important cause of morbidity and mortality in patients being treated with antibiotics. Two closely related large protein toxins produced byC. difficile, TcdA and TcdB, which act identically but at different efficiencies to glucosylate low-molecular-weight Rho GTPases, underlie the microbe's pathogenicity. Using antisense RNA encoded by a library of human expressed sequence tags (ESTs), we randomly inactivated host chromosomal genes in HeLa cells and isolated clones that survived exposure to ordinarily lethal doses of TcdB. This phenotypic screening and subsequent analysis identified solute carrier family 11 member 1 (SLC11A1; formerly NRAMP1), a divalent cation transporter crucial to host defense against certain microbes, as an enhancer of TcdB lethality. Whereas SLC11A1 normally is poorly expressed in human cells of nonmyeloid lineage, TcdB increased SLC11A1 mRNA abundance in such cells through the actions of the RNA-binding protein HuR. We show that short hairpin RNA (shRNA) directed against SLC11A1 reduced TcdB glucosylation of small Rho GTPases and, consequently, toxin lethality. Consistent with the previously known role of SLC11A1 in cation transport, these effects were enhanced by elevation of Mn2+in media; conversely, they were decreased by treatment with a chelator of divalent cations. Our findings reveal an unsuspected role for SLC11A1 in determiningC. difficilepathogenicity, demonstrate the novel ability of a bacterial toxin to increase its cytotoxicity, establish a mechanistic basis for these effects, and suggest a therapeutic approach to mitigate cell killing byC. difficiletoxins A and B.
The
c.
1000–900 Ma and
c.
550–500 Ma tectonothermal events in the Prince Charles Mountains–Prydz Bay region, East Antarctica, and their relations to supercontinent evolution
Authors: Liu Xiaochun , Zhao Yue , Hu Jianmin 
Published: May 2013

Abstract

The Prince Charles Mountains (PCM)–Prydz Bay region in East Antarctica experienced the late Mesoproterozoic/early Neoproterozoic (
c.
1000–900 Ma) and late Neoproterozoic/Cambrian (
c.
550–500 Ma) tectonothermal events. The late Mesoproterozoic/early Neoproterozoic tectonothermal event dominates the Rayner Complex and spreads over the main part of the Prydz Belt. This event includes two episodes (or stages) of metamorphism accompanying the intrusion of syn- to post-orogenic granitoids at
c.
1000–960 Ma and
c.
940–900 Ma. The
c.
1000–960 Ma metamorphism in the northern PCM and Mawson Coast records medium- to low-pressure granulite facies conditions accompanied by a near-isobaric cooling path, whereas the
c.
940–900 Ma metamorphism in Kemp Land reaches relatively higher
P
–
T
conditions followed by a near-isothermal decompression or decompressive cooling path. The late Mesoproterozoic/early Neoproterozoic orogeny (i.e. the Rayner orogeny) involved a long-lived (
c.
1380–1020 Ma) magmatic accretion along continental/oceanic arcs and a protracted or two-stage collision of the Indian craton with a portion of East Antarctica, forming the Indian–Antarctic continental block independent of the Rodinia supercontinent. The late Neoproterozoic/Cambrian tectonothermal event pervasively overprinted on both Archaean–Proterozoic basements and cover sequences in the Prydz Belt. Except for high-pressure granulite boulders from the Grove Mountains, the metamorphism of most rocks records medium-pressure granulite facies conditions with a clockwise
P–T
path. In contrast, this event is lower grade (greenschist–amphibolite facies) and localized in the PCM. Regionally, the late Neoproterozoic/Cambrian tectonothermal event seems to have developed on the southeastern margin of the Indo-Antarctic continental block, suggesting that the major suture should be located southeastwards of the presently exposed Prydz Belt. The precise dating for different rock types reveals that the late Neoproterozoic/Cambrian orogeny (i.e. the Prydz orogeny) commenced at
c.
570 Ma and lasted until
c.
490 Ma, which is roughly contemporaneous with the late collisional stage of the Brasiliano/Pan-African orogenic systems in Gondwanaland. Therefore, the final assembly of the Gondwana supercontinent may have been completed by the collision of a number of cratonic blocks during the same time period.
Targeting Natural Killer Cells to Acute Myeloid LeukemiaIn Vitrowith a CD16 × 33 Bispecific Killer Cell Engager and ADAM17 Inhibition
Authors: Wiernik Andres , Foley Bree , Zhang Bin , Verneris Michael R. , Warlick Erica , Gleason Michelle K. , Ross Julie A. , Luo Xianghua , Weisdorf Daniel J. , Walcheck Bruce , Vallera Daniel A. , Miller Jeffrey S. 
Published: May 2013

AbstractPurpose: The graft versus leukemia effect by natural killer (NK) cells prevents relapse following hematopoietic stem cell transplantation. We determined whether a novel bispecific killer cell engager (BiKE) signaling through CD16 and targeting CD33 could activate NK cells at high potency against acute myelogenous leukemia (AML) targets.Experimental Design: We investigated the ability of our fully humanized CD16 × CD33 (CD16 × 33) BiKE to trigger in vitro NK cell activation against HL60 (CD33+), RAJI (CD33−), and primary AML targets (de novo and refractory) to determine whether treatment with CD16 × 33 BiKE in combination with an ADAM17 inhibitor could prevent CD16 shedding (a novel inhibitory mechanism induced by NK cell activation) and overcome inhibition of class I MHC recognizing inhibitory receptors.Results: NK cell cytotoxicity and cytokine release were specifically triggered by the CD16 × 33 BiKE when cells were cultured with HL60 targets, CD33+de novo and refractory AML targets. Combination treatment with CD16 × 33 BiKE and ADAM17 inhibitor resulted in inhibition of CD16 shedding in NK cells, and enhanced NK cell activation. Treatment of NK cells from double umbilical cord blood transplant (UCBT) recipients with the CD16 × 33 BiKE resulted in activation, especially in those recipients with cytomegalovirus reactivation.Conclusion: CD16 × 33 BiKE can overcome self-inhibitory signals and effectively elicit NK cell effector activity against AML. These in vitro studies highlight the potential of CD16 × 33 BiKE ± ADAM17 inhibition to enhance NK cell activation and specificity against CD33+ AML, which optimally could be applied in patients with relapsed AML or for adjuvant antileukemic therapy posttransplantation. Clin Cancer Res; 19(14); 3844–55. ©2013 AACR.
Review of the systematics, distribution, biogeography and natural history of Moroccan amphibians
Authors: BEUKEMA WOUTER , DE POUS PHILIP , DONAIRE-BARROSO DAVID , BOGAERTS SERGÉ , GARCIA-PORTA JOAN , ESCORIZA DANIEL , ARRIBAS OSCAR J. , MOUDEN EL HASSAN EL , CARRANZA SALVADOR 
Published: May 2013

The amphibian fauna of the Kingdom of Morocco was traditionally regarded as poor and closely related to its European counterpart. However, an increase in research during the last decades revealed a considerable degree of endemism amongst Moroccan amphibians, as well as phenotypic and genotypic inter- and intraspecific divergence. Despite this increase in knowledge, a comprehensible overview is lacking while several systematic issues have remained unresolved. We herein present a contemporary overview of the distribution, taxonomy and biogeography of Moroccan amphibians. Fourteen fieldtrips were made by the authors and colleagues between 2000 and 2012, which produced a total of 292 new distribution records. Furthermore, based on the results of the present work, we (i) review the systematics of the genus Salamandra in Morocco, including the description of a new subspecies from the Rif- and Middle Atlas Mountains, Salamandra algira splendens ssp. nov.; (ii) present data on intraspecific morphological variability of Pelobates varaldiiand Pleurodeles waltl in Morocco; (iii) attempt to resolve the phylogenetic position of Bufo brongersmai and erect a new genus for this species, Barbarophryne gen. nov.; (iv) summarize and assess the availability of tadpole-specific characteristics and bioacoustical data, and (v) summarize natural history data.
Finescale Radar Observations of Tornado and Mesocyclone Structures
Authors: Wurman Joshua , Kosiba Karen 
Published: May 2013

Abstract
A variety of vortex configurations observed at finescale with Doppler On Wheels (DOW) radars in and near the hook echoes of supercell thunderstorms are described. These include marginal/weak tornadoes, often with no documented condensation funnels, debris rings, or low-reflectivity eyes; multiple-vortex mesocyclones; multiple simultaneous tornadoes; satellite tornadoes; cyclonic–anticyclonic tornado pairs; multiple vortices within other multiple vortices; tornadoes with quasi-concentric multiple wind field maxima; lines of vortices outside tornadoes; and horizontal vortices. The kinematic structures of these different phenomena are documented and compared. The process of multiple vortex circulations evolving from and into tornadoes is documented. DOW observations suggest that there is no clear spatial-scale separation between multiple-vortex tornadoes and larger multiple-vortex circulations.
These different vortex configurations motivate a refined definition of what constitutes a tornado, excluding many multiple, weak, embedded, and tornado-associated vortices.
Effects of montmorillonite (MMT) on morphological, tensile, physical barrier properties and biodegradability of polylactic acid/starch/MMT nanocomposites
Authors: Jalalvandi E , Majid RA , Ghanbari T , Ilbeygi H 
Published: May 2013

Biodegradable polymer nanocomposites have received great attention due to their synergistic properties of good mechanical and barrier properties; yet, they are biodegradable. In this research, prior to compression into thin sheets, polylactic acid (PLA), tapioca starch, glycerol and maleic anhydride (MA) were compounded with different loadings of montmorillonite (MMT) through a twin screw extruder. MMT was added to improve the mechanical and barrier properties of PLA/starch blend. The effects of MMT loadings on tensile property, morphology and biodegradability were studied. X-Ray diffraction analysis showed that samples with MMT loadings below 6 phr exhibited exfoliated structure, while samples that contained MMT above 6 phr (5.66 wt%) exhibited intercalated structure. The exfoliated-type structure was observed using transmission electron microscopy. These effects were manifested in the tensile results, which showed an increase in modulus, tensile strength and elongation at break. However, for the modulus, the MMT content was limited to 4 phr (3.85 wt%). Beyond that, the modulus decreased. It was thought that above 4 phr, the MMT particles agglomerated, thus reducing the modulus of the samples. This argument was supported by field emission scanning electron microscopic images, which showed big lump when MMT loadings were at 6 and 8 phr (7.41 wt%). Meanwhile, the addition of MMT has improved the water barrier property and hastened the rate of biodegradation. The nanosized MMT particles disturb the continuity of PLA/starch chain, which formed pathways for microorganisms to enter and attack the chain, thus increasing the biodegradation rate. The particle is also able to block a tortuous pathway for water to enter the starch chain, thus reducing the water uptake and improving the physical barrier of nanocomposite.
Modulating effects of hesperidin on key carbohydrate-metabolizing enzymes, lipid profile, and membrane-bound adenosine triphosphatases against 7,12-dimethylbenz(a)anthracene-induced breast carcinogenesis
Authors: Nandakumar N , Rengarajan T , Balamurugan A , Balasubramanian MP 
Published: May 2013

The aim of this study was to document the effect of hesperidin on the key enzyme activities of carbohydrate metabolism, lipid profile, and membrane-bound adenosine triphosphatases (ATPases) during 7,12-dimethylbenz( a)anthracene (DMBA)-induced breast carcinogenesis. Hesperidin has been reported to have multiple biological properties. Breast cancer was induced by single dose of DMBA (20 mg/kg body weight (bw)). The results revealed that there was a significant increase in the activities of hexokinase, phosphoglucoisomerase, and aldolase and a concomitant decrease in the activities of glucose-6-phosphatase and fructose-1,6-diphosphatase in cancer-induced animals. The activities of ATPases were found to be decreased both in erythrocyte membrane and in the liver of mammary cancer-bearing animals. The lipid profiles such as total cholesterol, free cholesterol, phospholipids, triglycerides, and free fatty acids significantly increased and in contrast the ester cholesterol in plasma was found to be decreased, whereas it was found to be elevated in the liver of cancer-bearing groups. The altered levels of the above-mentioned biochemical parameters in cancer-bearing animals were significantly ameliorated by the administration of hesperidin at the dosage of 30 mg/kg bw for 45 days. The histopathological analysis of breast and liver tissues were well supported the modulatory property of hesperidin, and this might be associated with normalizing the gluconeogenesis process, stabilization of cell membranes, and modulation of lipid biosynthesis.
Rearticulating Values Through Applied Theories at Children’s Hospital Colorado
Authors: Wukitsch Michael , Simmons Ryan , Hutt Mark 
Published: May 2013

The Problem A large, academically affiliated pediatric institution experienced a period of dramatic change leading to concerns of cultural fragmentation and a loss of shared cultural values. The Solution An intervention was crafted using theories of action learning, appreciative inquiry (AI), and Scharmer’s (2009) Theory U to reformulate organizational values. A project team representing different departments and organizational levels was created to develop a new values statement. The team facilitated staff listening sessions, distilled perspectives into themes, and synthesized the themes. A traditional values statement was replaced with a unique and original credo. The intervention demonstrates a unique approach to applying multiple theories to an organizational culture change effort. The Stakeholders Human resource development (HRD) practitioners and scholars who are interested in the application of theory to interventions in an organizational context.
Common and rare von Willebrand factor (VWF) coding variants, VWF levels, and factor VIII levels in African Americans: the NHLBI Exome Sequencing Project
Authors: Johnsen Jill M. , Auer Paul L. , Morrison Alanna C. , Jiao Shuo , Wei Peng , Haessler Jeffrey , Fox Keolu , McGee Sean R. , Smith Joshua D. , Carlson Christopher S. , Smith Nicholas , Boerwinkle Eric , Kooperberg Charles , Nickerson Deborah A. , Rich Stephen S. , Green David , Peters Ulrike , Cushman Mary , Reiner Alex P. 
Published: May 2013

Key PointsSeveral common and rare VWF missense variants contribute to phenotypic differences in VWF and FVIII among African Americans. Next-generation sequencing technology and improved genotype imputation can contribute to molecular genetics of VWD-related phenotypes.
Sum of squared logarithms - an inequality relating positive definite matrices and their matrix logarithm
Authors: Bîrsan Mircea , Neff Patrizio , Lankeit Johannes 
Published: May 2013

Abstract
Let

y
1

,

y
2

,

y
3

,

a
1

,

a
2

,

a
3

∈
(
0
,
∞
)

be such that

y
1

y
2

y
3

=

a
1

a
2

a
3

and

y
1

+

y
2

+

y
3

≥

a
1

+

a
2

+

a
3

,

y
1

y
2

+

y
2

y
3

+

y
1

y
3

≥

a
1

a
2

+

a
2

a
3

+

a
1

a
3

.

Then

(
log

y
1

)

2

+

(
log

y
2

)

2

+

(
log

y
3

)

2

≥

(
log

a
1

)

2

+

(
log

a
2

)

2

+

(
log

a
3

)

2

.

This can also be stated in terms of real positive definite

3
×
3

-matrices

P
1

,

P
2

: If their determinants are equal,

det

P
1

=
det

P
2

, then

tr

P
1

≥
tr

P
2

and

tr
Cof

P
1

≥
tr
Cof

P
2

⟹

∥
log

P
1

∥

F
2

≥

∥
log

P
2

∥

F
2

,

where log is the principal matrix logarithm and

∥
P
∥

F
2

=

∑

i
,
j
=
1

3

P

i
j

2

denotes the Frobenius matrix norm. Applications in matrix analysis and nonlinear elasticity are indicated.

MSC:26D05, 26D07.
Perturbing the metabolic dynamics of myo-inositol in developing Brassica napus seeds through in vivo methylation impacts its utilization as phytate precursor and affects downstream metabolic pathways
Authors: Dong Jinzhuo , Yan Wei , Bock Cheryl , Nokhrina Kateryna , Keller Wilf , Georges Fawzy 
Published: May 2013

AbstractBackgroundmyo-Inositol (Ins) metabolism during early stages of seed development plays an important role in determining the distributional relationships of some seed storage components such as the antinutritional factors, sucrose galactosides (also known as raffinose oligosaccharides) and phytic acid (PhA) (myo-inositol 1,2,3,4,5,6-hexakisphosphate). The former is a group of oligosaccharides, which plays a role in desiccation at seed maturation. They are not easily digested by monogastric animals, hence their flatulence-causing properties. Phytic acid is highly negatively charged, which chelates positive ions of essential minerals and decreases their bioavailability. It is also a major cause of phosphate-related water pollution. Our aim was to investigate the influence of competitive diversion of Ins as common substrate on the biosynthesis of phytate and sucrose galactosides.ResultsWe have studied the initial metabolic patterns of Ins in developing seeds ofBrassica napusand determined that early stages of seed development are marked by rapid deployment of Ins into a variety of pathways, dominated by interconversion of polar (Ins phosphates) and non-polar (phospholipids) species. In a time course experiment at early stages of seed development, we show Ins to be a highly significant constituent of the endosperm and seed coat, but with no phytate biosynthesis occurring in either tissue. Phytate accumulation appears to be confined mainly within the embryo throughout seed development and maturation. In our approach, the gene formyo-inositol methyltransferase (IMT), isolated fromMesembryanthemum crystallinum(ice plant), was transferred toB. napusunder the control of the seed-specific promoters, napin and phaseolin. Introduction of this new metabolic step during seed development prompted Ins conversion to the corresponding monomethyl ether, ononitol, and affected phytate accumulation. We were able to produce homozygous transgenic lines with 19% - 35% average phytate reduction. Additionally, changes in the raffinose content and related sugars occurred along with enhanced sucrose levels. Germination rates, viability and other seed parameters were unaffected by theIMTtransgene over-expression.ConclusionsCompetitive methylation of Ins during seed development reduces seed antinutritional components and enhances its nutritional characteristics while maintaining adequate phosphate reserves. Such approach should potentially raise the canola market value and likely, that of other crops.