bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prion reduction filter does not completely remove endogenous prion infectivity from sheep blood
Authors: McCutcheon Sandra , Alejo Blanco A. Richard , Tan Boon Chin , González Lorenzo , Martin Stuart , Mallinson Gary , Appleford Nigel E. , Turner Marc L. , Manson Jean C. , Houston E. Fiona 
Published: May 2015

BACKGROUNDVariant Creutzfeldt‐Jakob disease (vCJD) is a transmissible spongiform encephalopathy affecting humans, acquired initially through infection with bovine spongiform encephalopathy (BSE). A small number of vCJD cases have been acquired through the transfusion of blood from asymptomatic donors who subsequently developed vCJD. Filter devices that selectively bind the infectious agent associated with prion disease have been developed for removal of infection from blood. This study independently assessed one such filter, the P‐CAPT filter, for efficacy in removing infectivity associated with the BSE agent in sheep blood. The sheep BSE model has previously been used to evaluate the distribution of infectivity in clinically relevant blood components. This is the first study to assess the ability of the P‐CAPT filter to remove endogenous infectivity associated with blood components prepared from a large animal model.STUDY DESIGN AND METHODSPaired units of leukoreduced red blood cells (LR‐RBCs) were prepared from donors at the clinical stage of infection and confirmed as having BSE. One cohort of recipients was transfused with LR‐RBCs alone, whereas a parallel cohort received LR and P‐CAPT–filtered RBCs (LR‐RBCs‐P‐CAPT).RESULTSOf 14 recipients, two have been confirmed as having BSE. These sheep had received LR‐RBCs and LR‐RBCs‐P‐CAPT from the same donor.CONCLUSIONSThe results indicate that, after leukoreduction and P‐CAPT filtration, there can still be sufficient residual infectivity in sheep RBCs to transmit infection when transfused into a susceptible recipient.
Evaluation of efficacy of prion reduction filters using blood from an endogenously infected 263K scrapie hamster model
Authors: McLeod Neil P. , Nugent Philip , Dixon Douglas , Dennis Mike , Cornwall Mark , Mallinson Gary , Watkins Nicholas , Thomas Stephen , Sutton J. Mark 
Published: May 2015

BACKGROUNDThe P‐Capt prion reduction filter (MacoPharma) removes prion infectivity in model systems. This independent evaluation assesses prion removal from endogenously infected animal blood, using CE‐marked P‐Capt filters, and replicates the proposed use of the filter within the UK Blood Services.STUDY DESIGN AND METHODSTwo units of blood, generated from 263K scrapie–infected hamsters, were processed using leukoreduction filters (LXT‐quadruple, MacoPharma). Approximately 100 mL of the removed plasma was added back to the red blood cells (RBCs) and the blood was filtered through a P‐Capt filter. Samples of unfiltered whole blood, the prion filter input (RBCs plus plasma and SAGM [RBCPS]), and prion‐filtered leukoreduced blood (PFB) were injected intracranially into hamsters. Clinical symptoms were monitored for 500 ± 1 day, and brains were assessed for spongiosis and prion protein deposit.RESULTSIn Filtration Run 1, none of the 50 challenged animals were diagnosed with scrapie after inoculation with the RBCPS fraction, while two of 190 hamsters injected with PFB were infected. In Filtration Run 2, one of 49 animals injected with RBCPS and two of 193 hamsters injected with PFB were infected. Run 1 reduced the infectious dose (ID) by 1.467 log (>1.187 log and <0.280 log for leukoreduction and prion filtration, respectively). Run 2 reduced prion infectivity by 1.424 log (1.127 and 0.297 log, respectively). Residual infectivity was estimated at 0.212 ± 0.149 IDs/mL (Run 1) and 0.208 ± 0.147 IDs/mL (Run 2).CONCLUSIONLeukoreduction removed the majority of infectivity from 263K scrapie hamster blood. The P‐Capt filter removed a proportion of the remaining infectivity, but residual infectivity was observed in two independent processes.
Red blood cell storage duration is not associated with clinical outcomes for acute chest syndrome in children with sickle cell disease
Authors: Fields Melanie E. , Hulbert Monica L. , Chen Ling , Berlin Ari N. , Jackups Ron , Spinella Philip C. 
Published: May 2015

BACKGROUNDProviders commonly transfuse sickle cell disease (SCD) patients with fresh red blood cells (RBCs) as treatment for acute chest syndrome (ACS). The objective of this study was to determine if there is an association between the storage duration of RBCs and length of hospitalization and oxygen requirement after transfusion in pediatric SCD patients with ACS.STUDY DESIGN AND METHODSThis is a retrospective cohort study of pediatric SCD patients with ACS treated with a simple RBC transfusion over 8.5 years at a single institution. Multivariate generalized estimation equation analysis was used to identify associations between storage duration of RBCs and outcome measures.RESULTSA total of 234 ACS episodes in 131 subjects were included. The median storage duration of the oldest unit of transfused RBCs was 17 days (interquartile range, 11‐26). The majority of ACS episodes, 77.4%, were treated with 1 unit of transfused RBCs; 20.9% received 2 units; and 1.7% received 3 or more units of RBCs. There was no association between the storage duration of the oldest unit of transfused RBCs and either duration of hospitalization or supplemental oxygen requirement after transfusion in multivariate analyses.CONCLUSIONThis retrospective study is one of the first to investigate the role of the storage lesion in children with SCD and does not support the preferential transfusion of fresh RBCs for ACS. Ultimately, a randomized controlled trial is necessary to determine whether the storage age of RBCs affects outcomes for patients with SCD and ACS.
Romiplostim in the management of the thrombocytopenic surgical patient
Authors: Marshall Ariela L. , Goodarzi Katayoon , Kuter David J. 
Published: May 2015

BACKGROUNDThrombopoietin receptor agonists increase platelet (PLT) counts and are approved for the treatment of chronic immune thrombocytopenia (ITP). These agents may also be useful for the management of thrombocytopenia in patients requiring surgical procedures.STUDY DESIGN AND METHODSWe conducted a retrospective review of patients with thrombocytopenia (baseline PLT count, <150 × 109/L) who received romiplostim before planned operative procedures. We characterized patient demographics, dosing and duration of romiplostim use, success in achieving PLT counts high enough for surgery, and clinical outcomes.RESULTSEighteen patients underwent a total of 22 operative procedures, including three Jehovah's Witnesses who underwent five procedures. Etiologies of thrombocytopenia included mild ITP (not on romiplostim at baseline), liver disease, hematologic malignancy, and drug‐related thrombocytopenia. Median PLT count at romiplostim initiation was 47 × 109/L (range, 11 × 109‐120 × 109/L). All patients experienced a PLT count increase over a median of 4 weeks; median PLT count at surgery was 144 × 109/L (range, 28 × 109‐370 × 109/L). PLT counts increase to more than 150 × 109/L in four of five Jehovah's Witness patients by the time of surgery. There were no surgical delays or cancellations due to thrombocytopenia. Four bleeding events occurred; none were fatal and none occurred at a PLT count of fewer than 80 × 109/L. No definitive thromboembolic events occurred.CONCLUSIONRomiplostim successfully increased preoperative PLT counts allowing operative interventions, was well tolerated, did not lead to any significant thromboembolic events, and avoided the need for transfusion. Romiplostim may be of clinical utility in the preoperative management of thrombocytopenic patients, especially those unable to receive or unresponsive to PLT transfusion.
Expression of the cellular prion protein affects posttransfusion recovery and survival of red blood cells in mice
Authors: Glier Hana , Simak Jan , Panigaj Martin , Gelderman Monique P. , Vostal Jaroslav G. , Holada Karel 
Published: May 2015

BACKGROUNDCellular prion protein (PrPC) is expressed on various cell types including red blood cells (RBCs). The PrPC plays a key role in the pathogenesis of prion diseases, but its physiologic function remains unclear. PrPC is expressed on CD34+ hematopoietic stem cells and its expression is regulated during blood cell differentiation including the erythroid line.STUDY DESIGN AND METHODSWe investigated the role of PrPC in RBC survival in circulation by transfusing a mix of biotin‐labeled RBCs from wild‐type (WT) and PrP knockout (KO) mice to groups of recipient mice (WT and KO). The proportion of biotinylated RBCs in peripheral blood was estimated by flow cytometry.RESULTSKO RBCs displayed a markedly higher first‐day posttransfusion recovery but had a decreased survival in circulation when compared to WT RBCs. Similar results were obtained in all groups of transfused mice, irrespective of RBCs biotinylation level. In addition, we confirmed this finding in an analogous study using Tga20 mice overexpressing PrPC and KO mice of a different genetic background.CONCLUSIONOur results demonstrate that PrPC expression affects RBC recovery and survival in circulation.
Seeing double: pseudocryptic diversity in the Doriopsilla albopunctata‐Doriopsilla gemela species complex of the north‐eastern Pacific
Authors: Hoover Craig , Lindsay Tabitha , Goddard Jeffrey H. R. , Valdés Ángel 
Published: May 2015

Molecular analyses of samples of Doriopsilla albopunctata and its ‘twin’ species Doriopsilla gemela collected from their entire geographic ranges in the north‐eastern Pacific revealed an unexpected level of species diversity. Species delimitation analyses recovered five distinct species in the complex. When the specimens were re‐examined morphologically in the light of the molecular results, some external and internal differences between them became evident; thus, these species are considered pseudocryptic. The ranges of the three species previously named D. albopunctata overlap partially or entirely, and this along with anecdotal evidence of prezygotic isolation suggests sympatric speciation may be at play. On the contrary, the ranges of the two species previously named D. gemela do not overlap and their developmental modes differ. A review of the literature was conducted to clarify the taxonomy of the species complex, and we concluded that two available names (D. fulva and D. gemela) can be confidently assigned to two of the species. The original description of D. albopunctata is ambiguous, but the common usage of the name is fixed herein with the designation of a neotype for the most common intertidal southern California species. Finally, two new names are introduced for the remaining two species.
CysK Plays a Role in Biofilm Formation and Colonization by Vibrio fischeri
Authors: Singh Priyanka , Brooks John F. , Ray Valerie A. , Mandel Mark J. , Visick Karen L. 
Published: May 2015

ABSTRACT

A biofilm, or a matrix-embedded community of cells, promotes the ability of the bacterium
Vibrio fischeri
to colonize its symbiotic host, the Hawaiian squid
Euprymna scolopes
. Biofilm formation and colonization depend on
syp
, an 18-gene polysaccharide locus. To identify other genes necessary for biofilm formation, we screened for mutants that failed to form wrinkled colonies, a type of biofilm. We obtained several with defects in genes required for cysteine metabolism, including
cysH
,
cysJ
,
cysK
, and
cysN
. The
cysK
mutant exhibited the most severe wrinkling defect. It could be complemented with a wild-type copy of the
cysK
gene, which encodes
O
-acetylserine sulfhydrolase, or by supplementing the medium with additional cysteine. None of a number of other mutants defective for biosynthetic genes negatively impacted wrinkled colony formation, suggesting a specific role for CysK. CysK did not appear to control activation of Syp regulators or transcription of the
syp
locus, but it did influence production of the Syp polysaccharide. Under biofilm-inducing conditions, the
cysK
mutant retained the same ability as that of the parent strain to adhere to the agar surface. The
cysK
mutant also exhibited a defect in pellicle production that could be complemented by the
cysK
gene but not by cysteine, suggesting that, under these conditions, CysK is important for more than the production of cysteine. Finally, our data reveal a role for
cysK
in symbiotic colonization by
V. fischeri
. Although many questions remain, this work provides insights into additional factors required for biofilm formation and colonization by
V. fischeri
.
SnPKS19
Encodes the Polyketide Synthase for Alternariol Mycotoxin Biosynthesis in the Wheat Pathogen Parastagonospora nodorum
Authors: Chooi Yit-Heng , Muria-Gonzalez Mariano Jordi , Mead Oliver L. , Solomon Peter S. 
Published: May 2015

ABSTRACT

Alternariol (AOH) is an important mycotoxin from the
Alternaria
fungi. AOH was detected for the first time in the wheat pathogen
Parastagonospora nodorum
in a recent study. Here, we exploited reverse genetics to demonstrate that SNOG_15829 (
SnPKS19
), a close homolog of
Penicillium aethiopicum
norlichexanthone (NLX) synthase gene
gsfA
, is required for AOH production. We further validate that
SnPKS19
is solely responsible for AOH production by heterologous expression in
Aspergillus nidulans
. The expression profile of
SnPKS19
based on previous
P. nodorum
microarray data correlated with the presence of AOH
in vitro
and its absence
in planta
. Subsequent characterization of the Δ
SnPKS19
mutants showed that
SnPKS19
and AOH are not involved in virulence and oxidative stress tolerance. Identification and characterization of the
P. nodorum
SnPKS19
cast light on a possible alternative AOH synthase gene in
Alternaria alternata
and allowed us to survey the distribution of AOH synthase genes in other fungal genomes. We further demonstrate that phylogenetic analysis could be used to differentiate between AOH synthases and the closely related NLX synthases. This study provides the basis for studying the genetic regulation of AOH production and for development of molecular diagnostic methods for detecting AOH-producing fungi in the future.
“Wigglesworthia morsitans” Folate (Vitamin B
9
) Biosynthesis Contributes to Tsetse Host Fitness
Authors: Snyder Anna K. , Rio Rita V. M. 
Published: May 2015

ABSTRACT

Closely related ancient endosymbionts may retain minor genomic distinctions through evolutionary time, yet the biological relevance of these small pockets of unique loci remains unknown. The tsetse fly (Diptera: Glossinidae), the sole vector of lethal African trypanosomes (
Trypanosoma
spp.), maintains an ancient and obligate mutualism with species belonging to the gammaproteobacterium
Wigglesworthia
. Extensive concordant evolution with associated
Wigglesworthia
species has occurred through tsetse species radiation. Accordingly, the retention of unique symbiont loci between
Wigglesworthia
genomes may prove instrumental toward host species-specific biological traits. Genome distinctions between “
Wigglesworthia
morsitans
” (harbored within
Glossina morsitans
bacteriomes) and the basal species
Wigglesworthia glossinidia
(harbored within
Glossina brevipalpis
bacteriomes) include the retention of chorismate and downstream folate (vitamin B
9
) biosynthesis capabilities, contributing to distinct symbiont metabolomes. Here, we demonstrate that these
W. morsitans
pathways remain functionally intact, with folate likely being systemically disseminated through a synchronously expressed tsetse folate transporter within bacteriomes. The folate produced by
W. morsitans
is demonstrated to be pivotal for
G. morsitans
sexual maturation and reproduction. Modest differences between ancient symbiont genomes may still play key roles in the evolution of their host species, particularly if loci are involved in shaping host physiology and ecology. Enhanced knowledge of the
Wigglesworthia
-tsetse mutualism may also provide novel and specific avenues for vector control.
Resistance to Bacillus thuringiensis Toxin Cry2Ab in Trichoplusia ni Is Conferred by a Novel Genetic Mechanism
Authors: Song Xiaozhao , Kain Wendy , Cassidy Douglas , Wang Ping 
Published: May 2015

ABSTRACT

The resistance to the
Bacillus thuringiensis
(Bt) toxin Cry2Ab in a greenhouse-originated
Trichoplusia ni
strain resistant to both Bt toxins Cry1Ac and Cry2Ab was characterized. Biological assays determined that the Cry2Ab resistance in the
T. ni
strain was a monogenic recessive trait independent of Cry1Ac resistance, and there existed no significant cross-resistance between Cry1Ac and Cry2Ab in
T. ni
. From the dual-toxin-resistant
T. ni
strain, a strain resistant to Cry2Ab only was isolated, and the Cry2Ab resistance trait was introgressed into a susceptible laboratory strain to facilitate comparative analysis of the Cry2Ab resistance with the susceptible
T. ni
strain. Results from biochemical analysis showed no significant difference between the Cry2Ab-resistant and -susceptible
T. ni
larvae in midgut proteases, including caseinolytic proteolytic activity and zymogram profile and serine protease activities, in midgut aminopeptidase and alkaline phosphatase activity, and in midgut esterases and hemolymph plasma melanization activity. For analysis of genetic linkage of Cry2Ab resistance with potential Cry toxin receptor genes, molecular markers for the midgut cadherin, alkaline phosphatase (ALP), and aminopeptidase N (APN) genes were identified between the original greenhouse-derived dual-toxin-resistant and the susceptible laboratory
T. ni
strains. Genetic linkage analysis showed that the Cry2Ab resistance in
T. ni
was not genetically associated with the midgut genes coding for the cadherin, ALP, and 6 APNs (APN1 to APN6) nor associated with the ABC transporter gene
ABCC2
. Therefore, the Cry2Ab resistance in
T. ni
is conferred by a novel but unknown genetic mechanism.
DNA Microarray-Based Identification of Genes Regulated by NtrC in Bradyrhizobium japonicum
Authors: Franck William L. , Qiu Jing , Lee Hae-In , Chang Woo-Suk , Stacey Gary 
Published: May 2015

ABSTRACT

The
Bradyrhizobium japonicum
NtrBC two-component system is a critical regulator of cellular nitrogen metabolism, including the acquisition and catabolism of nitrogenous compounds. To better define the roles of this system, genome-wide transcriptional profiling was performed to identify the NtrC regulon during the response to nitrogen limitation. Upon cells perceiving low intracellular nitrogen, they stimulate the phosphorylation of NtrC, which induces genes responsible for alteration of the core glutamine synthetase/glutamate synthase nitrogen assimilation pathway, including the genes for the glutamine synthetases and PII proteins. In addition, genes responsible for the import and utilization of multiple nitrogen sources, specifically nitrate and nitrite, were upregulated by NtrC activation. Mutational analysis of a candidate nitrite reductase revealed a role for NtrC in regulating the assimilation of nitrite, since mutations in both
ntrC
and the gene encoding the candidate nitrite reductase abolished the ability to grow on nitrite as a sole nitrogen source.
Novel N4 Bacteriophages Prevail in the Cold Biosphere
Authors: Zhan Yuanchao , Buchan Alison , Chen Feng 
Published: May 2015

ABSTRACT
Coliphage N4 is a lytic bacteriophage discovered nearly half a century ago, and it was considered to be a “genetic orphan” until very recently, when several additional N4-like phages were discovered to infect nonenteric bacterial hosts. Interest in this genus of phages is stimulated by their unique genetic features and propagation strategies. To better understand the ecology of N4-like phages, we investigated the diversity and geographic patterns of N4-like phages by examining 56 Chesapeake Bay viral communities, using a PCR-clone library approach targeting a diagnostic N4-like DNA polymerase gene. Many new lineages of N4-like phages were found in the bay, and their genotypes shift from the lower to the upper bay. Interestingly, signature sequences of N4-like phages were recovered only from winter month samples, when water temperatures were below 4°C. An analysis of existing metagenomic libraries from various aquatic environments supports the hypothesis that N4-like phages are most prolific in colder waters. In particular, a high number of N4-like phages were detected in Organic Lake, Antarctica, a cold and hypersaline system. The prevalence of N4-like phages in the cold biosphere suggests these viruses possess yet-to-be-determined mechanisms that facilitate lytic infections under cold conditions.
Phenotypic Heterogeneity, a Phenomenon That May Explain Why Quorum Sensing Does Not Always Result in Truly Homogenous Cell Behavior
Authors: Grote Jessica , Krysciak Dagmar , Streit Wolfgang R. 
Published: May 2015

ABSTRACT

Phenotypic heterogeneity describes the occurrence of “nonconformist” cells within an isogenic population. The nonconformists show an expression profile partially different from that of the remainder of the population. Phenotypic heterogeneity affects many aspects of the different bacterial lifestyles, and it is assumed that it increases bacterial fitness and the chances for survival of the whole population or smaller subpopulations in unfavorable environments. Well-known examples for phenotypic heterogeneity have been associated with antibiotic resistance and frequently occurring persister cells. Other examples include heterogeneous behavior within biofilms, DNA uptake and bacterial competence, motility (i.e., the synthesis of additional flagella), onset of spore formation, lysis of phages within a small subpopulation, and others. Interestingly, phenotypic heterogeneity was recently also observed with respect to quorum-sensing (QS)-dependent processes, and the expression of autoinducer (AI) synthase genes and other QS-dependent genes was found to be highly heterogeneous at a single-cell level. This phenomenon was observed in several Gram-negative bacteria affiliated with the genera
Vibrio
,
Dinoroseobacter
,
Pseudomonas
,
Sinorhizobium
, and
Mesorhizobium
. A similar observation was made for the Gram-positive bacterium
Listeria monocytogenes
. Since AI molecules have historically been thought to be the keys to homogeneous behavior within isogenic populations, the observation of heterogeneous expression is quite intriguing and adds a new level of complexity to the QS-dependent regulatory networks. All together, the many examples of phenotypic heterogeneity imply that we may have to partially revise the concept of homogeneous and coordinated gene expression in isogenic bacterial populations.