bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA genetic diversity in Hungarians and Hungarian Gypsies: complementary differentiation patterns and demographic signals revealed by HLA‐A, ‐B and ‐DRB1 in Central Europe
Authors: Inotai D. , Szilvasi A. , Benko S. , Boros‐Major A. , Illes Z. , Bors A. , Kiss K. P. , Rajczy K. , Gelle‐Hossó A. , Buhler S. , Nunes J. M. , Sanchez‐Mazas A. , Tordai A. 
Published: July 2015

AbstractSystematic analyses of human leukocyte antigen (HLA) profiles in different populations may increase the efficiency of bone marrow donor selection and help reconstructing human peopling history. We typed HLA‐A, ‐B, and ‐DRB1 allele groups in two bone marrow donor cohorts of 2402 Hungarians and 186 Hungarian Gypsies and compared them with several Central‐European, Spanish Gypsy, and Indian populations. Our results indicate that different European Gypsy populations share a common origin but diverged genetically as a consequence of founder effect and rapid genetic drift, whereas other European populations are related genetically in relation to geography. This study also suggests that while HLA‐A accurately depicts the effects of genetic drift, HLA‐B, and ‐DRB1 conserve more signatures of ancient population relationships, as a result of balancing selection.
Selecting registration schemes in case of interstitial lung disease follow‐up in CT
Authors: Vlachopoulos Georgios , Korfiatis Panayiotis , Skiadopoulos Spyros , Kazantzi Alexandra , Kalogeropoulou Christina , Pratikakis Ioannis , Costaridou Lena 
Published: July 2015

Purpose:Primary goal of this study is to select optimal registration schemes in the framework of interstitial lung disease (ILD) follow‐up analysis in CT.Methods:A set of 128 multiresolution schemes composed of multiresolution nonrigid and combinations of rigid and nonrigid registration schemes are evaluated, utilizing ten artificially warped ILD follow‐up volumes, originating from ten clinical volumetric CT scans of ILD affected patients, to select candidate optimal schemes. Specifically, all combinations of four transformation models (three rigid: rigid, similarity, affine and one nonrigid: third order B‐spline), four cost functions (sum‐of‐square distances, normalized correlation coefficient, mutual information, and normalized mutual information), four gradient descent optimizers (standard, regular step, adaptive stochastic, and finite difference), and two types of pyramids (recursive and Gaussian‐smoothing) were considered. The selection process involves two stages. The first stage involves identification of schemes with deformation field singularities, according to the determinant of the Jacobian matrix. In the second stage, evaluation methodology is based on distance between corresponding landmark points in both normal lung parenchyma (NLP) and ILD affected regions. Statistical analysis was performed in order to select near optimal registration schemes per evaluation metric. Performance of the candidate registration schemes was verified on a case sample of ten clinical follow‐up CT scans to obtain the selected registration schemes.Results:By considering near optimal schemes common to all ranking lists, 16 out of 128 registration schemes were initially selected. These schemes obtained submillimeter registration accuracies in terms of average distance errors 0.18 ± 0.01 mm for NLP and 0.20 ± 0.01 mm for ILD, in case of artificially generated follow‐up data. Registration accuracy in terms of average distance error in clinical follow‐up data was in the range of 1.985–2.156 mm and 1.966–2.234 mm, for NLP and ILD affected regions, respectively, excluding schemes with statistically significant lower performance (Wilcoxon signed‐ranks test, p < 0.05), resulting in 13 finally selected registration schemes.Conclusions:Selected registration schemes in case of ILD CT follow‐up analysis indicate the significance of adaptive stochastic gradient descent optimizer, as well as the importance of combined rigid and nonrigid schemes providing high accuracy and time efficiency. The selected optimal deformable registration schemes are equivalent in terms of their accuracy and thus compatible in terms of their clinical outcome.
Optical delay encoding for fast timing and detector signal multiplexing in PET
Authors: Grant Alexander M. , Levin Craig S. 
Published: July 2015

Purpose:The large number of detector channels in modern positron emission tomography (PET) scanners poses a challenge in terms of readout electronics complexity. Multiplexing schemes are typically implemented to reduce the number of physical readout channels, but often result in performance degradation. Novel methods of multiplexing in PET must be developed to avoid this data degradation. The preservation of fast timing information is especially important for time‐of‐flight PET.Methods:A new multiplexing scheme based on encoding detector interaction events with a series of extremely fast overlapping optical pulses with precise delays is demonstrated in this work. Encoding events in this way potentially allows many detector channels to be simultaneously encoded onto a single optical fiber that is then read out by a single digitizer. A two channel silicon photomultiplier‐based prototype utilizing this optical delay encoding technique along with dual threshold time‐over‐threshold is demonstrated.Results:The optical encoding and multiplexing prototype achieves a coincidence time resolution of 160 ps full width at half maximum (FWHM) and an energy resolution of 13.1% FWHM at 511 keV with 3 × 3 × 5 mm3 LYSO crystals. All interaction information for both detectors, including timing, energy, and channel identification, is encoded onto a single optical fiber with little degradation.Conclusions:Optical delay encoding and multiplexing technology could lead to time‐of‐flight PET scanners with fewer readout channels and simplified data acquisition systems.
SR-2P Vaginal Microbicide Gel Provides Protection against Herpes Simplex Virus 2 When Administered as a Combined Prophylactic and Postexposure Therapeutic
Authors: Fields Scott A. , Bhatia Gaurav , Fong Julie M. , Liu Mingtao , Shankar Gita N. 
Published: July 2015

ABSTRACT
Previously, we demonstrated that a single prophylactic dose of SR-2P, a novel dual-component microbicide gel comprising acyclovir and tenofovir, led to a modest increase in mouse survival following a lethal challenge of herpes simplex virus 2 (HSV-2). Here, we show that a dose of SR-2P administered 24 h prior to infection provides some protection against the virus, but to a lesser degree than SR-2P administered either once a day for 2 days or 1 h prior to infection. None of the prophylactic doses blocked infection by the virus, and all resulted in 80 to 100% lethality. However, given that a prophylactic dose still provided a significant reduction in overall clinical score, reduced rate of body weight loss, and increased median survival of the mice, we examined whether a repetitive dose regimen (postinfection) in addition to the prophylactic dose could prevent death and reduce the levels of virus in mice. Nearly all (9 of 10 in each group) of the mice that received SR-2P for 2 days prior to infection or that received SR-2P 1 h prior to infection and were administered SR-2P once a day for 10 days after infection showed no clinical symptoms of infection and no viral loads in vaginal swabs and survived for 28 days postinfection. Conversely, mice receiving no treatment or an identical vehicle treatment demonstrated advanced clinical signs and did not survive past day 9 postinfection. We conclude that SR-2P is an effective anti-HSV-2 agent in mice.
Effective Sequestration of Clostridium difficile Protein Toxins by Calcium Aluminosilicate
Authors: Sturino Joseph M. , Pokusaeva Karina , Carpenter Robert 
Published: July 2015

ABSTRACT

Clostridium difficile
is a leading cause of antibiotic-associated diarrhea and the etiologic agent responsible for
C. difficile
infection. Toxin A (TcdA) and toxin B (TcdB) are nearly indispensable virulence factors for
Clostridium difficile
pathogenesis. Given the toxin-centric mechanism by which
C. difficile
pathogenesis occurs, the selective sequestration with neutralization of TcdA and TcdB by nonantibiotic agents represents a novel mode of action to prevent or treat
C. difficile-
associated disease. In this preclinical study, we used quantitative enzyme immunoassays to determine the extent by which a novel drug, calcium aluminosilicate uniform particle size nonswelling M-1 (CAS UPSN M-1), is capable of sequestering TcdA and TcdB
in vitro
. The following major findings were derived from the present study. First, we show that CAS UPSN M-1 efficiently sequestered both TcdA and TcdB to undetectable levels. Second, we show that CAS UPSN M-1's affinity for TcdA is greater than its affinity for TcdB. Last, we show that CAS UPSN M-1 exhibited limited binding affinity for nontarget proteins. Taken together, these results suggest that ingestion of calcium aluminosilicate might protect gastrointestinal tissues from antibiotic- or chemotherapy-induced
C. difficile
infection by neutralizing the cytotoxic and proinflammatory effects of luminal TcdA and TcdB.
Improving the Thermostability and Activity of a Thermophilic Subtilase by Incorporating Structural Elements of Its Psychrophilic Counterpart
Authors: Xu Bi-Lin , Dai Meihong , Chen Yuanhao , Meng Dongheng , Wang Yasi , Fang Nan , Tang Xiao-Feng , Tang Bing 
Published: July 2015

ABSTRACT

The incorporation of the structural elements of thermostable enzymes into their less stable counterparts is generally used to improve enzyme thermostability. However, the process of engineering enzymes with both high thermostability and high activity remains an important challenge. Here, we report that the thermostability and activity of a thermophilic subtilase were simultaneously improved by incorporating structural elements of a psychrophilic subtilase. There were 64 variable regions/residues (VRs) in the alignment of the thermophilic WF146 protease, mesophilic sphericase, and psychrophilic S41. The WF146 protease was subjected to systematic mutagenesis, in which each of its VRs was replaced with those from S41 and sphericase. After successive rounds of combination and screening, we constructed the variant PBL5X with eight amino acid residues from S41. The half-life of PBL5X at 85°C (57.1 min) was approximately 9-fold longer than that of the wild-type (WT) WF146 protease (6.3 min). The substitutions also led to an increase in the apparent thermal denaturation midpoint temperature (

T
m

) of the enzyme by 5.5°C, as determined by differential scanning calorimetry. Compared to the WT, PBL5X exhibited high caseinolytic activity (25 to 95°C) and high values of

K
m

and
k
cat
(25 to 80°C). Our study may provide a rational basis for developing highly stable and active enzymes, which are highly desired in industrial applications.
Arsenophonus and Sodalis Symbionts in Louse Flies: an Analogy to the Wigglesworthia and Sodalis System in Tsetse Flies
Authors: Nováková Eva , Husník Filip , Šochová Eva , Hypša Václav 
Published: July 2015

ABSTRACT

Symbiosis between insects and bacteria result in a variety of arrangements, genomic modifications, and metabolic interconnections. Here, we present genomic, phylogenetic, and morphological characteristics of a symbiotic system associated with
Melophagus ovinus
, a member of the blood-feeding family Hippoboscidae. The system comprises four unrelated bacteria representing different stages in symbiosis evolution, from typical obligate mutualists inhabiting bacteriomes to freely associated commensals and parasites. Interestingly, the whole system provides a remarkable analogy to the association between
Glossina
and its symbiotic bacteria. In both, the symbiotic systems are composed of an obligate symbiont and two facultative intracellular associates,
Sodalis
and
Wolbachia
. In addition, extracellular
Bartonella
resides in the gut of
Melophagus
. However, the phylogenetic origins of the two obligate mutualist symbionts differ. In
Glossina
, the mutualistic
Wigglesworthia
appears to be a relatively isolated symbiotic lineage, whereas in
Melophagus
, the obligate symbiont originated within the widely distributed
Arsenophonus
cluster. Although phylogenetically distant, the two obligate symbionts display several remarkably similar traits (e.g., transmission via the host's “milk glands” or similar pattern of genome reduction). To obtain better insight into the biology and possible role of the
M. ovinus
obligate symbiont, “
Candidatus
Arsenophonus melophagi,” we performed several comparisons of its gene content based on assignments of the Cluster of Orthologous Genes (COG). Using this criterion, we show that within a set of 44 primary and secondary symbionts, “
Ca
. Arsenophonus melophagi” is most similar to
Wigglesworthia
. On the other hand, these two bacteria also display interesting differences, such as absence of flagellar genes in
Arsenophonus
and their presence in
Wigglesworthia
. This finding implies that a flagellum is not essential for bacterial transmission via milk glands.
Copper Reduction and Contact Killing of Bacteria by Iron Surfaces
Authors: Mathews Salima , Kumar Ranjeet , Solioz Marc 
Published: July 2015

ABSTRACT

The well-established killing of bacteria by copper surfaces, also called contact killing, is currently believed to be a combined effect of bacterial contact with the copper surface and the dissolution of copper, resulting in lethal bacterial damage. Iron can similarly be released in ionic form from iron surfaces and would thus be expected to also exhibit contact killing, although essentially no contact killing is observed by iron surfaces. However, we show here that the exposure of bacteria to iron surfaces in the presence of copper ions results in efficient contact killing. The process involves reduction of Cu
2+
to Cu
+
by iron; Cu
+
has been shown to be considerably more toxic to cells than Cu
2+
. The specific Cu
+
chelator, bicinchoninic acid, suppresses contact killing by chelating the Cu
+
ions. These findings underline the importance of Cu
+
ions in the contact killing process and infer that iron-based alloys containing copper could provide novel antimicrobial materials.
Uterine Microbiota Progression from Calving until Establishment of Metritis in Dairy Cows
Authors: Jeon Soo Jin , Vieira-Neto Achilles , Gobikrushanth Mohanathas , Daetz Rodolfo , Mingoti Rodolfo D. , Parize Ana Carolina Brigolin , de Freitas Sabrina Lucas , da Costa Antonio Nelson Lima , Bicalho Rodrigo C. , Lima Svetlana , Jeong K. Casey , Galvão Klibs N. 
Published: July 2015

ABSTRACT

The objective of this study was to evaluate the progression of the uterine microbiota from calving until establishment of metritis. Uterine swabs (
n
= 72) collected at 0, 2, and 6 ± 2 days postpartum (dpp) from 12 metritic and 12 healthy cows were used for metagenomic sequencing of the 16S rRNA gene on the Illumina MiSeq platform. A heat map showed that uterine microbiota was established at calving. The microbiota changed rapidly from 0 to 6 ± 2 dpp, with a decrease in the abundance of
Proteobacteria
and an increase in the abundance of
Bacteroidetes
and
Fusobacteria
, which were dominant in metritic cows. Uterine microbiota composition was shared; however, metritic and healthy cows could be discriminated using relative abundance of bacterial genera at 0, 2, and 6 ± 2 dpp.
Bacteroides
was the main genus associated with metritis because it was the only genus that showed significantly greater abundance in cows with metritis. As the abundance of
Bacteroides
organisms increased, the uterine discharge score, a measure of uterine health, worsened.
Fusobacterium
was also an important genus associated with metritis because
Fusobacterium
abundance increased as
Bacteroides
abundance increased and the uterine discharge score worsened as the abundance increased. The correlation with uterine discharge score and the correlation with
Bacteroides
or
Fusobacterium
showed that other bacteria, such as
Helcoccocus
,
Filifactor
, and
Porphyromonas
, were also associated with metritis. There were also bacteria associated with uterine health, such as “
Candidatus
Blochmannia,”
Escherichia
,
Sneathia
, and
Pedobacter
.
Ineffective Phosphorylation of Mitogen-Activated Protein Kinase Hog1p in Response to High Osmotic Stress in the Yeast Kluyveromyces lactis
Authors: Velázquez-Zavala Nancy , Rodríguez-González Miriam , Navarro-Olmos Rocío , Ongay-Larios Laura , Kawasaki Laura , Torres-Quiroz Francisco , Coria Roberto 
Published: July 2015

ABSTRACT

When treated with a hyperosmotic stimulus,
Kluyveromyces lactis
cells respond by activating the mitogen-activated protein kinase (MAPK)
K. lactis
Hog1 (KlHog1) protein via two conserved branches, SLN1 and SHO1. Mutants affected in only one branch can cope with external hyperosmolarity by activating KlHog1p by phosphorylation, except for single Δ
Klste11
and Δ
Klste50
mutants, which showed high sensitivity to osmotic stress, even though the other branch (SLN1) was intact. Inactivation of both branches by deletion of
KlSHO1
and
KlSSK2
also produced sensitivity to high salt. Interestingly, we have observed that in Δ
Klste11
and Δ
Klsho1
Δ
Klssk2
mutants, which exhibit sensitivity to hyperosmotic stress, and contrary to what would be expected, KlHog1p becomes phosphorylated. Additionally, in mutants lacking both MAPK kinase kinases (MAPKKKs) present in
K. lactis
(KlSte11p and KlSsk2p), the hyperosmotic stress induced the phosphorylation and nuclear internalization of KlHog1p, but it failed to induce the transcriptional expression of
KlSTL1
and the cell was unable to grow in high-osmolarity medium. KlHog1p phosphorylation via the canonical HOG pathway or in mutants where the SHO1 and SLN1 branches have been inactivated requires not only the presence of KlPbs2p but also its kinase activity. This indicates that when the SHO1 and SLN1 branches are inactivated, high-osmotic-stress conditions activate an independent input that yields active KlPbs2p, which, in turn, renders KlHog1p phosphorylation ineffective. Finally, we found that KlSte11p can alleviate the sensitivity to hyperosmotic stress displayed by a Δ
Klsho1
Δ
Klssk2
mutant when it is anchored to the plasma membrane by adding the KlSho1p transmembrane segments, indicating that this chimeric protein can substitute for KlSho1p and KlSsk2p.
A Cyclic GMP-Dependent K
+
Channel in the Blastocladiomycete Fungus Blastocladiella emersonii
Authors: Avelar Gabriela Mól , Glaser Talita , Leonard Guy , Richards Thomas A. , Ulrich Henning , Gomes Suely L. 
Published: July 2015

ABSTRACT

Phototaxis in flagellated zoospores of the aquatic fungus
Blastocladiella emersonii
depends on a novel photosensor,
Blastocladiella emersonii
GC1 (BeGC1), comprising a type I (microbial) rhodopsin fused to a guanylyl cyclase catalytic domain, that produces the conserved second messenger cyclic GMP (cGMP). The rapid and transient increase in cGMP levels during the exposure of zoospores to green light was shown to be necessary for phototaxis and dependent on both rhodopsin function and guanylyl cyclase activity. It is noteworthy that BeGC1 was localized to the zoospore eyespot apparatus, in agreement with its role in the phototactic response. A putative cyclic nucleotide-gated channel (BeCNG1) was also identified in the genome of the fungus and was implicated in flagellar beating via the action of a specific inhibitor (
l
-
cis
-diltiazem) that compromised zoospore motility. Here we show that
B. emersonii
expresses a K
+
channel that is activated by cGMP. The use of specific channel inhibitors confirmed the activation of the channel by cGMP and its K
+
selectivity. These characteristics are consistent with the function of an ion channel encoded by the
BeCNG1
gene. Other blastocladiomycete fungi, such as
Allomyces macrogynus
and
Catenaria anguillulae
, possess genes encoding a similar K
+
channel and the rhodopsin–guanylyl cyclase fusion protein, while the genes encoding both these proteins are absent in nonflagellated fungi. The presence of these genes as a pair seems to be an exclusive feature of blastocladiomycete fungi. Taken together, these data demonstrate that the
B. emersonii
cGMP-activated K
+
channel is involved in the control of zoospore motility, most probably participating in the cGMP-signaling pathway for the phototactic response of the fungus.
Conserved Mode of Interaction between Yeast Bro1 Family V Domains and YP(X)
n
L Motif-Containing Target Proteins
Authors: Kimura Yoko , Tanigawa Mirai , Kawawaki Junko , Takagi Kenji , Mizushima Tsunehiro , Maeda Tatsuya , Tanaka Keiji 
Published: July 2015

ABSTRACT

Yeast Bro1 and Rim20 belong to a family of proteins which possess a common architecture of Bro1 and V domains. Alix and His domain protein tyrosine phosphatase (HD-PTP), mammalian Bro1 family proteins, bind YP(X)
n
L (
n
= 1 to 3) motifs in their target proteins through their V domains. In Alix, the Phe residue, which is located in the hydrophobic groove of the V domain, is critical for binding to the YP(X)
n
L motif. Although the overall sequences are not highly conserved between mammalian and yeast V domains, we show that the conserved Phe residue in the yeast Bro1 V domain is important for binding to its YP(X)
n
L-containing target protein, Rfu1. Furthermore, we show that Rim20 binds to its target protein Rim101 through the interaction between the V domain of Rim20 and the YPIKL motif of Rim101. The mutation of either the critical Phe residue in the Rim20 V domain or the YPIKL motif of Rim101 affected the Rim20-mediated processing of Rim101. These results suggest that the interactions between V domains and YP(X)
n
L motif-containing proteins are conserved from yeast to mammalian cells. Moreover, the specificities of each V domain to their target protein suggest that unidentified elements determine the binding specificity.
Parasite Proximity Drives the Expansion of Regulatory T Cells in Peyer's Patches following Intestinal Helminth Infection
Authors: Mosconi Ilaria , Dubey Lalit Kumar , Volpe Beatrice , Esser-von Bieren Julia , Zaiss Mario M. , Lebon Luc , Massacand Joanna C. , Harris Nicola L. 
Published: July 2015

ABSTRACT

Helminth infections are typically chronic in nature; however, the exact molecular mechanisms by which these parasites promote or thwart host immunity remain unclear. Worm expulsion requires the differentiation of CD4
+
T cells into Th2 cells, while regulatory T cells (Tregs) act to dampen the extent of the Th2 response. Priming of T cells requires drainage or capture of antigens within lymphoid tissues, and in the case of intestinal helminths, such sites include the mucosa-associated Peyer's patches (PPs) and the draining mesenteric lymph nodes (MLN). To gain insight into when and where the activation of the adaptive T cell response takes place following intestinal helminth infection, we analyzed Th2 and Treg responses in the PPs and MLN following infection with the murine intestinal helminth
Heligmosomoides polygyrus
bakeri
. Protective Th2 responses were observed to be largely restricted to the MLN, while a greater expansion of Tregs occurred within the PPs. Interestingly, those PPs that formed a contact with the parasite showed the greatest degree of Treg expansion and no evidence of type 2 cytokine production, indicating that the parasite may secrete products that act in a local manner to selectively promote Treg expansion. This view was supported by the finding that
H. polygyrus
bakeri
larvae could promote Treg proliferation
in vitro
. Taken together, these data indicate that different degrees of Treg expansion and type 2 cytokine production occur within the PPs and MLN following infection with the intestinal helminth
H. polygyrus
bakeri
and indicate that these organs exhibit differential responses following infection with intestinal helminths.