bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour‐associated macrophages are associated with vascular endothelial growth factor expression in canine mammary tumours
Authors: Raposo T. P. , Pires I. , Carvalho M. I. , Prada J. , Argyle D. J. , Queiroga F. L. 
Published: October 2013

AbstractTumour‐associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin‐fixed paraffin‐embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease.
Identification of potential platelet alloantigens in the Equidae family by comparison of gene sequences encoding major platelet membrane glycoproteins
Authors: Boudreaux Mary K. , Humphries Drew M. 
Published: October 2013

BackgroundPlatelet alloantigens in horses may play an important role in the development of neonatal alloimmune thrombocytopenia (NAIT).ObjectiveThe objective of this study was to evaluate genes encoding major platelet glycoproteins within the Equidae family in an effort to identify potential alloantigens.MethodsDNA was isolated from blood samples obtained from Equidae family members, including a Holsteiner‐Oldenburg cross, a Quarter horse, a donkey, and a Plains zebra (Equus burchelli). Gene sequences encoding equine platelet membrane glycoproteins IIb, IIIa (integrin subunits αIIb and β3), Ia (integrin subunit α2), and Ibα were determined using PCR. Gene sequences were compared to the equine genome available on GenBank. Polymorphisms that would be predicted to result in amino acid changes on platelet surfaces were documented and compared with known alloantigenic sites documented on human platelets.ResultsAmino acid differences were predicted based on nucleotide sequences for all 4 genes. Nine differences were documented for αIIb, 5 differences were documented for β3, 7 differences were documented for α2, and 16 differences were documented for Ibα outside the macroglycopeptide region.ConclusionsThis study represents the first effort at identifying potential platelet alloantigens in members of the Equidae Family based on evaluation of gene sequences. The data obtained form the groundwork for identifying potential platelet alloantigens involved in transfusion reactions and neonatal alloimmune thrombocytopenia (NAIT). More work is required to determine whether the predicted amino acid differences documented in this study play a role in alloimmunity, and whether other polymorphisms not detected in this study are present that may result in alloimmunity.
Defining and measuring blood donor altruism: a theoretical approach from biology, economics and psychology
Authors: Evans R. , Ferguson E. 
Published: October 2013

Background and ObjectivesWhile blood donation is traditionally described as a behaviour motivated by pure altruism, the assessment of altruism in the blood donation literature has not been theoretically informed. Drawing on theories of altruism from psychology, economics and evolutionary biology, it is argued that a theoretically derived psychometric assessment of altruism is needed. Such a measure is developed in this study that can be used to help inform both our understanding of the altruistic motives of blood donors and recruitment intervention strategies.Materials and MethodsA cross‐sectional survey (N = 414), with a 1‐month behavioural follow‐up (time 2, N = 77), was designed to assess theoretically derived constructs from psychological, economic and evolutionary biological theories of altruism. Theory of planned behaviour (TPB) variables and co‐operation were also assessed at time 1 and a measure of behavioural co‐operation at time 2.ResultsFive theoretical dimensions (impure altruism, kinship, self‐regarding motives, reluctant altruism and egalitarian warm glow) of altruism were identified through factor analyses. These five altruistic motives differentiated blood donors from non‐donors (donors scored higher on impure altruism and reluctant altruism), showed incremental validity over TPB constructs to predict donor intention and predicted future co‐operative behaviour.ConclusionsThese findings show that altruism in the context of blood donation is multifaceted and complex and, does not reflect pure altruism. This has implication for recruitment campaigns that focus solely on pure altruism.
Residual aggregates in platelet products: what do we know?
Authors: Ringwald J. , Antoon M. , Eckstein R. , Cardoso M. 
Published: October 2013

Background and ObjectivesPlatelet (PLT) aggregates can occur during or after PLT component processing. However, very few reports investigating the phenomenon and its clinical significance have been published. In this review, currently available information about aggregates in PLT products is summarized and possible causal factors as well as preventive strategies are discussed.Materials and MethodsA review of the MEDLINE® database for relevant publications from 1960 to May 2013 was conducted.ResultsIt is well known that PLT aggregates may occur during or after the PLT product preparation process. These aggregates normally dissipate with rest and agitation. However, in some rare cases, the aggregates do not dissipate within 24 h and can persist up to the end of storage. Exposure to low temperature, low pH, short resting period after collection, different collection systems, presence of bubbles or foam inside the PLT bag, PLT‐container interactions, proper product mixing and donor‐dependent variables may have an impact on the formation of PLT aggregates. Although publications are rare, the presence of small numbers of PLT aggregates appears to have only limited impact on PLT in vitro quality. Furthermore, data on the clinical impact of PLT aggregates are lacking.ConclusionDespite the fact that PLT aggregates occur in PLT products, published data on this topic remain scant. Considering the concern of clinicians about this phenomenon, more studies are needed which should focus on the possible clinical impact of such aggregates and precautions to avoid PLT aggregate formation in PLT products.
Endoplasmic reticulum stress in vasopressin neurons of familial diabetes insipidus model mice: aggregate formation and mRNA poly(A) tail shortening
Authors: Arima Hiroshi , Morishita Yoshiaki , Hagiwara Daisuke , Hayashi Masayuki , Oiso Yutaka 
Published: October 2013

New findings
What is the topic of this review?Familial neurohypophysial diabetes insipidus (FNDI) is caused by a mutation in the vasopressin (AVP) gene locus. While mutant AVP precursors are reported to accumulate in the endoplasmic reticulum of AVP neurons, it is not clear how AVP neurons cope with the accumulation of misfolded proteins.
What advances does it highlight?We show that AVP mRNA poly(A) tail length is shortened and the mRNA expression is decreased in the FNDI mouse model. The shortening of the mRNA poly(A) tail could be a novel unfolded protein response by which aggregate accumulation is reduced.
The immunoglobulin heavy chain binding protein (BiP) is an endoplasmic reticulum (ER) chaperone, which binds to newly synthesized secretory and transmembrane proteins to facilitate protein folding. BiP mRNA is expressed in the arginine vasopressin (AVP) neurons in the supraoptic nucleus of wild‐type mice even in basal conditions, and the expression levels increase in response to dehydration. These data suggest that AVP neurons are subjected to ER stress. Familial neurohypophysial diabetes insipidus (FNDI) is caused by mutations in the gene locus of AVP. The mutant proteins could accumulate in the ER and possibly increase ER stress in the AVP neurons. We bred mice possessing a mutation causing FNDI, which manifested progressive polyuria, as do the patients with FNDI. Electron microscopic analyses demonstrated that aggregates accumulated in the ER of AVP neurons in FNDI mice. Despite polyuria, which could potentially induce dehydration, AVP mRNA expression was decreased in the supraoptic nucleus, and the AVP mRNA poly(A) tail length was shortened in FNDI mice compared with wild‐type mice. Incubation of hypothalamic explants of wild‐type mice with ER stressors caused shortening of the poly(A) tail length of AVP mRNA, accompanied by decreases in the expression. These data revealed a mechanism by which ER stress decreases poly(A) tail length of AVP mRNA, and this reduces the load of unfolded proteins that form the aggregates in ER of the AVP neurons in FNDI mice.
Kv7 and Kv11 channels in myometrial regulation
Authors: Greenwood Iain A. , Tribe Rachel M. 
Published: October 2013

New Findings
What is the topic of this review?
The topic of this review is how ion channels contribute to the physiology of the uterus, with particular focus on novel potassium channels.
What advances does it highlight?
Two families of potassium channels, encoded by KCNQ and KCNH genes, have been identified as important players in the control of myometrial contraction and may represent interesting novel therapeutic targets.
Ion channels play a key role in defining myometrial contractility. Modulation of ion channel populations is proposed to underpin gestational changes in uterine contractility associated with the transition from uterine quiescence to active labour. Of the myriad ion channels present in the uterus, this article will focus upon potassium channels encoded by the KCNQ genes and ether‐à‐go‐go‐related (ERG) genes. Voltage‐gated potassium channels encoded by KCNQ and ERG (termed Kv7 and Kv11, respectively) are accepted as major determinants of neuronal excitability and the duration of the cardiac action potential. However, there is now growing appreciation that these ion channels have a major functional impact in vascular and non‐vascular smooth muscle. Moreover, Kv7 channels may be potential therapeutic targets for the treatment of preterm labour.
Physical and biological factors determining the effective proton range
Authors: Grün Rebecca , Friedrich Thomas , Krämer Michael , Zink Klemens , Durante Marco , Engenhart‐Cabillic Rita , Scholz Michael 
Published: October 2013

Purpose:Proton radiotherapy is rapidly becoming a standard treatment option for cancer. However, even though experimental data show an increase of the relative biological effectiveness (RBE) with depth, particularly at the distal end of the treatment field, a generic RBE of 1.1 is currently used in proton radiotherapy. This discrepancy might affect the effective penetration depth of the proton beam and thus the dose to the surrounding tissue and organs at risk. The purpose of this study was thus to analyze the impact of a tissue and dose dependent RBE of protons on the effective range of the proton beam in comparison to the range based on a generic RBE of 1.1.Methods:Factors influencing the biologically effective proton range were systematically analyzed by means of treatment planning studies using the Local Effect Model (LEM IV) and the treatment planning software TRiP98. Special emphasis was put on the comparison of passive and active range modulation techniques.Results:Beam energy, tissue type, and dose level significantly affected the biological extension of the treatment field at the distal edge. Up to 4 mm increased penetration depth as compared to the depth based on a constant RBE of 1.1. The extension of the biologically effective range strongly depends on the initial proton energy used for the most distal layer of the field and correlates with the width of the distal penumbra. Thus, the range extension, in general, was more pronounced for passive as compared to active range modulation systems, whereas the maximum RBE was higher for active systems.Conclusions:The analysis showed that the physical characteristics of the proton beam in terms of the width of the distal penumbra have a great impact on the RBE gradient and thus also the biologically effective penetration depth of the beam.
Evolved Cobalamin-Independent Methionine Synthase (MetE) Improves the Acetate and Thermal Tolerance of Escherichia coli
Authors: Mordukhova Elena A. , Pan Jae-Gu 
Published: October 2013

ABSTRACT

Acetate-mediated growth inhibition of
Escherichia coli
has been found to be a consequence of the accumulation of homocysteine, the substrate of the cobalamin-independent methionine synthase (MetE) that catalyzes the final step of methionine biosynthesis. To improve the acetate resistance of
E. coli
, we randomly mutated the MetE enzyme and isolated a mutant enzyme, designated MetE-214 (V39A, R46C, T106I, and K713E), that conferred accelerated growth in the
E. coli
K-12 WE strain in the presence of acetate. Additionally, replacement of cysteine 645, which is a unique site of oxidation in the MetE protein, with alanine improved acetate tolerance, and introduction of the C645A mutation into the MetE-214 mutant enzyme resulted in the highest growth rate in acetate-treated
E. coli
cells among three mutant MetE proteins.
E. coli
WE strains harboring acetate-tolerant MetE mutants were less inhibited by homocysteine in
l
-isoleucine-enriched medium. Furthermore, the acetate-tolerant MetE mutants stimulated the growth of the host strain at elevated temperatures (44 and 45°C). Unexpectedly, the mutant MetE enzymes displayed a reduced melting temperature (

T
m

) but an enhanced
in vivo
stability. Thus, we demonstrate improved
E. coli
growth in the presence of acetate or at elevated temperatures solely due to mutations in the MetE enzyme. Furthermore, when an
E. coli
WE strain carrying the MetE mutant was combined with a previously found MetA (homoserine
o
-succinyltransferase) mutant enzyme, the MetA/MetE strain was found to grow at 45°C, a nonpermissive growth temperature for
E. coli
in defined medium, with a similar growth rate as if it were supplemented by
l
-methionine.
Feeding the Probiotic Enterococcus faecium Strain NCIMB 10415 to Piglets Specifically Reduces the Number of Escherichia coli Pathotypes That Adhere to the Gut Mucosa
Authors: Bednorz Carmen , Guenther Sebastian , Oelgeschläger Kathrin , Kinnemann Bianca , Pieper Robert , Hartmann Susanne , Tedin Karsten , Semmler Torsten , Neumann Konrad , Schierack Peter , Bethe Astrid , Wieler Lothar H. 
Published: October 2013

ABSTRACT

Feed supplementation with the probiotic
Enterococcus faecium
for piglets has been found to reduce pathogenic gut microorganisms. Since
Escherichia coli
is among the most important pathogens in pig production, we performed comprehensive analyses to gain further insight into the influence of
E. faecium
NCIMB 10415 on porcine intestinal
E. coli
. A total of 1,436
E. coli
strains were isolated from three intestinal habitats (mucosa, digesta, and feces) of probiotic-supplemented and nonsupplemented (control) piglets.
E. coli
bacteria were characterized via pulsed-field gel electrophoresis (PFGE) for clonal analysis. The high diversity of
E. coli
was reflected by 168 clones. Multilocus sequence typing (MLST) was used to determine the phylogenetic backgrounds, revealing 79 sequence types (STs). Pathotypes of
E. coli
were further defined using multiplex PCR for virulence-associated genes. While these analyses discerned only a few significant differences in the
E. coli
population between the feeding groups, analyses distinguishing clones that were uniquely isolated in either the probiotic group only, the control group only, or both groups (shared group) revealed clear effects at the habitat level. Interestingly, extraintestinal pathogenic
E. coli
(ExPEC)-typical clones adhering to the mucosa were significantly reduced in the probiotic group. Our data show a minor influence of
E. faecium
on the overall population of
E. coli
in healthy piglets. In contrast, this probiotic has a profound effect on mucosa-adherent
E. coli
. This finding further substantiates a specific effect of
E. faecium
strain NCIMB 10415 in piglets against pathogenic
E. coli
in the intestine. In addition, these data question the relevance of data based on sampling fecal
E. coli
only.
Structural and Population Characterization of MrkD, the Adhesive Subunit of Type 3 Fimbriae
Authors: Stahlhut Steen G. , Chattopadhyay Sujay , Kisiela Dagmara I. , Hvidtfeldt Kristian , Clegg Steven , Struve Carsten , Sokurenko Evgeni V. , Krogfelt Karen A. 
Published: October 2013

ABSTRACT

Type 3 fimbriae are adhesive organelles found in enterobacterial pathogens. The fimbriae promote biofilm formation on biotic and abiotic surfaces; however, the exact identity of the receptor for the type 3 fimbriae adhesin, MrkD, remains elusive. We analyzed naturally occurring structural and functional variabilities of the MrkD adhesin from
Klebsiella pneumoniae
and
Escherichia coli
isolates of diverse origins. We identified a total of 33 allelic variants of
mrkD
among 90
K. pneumoniae
isolates and 10 allelic variants among 608
E. coli
isolates, encoding 11 and 9 protein variants, respectively. Based on the level of accumulated silent variability between the alleles,
mrkD
was acquired a relatively long time ago in
K. pneumoniae
but recently in
E. coli
. However, unlike
K. pneumoniae
,
mrkD
in
E. coli
is actively evolving under a strong positive selection by accumulation of mutations, often targeting the same positions in the protein. Several naturally occurring MrkD protein variants from
E. coli
were found to be significantly less adherent when tested in a mannan-binding assay and showed reduced biofilm-forming capacity. Functional examination of the MrkD adhesin in flow chamber experiments determined that it interacts with
Saccharomyces cerevisiae
cells in a shear-dependent manner, i.e., the binding is catch-bond-like and enhanced under increasing shear conditions. Homology modeling strongly suggested that MrkD has a two-domain structure, comprising a pilin domain anchoring the adhesin to the fimbrial shaft and a lectin domain containing the binding pocket; this is similar to structures found in other catch-bond-forming fimbrial adhesins in enterobacteria.
A Zn-Dependent Metallopeptidase Is Responsible for Sensitivity to LsbB, a Class II Leaderless Bacteriocin of Lactococcus lactis subsp. lactis BGMN1-5
Authors: Uzelac Gordana , Kojic Milan , Lozo Jelena , Aleksandrzak-Piekarczyk Tamara , Gabrielsen Christina , Kristensen Tom , Nes Ingolf F. , Diep Dzung B. , Topisirovic Ljubisa 
Published: October 2013

ABSTRACT

Lactococcus lactis
subsp.
lactis
BGMN1-5 produces a leaderless class II bacteriocin called LsbB. To identify the receptor for LsbB, a cosmid library of the LsbB-sensitive strain BGMN1-596 was constructed. About 150 cosmid clones were individually isolated and transferred to LsbB-resistant mutants of BGMN1-596. Cosmid pAZILcos/MN2, carrying a 40-kb insert, was found to restore LsbB sensitivity in LsbB-resistant mutants. Further subcloning revealed that a 1.9-kb fragment, containing only one open reading frame, was sufficient to restore sensitivity. The fragment contains the gene
yvjB
coding for a Zn-dependent membrane-bound metallopeptidase, suggesting that this gene may serve as the receptor for LsbB. Further support for this notion derives from several independent experiments: (i) whole-genome sequencing confirmed that all LsbB-resistant mutants contain mutations in
yvjB
; (ii) disruption of
yvjB
by direct gene knockout rendered sensitive strains BGMN1-596 and IL1403 resistant to LsbB; and (iii) most compellingly, heterologous expression of
yvjB
in naturally resistant strains of other species, such as
Lactobacillus paracasei
and
Enterococcus faecalis
, also rendered them sensitive to the bacteriocin. To our knowledge, this is the first time a membrane-bound peptidase gene has been shown to be involved in bacteriocin sensitivity in target cells. We also demonstrated a novel successful approach for identifying bacteriocin receptors.
Acupuncture for Vascular Mild Cognitive Impairment: A Systematic Review of Randomised Controlled Trials
Authors: Cao Huijuan , Wang Yuyi , Chang Dennis , Zhou Li , Liu Jianping 
Published: October 2013

Background Vascular mild cognitive impairment (VMCI) is the most common type of vascular cognitive impairment induced by cerebrovascular disease. No effective medicines are currently available for VMCI. Objective To assess the effectiveness and safety of acupuncture for VMCI. Methods Seven electronic databases were searched for randomised controlled trials which investigated the effects of acupuncture compared with no treatment, placebo or conventional therapies on cognitive function or other clinical outcomes in patients with VMCI. The quality of the trials selected was evaluated according to the ‘risk of bias’ assessment provided by the Cochrane Handbook for Systematic Reviews of Interventions. RevMan V.5.1 software was employed for data analysis. Results Twelve trials with 691 participants were included. The methodological quality of all included trials was unclear and/or they had a high risk of bias. Meta-analysis showed acupuncture in conjunction with other therapies could significantly improve Mini-Mental State Examination scores (mean difference 1.99, 95% CI 1.09 to 2.88, random model, p<0.0001, 6 trials). No included trials mentioned any adverse events of the treatment. Conclusions The current clinical evidence is not of sufficient quality for wider application of acupuncture to be recommended for the treatment of VMCI, and further large, rigorously designed trials are warranted.
Mechanical instability destabilises the ankle joint directly in the ankle-sprain mechanism
Authors: Gehring Dominic , Faschian Katrin , Lauber Benedikt , Lohrer Heinz , Nauck Tanja , Gollhofer Albert 
Published: October 2013

BackgroundDespite massive research efforts, it remains unclear how mechanical ankle instability (MAI) and functional ankle instability (FAI) affect joint control in the situation of ankle sprain. Thus, the purpose of this study was to evaluate whether individuals with MAI have deficits in stabilising their ankle joint in a close-to-injury situation compared with those with FAI and healthy controls.MethodsAnkle-joint control was assessed by means of three-dimensional motion analysis and electromyography in participants with FAI and MAI (n=19), in participants with pure FAI (n=9) and in healthy controls (n=18). Close-to-injury situations were simulated during standing, walking and jumping by means of a custom-made tilt platform.ResultsIndividuals with FAI and MAI displayed significantly greater maximum ankle inversion angles (+5°) and inversion velocities (+50°/s) in the walking and jumping conditions compared to those with pure FAI and controls. Furthermore, individuals in the FAI and MAI group showed a significantly decreased pre-activation of the peroneus longus muscle during jumping compared to those with FAI. No differences between groups were found for plantar flexion and internal rotation, or for muscle activities following tilting of the platform.ConclusionsThe present study demonstrates that MAI is characterised by impairments of ankle-joint control in close-to-injury situations. This could make these individuals more prone to recurrent ankle sprains, and suggests the need for additional mechanical support such as braces or even surgery. In addition, the study highlights the fact that dynamic experimental test conditions in the acting participant are needed to further unravel the mystery of chronic ankle instability.