bluuebunny/crossref_metadata_2025 huggingface dataset:
Phospholipid:diacylglycerol acyltransferase‐mediated triacylglycerol biosynthesis is crucial for protection against fatty acid‐induced cell death in growing tissues of Arabidopsis
Authors: Fan Jilian , Yan Chengshi , Xu Changcheng
Published: October 2013

Phospholipid:diacylglycerol acyltransferase (PDAT) and diacylglycerol:acyl CoA acyltransferase play overlapping roles in triacylglycerol (TAG) assembly in Arabidopsis, and are essential for seed and pollen development, but the functional importance of PDAT in vegetative tissues remains largely unknown. Taking advantage of the Arabidopsis tgd1–1 mutant that accumulates oil in vegetative tissues, we demonstrate here that PDAT1 is crucial for TAG biosynthesis in growing tissues. We show that disruption of PDAT1 in the tgd1–1 mutant background causes serious growth retardation, gametophytic defects and premature cell death in developing leaves. Lipid analysis data indicated that knockout of PDAT1 results in increases in the levels of free fatty acids (FFAs) and diacylglycerol. In vivo 14C‐acetate labeling experiments showed that, compared with wild‐type, tgd1–1 exhibits a 3.8‐fold higher rate of fatty acid synthesis (FAS), which is unaffected by disruption or over‐expression of PDAT1, indicating a lack of feedback regulation of FAS in tgd1–1. We also show that detached leaves of both pdat1–2 and tgd1–1 pdat1–2 display increased sensitivity to FFA but not to diacylglycerol. Taken together, our results reveal a critical role for PDAT1 in mediating TAG synthesis and thereby protecting against FFA‐induced cell death in fast‐growing tissues of plants.
SUPPRESSOR OF LLP1 1‐mediated C–terminal processing is critical for CLE19 peptide activity
Authors: Tamaki Takayuki , Betsuyaku Shigeyuki , Fujiwara Masayuki , Fukao Yoichiro , Fukuda Hiroo , Sawa Shinichiro
Published: October 2013

Cell‐to‐cell communication is essential for the coordinated development of multicellular organisms. Members of the CLAVATA3/EMBRYO‐SURROUNDING REGION‐RELATED (CLE) family, a group of small secretory peptides, are involved in these processes in plants. Although post‐translational modifications are considered to be indispensable for their activity, the detailed mechanisms governing these modifications are not well understood. Here, we report that SUPPRESSOR OF LLP1 1 (SOL1), a putative Zn2+ carboxypeptidase previously isolated as a suppressor of the CLE19 over‐expression phenotype, functions in C–terminal processing of the CLE19 proprotein to produce the functional CLE19 peptide. Newly isolated sol1 mutants are resistant to CLE19 over‐expression, consistent with the previous report (Casamitjana‐Martinez, E., Hofhuis, H.F., Xu, J., Liu, C.M., Heidstra, R. and Scheres, B. (2003) Curr. Biol. 13, 1435–1441). As expected, our experiment using synthetic CLE19 peptide revealed that the sol1 mutation does not compromise CLE signal transduction pathways per se. SOL1 possesses enzymatic activity to remove the C–terminal arginine residue of CLE19 proprotein in vitro, and SOL1‐dependent cleavage of the C–terminal arginine residue is necessary for CLE19 activity in vivo. Additionally, the endosomal localization of SOL1 suggests that this processing occurs in endosomes in the secretory pathway. Thus, our data indicate the importance of C–terminal processing of CLE proproteins to ensure CLE activities.
Legume adaptation to sulfur deficiency revealed by comparing nutrient allocation and seed traits in Medicago truncatula
Authors: Zuber Hélène , Poignavent Germain , Le Signor Christine , Aimé Delphine , Vieren Eric , Tadla Charlène , Lugan Raphaël , Belghazi Maya , Labas Valérie , Santoni Anne‐Lise , Wipf Daniel , Buitink Julia , Avice Jean‐Christophe , Salon Christophe , Gallardo Karine
Published: October 2013

Reductions in sulfur dioxide emissions and the use of sulfur‐free mineral fertilizers are decreasing soil sulfur levels and threaten the adequate fertilization of most crops. To provide knowledge regarding legume adaptation to sulfur restriction, we subjected Medicago truncatula, a model legume species, to sulfur deficiency at various developmental stages, and compared the yield, nutrient allocation and seed traits. This comparative analysis revealed that sulfur deficiency at the mid‐vegetative stage decreased yield and altered the allocation of nitrogen and carbon to seeds, leading to reduced levels of major oligosaccharides in mature seeds, whose germination was dramatically affected. In contrast, during the reproductive period, sulfur deficiency had little influence on yield and nutrient allocation, but the seeds germinated slowly and were characterized by low levels of a biotinylated protein, a putative indicator of germination vigor that has not been previously related to sulfur nutrition. Significantly, plants deprived of sulfur at an intermediary stage (flowering) adapted well by remobilizing nutrients from source organs to seeds, ensuring adequate quantities of carbon and nitrogen in seeds. This efficient remobilization of photosynthates may be explained by vacuolar sulfate efflux to maintain leaf metabolism throughout reproductive growth, as suggested by transcript and metabolite profiling. The seeds from these plants, deprived of sulfur at the floral transition, contained normal levels of major oligosaccharides but their germination was delayed, consistent with low levels of sucrose and the glycolytic enzymes required to restart seed metabolism during imbibition. Overall, our findings provide an integrative view of the legume response to sulfur deficiency.
Removal of exogenous prion infectivity in leukoreduced red blood cells unit by a specific filter designed for human transfusion
Authors: Lescoutra‐Etchegaray Nathalie , Sumian Chryslain , Culeux Audrey , Durand Valérie , Gurgel Patrick V. , Deslys Jean‐Philippe , Comoy Emmanuel E.
Published: October 2013

Background

Five cases of variant Creutzfeldt‐Jakob disease (vCJD) infections were attributed to infusion of contaminated blood components, turning to real the interhuman transmissibility of this prion disease from asymptomatic carriers. Preventive policies rely on exclusion from blood donation and benefit of leukoreduction initially implemented against leukotropic viruses. In the absence of available antemortem diagnostic tests, the updated prevalence of silent vCJD infections (1/2000 in the United Kingdom) urges the necessity to enforce blood safety with more efficient active measures able to remove the remaining infectivity.

Study Design and Methods

Several affinity resins were demonstrated to reduce high levels of brain‐spiked infectivity from human leukoreduced red blood cells (L‐RBCs). One was integrated in a device adapted to field constraints (volumes, duration) of human transfusion. We assessed here the ability of the resulting removal filter, termed P‐Capt, to remove infectivity from human L‐RBC units spiked with scrapie‐infected hamster brain (≥10,000 infectious units/mL), through inoculation of hamsters with pre‐ and post–blood filtration samples.

Results

Incubation periods of recipient animals suggest around a 3‐log removal of brain‐derived prion infectivity by filtration through the P‐Capt.

Conclusion

On brain‐derived spiked infectivity, the P‐Capt filter provided a performance similar to the resin packed in columns used for initial proof‐of‐concept studies, suggesting an appropriate scale‐up to efficiently remove infectivity from an individual human blood bag. According to the ability of resin to completely remove apparent endogenous infectivity from hamster leukoreduced blood, the implementation of such a filter, now commercially available, might seriously improve blood safety toward prions.
Analysis of the recovery of cryopreserved and thawed CD34+ and CD3+ cells collected for hematopoietic transplantation
Authors: Fisher Virginia , Khuu Hanh , David‐OCampo Virginia , Byrne Karen , Pavletic Steven , Bishop Michael , Fowler Daniel H. , Barrett A. John , Stroncek David F.
Published: October 2013

Background

Cryopreservation is often used to store cellular therapies, but little is known about how well CD3+ or CD34+ cells tolerate this process.

Study Design and Methods

Viable CD34+ cell recoveries were analyzed from related and unrelated donor granulocyte–colony‐stimulating factor (G‐CSF)–mobilized peripheral blood stem cell (PBSC) products and viable CD3+ cell recoveries from G‐CSF–mobilized and nonmobilized apheresis products from related and unrelated donors. All products were cryopreserved with 5% dimethyl sulfoxide and 6% pentastarch using a controlled‐rate freezer and were stored in liquid nitrogen. Related donor products were cryopreserved immediately after collection and unrelated donor products greater than 12 hours postcollection.

Results

The postthaw recovery of CD34+ cells from related donor PBSCs was high (n = 86; 97.5 ± 23.1%) and there was no difference in postthaw CD34+ cell recovery from unrelated donor PBSCs (n = 14; 98.8 ± 37.2%; p = 0.863). In related donor lymphocyte products the postthaw CD3+ cell recovery (n = 48; 90.7 ± 21.4%) was greater than that of unrelated donor products (n = 14; 66.6 ± 35.8%; p = 0.00251). All unrelated donor lymphocyte products were from G‐CSF–mobilized products, while most related donor lymphocyte products were from nonmobilized products. A comparison of the CD3+ cell recovery from related donor G‐CSF–mobilized products (n = 19; 85.0 ± 29.2%) with that of unrelated donor products found no significant difference (p = 0.137).

Conclusions

The postthaw recovery of CD34+ cells was high in both related and unrelated donor products, but the recovery of CD3+ cells in unrelated donor G‐CSF–mobilized products was lower. G‐CSF–mobilized unrelated donor products may contain fewer CD3+ cells than non–G‐CSF–exposed products upon thaw and, when indicated, cell doses should be monitored.
Early fresh‐frozen plasma transfusion decreases the risk of retinopathy of prematurity
Authors: Dani Carlo , Poggi Chiara , Bresci Cecilia , Corsini Iuri , Frosini Saverio , Pratesi Simone
Published: October 2013

Background

Insulin‐like growth factor 1 (IGF‐1) and IGF‐binding protein‐3 (IGFBP‐3) play a main role in the pathogenesis of retinopathy of prematurity (ROP). Fresh‐frozen plasma (FFP) from adult donors may be an actual source of IGF‐1 and IGFBP‐3 because it contains higher concentrations. The objective was to evaluate whether FFP transfusions can decrease the occurrence of ROP in a cohort of preterm infants.

Study Design and Methods

We retrospectively analyzed data from 218 infants with gestational age of less than 29 weeks who either received FFP or did not and correlated this procedure to the development of any grade of ROP.

Results

Logistic regression analysis demonstrated that two or more transfusions of FFP was effective in decreasing the risk of development of any grade of ROP (relative risk, 0.46; 95% confidence interval, 0.23‐0.93). Other factors that affected the risk of ROP were gestational age, birthweight, antenatal steroid treatment, FiO2 of at least 0.40, mechanical ventilation, and sepsis.

Conclusions

We found that two or more transfusions of FFP in the first week of life decrease the risk of developing any grade of ROP in preterm infants with gestational age of less than 29 weeks.
Engraftment and outcome after autologous stem cell transplantation in plerixafor‐mobilized non‐Hodgkin's lymphoma patients
Authors: Varmavuo Ville , Rimpiläinen Johanna , Kuitunen Hanne , Nihtinen Anne , Vasala Kaija , Mikkola Maija , Kutila Anu , Lehtonen Päivi , Kuittinen Taru , Mäntymaa Pentti , Nousiainen Tapio , Kuittinen Outi , Jantunen Esa
Published: October 2013

Background

Plerixafor is used in combination with granulocyte–colony‐stimulating factor to enhance the mobilization of hematopoietic stem cells. Limited data are available in regard to effects of plerixafor on posttransplant outcomes in chemomobilized patients who appear to mobilize poorly.

Study Design and Methods

Eighty‐nine chemomobilized patients with non‐Hodgkin's lymphoma (NHL) were included in this retrospective study. Thirty‐three patients had received plerixafor preemptively (plerixafor group) and 56 patients served as controls. Posttransplantation outcomes including infections, hematologic recovery, and relapse were recorded.

Results

The median fold increase of CD34+ cells after the first plerixafor dose was 4.1 in patients mobilized with chemotherapy plus filgrastim and 7.2 in those mobilized with chemotherapy plus pegfilgrastim (p = 0.027). The median number of collected CD34+ cells was 3.5 × 106 CD34+ cells/kg in the plerixafor group and 4.2 × 106 CD34+ cells/kg in the control group (p = 0.076). Early engraftment was comparable between the groups (10 days for neutrophils >0.5 × 109/L and 14 days for platelets >20 × 109/L, respectively). Also late engraftment within 12 months was comparable except higher hemoglobin level at 3 months in the control group (121 g/L vs. 112 g/L, p = 0.009). Progression‐free survival at 1 year after autologous stem cell transplantation (ASCT) was 79% in the plerixafor group and 86% in the control group (p = 0.399).

Conclusions

Long‐term engraftment and outcome after ASCT seem to be comparable in NHL patients receiving plerixafor compared to chemomobilized patients. These observations support the use of plerixafor in patients who mobilize poorly.
Peripheral blood progenitor cell collection by two programs for autologous and allogeneic transplantation
Authors: Ikeda Kazuhiko , Ohto Hitoshi , Kanno Takahiro , Gonda Kenji , Suzuki Yuhko , Ono Takako , Saito Shunnichi , Takahashi Hiroshi , Kimura Satoshi , Harada‐Shirado Kayo , Yamauchi Hiroyuki , Hoshino Yasuto , Mashimo Yumiko , Nollet Kenneth E. , Kikuta Atsushi , Ogawa Kazuei , Takeishi Yasuchika
Published: October 2013

Background

In the Spectra apheresis instrument (Terumo BCT), both manual (Spectra‐MNC) and automated (Spectra‐Auto) programs have been widely used to collect peripheral blood progenitor cells (PBPCs). However, direct comparison of these programs remains extremely limited.

Study Design and Methods

We investigated 188 collections and products from autologous (patient) and allogeneic (donor) subjects and analyzed a subset of 89 allogeneic collections and products. Twenty‐nine subjects who received apheresis for 2 consecutive days using both programs were also evaluated with a paired crossover comparison.

Results

The two programs processed similar volumes, but run time was longer with Spectra‐Auto. Yield and efficiency of CD34+ cell collection were similar between these programs in the whole cohort, although white blood cell (WBC) and mononuclear cell (MNC) yields were higher with Spectra‐MNC. In the allogeneic cohort, yield and efficiency of WBC collection were greater in Spectra‐MNC. However, collected WBCs, MNCs, and CD34+ cells were similar between these programs in paired comparison. Regardless of program, preapheresis peripheral WBC, MNC, and CD34+ cell counts correlated with the number of cells collected. In contrast, preapheresis WBC counts in the whole cohort were negatively correlated with collection efficiencies of CD34+ cells in Spectra‐MNC but not Spectra‐Auto. The products collected using Spectra‐MNC contained more contaminating platelets (PLTs) than Spectra‐Auto, with a corresponding reduction in postdonation circulating PLTs.

Conclusion

Spectra‐MNC and Spectra‐Auto showed distinct features that should be considered on a case‐by‐case basis. Similar investigations should be undertaken as new collection platforms are introduced.
Does bleeding affect patient‐reported outcome measures in patients with myelodysplasia or hematologic malignancies: a systematic review
Authors: Estcourt Lise J. , Pinchon Deborah , Symington Emily , Kelly Anne M. , Doree Carolyn , Brunskill Susan , Glidewell Liz , Stanworth Simon
Published: October 2013

Background

Relatively minor bleeding (e.g., bruising and/or petechiae) may cause patient distress. This systematic review's objective was to assess whether bleeding affects health‐related quality of life (HRQoL) or illness perceptions or representations (IPs) in patients with hematologic malignancies or myelodysplasia (MDS).

Study Design and Methods

We searched, in full, 12 electronic databases (including CENTRAL, MEDLINE, and EMBASE) up to January 7, 2013, for eligible randomized controlled trials (RCTs), prospective cohort studies, and cross‐sectional studies.

Results

A total of 6247 studies were initially identified; 5945 studies were excluded on the basis of the abstract. A total of 302 full‐text articles were evaluated independently by two reviewers; of these, six studies within seven citations were eligible for inclusion. Two studies are still in progress, four studies within five citations were included in this review (one RCT, one prospective observational study, one interview study, and one Web‐based survey). None of the included studies were designed to assess the impact bleeding had on HRQoL or IPs. The Web‐based survey and observational study used two new patient‐reported outcome scales which specifically assessed patient distress or concern due to bleeding. The majority of patients within these two studies either did not experience bleeding or did not have severe thrombocytopenia.

Conclusion

There is insufficient evidence to demonstrate whether bleeding is a significant clinical problem that affects patients' HRQoL or IPs in either patients with MDS or patients with hematologic malignancies. Rigorously designed studies to assess the scale of this problem in both of these groups of patients are required.
Peripheral blood stem cell collection in low‐weight children: retrospective comparison of two apheresis devices
Authors: Cherqaoui Bilade , Rouel Nadège , Auvrignon Anne , Defachelles Anne‐Sophie , Deméocq François , Kanold Justyna , Merlin Etienne
Published: October 2013

Background

Apheresis is a major challenge in peripheral stem cell collection from low‐weight children with cancer. Comparisons between the new apheresis device Optia (TerumoBCT) and the earlier COBE Spectra (CaridianBCT) have been performed in adults but not in low‐weight children. The objective was to compare the performance of these two devices in small children.

Study Design and Methods

In this retrospective study, all patients were reviewed weighing less than 15 kg undergoing stem cell collection using the Optia device between April 2011 and April 2012. They were paired on weight in a 3:1 ratio with patients whose cells had been collected with the COBE Spectra since 2006.

Results

Six patients were treated with the Optia and were matched with 18 patients treated with the Spectra. No side effects occurred. Collection efficiency (CE) was similar between the two groups (50% vs. 47%), but CD34 cell blood clearance was lower with the Optia (0.4 mL/min/kg vs. 0.6 mL/min/kg, p < 0.01). Platelet (PLT) loss and hemoglobin (Hb) loss were significantly reduced with the Optia (respectively, 32% vs. 54%, p < 0.01; and 1.4 g/dL vs. 2.9 g/dL, p < 0.01). Apheresis duration was increased with the Optia (159 min vs. 134 min, p < 0.05). The cell product harvested with the Optia had a lower volume and lower hematocrit, but similar white blood cell and PLT content.

Conclusion

Compared with the Spectra, the Optia allows similar CE with a reduced PLT and Hb loss but with a longer duration.
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

Tumour‐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

Background

Platelet alloantigens in horses may play an important role in the development of neonatal alloimmune thrombocytopenia (NAIT).

Objective

The objective of this study was to evaluate genes encoding major platelet glycoproteins within the Equidae family in an effort to identify potential alloantigens.

Methods

DNA 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.

Results

Amino 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.

Conclusions

This 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 Objectives

While 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 Methods

A 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.

Results

Five 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.

Conclusions

These 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 Objectives

Platelet (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 Methods

A review of the MEDLINE® database for relevant publications from 1960 to May 2013 was conducted.

Results

It 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.

Conclusion

Despite 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.
VALIDATION OF A NOVEL TRANSLUMBAR ULTRASOUND TECHNIQUE FOR MEASURING RENAL DIMENSIONS IN HORSES
Authors: Habershon‐Butcher Jocelyn , Bowen Mark , Hallowell Gayle
Published: October 2013

A reliable method for obtaining renal ultrasonographic measurements in the horse is important for diagnosis and monitoring of clinical renal disease. The aims of this prospective study were to develop and validate a novel translumbar ultrasound technique for measuring renal dimensions in horses. Six Thoroughbred or Thoroughbred part bred horses were recruited. All horses were scheduled for euthanasia due to reasons unrelated to the kidneys. Two observers recorded renal length, width, and depth; and dimensions of the cortex, medulla, pyramids, and pelvis for both kidneys in each horse using novel translumbar and conventional transabdominal ultrasound methods. The same measurements were recorded from post‐mortem renal specimens. Both kidneys were consistently identified by both methods in the 15–17th intercostal spaces and paralumbar fossa. Using the translumbar technique, maximal dimensions were obtained for the left kidney in the 16th intercostal space (length 16.2 ± 2.0 cm, width 11.8 ± 0.5 cm, depth 6.4 ± 0.9 cm) and for the right kidney in the 15th intercostal space (length 16.1 ± 1.2 cm, width 13.4 ± 1.2 cm, depth 6.7 ± 0.7 cm). Renal dimensions obtained by transabdominal and translumbar projections did not differ (P> 0.05). Good correlations were found between overall renal dimensions and post‐mortem measurements for both ultrasound techniques (r2> 0.8), but were better for the translumbar method (meanr2= 0.92 cf. 0.88). Good‐to‐excellent reliability was found for all translumbar ultrasound measurements except for the renal cortex. Reproducibility was better for the larger (overall length, width, and depth) than the smaller (cortex, medulla, and pyramids) structures. Findings indicated that translumbar ultrasonography is a valid method for measuring renal dimensions in horses.
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.
Cross Diffusion Effects on Chemically Reacting Magnetohydrodynamic Micropolar Fluid Between Concentric Cylinders
Authors: Srinivasacharya D. , Shiferaw Mekonnen
Published: October 2013

The present study investigates magnetic, first-order chemical reaction, Soret and Dufour effects on electrically conducting micropolar fluid flow between two circular cylinders. The inner and outer surfaces of the annular cylinder are maintained at different constant wall temperature where the outer cylinder is rotating and inner cylinder remains stationary. The governing nonlinear partial differential equations are transformed into a system of ordinary differential equations (ODEs) using similarity transformations. The resulting equations are then solved for approximate analytical series solutions using homotopy analysis method (HAM). The effects of various parameters on the velocity, microrotation temperature and concentration are discussed and shown graphically.
Effect of trimethylsilane pressure on hot-wire chemical vapor deposition chemistry using vacuum ultraviolet laser ionization mass spectrometry
Authors: Toukabri Rim , Shi Yujun
Published: October 2013

In this study, the authors investigated the effect of sample pressure on the reaction chemistry of trimethylsilane (TriMS) in the hot-wire chemical vapor deposition (CVD) process. The secondary gas-phase reaction products were examined in a reactor with varying TriMS pressures. The reaction products were analyzed using a laser ionization source with a vacuum ultraviolet wavelength of 118 nm, coupled with mass spectrometry. By increasing TriMS pressure, methane formation was observed. To our knowledge, this is the first successful use of either open-chain alkylsilanes or four-membered-ring (di)silacyclobutane molecules as an independent precursor gas in the hot-wire CVD reactor to achieve methane formation. Our results showed that methane was formed mainly from the radical chain reactions with minor contributions from molecular elimination. The increase in the sample pressure also led to the formation of other small hydrocarbon molecules including acetylene, ethene, propyne, and propene. The formation of hydrogen molecules was enhanced when the sample pressure was increased. In addition, the change in the sample pressure had a direct effect on the radical recombination and disproportionation reactions. This is reflected in the different behavior assumed by the main products from these two types of reactions, i.e., tetramethylsilane, hexamethyldisilane from the former, and three methyl-substituted disilacyclobutanes from the latter. The trapping of free radicals resulting from the in-situ produced ethene and propene molecules is responsible for the observed difference.
Spray deposition of nanostructured metal films using hydrodynamically stabilized, high pressure microplasmas
Authors: Koh Travis L. , Gordon Michael J.
Published: October 2013

Cu, Pd, and Ni nanoparticles and films compose of fibers, matchsticks, and dense columns were grown using a hydrodynamically stabilized, high pressure (∼Torr) microplasma jet source at low substrate temperatures. Organometallic precursors were dissociated in the microplasma jet under highly reducing conditions, creating a directed flux of active metal species for the subsequent growth of nanostructured films. The growth process can be tuned (e.g., from nanoparticles, to competitive columns, to dense films with nanoscale grain structure) by adjusting the precursor flux, plasma current, background gas atmosphere, and jet–substrate distance. Microplasma jet operation, dynamics of the growth process, and the resulting metallic films are discussed.
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.
Unexpected intensity changes in the ear canal during a F-shifted feedback experiment
Authors: Tlumak Abreena I. , Szuminsky Neil J. , Shaiman Susan , Pratt Sheila R.
Published: October 2013

Effects of frequency-shifted feedback are typically examined using Eventide Harmonizer Series processors to shift the fundamental frequency (F0) of auditory feedback during vocalizations, eliciting compensatory shifts in speaker F0. Recently, unexpected intensity changes were observed in speakers' ear canals, corresponding with F0 shifts. An investigation revealed that feedback time delays introduced by the processor resulted in phase shifts between feedback and unprocessed voice signals radiating into the ear canal via bone conduction, producing combination waves with gains as high as 6 dB. Shifts of this magnitude potentially alter the interpretation of previously published results and should be controlled in future studies.
On the suitability of ISO 16717-1 reference spectra for rating airborne sound insulation
Authors: Mašović Draško B. , Pavlović Dragana S. Šumarac , Mijić Miomir M.
Published: October 2013

A standard proposal for rating airborne sound insulation in buildings [ISO 16717-1 (2012)] defines the reference noise spectra. Since their shapes influence the calculated values of single-number descriptors, reference spectra should approximate well typical noise spectra in buildings. There is, however, very little data in the existing literature on a typical noise spectrum in dwellings. A spectral analysis of common noise sources in dwellings is presented in this paper, as a result of an extensive monitoring of various noisy household activities. Apart from music with strong bass content, the proposed “living” reference spectrum overestimates noise levels at low frequencies.
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

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

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

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

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.