bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Arabidopsis vacuolar malate channel is a member of the ALMT family
Authors: Kovermann Peter , Meyer Stefan , Hörtensteiner Stefan , Picco Cristiana , Scholz‐Starke Joachim , Ravera Silvia , Lee Youngsook , Martinoia Enrico 
Published: April 2010

SummaryIn plants, malate is a central metabolite and fulfills a large number of functions. Vacuolar malate may reach very high concentrations and fluctuate rapidly, whereas cytosolic malate is kept at a constant level allowing optimal metabolism. Recently, a vacuolar malate transporter (Arabidopsis thaliana tonoplast dicarboxylate transporter, AttDT) was identified that did not correspond to the well‐characterized vacuolar malate channel. We therefore hypothesized that a member of the aluminum‐activated malate transporter (ALMT) gene family could code for a vacuolar malate channel. Using GFP fusion constructs, we could show that AtALMT9 (A. thaliana ALMT9) is targeted to the vacuole. Promoter‐GUS fusion constructs demonstrated that this gene is expressed in all organs, but is cell‐type specific as GUS activity in leaves was detected nearly exclusively in mesophyll cells. Patch‐clamp analysis of an Atalmt9 T‐DNA insertion mutant exhibited strongly reduced vacuolar malate channel activity. In order to functionally characterize AtALMT9 as a malate channel, we heterologously expressed this gene in tobacco and in oocytes. Overexpression of AtALMT9‐GFP in Nicotiana benthamiana leaves strongly enhanced the malate current densities across the mesophyll tonoplasts. Functional expression of AtALMT9 in Xenopus oocytes induced anion currents, which were clearly distinguishable from endogenous oocyte currents. Our results demonstrate that AtALMT9 is a vacuolar malate channel. Deletion mutants for AtALMT9 exhibit only slightly reduced malate content in mesophyll protoplasts and no visible phenotype, indicating that AttDT and the residual malate channel activity are sufficient to sustain the transport activity necessary to regulate the cytosolic malate homeostasis.
Germline mosaicism in keratitis–ichthyosis–deafness syndrome: pre‐natal diagnosis in a familial lethal form
Authors: Sbidian E , Feldmann D , Bengoa J , Fraitag S , Abadie V , de Prost Y , Bodemer C , Hadj‐Rabia S 
Published: April 2010

Sbidian E, Feldmann D, Bengoa J, Fraitag S, Abadie V, de Prost Y, Bodemer C, Hadj‐Rabia S. Germline mosaicism in keratitis–ichthyosis–deafness syndrome: pre‐natal diagnosis in a familial lethal form.Keratitis–ichthyosis–deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin‐26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre‐natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non‐consanguineous healthy parents lead to perform pre‐natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin.
Clinical involvement in daughters of men with fragile X‐associated tremor ataxia syndrome
Authors: Chonchaiya W , Nguyen DV , Au J , Campos L , Berry‐Kravis EM , Lohse K , Mu Y , Utari A , Hervey C , Wang L , Sorensen P , Cook K , Gane L , Tassone F , Hagerman RJ 
Published: April 2010

Chonchaiya W, Nguyen DV, Au J, Campos L, Berry‐Kravis EM, Lohse K, Mu Y, Utari A, Hervey C, Wang L, Sorensen P, Cook K, Gane L, Tassone F, Hagerman RJ. Clinical involvement in daughters of men with fragile X‐associated tremor ataxia syndrome.Women with the fragile X mental retardation 1 (FMR1) premutation often have concerns about neurological and medical problems, as they become older and if their fathers experience fragile X‐associated tremor/ataxia syndrome (FXTAS). We therefore determined the prevalence of these problems in 110 daughters of men with FXTAS [mean age of 44.8 years (SD 8.2)]. We compared them with 43 female controls with normal FMR1 alleles [mean age of 43.8 years (SD 8.1)] and 36 premutation carrier daughters of parents with the premutation, but without FXTAS [mean age of 43.5 years (SD 7.7)]. Overall, daughters of men with FXTAS have a higher prevalence of neurological symptoms including tremor, balance problems, memory problems, and dizziness, menopausal symptoms, and psychiatric involvement including sleep problems and anxiety when compared with non‐carrier female controls. Reported balance problems and menopausal symptoms were significantly higher in daughters of men with FXTAS than in carrier daughters of parents without FXTAS, suggesting the potential influence of background gene effects. Therefore, neurological, psychological and gynecological surveillance should be warranted to better provide appropriate counseling, management and care for daughters of men with FXTAS. Biological markers of additional gene effects that predispose individuals with the premutation to FXTAS need to be developed.
Rationale and timeliness for IL‐1β‐targeted therapy to reduce allogeneic organ injury at procurement and to diminish risk of rejection after transplantation
Authors: Wanderer Alan A. 
Published: April 2010

Wanderer AA. Rationale and timeliness for IL‐1β‐targeted therapy to reduce allogeneic organ injury at procurement and to diminish risk of rejection after transplantation. Clin Transplant 2010: 24: 307–311. © 2010 John Wiley & Sons A/S.Abstract:  Ischemia‐reperfusion injury (IRI) involving allograft transplantation and procured organs may in part be induced by stimulation of a newly described innate pro‐inflammatory immune system (i.e., NALP‐3‐inflammasome), which can cause secretion of IL‐1β and subsequent neutrophilic inflammation. Ischemia and/or hypoxia/anoxia can induce anaerobic metabolism with metabolic acidosis and subsequent development of danger signals known to stimulate IL‐1β secretion from the NALP‐3 inflammasome. Observations from IRI studies and hereditary auto‐inflammatory syndromes with NALP‐3 inflammasome mutations suggest that IL‐1β secretion can induce robust neutrophilic inflammation that is responsive to IL‐1β targeted therapy. Based on these observations and data from transplantation studies, it may be timely to consider commercially available IL‐1β targeted biologic therapy to improve allograft tolerance and viability of procured organs.
Systematic evaluation of the highest current threshold for regional anaesthesia in a porcine model
Authors: STEINFELDT T. , GRAF J. , VASSILIOU T. , NIMPHIUS W. , STURM K. , KILL C. , WIESMANN T. , WULF H. , MÜLLER H.‐H. 
Published: April 2010

Background: The purpose of this study was to determine systematically the highest minimal stimulation current threshold for regional anaesthesia in pigs.Methods: In an established pig model for regional anaesthesia, needle placements applying electric nerve stimulation were performed. The primary outcome was the frequency of close needle to nerve placements as assessed by resin injectates and subsequent anatomical evaluation. Following a statistical model (continual reassessment method), the applied output currents were selected to limit the necessary number of punctures, while providing guidance towards the highest output current range.Results: Altogether 186 punctures were performed in 11 pigs. Within the range of 0.3–1.4 mA, no distant needle to nerve placement was found. In the range of 1.5–4.1 mA, 43 distant needle to nerve placements occurred. The range of 1.2–1.4 mA was the highest interval that resulted in a close needle to nerve placement rate of ≥95%.Conclusions: In the range of 0.3–1.4 mA, all resin deposition was found to be adjacent to nerve epineurium. The application of minimal current intensities up to 1.4 mA does not obviously lead to a reduction of epineural injectate contacts in pigs. These findings suggest that stimulation current thresholds up to 1.4 mA result in equivalent needle tip localisation in pigs.
Nest‐Site Defense by Competing Honey Bee Swarms During House‐Hunting
Authors: Rangel Juliana , Griffin Sean R. , Seeley Thomas D. 
Published: April 2010

AbstractCavity‐nesting animals must often defend their homes against intruders, especially when the availability of suitable cavities is limited. Competition for nest sites is particularly strong when multiple groups of the same species migrate synchronously to found a new home. This may be the case for honey bees during the reproductive season, because neighboring colonies often cast swarms simultaneously, leading to potential competition for high‐quality nesting cavities. To test the idea that honey bee swarms may compete for and defend potential nest sites as they search for a new home, we observed pairs of artificial swarms that were house‐hunting concurrently. Workers from one swarm in each pair carried a gene influencing body color, so that the bees from the two swarms were easily distinguished. We set up a high‐quality nest box and waited for nest‐site scouts from each swarm to explore and recruit swarm mates to it. We recorded all the interactions between competing scouts at the nest box and found that when scouts from both swarms explored the box simultaneously they behaved agonistically toward bees from the other swarm. The level of aggression depended on the number of scouts from each swarm present at the nest box. When only one to three scouts from each swarm were at the box, they rarely fought. But when the scouts from one swarm outnumbered those from the other swarm (4–20 vs. one to three bees), those in the majority advertised their presence with a buzzing behavior at the entrance opening, and started mobbing and killing those in the minority. When one swarm gained clear control of the nest box (20+ vs. zero to one bees), some of its scouts guarded the box’s entrance, preventing entry by foreign scouts. Our study exemplifies how cavity‐nesting animals may compete for and defend suitable nesting sites.
Barth and Anselm: God, Christ and the Atonement
Authors: JONES PAUL DAFYDD 
Published: April 2010

AbstractThis article considers God, Christ and the atonement in the work of Anselm and Barth. It identifies key points of agreement regarding God's self‐assigned identity and the importance of dyothelitism; it discerns a marked divergence of opinion with respect to the atonement. Anselm construes the atonement in terms of a gift that Christ offers on behalf of sinful humankind. Barth, on the other hand, presents a view of atonement that builds on his revolutionary doctrine of election. He describes the cross as an event in which sin is ‘burned up’, cancelled and overcome within the time and space of God's being.
Mothers and Fathers at Play with their Children with Down Syndrome: Influence on Child Exploratory and Symbolic Activity
Authors: De Falco Simona , Esposito Gianluca , Venuti Paola , Bornstein Marc H. 
Published: April 2010

Background  Through play children exercise their emerging mental abilities, and for their part, when in collaborative play, caregivers often adjust their behaviours to assist their children’s progress. In this study, we focused on comparisons between play of Down Syndrome (DS) children with their two parents as well as on comparisons between the two parents’ play behaviours.Method  Altogether 40 parent–child dyads participated: 20 children with DS (M age = 36.14 months) with their mothers and separately with their fathers. We coded participants’ play behaviours during child solitary and mother–child and father–child collaborative sessions.Results  Although children increased exploratory play from solitary to collaborative sessions with both parents, symbolic play increased only during joint play with fathers. Fathers displayed less symbolic and more exploratory activity compared to mothers. Mothers and fathers alike were attuned to their children, although fathers showed a higher degree of attunement.Conclusions  This study shows that maternal and paternal contributions to DS child play skills are positive but different. During collaborative play children received specific and nonoverlapping scaffolding from their two parents, and fathers’ contributions were unique.
Postnatal testis development, Sertoli cell proliferation and number of different spermatogonial types in C57BL/6J mice made transiently hypo‐ and hyperthyroidic during the neonatal period
Authors: Auharek Sarah Alves , De França Luiz Renato 
Published: April 2010

AbstractThe role of thyroid hormones in testis structure and function has been fairly well studied in laboratory rodents. However, there are no comprehensive data in the literature for mice regarding the effects of transiently induced neonatal hypo‐ and hyperthyroidism on testis and spermatogonial cell development from birth to adulthood. Our goals were to evaluate the effects of propylthiouracil (PTU) and triidothyronine (T3) on Sertoli cell proliferation/differentiation and to correlate these events with the evolution of the spermatogenic process, tubular lumen formation, blood vessel volume density, and size and number of different spermatogonial types. Although Sertoli cell maturation was accelerated or delayed, respectively, in T3‐ and PTU‐treated mice, the pace of the germ cell maturation was only slightly altered before puberty and the period of Sertoli cell proliferation was apparently not affected by the treatments. However, compared with controls, the total number of Sertoli cells per testis from 10 days of age to adulthood was significantly increased and decreased in PTU‐ and T3‐treated mice, respectively. In comparison to all other spermatogonia, type A2 was the largest cell in all ages and groups investigated. The PTU‐treated mice had a significantly increased total number of undifferentiated spermatogonia as well as volume and percentage of vessels/capillaries, probably due to the higher number of Sertoli cells, particularly at 10 days of age. Taken together, our results suggest that neonatal hypothyroidism may be a valuable tool for studying spermatogonial biology as well as a means for providing more spermatogonial stem cells that could potentially be used for spermatogonial transplantation, thereby optimizing the efficiency of this technique when young mice are used as donors.
VEGF and its role in the early development of the long bone epiphysis
Authors: Allerstorfer Doris , Longato Stefano , Schwarzer Christoph , Fischer‐Colbrie Reiner , Hayman Alison R. , Blumer Michael J. F. 
Published: April 2010

AbstractIn long bones of murine species, undisturbed development of the epiphysis depends on the generation of vascularized cartilage canals shortly after birth. Despite its importance, it is still under discussion how this event is exactly regulated. It was suggested previously that, following increased hypoxia in the epiphyseal core, angiogenic factors are expressed and hence stimulate the ingrowth of the vascularized canals. In the present study, we tested this model and examined the spatio‐temporal distribution of two angiogenic molecules during early development in mice. In addition, we investigated the onset of cartilage hypertrophy and mineralization. Our results provide evidence that the vascular endothelial growth factor is expressed in the epiphyseal resting cartilage prior to the moment of canal formation and is continuously expressed until the establishment of a large secondary ossification centre. Interestingly, we found no expression of secretoneurin before the establishment of the canals although this factor attracts blood vessels under hypoxic conditions. Epiphyseal development further involves maturation of the resting chondrocytes into hypertrophic ones, associated with the mineralization of the cartilage matrix and eventual death of the latter cells. Our results suggest that vascular endothelial growth factor is the critical molecule for the generation of the epiphyseal vascular network in mice long bones. Secretoneurin, however, does not appear to be a player in this event. Hypertrophic chondrocytes undergo cell death by a mechanism interpreted as chondroptosis.
Inner ear of a notoungulate placental mammal: anatomical description and examination of potentially phylogenetically informative characters
Authors: Macrini Thomas E. , Flynn John J. , Croft Darin A. , Wyss André R. 
Published: April 2010

AbstractWe provide the first detailed description of the inner ear of a notoungulate, an extinct group of endemic South American placental mammals, based on a three‐dimensional reconstruction extracted from CT imagery of a skull of Notostylops murinus. This description provides new anatomical data that should prove to be phylogenetically informative, an especially significant aspect of this research given that both the interrelationships of notoungulates and the position of Notoungulata within Placentalia are still unresolved. We also assess the locomotor agility of Notostylops based on measurements of the semicircular canals. This is the best available data on the locomotion of a notostylopid because significant postcranial remains for this group have not been described. The cochlea of Notostylops has 2.25 turns, and the stapedial ratio is 1.6. The stapedial ratio is one of the lowest recorded for a eutherian, which typically have ratios greater than 1.8. The fenestra cochleae is located posterior to the fenestra vestibuli, a condition previously only reported for some stem primates. The separation of the saccule and utricule of the vestibule is visible on the digital endocast of the bony labyrinth. The posterior arm of the LSC and the inferior arm of the PSC are confluent, but these do not form a secondary crus commune, and the phylogenetic or functional significance of this confluence is unclear at this time. Locomotor agility scores for Notostylops suggest a medium or ‘average’ degree of agility of motion compared to extant mammals. In terms of its locomotion, we tentatively predict that Notostylops was a generalized terrestrial mammal, with cursorial tendencies, based on its agility scores and the range of locomotor patterns inferred from postcranial analyses of other notoungulates.
Neutral endopeptidase inhibition: could it have a role in the treatment of female sexual arousal disorder?
Authors: Angulo Javier 
Published: April 2010

Female sexual arousal disorder (FSAD) is the inability to attain or maintain an adequate lubrication‐swelling response of sexual excitement. The potentiation of vascular responses leading to increased blood flow in clitoris and vagina has represented the main focus in the pharmacological treatment of FSAD, including the evaluation of the type 5 phosphodiesterase (PDE5) inhibitors. However, due to a lack of clear efficacy, there is no approved pharmacotherapy for FSAD to date. In the present issue of the British Journal of Pharmacology, Wayman et al. show that the administration by intravenous or intravaginal routes of a novel neutral endopeptidase inhibitor, UK‐414,445, results in enhanced genital blood flow responses to pelvic nerve stimulation in female rabbits, without significantly affecting blood pressure. Neutral endopeptidase inhibition, by preserving vasoactive peptides such as vasoactive intestinal polypeptide, raises the possibility of a new pharmacological approach to the treatment of FSAD.This article is a commentary on Wayman et al., pp. 51–59 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2010.00691.x
Histamine inhibits adhesion molecule expression in human monocytes, induced by advanced glycation end products, during the mixed lymphocyte reaction
Authors: Zhang J , Takahashi HK , Liu K , Wake H , Liu R , Sadamori H , Matsuda H , Yagi T , Yoshino T , Mori S , Nishibori M 
Published: April 2010

Background and purpose:  Post‐transplant diabetes mellitus is a frequent complication among transplant recipients. Ligation of advanced glycation end products (AGEs) with their receptor on monocytes/macrophages plays important roles in the genesis of diabetic complications. The enhancement of adhesion molecule expression on monocytes/macrophages activates T‐cells, reducing allograft survival. Out of four distinct AGE subtypes (AGE‐2, AGE‐3, AGE‐4 and AGE‐5), only AGE‐2 and AGE‐3 induced expression of intercellular adhesion molecules (ICAMs), output of cytokines and proliferation of lymphocytes, during the mixed lymphocyte reaction (MLR). Here we have assessed the role of histamine in the actions of AGEs during the MLR.Experimental approach:  Human peripheral blood cells were used in these experiments. Flow cytometry was used to examine the expression of the ICAM‐1, B7.1, B7.2 and CD40. Production of the cytokine interferon‐γ, and levels of cAMP were determined by elisa. Lymphocyte proliferation was determined by [3H]‐thymidine uptake.Key results:  Histamine concentration dependently inhibited the action of AGE‐2 and AGE‐3. The actions of histamine were antagonized by an H2‐receptor antagonist, famotidine, and mimicked by H2/H4‐receptor agonists, dimaprit and 4‐methylhistamine. The effects of histamine were reversed by a protein kinase A (PKA) inhibitor, H89, and mimicked by dibutyryl cAMP and an adenylate cyclase activator, forskolin.Conclusions and implications:  Histamine down‐regulated AGE‐2‐ and AGE‐3‐induced expression of adhesion molecules, cytokine production and lymphocyte proliferation via histamine H2 receptors and the cAMP/PKA pathway.
Differences in the expression of endogenous efflux transporters inMDR1‐transfected versus wildtype cell lines affect P‐glycoprotein mediated drug transport
Authors: Kuteykin‐Teplyakov Konstantin , Luna‐Tortós Carlos , Ambroziak Kamila , Löscher Wolfgang 
Published: April 2010

Background and purpose: P‐glycoprotein (Pgp) efflux assays are widely used to identify Pgp substrates. The kidney cell lines Madin‐Darby canine kidney (MDCK)‐II and LLC‐PK1, transfected with humanMDR1(ABCB1) are used to provide recombinant models of drug transport. Endogenous transporters in these cells may contribute to the activities of recombinant transporters, so that drug transport inMDR1‐transfected cells is often corrected for the transport obtained in parental (wildtype) cells. However, expression of endogenous transporters may vary between transfected and wildtype cells, so that this correction may cause erroneous data. Here, we have measured the expression of endogenous efflux transporters in transfected and wildtype MDCK‐II or LLC cells and the consequences for Pgp‐mediated drug transport.Experimental approach: Using quantitative real‐time RT‐PCR, we determined the expression of endogenousMdr1mRNA and other efflux transporters in wildtype andMDR1‐transfected MDCK‐II and LLC cells. Transcellular transport was measured with the test substrate vinblastine.Key results: InMDR1‐transfected MDCK cells, expression of endogenous (canine)Mdr1andMrp2(Abcc2) mRNA was markedly lower than in wildtype cells, whereasMDR1‐transfected LLC cells exhibited comparableMdr1but strikingly higherMrp2mRNA levels than wildtype cells. As a consequence, transport of vinblastine by human Pgp in efflux experiments was markedly underestimated when transport inMDR1‐transfected MDCK cells was corrected for transport obtained in wildtype cells. This problem did not occur in LLC cells.Conclusions and implications: Differences in the expression of endogenous efflux transporters between transfected and wildtype MDCK cells provide a potential bias forin vitrostudies on Pgp‐mediated drug transport.