bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of inducible nitric oxide synthase expression in ammonia‐exposed cultured astrocytes is coupled to increased arginine transport by upregulated y+LAT2 transporter
Authors: Zielińska Magdalena , Milewski Krzysztof , Skowrońska Marta , Gajos Anna , Ziemińska Elżbieta , Beręsewicz Andrzej , Albrecht Jan 
Published: October 2015

AbstractOne of the aspects of ammonia toxicity to brain cells is increased production of nitric oxide (NO) byNOsynthases (NOSs). Previously we showed that ammonia increases arginine (Arg) uptake in cultured rat cortical astrocytes specificallyviay+L amino acid transport system, by activation of its member, a heteromeric y+LAT2 transporter. Here, we tested the hypothesis that up‐regulation of y+LAT2 underlies ammonia‐dependent increase ofNOproductionviainducible NOS (iNOS) induction, and protein nitration. Treatment of rat cortical astrocytes for 48 with 5 mM ammonium chloride (‘ammonia’) (i) increased the y+L‐mediated Arg uptake, (ii) raised the expression of iNOS and endothelial NOS (eNOS), (iii) stimulatedNOproduction, as manifested by increased nitrite+nitrate (Griess) and/or nitrite alone (chemiluminescence), and consequently, (iv) evoked nitration of tyrosine residues of proteins in astrocytes. Except for the increase of eNOS, all the above described effects of ammonia were abrogated by pre‐treatment of astrocytes with either siRNAsilencing of the Slc7a6 gene coding for y+LAT2 protein, or antibody to y+LAT2, indicating their strict coupling to y+LAT2 activity. Moreover, induction of y+LAT2 expression by ammonia was sensitive to Nf‐κB inhibitor,BAY11‐7085, linking y+LAT2 upregulation to the Nf‐κB activation in this experimental setting as reported earlier and here confirmed. Importantly, ammonia did not affect y+LAT2 expression nor y+L‐mediated Arg uptake activity in the cultured cerebellar neurons, suggesting astroglia‐specificity of the above described mechanism. The described coupling of up‐regulation of y+LAT2 transporter with iNOS in ammonia‐exposed astrocytes may be considered as a mechanism to ensureNOsupply for protein nitration.imageAmmonia (NH4+) increases the expression and activity of the L‐arginine (Arg) transporter (Arg/neutral amino acids [NAA] exchanger) y+LAT2 in cultured rat cortical astrocytes by a mechanism involving activation (nuclear translocation) of the transcription factor nuclear factor‐Nuclear factor‐κB (Nf‐κB‐p65). Up‐regulation of y+LAT2 transporter is coupled with increased inducible nitric oxide synthase (iNOS) expression, which leads to increase nitric oxide (NO) synthesis and protein nitration.
Progesterone receptor signalling in retinal photoreceptor neuroprotection
Authors: Wyse Jackson Alice C. , Roche Sarah L. , Byrne Ashleigh M. , Ruiz‐Lopez Ana M. , Cotter Thomas G. 
Published: October 2015

Abstract‘Norgestrel’, a synthetic form of the female hormone progesterone has been identified as potential drug candidate for the treatment of the degenerative eye disease retinitis pigmentosa. However, to date, no work has looked at the compound's specific cellular target. Therefore, this study aimed to identify the receptor target of Norgestrel and begin to examine its potential mechanism of action in the retina. In this work, we identify and characterize the expression of progesterone receptors present in the C57 wild type and rd10 mouse model of retinitis pigmentosa. Classical progesterone receptors A and B (PR A/B), progesterone receptor membrane components 1 and 2 (PGRMC1, PGRMC2) and membrane progesterone receptors α, β and γ were found to be expressed. All receptors excluding PR A/B were also found in the 661W photoreceptor cell line. PGRMC1 is a key regulator of apoptosis and its expression is up‐regulated in the degenerating rd10 mouse retina. Activated by Norgestrel through nuclear trafficking, siRNA knock down of PGRMC1 abrogated the protective properties of Norgestrel on damaged photoreceptors. Furthermore, specific inhibition of PGRMC1 by AG205 blocked Norgestrel‐induced protection in stressed retinal explants. Therefore, we conclude that PGRMC1 is crucial to the neuroprotective effects of Norgestrel on stressed photoreceptors.
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The synthetic progestin ‘Norgestrel’ has been identified as a potential therapeutic for the treatment of Retinitis Pigmentosa, a degenerative eye disease. However, the mechanism behind this neuroprotection is currently unknown. In this work, we identify ‘Progesterone Receptor Membrane Component 1’ as the major progesterone receptor eliciting the protective effects of Norgestrel, both in vitro and ex vivo. This furthers our understanding of Norgestrel's molecular mechanism, which we hope will help bring Norgestrel one step closer to the clinic.
The Effect of Fingolimod on Conversion of Acute Gadolinium‐Enhancing Lesions to Chronic T1 Hypointensities in Multiple Sclerosis
Authors: Oommen Vinit V. , Tauhid Shahamat , Healy Brian C. , Chua Alicia S. , Malik Muhammad T. , Diaz‐Cruz Camilo , Dupuy Sheena L. , Weiner Howard L. , Chitnis Tanuja , Bakshi Rohit 
Published: October 2015

ABSTRACTBACKGROUNDBrain lesions converting to chronic T1 hypointensities (“chronic black holes” [CBH]), indicate severe tissue destruction (axonal loss and irreversible demyelination) in multiple sclerosis (MS). Two mechanisms by which fingolimod could limit MS lesion evolution include sequestration of lymphocytes in the periphery or direct neuroprotective effects. We investigated the effect of fingolimod on the evolution of acute gadolinium‐enhancing (Gd+) brain lesions to CBH in patients with MS.METHODSThis was a retrospective nonrandomized comparison of patients with Gd+ brain lesions at the time of starting oral fingolimod [.5 mg/day,n= 26, age (mean ± SD) 39.2 ± 10.6 years, Expanded Disability Status Scale (EDSS) score ‐ median (range): 1.75 (0, 6.5)] to those on no therapy [n= 30, age 41.7 ± 9.3 years; EDSS 1.0 (0, 6)]. Each lesion was classified by whether it converted to a CBH in the year following treatment.RESULTSIn the fingolimod group, 99 Gd+ baseline lesions (mean ± SD, range: 3.8 ± 5.1; 1, 21 per patient) were identified of which 25 (25%) evolved to CBH (1.0 ± 2.0; 0, 10 per patient). The untreated group had 62 baseline Gd+ lesions (2.1 ± 2.3; 1, 13), 26 (42%) of which evolved to CBH (.9 ± 1.4; 0, 7) (P= .063). Thirteen patients (50%) receiving fingolimod and 17 untreated patients (57%) developed CBH (P= .79).CONCLUSIONThis pilot study shows a trend of fingolimod on reducing the conversion rate from acute to chronic destructive MS lesions. Such an effect awaits verification in larger randomized prospective studies.
Different Intraorbital Implant Situations and Ocular Prosthetic Rehabilitation
Authors: Aggarwal Himanshi , Kumar Pradeep , Eachempati Prashanti , Alvi Habib A. 
Published: October 2015

AbstractEnucleation is the removal of the entire globe of the eye and a portion of the optic nerve, while evisceration involves the removal of the contents of the globe leaving the sclera, extraocular muscles, and optic nerve. Following enucleation or evisceration, intraorbital implants are routinely placed to enhance the prosthetic outcome in addition to restoring the lost orbital volume. Current practice employs intraorbital implants made of nonporous silicone, hydroxyapatite, or porous polyethylene. Intraorbital implant selection and placement, being a highly demanding procedure in terms of knowledge, skill, and expertise, may be associated with a multiplicity of technical and surgical errors. Complications are usually minimal with these implants, but they do occur. The literature reveals many articles related to intraorbital implants, their benefits, and complications; however, the literature regarding the effect of various intraorbital implant situations on the subsequent prosthetic rehabilitation is markedly scarce. Moreover, the need for interdisciplinary surgical and prosthetic interventions required for successful rehabilitation in cases of compromised implant situations has been underemphasized. Hence, this review aimed to evaluate the effect of different intraorbital implant situations on ocular rehabilitation and the required interdisciplinary surgical and prosthetic treatment approach for rehabilitation of enucleated/eviscerated sockets with compromised implant situations, to provide a critical appraisal, and to present a simplified management strategy.
Lower levels of human milk adiponectin predict offspring weight for age: a study in a lean population of Filipinos
Authors: Anderson Justine , McKinley Kassielle , Onugha Jason , Duazo Paulita , Chernoff Meytal , Quinn Elizabeth A. 
Published: October 2015

AbstractPrior studies have reported a significant, inverse association between adiponectin in human milk and offspring growth velocity. Less is known about this association in populations characterised by a loss of weight for age z‐scores (WAZs) in early life. We investigated the association between maternal body composition and milk adiponectin in a sample of Filipino mothers. We then tested for an association between milk adiponectin and size for age in their infants. A total of 117 Filipino mothers nursing infants from 0 to 24 months were recruited from Cebu, Philippines. Anthropometrics, interviews and milk samples were collected and analysed using standard protocols. Mean milk adiponectin in this sample was 7.47 ± 5.75 ng mL−1. Mean infant WAZ and weight for length (WLZ) decreased with age. Maternal body composition was not associated with milk adiponectin content. Milk adiponectin had a significant, positive association with infant WAZ and WLZ. Prior reports have found an inverse association between milk adiponectin and infant WAZ. Here, we report that in lean populations with lower milk adiponectin, there is a positive association with infant WAZ, possibly reflecting pleiotropic biological functions of adiponectin for post‐natal growth. This study increases the understanding of normal biological variation in milk adiponectin and the consequences of low levels of milk adiponectin for offspring growth.
Motility in cyanobacteria: polysaccharide tracks and Type IV pilus motors
Authors: Wilde Annegret , Mullineaux Conrad W. 
Published: October 2015

SummaryMotility in cyanobacteria is useful for purposes that range from seeking out favourable light environments to establishing symbioses with plants and fungi. No known cyanobacterium is equipped with flagella, but a diverse range of species is able to ‘glide’ or ‘twitch’ across surfaces. Cyanobacteria with this capacity range from unicellular species to complex filamentous forms, including species such as Nostoc punctiforme, which can generate specialised motile filaments called hormogonia. Recent work on the model unicellular cyanobacterium Synechocystis sp. PCC 6803 has shown that its means of propulsion has much in common with the twitching motility of heterotrophs such as Pseudomonas and Myxococcus. Movement depends on Type IV pili, which are extended, adhere to the substrate and then retract to pull the cell across the surface. Previous work on filamentous cyanobacteria suggested a very different mechanism, with movement powered by the directional extrusion of polysaccharide from pores close to the cell junctions. Now a new report by Khayatan and colleagues in this issue of Molecular Microbiology suggests that the motility of Nostoc hormogonia has much more in common with Synechocystis than was previously thought. In both cases, polysaccharide secretion is important for preparing the surface, but the directional motive force comes from Type IV pili.
The EutQ and EutP proteins are novel acetate kinases involved in ethanolamine catabolism: physiological implications for the function of the ethanolamine metabolosome in Salmonella enterica
Authors: Moore Theodore C. , Escalante‐Semerena Jorge C. 
Published: October 2015

SummarySalmonella enterica catabolizes ethanolamine inside a compartment known as the metabolosome. The ethanolamine utilization (eut) operon of this bacterium encodes all functions needed for the assembly and function of this structure. To date, the roles of EutQ and EutP were not known. Herein we show that both proteins have acetate kinase activity and that EutQ is required during anoxic growth of S. enterica on ethanolamine and tetrathionate. EutP and EutQ‐dependent ATP synthesis occurred when enzymes were incubated with ADP, Mg(II) ions and acetyl‐phosphate. EutQ and EutP also synthesized acetyl‐phosphate from ATP and acetate. Although EutP had acetate kinase activity, ΔeutP strains lacked discernible phenotypes under the conditions where ΔeutQ strains displayed clear phenotypes. The kinetic parameters indicate that EutP is a faster enzyme than EutQ. Our evidence supports the conclusion that EutQ and EutP represent novel classes of acetate kinases. We propose that EutQ is necessary to drive flux through the pathway under physiological conditions, preventing a buildup of acetaldehyde. We also suggest that ATP generated by these enzymes may be used as a substrate for EutT, the ATP‐dependent corrinoid adenosyltransferase and for the EutA ethanolamine ammonia‐lyase reactivase.
The zinc cluster proteins Upc2 and Ecm22 promote filamentation in Saccharomyces cerevisiae by sterol biosynthesis‐dependent and ‐independent pathways
Authors: Woods Kelly , Höfken Thomas 
Published: October 2015

SummaryThe transition between a unicellular yeast form to multicellular filaments is crucial for budding yeast foraging and the pathogenesis of many fungal pathogens such as Candida albicans. Here, we examine the role of the related transcription factors Ecm22 and Upc2 in Saccharomyces cerevisiae filamentation. Overexpression of either ECM22 or UPC2 leads to increased filamentation, whereas cells lacking both ECM22 and UPC2 do not exhibit filamentous growth. Ecm22 and Upc2 positively control the expression of FHN1, NPR1, PRR2 and sterol biosynthesis genes. These genes all play a positive role in filamentous growth, and their expression is upregulated during filamentation in an Ecm22/Upc2‐dependent manner. Furthermore, ergosterol content increases during filamentous growth. UPC2 expression also increases during filamentation and is inhibited by the transcription factors Sut1 and Sut2. The expression of SUT1 and SUT2 in turn is under negative control of the transcription factor Ste12. We suggest that during filamentation Ste12 becomes activated and reduces SUT1/SUT2 expression levels. This would result in increased UPC2 levels and as a consequence to transcriptional activation of FHN1, NPR1, PRR2 and sterol biosynthesis genes. Higher ergosterol levels in combination with the proteins Fhn1, Npr1 and Prr2 would then mediate the transition to filamentous growth.
cyp51A gene silencing using RNA interference in azole‐resistant Aspergillus fumigatus
Authors: Mousavi Bita , Hedayati Mohammad T. , Teimoori‐Toolabi Ladan , Guillot Jacques , Alizadeh Ahad , Badali Hamid 
Published: October 2015

SummaryAn increasing number of reports have described the emergence of acquired resistance of Aspergillus fumigatus to azole compounds. The primary mechanism of resistance in clinical isolates is the mutation of the azole drug target enzyme, which is encoded by the cyp51A gene. The aim of this study was to evaluate the impact of silencing the cyp51A gene in azole‐resistant A. fumigatus isolates. A 21‐nucleotide small‐interfering RNA (siRNA) was designed based on the cDNA sequence of the A. fumigatus cyp51A gene. After silencing the cyp51A gene in germinated conidia (15, 20, 25 and 50 nM), azole‐resistant A. fumigatus was cultured on broth media and gene expression was analysed by measuring the cyp51A mRNA level using RT‐PCR assay. Hyphae were successfully transfected by siRNA and expression of the cyp51A gene was significantly reduced by siRNA at the concentration of 50 nM (P ≤ 0.05). In addition, at this siRNA concentration, the minimum inhibitory concentration of itraconazole for the treated cells was decreased, compared with that for untreated control cells, from 16 to 4 μg/ml.
Escherichia coli Urinary Infection as a Cause of Acute Hemorrhagic Edema in Infancy
Authors: Breda Luciana , Franchini Simone , Marzetti Valentina , Chiarelli Francesco 
Published: October 2015

AbstractAcute hemorrhagic edema of infancy (AHEI) is a benign leukocytoclastic small‐vessel vasculitis that affects infants, presenting with a classic clinical triad. Because of the self‐limited progression, conservative management is the most common approach. We describe a case of AHEI apparently triggered by an Escherichia coli urinary tract infection.
Hoyeraal–Hreidarsson Syndrome: An Extremely Rare Dyskeratosis Congenita Phenotype
Authors: Bakar Özgür , Işik Ugˇur , Canpolat Cengiz , Alanay Yasemin 
Published: October 2015

AbstractHoyeraal–Hreidarsson syndrome is a rare telomere biology disorder that is recognized as a severe variant of dyskeratosis congenita. We present a Libyan boy with hematologic and neurologic abnormalities with typical dermatologic manifestations of dyskeratosis congenita. Death usually occurs before the age of 4 years as a result of pancytopenia or malignant transformation of mucocutaneous lesions. The boy presented survived longer than 5 years. Early recognition and appropriate genetic counseling are crucial because of the high mortality of this genetic disorder.
Maternal Recall Error in Retrospectively Reported Time‐to‐Pregnancy: an Assessment and Bias Analysis
Authors: Radin Rose G. , Rothman Kenneth J. , Hatch Elizabeth E. , Mikkelsen Ellen M. , Sorensen Henrik T. , Riis Anders H. , Fox Matthew P. , Wise Lauren A. 
Published: October 2015

AbstractBackgroundEpidemiologic studies of fecundability often use retrospectively measured time‐to‐pregnancy (TTP), thereby introducing potential for recall error. Little is known about how recall error affects the bias and precision of the fecundability odds ratio (FOR) in such studies.MethodsUsing data from the Danish Snart‐Gravid Study (2007–12), we quantified error for TTP recalled in the first trimester of pregnancy relative to prospectively measured TTP among 421 women who enrolled at the start of their pregnancy attempt and became pregnant within 12 months. We defined recall error as retrospectively measured TTP minus prospectively measured TTP. Using linear regression, we assessed mean differences in recall error by maternal characteristics. We evaluated the resulting bias in the FOR and 95% confidence interval (CI) using simulation analyses that compared corrected and uncorrected retrospectively measured TTP values.ResultsRecall error (mean = −0.11 months, 95% CI −0.25, 0.04) was not appreciably associated with maternal age, gravidity, or recent oral contraceptive use. Women with TTP > 2 months were more likely to underestimate their TTP than women with TTP ≤ 2 months (unadjusted mean difference in error: −0.40 months, 95% CI −0.71, −0.09). FORs of recent oral contraceptive use calculated from prospectively measured, retrospectively measured, and corrected TTPs were 0.82 (95% CI 0.67, 0.99), 0.74 (95% CI 0.61, 0.90), and 0.77 (95% CI 0.62, 0.96), respectively.ConclusionsRecall error was small on average among pregnancy planners who became pregnant within 12 months. Recall error biased the FOR of recent oral contraceptive use away from the null by 10%. Quantitative bias analysis of the FOR can help researchers quantify the bias from recall error.
Comparison of Whole Ovary Cryotreatments for Fertility Preservation
Authors: Lotz L , Hauenstein T , Nichols‐Burns SM , Strissel P , Hoffmann I , Findeklee S , Dittrich R , Beckmann MW , Oppelt PG 
Published: October 2015

ContentsThe goal of this study was to compare a traditional slow‐freeze method (TF) with an open unidirectional slow freeze cooling system (UF) for whole ovary cryopreservation. Therefore, whole pig ovaries were randomly assigned to (A) fresh control, (B) traditional slow freeze (TF) or (C) unidirectional slow freeze (UF). Ovaries were perfused with 10% DMSO in Krebs‐Ringer. For TF, whole ovaries were placed in specimen jars containing 10% DMSO and placed into a specialized container for freezing filled with propan‐2‐ol. For UF, whole ovaries were placed within a specially designed container containing 10% DMSO and transferred to a specialized freezing machine (CTE 920). Histological evaluation demonstrated intact morphology of follicles in all groups; however, an overall decrease of follicle numbers in TF (46%) and UF (50%) compared to fresh control. Live/dead assay indicated significantly lower populations of live cells in both TF (60%) and UF (58%) compared to fresh tissue (74%). TUNEL assay confirmed a difference in percentage of apoptotic follicles between fresh and TF, but there was no significant difference between fresh and UF. To improve the structural and functional integrity of whole ovaries, further investigation, especially into directional freezing, is needed. Whole ovary cryopreservation could provide opportunities for women facing fertility loss due to chemo‐ or radiotherapy treatment.
Fertility in Adult Bitches Previously Treated with a 4.7 mg Subcutaneous Deslorelin Implant
Authors: Borges P , Fontaine E , Maenhoudt C , Payan‐Carreira R , Santos N , Leblond E , Fontaine C , Fontbonne A 
Published: October 2015

ContentThe absence of fertility problems in male dogs after a single treatment with deslorelin acetate (Suprelorin®) is well acknowledged. However, reports on the application of deslorelin in the bitch and information concerning fertility after implant treatment are still limited. In this retrospective study, data concerning induced and spontaneous oestruses of 39 bitches from 17 breeds, treated with deslorelin acetate implants (4.7 mg Suprelorin®, Virbac, France), were retrieved to assess post‐treatment fertility (ovulation rate, pregnancy rate and litter size). Animals were grouped according to treatment characteristics: group 1 (Gr1) – females submitted to oestrus induction, showing natural oestruses afterwards (n = 19); group 2 (Gr2) – females re‐implanted with 4.7 mg deslorelin acetate to re‐induce oestrus, showing subsequent spontaneous post‐implant oestruses (n = 7); and group 3 (Gr3) – females submitted to a 4.7 mg deslorelin acetate implant for oestrus suppression, evaluated at subsequent spontaneous post‐implant oestruses (n = 13). Comparison of fertility traits between induced and post‐treatment spontaneous oestruses in Gr1 and Gr2 (short treatments), or between spontaneous oestruses after long‐treatment schedules (Gr 3) revealed a slightly better performance in spontaneous cycles compared with induced cycles: ovulation rate post‐treatment was 97.1%, 94.1% and 94.4% and the pregnancy rate post‐treatment was 91.2%, 88.9% and 84.6% for groups 1, 2 and 3, respectively. Nevertheless, fertility in induced and post‐treatment oestruses was considered normal. Moreover, the individual litter size did not differ within groups between induced and spontaneous cycles. From these findings, we concluded that treatment with 4.7 mg deslorelin implants did not compromise the bitches' fertility in subsequent oestruses.