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1.
J Dairy Sci ; 106(7): 4759-4772, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37268567

ABSTRACT

The increased average Irish dairy herd size in a post-quota environment has put heightened pressure on grazing infrastructure. In a rotational grazing system, grazing infrastructure consists of the paddock system, which delineates the grazing areas into appropriately sized grazing parcels, and the roadway network, which connects these paddocks to the milking parlor. Where herd size has increased without corresponding adaptations to the infrastructure, farm management and roadway network performance has been affected. The links between suboptimal grazing infrastructure and roadway network efficiency are poorly understood and not widely documented. The aims of this study were to (1) analyze the effect of herd expansion and paddock size on pasture allocations per paddock, (2) identify the factors that affect the total distance walked per year, and (3) create a metric to compare the efficiency of roadway networks across farms of varying grazing platforms. A sample population of 135 Irish dairy farms with a median herd size of 150 cows was used for this analysis. Herds were split into the following 5 categories: <100 cows, 100 to 149 cows, 150 to 199 cows, 200 to 249 cows, and ≥250 cows. Herds with ≥250 cows had a greater number of paddocks per farm and rotated around the grazing paddocks more frequently, with 46% of paddocks only suitable for 12 h allocations relative to herd size, compared with just 10% to 27% of paddocks for herds with <100 cows to herds with 200-249 cows. When predicting the total distance walked per year on each study farm, the mean distance from a paddock to the milking parlor was the strongest indicator (R2 = 0.8247). Other metrics, such as herd size, have failed to account for the location of the milking parlor relative to the grazing platform. The creation of the relative mean distance from a paddock to milking parlor (RMDMP) metric allowed the calculation of a farm's roadway network efficiency for moving the herd between paddocks and the milking parlor. The analyzed farms increased their efficiency in terms of RMDMP (0.34-40.74%) as they increased herd size post quota. However, the position of new additional paddocks relative to the milking parlor substantially affected their RMDMP.


Subject(s)
Dairying , Milk , Female , Cattle , Animals , Farms , Walking , Adaptation, Physiological , Lactation
2.
Radiat Prot Dosimetry ; 198(8): 441-447, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35640248

ABSTRACT

This study investigated the effects of cone-beam computed tomography (CBCT) guidance in trans-arterial chemoembolisation (TACE) procedures on the number of digital subtraction angiography (DSA) runs acquired and total patient radiation exposure in patients with hepatocellular carcinoma (HCC). A retrospective, analytical cross-sectional, single institution, study was conducted. Dose data were compared across the control (DSA guidance alone) and study (DSA and CBCT guidance) groups. A total of 122 procedures were included within the study. There was a significant reduction in the number of DSA runs (3 vs 5, p < 0.001) and DSA air kerma-area product (PKA) (3077.3 vs 4276.6 µGym2, p = 0.042) for the study group when compared to the control group. Total procedural PKA and total procedural reference air kerma (Ka,r) were shown to be 50 and 73% higher, respectively, for the study group when compared to the control group. CBCT imaging guidance does reduce the number of DSA runs and DSA PKA required to complete the TACE procedure for patients diagnosed with HCC; however, a substantial increase in total procedural PKA is to be expected and it is thus important that this increased dose is carefully considered and justified.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Radiation Exposure , Angiography, Digital Subtraction/methods , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Cone-Beam Computed Tomography/methods , Cross-Sectional Studies , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Retrospective Studies
4.
Fungal Syst Evol ; 2: 45-56, 2018 Dec.
Article in English | MEDLINE | ID: mdl-32467887

ABSTRACT

Caliciopsis pleomorpha sp. nov. is described from a severe stem canker disease of cultivated Eucalyptus cladocalyx 'Nana' (dwarf sugar gum) in Australia. The fungus is a pleomorphic ascomycete (Coryneliales), with pycnidial (pleurophoma-like) and hyphomycetous (phaeoacremonium-like) morphs, and differs in these respects and in ITS sequences from other Caliciopsis spp. The fungus was also found associated with cankers on other Eucalyptus species growing in native habitats, and was successfully inoculated under glasshouse conditions into a wide range of Eucalyptus species on which it caused cankers of varying severity.

5.
Int. j. morphol ; 35(1): 212-218, Mar. 2017. ilus
Article in English | LILACS | ID: biblio-840957

ABSTRACT

The present paper describes the ultrastructural characteristics of the bulbo-urethral gland (Cowper' glands) of the Indian fruit bat, R. leschenaulti during sexually inactive-breeding cycle. Cyclic histological changes during the seasonal breeding quiescence cycle are not well marked. There are no marked differences. The ultrastructural characteristic of the secretory epithelial cells of Bulbo-Uretrhal Gland gland have been studied during different phases of reproductive cycle. The secretory epithelial cells are characterized by the well-developed rough endoplasmic reticulum, extensive developed complexus golgiensis (Golgi apparatus) and mitochondria. Mitochondria with lamellate cristae are dispersed in the cytoplasm. Three different types of secretory granules can be identified on the basis of electron density. These granules are not of different types but they represent the different stages of granule maturation. The secretory products of bulbo-urethral gland of bat are released into lumen both by apocrine and merocrine modes. The functional significance of the secretions of the bulbo-urethral glands in reproduction is discussed.


El presente trabajo describe las características ultraestructurales de las glándulas bulbouretrales (glándulas de Cowper) del murciélago de la fruta de la India, R. leschenaulti durante el ciclo inactivo de reproducción sexual. Los cambios histológicos cíclicos durante el ciclo de quiescencia estacional de la cría no están bien determinados. No hay diferencias marcadas. La característica ultra estructural de las células epiteliales secretoras de la glándula bulbouretral ha sido estudiada durante diferentes fases del ciclo reproductivo. Las células epiteliales secretoras se caracterizan por un retículo endoplasmático rugoso bien desarrollado, el complexus golgiensis (complejo de Golgi) y mitocondrias desarrollados extensamente. Las mitocondrias con crestas lamelares se encontraron dispersas en el citoplasma. Se pueden identificar tres tipos diferentes de gránulos secretores en base a la densidad de electrones. Estos gránulos no son de tipos diferentes, sino que representan las diferentes etapas de maduración del gránulo. Los productos secretores de las glándulas bulbouretrales de murciélagos son liberados en el lumen tanto por modos apócrinos como merócrinos. Se discute la importancia funcional de las secreciones de la glándula bulbouretral en la reproducción.


Subject(s)
Animals , Bulbourethral Glands/ultrastructure , Chiroptera/anatomy & histology , Epithelial Cells/ultrastructure , Acinar Cells/ultrastructure , Bulbourethral Glands/metabolism , Reproduction
6.
Mol Psychiatry ; 21(2): 205-15, 2016 Feb.
Article in English | MEDLINE | ID: mdl-25869802

ABSTRACT

Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP) suppression of PPI in animals has been studied to elucidate the pathological elements of schizophrenia. However, the molecular mechanisms underlying PCP treatment or PPI in the brain are still poorly understood. In this study, quantitative phosphoproteomic analysis was performed on the prefrontal cortex from rats that were subjected to PPI after being systemically injected with PCP or saline. PCP downregulated phosphorylation events were significantly enriched in proteins associated with long-term potentiation (LTP). Importantly, this data set identifies functionally novel phosphorylation sites on known LTP-associated signaling molecules. In addition, mutagenesis of a significantly altered phosphorylation site on xCT (SLC7A11), the light chain of system xc-, the cystine/glutamate antiporter, suggests that PCP also regulates the activity of this protein. Finally, new insights were also derived on PPI signaling independent of PCP treatment. This is the first quantitative phosphorylation proteomic analysis providing new molecular insights into sensorimotor gating.


Subject(s)
Phencyclidine/therapeutic use , Prefrontal Cortex/metabolism , Prepulse Inhibition/drug effects , Acoustic Stimulation , Animals , Disease Models, Animal , Long-Term Potentiation/drug effects , Male , Phosphorylation , Rats , Rats, Sprague-Dawley , Reflex, Startle/drug effects , Schizophrenia/metabolism , Sensory Gating/drug effects , Signal Transduction/drug effects
7.
Mol Psychiatry ; 21(3): 426-36, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26055422

ABSTRACT

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder of unknown etiology, but very likely resulting from both genetic and environmental factors. There is good evidence for immune system dysregulation in individuals with ASD. However, the contribution of insults such as dietary factors that can also activate the immune system have not been explored in the context of ASD. In this paper, we show that the dietary glycemic index has a significant impact on the ASD phenotype. By using BTBR mice, an inbred strain that displays behavioral traits that reflect the diagnostic symptoms of human ASD, we found that the diet modulates plasma metabolites, neuroinflammation and brain markers of neurogenesis in a manner that is highly reflective of ASD in humans. Overall, the manuscript supports the idea that ASD results from gene-environment interactions and that in the presence of a genetic predisposition to ASD, diet can make a large difference in the expression of the condition.


Subject(s)
Autism Spectrum Disorder/complications , Autism Spectrum Disorder/metabolism , Behavioral Symptoms/etiology , Glycemic Index , Animals , Autism Spectrum Disorder/genetics , C-Reactive Protein/metabolism , Calcium-Binding Proteins/metabolism , Carrier Proteins/genetics , Carrier Proteins/metabolism , Disease Models, Animal , Doublecortin Domain Proteins , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Gliosis/etiology , Grooming/physiology , Homer Scaffolding Proteins , Humans , Inositol 1,4,5-Trisphosphate Receptors/genetics , Interpersonal Relations , Maze Learning/classification , Maze Learning/drug effects , Maze Learning/physiology , Mice , Mice, Transgenic , Microfilament Proteins/metabolism , Microtubule-Associated Proteins/metabolism , Mutation/genetics , Nerve Tissue Proteins/metabolism , Neuropeptides/metabolism , Oxidoreductases/metabolism , ras GTPase-Activating Proteins/metabolism
8.
J Microsc Ultrastruct ; 4(3): 156-161, 2016.
Article in English | MEDLINE | ID: mdl-30023222

ABSTRACT

The present paper describes the ultrastructural characteristics of the Cowper' glands of the Indian fruit bat, Rousettus leschenaulti during its sexually inactive-breeding cycle. The functional significance of the secretions of the Cowper's gland in reproduction is discussed. In Rousettus, Cowper's glands are small, pear-shaped, bilaterally symmetrical and are situated on either side of the base of the penis. Each lobule is made up of secretory acini lined by columnar or pyramidal cells. Ultrastructurally, the secretory epithelial cells are characterized by well-developed rough endoplasmic reticulum, extensively developed Golgi complex, and mitochondria. Three different types of secretory granules can be identified on the basis of electron density. These granules represent the different stages of granule maturation. The secretory products are released into the lumen both by apocrine and merocrine modes. The secretory material synthesized by the Cowper' gland may be involved in various male reproductive processes of this species of bat.

9.
Free Radic Biol Med ; 89: 8-19, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26165190

ABSTRACT

Methylglyoxal (MGO) is a major glycating agent that reacts with basic residues of proteins and promotes the formation of advanced glycation end products (AGEs) which are believed to play key roles in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. Here, we examined the effects of MGO on immortalized mouse hippocampal HT22 nerve cells. The endpoints analyzed were MGO and thiol status, the glyoxalase system, comprising glyoxalase 1 and 2 (GLO1/2), and the cytosolic and mitochondrial Trx/TrxR systems, as well as nuclear Nrf2 and its target genes. We found that nuclear Nrf2 is induced by MGO treatment in HT22 cells, as corroborated by induction of the Nrf2-controlled target genes and proteins glutamate cysteine ligase and heme oxygenase 1. Nrf2 knockdown prevented MGO-dependent induction of glutamate cysteine ligase and heme oxygenase 1. The cystine/glutamate antiporter, system xc(-), which is also controlled by Nrf2, was also induced. The increased cystine import (system xc(-)) activity and GCL expression promoted GSH synthesis, leading to increased levels of GSH. The data indicate that MGO can act as both a foe and a friend of the glyoxalase and the Trx/TrxR systems. At low concentrations of MGO (0.3mM), GLO2 is strongly induced, but at high MGO (0.75 mM) concentrations, GLO1 is inhibited and GLO2 is downregulated. The cytosolic Trx/TrxR system is impaired by MGO, where Trx is downregulated yet TrxR is induced, but strong MGO-dependent glycation may explain the loss in TrxR activity. We propose that Nrf2 can be the unifying element to explain the observed upregulation of GSH, GCL, HO1, TrxR1, Trx2, TrxR2, and system xc(-) system activity.


Subject(s)
Alcohol Oxidoreductases/metabolism , Gene Expression Regulation/drug effects , Hippocampus/metabolism , Neurons/metabolism , Pyruvaldehyde/pharmacology , Thioredoxin Reductase 1/metabolism , Thioredoxins/metabolism , Alcohol Oxidoreductases/genetics , Animals , Apoptosis , Blotting, Western , Cell Proliferation , Cells, Cultured , Glutathione/metabolism , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Hippocampus/cytology , Hippocampus/drug effects , Immunoprecipitation , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Neurons/cytology , Neurons/drug effects , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Thioredoxin Reductase 1/genetics , Thioredoxins/genetics
11.
Bone Joint Res ; 3(5): 150-4, 2014 May.
Article in English | MEDLINE | ID: mdl-24842931

ABSTRACT

OBJECTIVES: Metal-on-metal hip resurfacing (MOMHR) is available as an alternative option for younger, more active patients. There are failure modes that are unique to MOMHR, which include loosening of the femoral head and fractures of the femoral neck. Previous studies have speculated that changes in the vascularity of the femoral head may contribute to these failure modes. This study compares the survivorship between the standard posterior approach (SPA) and modified posterior approach (MPA) in MOMHR. METHODS: A retrospective clinical outcomes study was performed examining 351 hips (279 male, 72 female) replaced with Birmingham Hip Resurfacing (BHR, Smith and Nephew, Memphis, Tennessee) in 313 patients with a pre-operative diagnosis of osteoarthritis. The mean follow-up period for the SPA group was 2.8 years (0.1 to 6.1) and for the MPA, 2.2 years (0.03 to 5.2); this difference in follow-up period was statistically significant (p < 0.01). Survival analysis was completed using the Kaplan-Meier method. RESULTS: At four years, the Kaplan-Meier survival curve for the SPA was 97.2% and 99.4% for the MPA; this was statistically significant (log-rank; p = 0.036). There were eight failures in the SPA and two in the MPA. There was a 3.5% incidence of femoral head collapse or loosening in the SPA and 0.4% in the MPA, which represented a significant difference (p = 0.041). There was a 1.7% incidence of fractures of the femoral neck in the SPA and none in the MPA (p = 0.108). CONCLUSION: This study found a significant difference in survivorship at four years between the SPA and the MPA (p = 0.036). The clinical outcomes of this study suggest that preserving the vascularity of the femoral neck by using the MPA results in fewer vascular-related failures in MOMHRs. Cite this article: Bone Joint Res 2014;3:150-4.

12.
Nature ; 497(7451): 598-602, 2013 May 30.
Article in English | MEDLINE | ID: mdl-23676673

ABSTRACT

Electrons moving through a spatially periodic lattice potential develop a quantized energy spectrum consisting of discrete Bloch bands. In two dimensions, electrons moving through a magnetic field also develop a quantized energy spectrum, consisting of highly degenerate Landau energy levels. When subject to both a magnetic field and a periodic electrostatic potential, two-dimensional systems of electrons exhibit a self-similar recursive energy spectrum. Known as Hofstadter's butterfly, this complex spectrum results from an interplay between the characteristic lengths associated with the two quantizing fields, and is one of the first quantum fractals discovered in physics. In the decades since its prediction, experimental attempts to study this effect have been limited by difficulties in reconciling the two length scales. Typical atomic lattices (with periodicities of less than one nanometre) require unfeasibly large magnetic fields to reach the commensurability condition, and in artificially engineered structures (with periodicities greater than about 100 nanometres) the corresponding fields are too small to overcome disorder completely. Here we demonstrate that moiré superlattices arising in bilayer graphene coupled to hexagonal boron nitride provide a periodic modulation with ideal length scales of the order of ten nanometres, enabling unprecedented experimental access to the fractal spectrum. We confirm that quantum Hall features associated with the fractal gaps are described by two integer topological quantum numbers, and report evidence of their recursive structure. Observation of a Hofstadter spectrum in bilayer graphene means that it is possible to investigate emergent behaviour within a fractal energy landscape in a system with tunable internal degrees of freedom.

13.
Cell Death Dis ; 4: e470, 2013 Jan 24.
Article in English | MEDLINE | ID: mdl-23348584

ABSTRACT

The mouse hippocampal cell line HT22 is an excellent model for studying the consequences of endogenous oxidative stress. Addition of extracellular glutamate depletes the cells of glutathione (GSH) by blocking the glutamate-cystine antiporter system x(c)(-). GSH is the main antioxidant in neurons and its depletion induces a well-defined program of cell death called oxytosis, which is probably synonymous with the iron-dependent form of non-apoptotic cell death termed ferroptosis. Oxytosis is characterized by an increase of reactive oxygen species and a strong calcium influx preceding cell death. We found a significant reduction in store-operated calcium entry (SOCE) in glutamate-resistant HT22 cells caused by downregulation of the Ca(2+) channel ORAI1, but not the Ca(2+) sensors STIM1 or STIM2. Pharmacological inhibition of SOCE mimicked this protection similarly to knockdown of ORAI1 by small interfering RNAs. Long-term calcium live-cell imaging after induction of the cell death program showed a specific reduction in Ca(2+)-positive cells by ORAI1 knockdown. These results suggest that dysregulated Ca(2+) entry through ORAI1 mediates the detrimental Ca(2+) entry in programmed cell death induced by GSH depletion. As this detrimental Ca(2+) influx occurs late in the course of the cell death program, it might be amenable to therapeutic intervention in diseases caused by oxidative stress.


Subject(s)
Calcium Channels/metabolism , Calcium/metabolism , Cell Membrane/metabolism , Oxidative Stress , Animals , Antioxidants/pharmacology , Apoptosis/drug effects , Calcium Channels/chemistry , Calcium Channels/genetics , Cell Line , Glutathione/metabolism , Membrane Glycoproteins/antagonists & inhibitors , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Mice , ORAI1 Protein , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Stromal Interaction Molecule 1 , Stromal Interaction Molecule 2
14.
Neuroscience ; 208: 143-9, 2012 Apr 19.
Article in English | MEDLINE | ID: mdl-22387108

ABSTRACT

Glial fibrillary acidic protein (GFAP) is a protein widely used as a molecular marker for astroglial differentiation and mature astrocytes. We and others have shown previously that retinoic acid and specific cytokines induce the expression of GFAP in neural precursor cells by activating the phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K) phosphorylation pathway. Here, we extend our previous work and show that retinoic acid also activates specifically the c-Jun N-terminal kinase (JNK) phosphorylation pathway, which in turn inhibits GFAP expression. Our results suggest the existence of a negative self-regulatory loop in the phosphorylation pathways that regulates GFAP expression. This loop is constitutively repressed by the PI3K pathway. Our results could be relevant for disorders involving sustained GFAP overexpression in precursor cells, such as glioblastoma and Alexander disease.


Subject(s)
Glial Fibrillary Acidic Protein/biosynthesis , Glial Fibrillary Acidic Protein/genetics , JNK Mitogen-Activated Protein Kinases/physiology , Tretinoin/pharmacology , Animals , Astrocytes/drug effects , Astrocytes/metabolism , Blotting, Western , Cytokines/pharmacology , Electrophoresis, Gel, Two-Dimensional , Enzyme Activation/drug effects , Enzyme Inhibitors/pharmacology , Gene Expression Regulation/drug effects , Hippocampus/cytology , Hippocampus/drug effects , Hippocampus/metabolism , Immunohistochemistry , JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/physiology , Nerve Tissue Proteins/metabolism , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Neural Stem Cells/physiology , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation , Rats
15.
Med Hypotheses ; 78(4): 548-52, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22325990

ABSTRACT

Autism is a complex and heterogeneous neurodevelopmental disorder of unknown etiology but very likely resulting from both genetic and environmental factors. Recent estimates suggest that it affects 1 in 100-150 individuals in the US. Oxidative stress, inflammation and mitochondrial dysfunction have all been suggested to play key roles in autism and may be linked via alterations in cellular redox homeostasis. The glutathione/glutathione disulfide (GSH/GSSG) redox pair forms the major redox couple in cells and as such plays a critical role in regulating redox-dependent cellular functions. A number of studies have shown that variations in genes involved in GSH metabolism are associated with autism. GSH also modulates the activity of glyoxalase 1 (Glo-1), the rate-limiting enzyme for the removal of reactive dicarbonyls such as methylglyoxal (MG). MG is the major precursor for the formation of advanced glycation end products (AGEs). Both MG and AGEs can induce oxidative stress, inflammation and mitochondrial dysfunction and are implicated in diabetic complications and multiple, age-related neurological diseases. Dietary consumption of AGEs and MG correlates with food intake which has increased 20-30% over the past 20 years. Both MG and AGEs are orally absorbed, leading to increased levels in the blood. Furthermore, in humans, increased MG and AGE levels in maternal blood correlate with increased MG and AGE levels in newborn blood, potentially exposing infants to high oxidative stress and inflammation. It is hypothesized that diet derived MG and AGEs in combination with inborn genetic vulnerabilities that affect the cellular redox status are major contributors to the development of autism and provide a causal link between oxidative stress, inflammation and mitochondrial dysfunction. If future research supports this hypothesis, then by reducing the exposure to these diet-derived factors, it might be possible to decrease the prevalence of at least a subset of autism cases.


Subject(s)
Autistic Disorder/chemically induced , Glycation End Products, Advanced/toxicity , Prenatal Exposure Delayed Effects/blood , Pyruvaldehyde/toxicity , Female , Glutathione/metabolism , Glycation End Products, Advanced/blood , Humans , Models, Biological , Oxidative Stress/drug effects , Pregnancy , Pyruvaldehyde/blood
16.
Cell Death Differ ; 19(5): 847-58, 2012 May.
Article in English | MEDLINE | ID: mdl-22095285

ABSTRACT

Selecting neuronal cell lines for resistance against oxidative stress might recapitulate some adaptive processes in neurodegenerative diseases where oxidative stress is involved like Parkinson's disease. We recently reported that in hippocampal HT22 cells selected for resistance against oxidative glutamate toxicity, the cystine/glutamate antiporter system x(c)(-), which imports cystine for synthesis of the antioxidant glutathione, and its specific subunit, xCT, are upregulated. (Lewerenz et al., J Neurochem 98(3):916-25). Here, we show that in these glutamate-resistant HT22 cells upregulation of xCT mediates glutamate resistance, and xCT expression is induced by upregulation of the transcription factor ATF4. The mechanism of ATF4 upregulation consists of a 13 bp deletion in the upstream open reading frame (uORF2) overlapping the ATF4 open reading frame. The resulting uORF2-ATF4 fusion protein is efficiently translated even at a low phosphorylation levels of the translation initiation factor eIF2α, a condition under which ATF4 translation is normally suppressed. A similar ATF4 mutation associated with prominent upregulation of xCT expression was identified in PC12 cells selected for resistance against amyloid ß-peptide. Our data indicate that ATF4 has a central role in regulating xCT expression and resistance against oxidative stress. ATF4 mutations might have broader significance as upregulation of xCT is found in tumor cells and associated with anticancer drug resistance.


Subject(s)
Activating Transcription Factor 4/genetics , Activating Transcription Factor 4/metabolism , Amino Acid Transport System y+/metabolism , Neurons/metabolism , Oxidative Stress/physiology , Amino Acid Transport System y+/genetics , Amino Acid Transport Systems, Acidic , Animals , Blotting, Western , Cell Line , Electrophoretic Mobility Shift Assay , Glutathione , Mice , Mutation , Oxidative Stress/genetics , PC12 Cells , Rats , Reverse Transcriptase Polymerase Chain Reaction
17.
Cell Death Differ ; 16(6): 910-20, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19282871

ABSTRACT

There is increasing interest in gliogenesis as the relevance of glia to both brain development and pathology becomes better understood. However, little is known about this process. The use of multidimensional protein identification technology (MudPIT) to identify changes in phosphoprotein levels in rat neural precursor cells treated with cytokines or retinoic acid showed that phosphorylation of the catalytic subunit of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K p110alpha) and dephosphorylation of the inositol phosphatase synaptojanin-1 were common to the gliogenic stimuli. Although PI3K was found to be involved in both neuro- and astrogliogenesis, synaptojanin-1 was specifically involved in astrogliogenesis of neural precursor cells. The role of synaptojanin-1 in astrogliogenesis was further confirmed by analysis of neuron- and glia-specific markers in synaptojanin-1 knockout mouse brain. Additional experiments showed that the Sac1-like phosphatase domain of synaptojanin-1 is responsible for the observed astrogliogenic effect. Our results strongly indicate that phosphatidylinositol metabolism plays a key role in astrogliogenesis. The relevance of our findings for Down's syndrome pathology is discussed.


Subject(s)
Astrocytes/enzymology , Down Syndrome/enzymology , Nerve Tissue Proteins/metabolism , Phosphoric Monoester Hydrolases/metabolism , Animals , Astrocytes/cytology , Brain/enzymology , Cell Differentiation , Cell Line , Cytokines/pharmacology , Down Syndrome/metabolism , Mice , Mice, Knockout , Nerve Tissue Proteins/deficiency , Phosphatidylinositol 3-Kinases/metabolism , Phosphatidylinositols/metabolism , Phosphoric Monoester Hydrolases/deficiency , Phosphorylation , Rats , Stem Cells/enzymology , Tretinoin/pharmacology
18.
Ir Vet J ; 61(7): 455-63, 2008 Jul 01.
Article in English | MEDLINE | ID: mdl-21851717

ABSTRACT

Cows are the main economic production units of Ireland's cattle industry. Therefore, demographic information, including overall numbers and survival rates, are relevant to the Irish agricultural industry. However, few data are available on the demographics of cows within a national population, either in Ireland or elsewhere, despite the recent development of comprehensive national cattle databases in many EU Member States. This study has sought: to determine the rate of cow culling from the national herd; to determine the rate of culling by type (dairy, beef), age, method of exit, date of exit and interval between last calving and exit; to calculate the national cow on-farm mortality rate; and to compare the Irish rates with published data from other countries. This work was conducted using data recorded in the national Cattle Movement Monitoring System (CMMS). Culling refers to the exit of cows from the national herd, as a result of death but regardless of reason, and cow-culling rate was calculated as the number of cow exits (as defined above) each year divided by the number of calf births in the same year. Culling rate was determined by type (dairy or beef), date of birth, method of exit (slaughter or on-farm death), month of exit and interval between last calving and exit. The average cow-culling rate during 2003 to 2006 was 19.6% (21.3% for dairy, 18% for beef). While comparisons must be treated with caution, it concluded that the overall rates of culling in Ireland fell within published internationally accepted norms. The on-farm mortality rate of 3.2-4.1% was similar to that reported in comparable studies.

19.
Neuroscience ; 150(3): 585-91, 2007 Dec 12.
Article in English | MEDLINE | ID: mdl-17942241

ABSTRACT

The present study assessed whether baicalein (5,6,7-trihydroxyflavone), a polyphenolic antioxidant 12/15-lipoxygenase inhibitor would attenuate oxidative cell death in vitro using a mouse hippocampal HT22 cell assay. Moreover, we determined if baicalein would be useful to attenuate behavioral deficits associated with multiple infarct ischemic events in vivo using a rabbit small clot embolic stroke model (RSCEM). Using HT22 cell in vitro, baicalein was shown to significantly promote cell survival with an estimated dose for 50% cell survival of 2 muM following incubation in the presence of iodoacetic acid (20 muM), an irreversible inhibitor of the glycolytic pathway that results in the free radical production, lipid peroxidation and cell death. Since baicalein was neuroprotective and attenuated iodoacetic acid (IAA) toxicity in vitro, we studied its effects in vivo in an embolic stroke model using behavioral measures as the endpoint. Quantal analysis for each treatment in the embolism model identifies the quantity of microclots (mg) that produce neurologic dysfunction in 50% of a group of animals (P(50)), with intervention considered neuroprotective if it increases the P(50) compared with controls. Baicalein (100 mg/kg, s.c.) injected 5 and 60 min post-embolization significantly (P<0.05) improved behavioral function. The calculated P(50) values were 2.85+/-0.64 mg (n=21) and 2.15+/-0.12 mg (n=14), respectively compared with 1.37+/-0.20 mg (n=23) for the control group. In conclusion, we have shown that baicalein effectively attenuated cell death in vitro using HT22 cells and also significantly reduced behavioral deficits in rabbits when given up to 1 h following an embolic stroke. The results suggest that baicalein, or derivatives of baicalein with multiple pharmacological activities may be useful to develop as novel treatments for acute ischemic stroke.


Subject(s)
Antioxidants/pharmacology , Flavanones/pharmacology , Intracranial Embolism/drug therapy , Lipoxygenase Inhibitors , Stroke/drug therapy , Animals , Arachidonate 12-Lipoxygenase , Arachidonate 15-Lipoxygenase , Cell Survival/drug effects , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Drug , Intracranial Embolism/metabolism , Intracranial Embolism/pathology , Male , Motor Activity , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Rabbits , Severity of Illness Index , Stroke/metabolism , Stroke/pathology
20.
J Neurosurg Spine ; 4(6): 478-84, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16776359

ABSTRACT

OBJECT: The standard treatment for lumbosacral tethered cord syndrome (TCS) in adults is surgical detethering. In patients with recurrent TCS, additional detethering operations are associated with increased risk of complications and subsequent scar formation. The authors studied the effect of undertaking a vertebral column subtraction osteotomy (VCSO) at the thoracolumbar junction to shorten the vertebral column and reduce neural element tension. METHODS: A model of TCS, developed in fresh-frozen human cadavers, was evaluated in three experiments. In Experiment 1, VCSO of 20 to 25 mm was performed at the T11-12 level. The vertebral column was sequentially shortened and the reduction in tension was measured separately in the terminal filum and the L-1 to S-3 or S-4 nerve roots. In Experiments 2 and 3 the reduction in tension was measured in the spinal cord after a VCSO and after simulating a traditional detethering operation. Vertebral column shortening produced tension reduction in all experiments. Tension decreased to less than 0.6 g in the terminal filum, L1-S3/4 nerve roots, and spinal cord after closure of a 20- to 25-mm VCSO. The mean +/- standard deviation of the deltatension/deltadistance was -0.242 +/- 0.019 g/mm for the terminal filum, -0.246 +/- 0.019 g/mm for the lumbar nerve roots, and -0.216 +/- 0.040 g/mm for the sacral nerve roots. A simulated traditional detethering operation required significant neural element release (detethering) to achieve spinal cord tension reduction equivalent to VCSO. CONCLUSIONS: A VCSO significantly reduced neural tension at the thoracolumbar junction. This novel procedure may provide an alternative to traditional surgical detethering when scarring is excessive and the risk of complications and retethering are high.


Subject(s)
Lumbar Vertebrae/surgery , Neural Tube Defects/surgery , Osteotomy/methods , Spinal Cord/physiopathology , Spinal Nerve Roots/physiopathology , Thoracic Vertebrae/surgery , Adult , Cadaver , Humans , Neural Tube Defects/physiopathology , Recurrence , Stress, Mechanical
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