Bovine spongiform encephalopathy (BSE) is a prion disease of domesticated cattle, first identified in Great Britain (GB) in 1986. The disease has been characterized by histopathological, ...immunohistochemical, biochemical and biological properties, which have shown a consistent disease phenotype among cases obtained by passive surveillance. With the advent of active surveillance in 2001, immunological tests for detection of the prion protein revealed some cases with different biochemical characteristics and, in certain instances, differences in pathology that have indicated variant phenotypes and the possibility of agent strain variation. This study examines a case set of 523 bovine brains derived from archived material identified through passive surveillance in GB. All cases conformed to the phenotype of classical BSE (BSE-C) by histopathological, immunohistochemical and biochemical approaches. The analyses consolidated an understanding of BSE-C and, by western blotting, confirmed differentiation from the known atypical BSE cases which exhibit higher or lower molecular masses than BSE-C (BSE-H and BSE-L respectively).
Spinobulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by polyglutamine (polyQ) expansion in the androgen receptor (AR) gene. SBMA belongs to the family of polyQ diseases, ...which are fatal neurodegenerative disorders mainly caused by protein-mediated toxic gain-of-function mechanisms and characterized by deposition of misfolded proteins in the form of aggregates. The neurotoxicity of the polyQ proteins can be modified by phosphorylation at specific sites, thereby providing the rationale for the development of disease-specific treatments. We sought to identify signaling pathways that modulate polyQ-AR phosphorylation for therapy development. We report that cyclin-dependent kinase 2 (CDK2) phosphorylates polyQ-AR specifically at Ser
Phosphorylation of polyQ-AR by CDK2 increased protein stabilization and toxicity and is negatively regulated by the adenylyl cyclase (AC)/protein kinase A (PKA) signaling pathway. To translate these findings into therapy, we developed an analog of pituitary adenylyl cyclase activating polypeptide (PACAP), a potent activator of the AC/PKA pathway. Chronic intranasal administration of the PACAP analog to knock-in SBMA mice reduced Ser
phosphorylation, promoted polyQ-AR degradation, and ameliorated disease outcome. These results provide proof of principle that noninvasive therapy based on the use of PACAP analogs is a therapeutic option for SBMA.
Activation of the epidermal growth factor (EGF) receptor regulates many processes associated with metastasis, including modulation of cell:cell and cell:substrate interactions, production of ...matrix-degrading proteinases, and cellular migration. We have demonstrated previously that EGF stimulates migration and matrix metalloproteinase (MMP)-9-dependent invasion of ovarian cancer cells. In this study, we compare the roles of EGF-induced phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) activities in regulation of cellular responses associated with ovarian tumor cell metastasis. Inhibition of PI3K and MAPK activity impairs EGF-stimulated cell migration, in vitro invasion, and MMP-9 production. PI3K activity is not required for growth factor disruption of cell:cell junctions, whereas inhibitors of extracellular signal-regulated kinase (ERK)1/ERK2 activation and p38 MAPK activity block EGF-dependent junction dissolution. EGF promotes pro-MMP-9 binding to the cell surface through a mechanism that is independent of extracellular enzyme concentration. Interestingly, inhibition of PI3K activity abolishes EGF-induced cell surface association of pro-MMP-9, whereas inhibitors of MAPKs only partially block the response. These data suggest that EGF receptor activation promotes a PI3K-dependent induction of a cell surface pro-MMP-9 binding component that may facilitate gelatinase-mediated cellular invasion and supports an expanded role for elevated PI3K activity in cellular responses associated with ovarian tumor metastasis. In addition, our findings support the hypothesis that divergent kinase activities regulate distinct cellular events associated with growth factor-induced invasion of ovarian cancer cells.
Conservation in urban areas typically focuses on biodiversity and large green spaces. However, opportunities exist throughout urban areas to enhance ecological functions. An important function of ...urban landscapes is retaining nitrogen thereby reducing nitrate pollution to streams and coastal waters. Control of nonpoint nitrate pollution in urban areas was originally based on the documented importance of riparian zones in agricultural and forested ecosystems. The watershed and boundary frameworks have been used to guide stream research and a riparian conservation strategy to reduce nitrate pollution in urban streams. But is stream restoration and riparian-zone conservation enough? Data from the Baltimore Ecosystem Study and other urban stream research indicate that urban riparian zones do not necessarily prevent nitrate from entering, nor remove nitrate from, streams. Based on this insight, policy makers in Baltimore extended the conservation strategy throughout larger watersheds, attempting to restore functions that no longer took place in riparian boundaries. Two urban revitalization projects are presented as examples aimed at reducing nitrate pollution to stormwater, streams, and the Chesapeake Bay. An adaptive cycle of ecological urban design synthesizes the insights from the watershed and boundary frameworks, from new data, and from the conservation concerns of agencies and local communities. This urban example of conservation based on ameliorating nitrate water pollution extends the initial watershed-boundary approach along three dimensions: 1) from riparian to urban land-water-scapes; 2) from discrete engineering solutions to ecological design approaches; and 3) from structural solutions to inclusion of individual, household, and institutional behavior.
Objective
To investigate non-dietary correlates and determinants of plasma lutein (L) and zeaxanthin (Z) concentrations in The Irish Longitudinal Study on Ageing (TILDA) sample.
Setting
Community ...dwelling adults in the Republic of Ireland (ROI). Participants: 3,681 participants aged 50 years and older.
Measurements
TILDA is a nationally representative prospective cohort study of community dwelling adults aged 50 years and over in the ROI. Demographic and health variables were collected during a face-to-face interview carried out in the home (n=8175), and a substantial proportion of these (n=5035; 62%) also attended a study visit in a health assessment centre. Blood samples collected at baseline (wave 1, the subject of the current study), were analysed for plasma concentrations of L and Z by reversed-phase high performance liquid chromatography, and macular pigment (MP) optical density was also measured (using customized heterochromatic flicker photometry).
Results
After excluding participants with eye disease, data from 3,681 participants were available for analysis. For this group of participants, plasma L and Z were inversely and significantly associated with body mass index (BMI), and were positively and significantly associated with MP, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (p<0.001, for all). Plasma L and Z were significantly lower in males, current smokers, participants reporting less physical exercise, and participants reporting lower levels of education (p<0.05, for all). Plasma L was significantly higher in participants reporting a family history of age-related macular degeneration (AMD) (p=0.001), and in the group of ≥75 years old (p<0.05). For each of these variables, the significant associations remained after controlling for other potential confounding variables.
Conclusion
The findings of this large study indicate that plasma concentrations of L and Z were lower in association with indicators of a poor lifestyle (high BMI, tobacco use, and less physical exercise) and in association with lower education, indicating that modifying lifestyle in a positive way is likely to be reflected in higher concentrations of plasma carotenoids, with consequential and putative health benefits.
The VPS34 gene product (Vps34p) is required for protein sorting to the lysosome-like vacuole of the yeast Saccharomyces cerevisiae. Vps34p shares significant sequence similarity with the catalytic ...subunit of bovine phosphatidylinositol (PI) 3-kinase the 110-kilodalton (p 110) subunit of PI 3-kinase, which is known to interact with activated cell surface receptor tyrosine kinases. Yeast strains deleted for the VPS34 gene or carrying vps34 point mutations lacked detectable PI 3-kinase activity and exhibited severe defects in vacuolar protein sorting. Overexpression of Vps34p resulted in an increase in PI 3-kinase activity, and this activity was specifically precipitated with antisera to Vps34p. VPS34 encodes a yeast PI 3-kinase, and this enzyme appears to regulate intracellular protein trafficking decisions
To systematically review the current preoperative diagnostic modalities, surgical treatments, and glandular pathologies associated with primary hyperparathyroidism.
A systematic literature review.
Of ...the 20,225 cases of primary hyperparathyroidism reported, solitary adenomas (SA), multiple gland hyperplasia disease (MGHD), double adenomas (DA), and parathyroid carcinomas (CAR) occurred in 88.90%, 5.74%, 4.14%, and 0.74% of cases respectively. Tc 99m -sestamibi and ultrasound were 88.44% and 78.55% sensitive, respectively, for SA, 44.46% and 34.86% for MGHD, and 29.95% and 16.20% for DA, respectively. Postoperative normocalcemia was achieved in 96.66%, 95.25%, and 97.69% of patients offered minimally invasive radio-guided parathyroidectomy (MIRP), unilateral, and bilateral neck exploration (BNE). Intraoperative PTH assays (IOPTH) were helpful in approximately 60% of bilateral neck exploration conversion (BNEC) surgeries.
The overall prevalence of multiple gland disease (MGD and DA) was lower than often suggested by conventional wisdom. Furthermore, preoperative imaging was less accurate than it is often perceived for accurately imaging MGD. MIRP and UNE were more successful in achieving normocalcemia than is typically quoted. IOPTH was a helpful but not "fool-proof" adjunct in parathyroid exploration surgery.
These results support a greater role for the treatment of primary hyperparathyroidism using less invasive approaches. EMB rating: B-3.
Measurement-based quantum error correction relies on the ability to determine the state of a subset of qubits (ancillas) within a processor without revealing or disturbing the state of the remaining ...qubits. Among neutral-atom-based platforms, a scalable, high-fidelity approach to midcircuit measurement that retains the ancilla qubits in a state suitable for future operations has not yet been demonstrated. In this work, we perform maging using a narrow-linewidth transition in an array of tweezer-confined ^{171}Yb atoms to demonstrate nondestructive state-selective and site-selective detection. By applying site-specific light shifts, selected atoms within the array can be hidden from imaging light, which allows a subset of qubits to be measured while causing only percent-level errors on the remaining qubits. As a proof-of-principle demonstration of conditional operations based on the results of the midcircuit measurements, and of our ability to reuse ancilla qubits, we perform conditional refilling of ancilla sites to correct for occasional atom loss, while maintaining the coherence of data qubits. Looking toward true continuous operation, we demonstrate loading of a magneto-optical trap with a minimal degree of qubit decoherence.
New and Interesting Fungi. 3 Crous, P.W.; Wingfield, M.J.; Schumacher, R.K. ...
Fungal Systematics and Evolution,
12/2020, Letnik:
6, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Seven new genera, 26 new species, 10 new combinations, two epitypes, one new name, and 20 interesting new host and / or geographical records are introduced in this study. New genera are: Italiofungus ...(based on Italiofungus phillyreae) on leaves of Phillyrea latifolia
(Italy); Neolamproconium (based on Neolamproconium silvestre) on branch of Tilia sp. (Ukraine); Neosorocybe (based on Neosorocybe pini) on trunk of Pinus sylvestris (Ukraine); Nothoseptoria (based on Nothoseptoria caraganae) on leaves
of Caragana arborescens (Russia); Pruniphilomyces (based on Pruniphilomyces circumscissus) on Prunus cerasus (Russia); Vesiculozygosporium (based on Vesiculozygosporium echinosporum) on leaves of Muntingia calabura (Malaysia); Longiseptatispora
(based on Longiseptatispora curvata) on leaves of Lonicera tatarica (Russia). New species are: Barrmaelia serenoae on leaf of Serenoa repens (USA); Chaetopsina gautengina on leaves of unidentified grass (South Africa); Chloridium pini on fallen trunk
of Pinus sylvestris (Ukraine); Cadophora fallopiae on stems of Reynoutria sachalinensis (Poland); Coleophoma eucalyptigena on leaf litter of Eucalyptus sp. (Spain); Cylindrium corymbiae on leaves of Corymbia maculata (Australia); Diaporthe
tarchonanthi on leaves of Tarchonanthus littoralis (South Africa); Elsinoe eucalyptorum on leaves of Eucalyptus propinqua (Australia); Exophiala quercina on dead wood of Quercus sp., (Germany); Fusarium californicum on cambium of budwood of
Prunus dulcis (USA); Hypomyces gamsii on wood of Alnus glutinosa (Ukraine); Kalmusia araucariae on leaves of Araucaria bidwillii (USA); Lectera sambuci on leaves of Sambucus nigra (Russia); Melanomma populicola on fallen twig of Populus
canadensis (Netherlands), Neocladosporium syringae on branches of Syringa vulgarishorus (Ukraine); Paraconiothyrium iridis on leaves of Iris pseudacorus (Ukraine); Pararoussoella quercina on branch of Quercus robur (Ukraine); Phialemonium
pulveris from bore dust of deathwatch beetle (France); Polyscytalum pinicola on needles of Pinus tecunumanii (Malaysia); Acervuloseptoria fraxini on Fraxinus pennsylvanica (Russia); Roussoella arundinacea on culms of Arundo donax (Spain);
Sphaerulina neoaceris on leaves of Acer negundo (Russia); Sphaerulina salicicola on leaves of Salix fragilis (Russia); Trichomerium syzygii on leaves of Syzygium cordatum (South Africa); Uzbekistanica vitis-viniferae on dead stem of Vitis
vinifera (Ukraine); Vermiculariopsiella eucalyptigena on leaves of Eucalyptus sp. (Australia).
ObjectiveTo determine the impact of one probiotics combination on the neurodevelopment of very preterm children at 2–5 years corrected gestational age (CA).DesignFollow-up study of survivors of a ...double-blinded, placebo-controlled, randomised trial of probiotic effects on late-onset sepsis in very preterm infants that found reduced necrotising enterocolitis.Setting10 tertiary perinatal centres in Australia and New Zealand.Patients1099 very preterm infants born <32 weeks’ gestation and weighing <1500 g.InterventionProbiotics (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis) or placebo administered from birth until discharge home or term CA, whichever came sooner.Main outcome measuresMajor neurodevelopmental impairment comprised any of moderate/severe cerebral palsy (Gross Motor Function Classification System score 2–5), motor impairment (Bayley-III Motor Composite Scale <–2SD or Movement Assessment Battery for Children <15th centile if >42 months’ CA), cognitive impairment (Bayley-III Composite Cognitive or Language Scales <–2SD or Wechsler Preschool and Primary Scale of Intelligence Full Scale Intelligence Quotient <–2SD if >42 months’ CA), blindness or deafness.ResultsOutcome data were available for 735 (67%) participants, with 71 deaths and 664/1028 survivors assessed at a mean age of 30 months. Survival free of major neurodevelopmental impairment was comparable between groups (probiotics 281 (75.3%) vs placebo 271 (74.9%); relative risk 1.01 (95% CI 0.93 to 1.09)). Rates of deafness were lower in probiotic-treated children (0.6% vs 3.4%).ConclusionAdministration of the probiotics combination Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis to very preterm babies from soon after birth until discharge home or term CA did not adversely affect neurodevelopment or behaviour in early childhood.Trial registration numberAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN012607000144415.
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