1995 Data Acquisition Program At The Michigan Reservoir Delineation Research Facility

1995 was the most active year in recent history at the test site. Although the initial year of 1983 saw more work, we were still basking in the glow of the modern "oil boom"; the downsizing crash was ahead of us. In 1983, working around the clock, we recorded 13 VSPs, a suite of logs, a reverse VSP, borehole gravity survey, and a 3-D survey in two months of field time. In 1995, a single, four-man Conoco crew worked ten to twelve hour days, for 70 days, and recorded a massive cross-well, orbital vibrator data set-clearly a Herculean task. This paper outlines the pre-survey planning that took place in anticipation of that effort. In addition, we document the single well data acquisition efforts of Conoco, Inc. and Lawrence .Berkeley Laboratory (LBL), and the dipole logging work of Halliburton Energy Services. These data are in the handling stages and processing has not yet begun

ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing.

Constitutive heterochromatin in Arabidopsis thaliana is marked by repressive chromatin modifications, including DNA methylation, histone H3 dimethylation at Lys9 (H3K9me2) and monomethylation at Lys27 (H3K27me1). The enzymes catalyzing DNA methylation and H3K9me2 have been identified; alterations in these proteins lead to reactivation of silenced heterochromatic elements. The enzymes responsible for heterochromatic H3K27me1, in contrast, remain unknown. Here we show that the divergent SET-domain proteins ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 (ATXR5) and ATXR6 have H3K27 monomethyltransferase activity, and atxr5 atxr6 double mutants have reduced H3K27me1 in vivo and show partial heterochromatin decondensation. Mutations in atxr5 and atxr6 also lead to transcriptional activation of repressed heterochromatic elements. Notably, H3K9me2 and DNA methylation are unaffected in double mutants. These results indicate that ATXR5 and ATXR6 form a new class of H3K27 methyltransferases and that H3K27me1 represents a previously uncharacterized pathway required for transcriptional repression in Arabidopsis

Studies on the mechanism of action of the antimicrobial S-linked glycopeptide sublancin

Infectious diseases are a continuing threat to human health. In particular, the rapid development of bacterial antibiotic resistance not only decreases the effectiveness of known antibiotics, but also increases the need for the ongoing discovery of novel drugs. Since the discovery of penicillin, natural products have become a great source of templates for the development of new antibiotics. Derivatization of known drugs is one approach commonly used to combat rapidly evolving bacterial strains. However, the mechanisms of actions of derivatized drugs are more often than not very similar to the parent compound, making it difficult to develop drugs with new and unique modes of action by generating analogs. Ribosomally synthesized and post-translationally modified peptide (RiPP) natural products are a rapidly expanding class of compounds with antimicrobial activity. Sublancin is one of five members of the glycocin family of RiPPs, and contains an unusual S-linked glycosylation. This unprecedented post-translational modification, as well as its increased stability, when compared to known RiPP antimicrobials, suggests a unique antibacterial mode of action. In an effort to understand the remarkable stability of sublancin, the three-dimensional NMR structure was solved, as described in chapter 2, revealing that hydrophobic interactions as well as hydrogen bonding are responsible for the stable and well-structured peptide. Unlike better-understood natural products, the molecular target of sublancin is currently unknown. In order to further understand how sublancin exerts its activity against bacteria, a number of sublancin analogues were made. These analogues were prepared either by heterologous expression followed by in vitro modification, as well as by solid phase peptide synthesis. The antimicrobial activity of all analogues was then assessed against sensitive bacteria and sublancin-resistant mutant strains. While sublancin exhibits sub-micromolar activity against Gram-positive bacteria, its molecular target is currently unknown. Chapter 3 describes studies focused on understanding sublancin’s mode of action. In chapter 4 we performed super resolution microscopy and determined that sublancin localizes to the cell membrane. Furthermore, the mechanism of action of the S-glycosyltransferase SunS, the enzyme responsible for installing an S-linked sugar onto sublancin, was studied in chapter 5, which provided insights into its enzymatic mechanism. The understanding of the biosynthesis of these unique peptides can aid in the bioengineering of other, more potent complex molecules

What’s new in using platelet research? To unravel thrombopathies and other human disorders

This review on platelet research focuses on defects of adhesion, cytoskeletal organisation, signal transduction and secretion. Platelet defects can be studied by different laboratory platelet functional assays and morphological studies. Easy bruising or a suspected platelet-based bleeding disorder is of course the most obvious reason to test the platelet function in a patient. However, nowadays platelet research also contributes to our understanding of human pathology in other disciplines such as neurology, nephrology, endocrinology and metabolic diseases. Apart from a discussion on classical thrombopathies, this review will also deal with the less commonly known relation between platelet research and disorders with a broader clinical phenotype. Classical thrombopathies involve disorders of platelet adhesion such as Glanzmann thrombastenia and Bernard-Soulier syndrome, defective G protein signalling diseases with impaired phospholipase C activation, and abnormal platelet granule secretion disorders such as gray platelet disorder and delta-storage pool disease. Other clinical symptoms besides a bleeding tendency have been described in MYH9-related disorders and Duchenne muscular dystrophy due to adhesion defects, and also in disorders of impaired Gs signalling, in Hermansky Pudlack disease and Chediak Higashi disease with abnormal secretion. Finally, platelet research can also be used to unravel novel mechanisms involved in many neurological disorders such as depression and autism with only a subclinical platelet defect

Canadian Postsecondary Students With Disabilities: Where Are They?

Results of a Canada-wide and a Quebec based study of students with a variety of disabilities in Canadian postsecondary education are presented. Study 1 involved 156 professionals. They represent 80% of the population of professionals who provide on-campus disability support services. Results indicate that (1) 8% of postsecondary institutions reported not having any students with disabilities, (2) overall, 2% of students are registered to receive disability related services from their post- secondary institutions, and (3) this varies from 1/2% to 6% across the country. Junior/community colleges had a higher percentage of students with disabilities registered to receive disability related services (3 3/4%) than universities (1 2/3%). (4) Distance education had 3%. (5) Quebec has a smaller proportion of both college (2/3% vs 6%) and university (1/2%) vs 2 1/2%) students with disabilities than the rest of Canada. A targeted study involving 46 professionals who provide disability related services in Quebec's public junior/community colleges, the CEGEPs, revealed that lack of recognition of learning disabilities for postsecondary funding by the Quebec government is an important contributor to the small percentages, although it cannot explain the huge discrepancies between Quebec and the rest of Canada. Extrapolation suggests that there are over 100,000 students with disabilities currently enrolled in Canadian postsecondary education, although only 1/4 to 1/2 of them register to receive disability related services.Les résultats d'une étude pancanadienne basée au Québec portant sur des étudiants ayant diverses incapacités dans des institutions postsecondaires canadiennes sont présentés. L'étude 1 impliquait 156 professionnels. Ils représentent 80% de la population des intervenants qui fournissent de l'appui, sur les campus, aux étudiants ayant des incapacités. Les résultats révèlent que (1) 8% des institutions postsecondaires rapportent qu'elles n'ont pas d'étudiants ayant des incapacités, (2) globalement, 2 % des étudiants sont inscrits aux services offerts aux étudiants ayant des incapacités de leur institution postsecondaire, et (3) cette donnée varie de 1/2% à 6% à travers le pays. Les collèges communautaires ont un pourcentage plus élevé d'étudiants ayant des incapacités inscrits aux services d'appui (3 3/4%) par rapport aux universités (1 2/3%). (4) La formation à distance a 3% d'étudiants nécessitant des services de cette nature. (5) Le Québec a le pourcentage le plus faible au Canada d'étudiants ayant des incapacités aux niveaux collégial (2/3%) contre 6%) et universitaire (1/2% contre 2 1/2%). Une étude cible impliquant 46 intervenants qui fournissent des services aux étudiants ayant des incapacités dans les collèges au Québec, les CEGEPs, révèle qu'un des facteurs contribuant aux faibles pourcentages est le fait que le gouvernement du Québec ne tient pas compte des difficultés d'apprentissage lors du financement. Cependant, ceci ne peut expliquer les différences énormes entre le Québec et le reste du Canada. Par extrapolation, il est possible d'avancer qu'il y a plus de 100 000 étudiants ayant des incapacités présentement inscrits dans des institutions postsecondaires canadiennes, quoique seulement 25 à 50 % de ceux-ci soient inscrits aux services offerts aux étudiants ayant des incapacités

Різнолігандні комплекси ренію(i): від флуоресцентних міток до гетеробіметалічних зон- дів з цікавою топологією для подвійної візуалізації

In this paper, five new ternary tricarbonylrhenium(I) complexes based on a pyridinetriazole moiety, the so-called pyta, have been investigated. These cationic complexes of the general formula [Re(CO)3(pyta-COOMe)L] (L = substituted pyridine derivatives) combine a carboxylate functionalization, for further biomolecule conjugation, with a metal chelating site – a pyta-based tricarbonylrhenium moiety – which can act as a fluorescent reporter. The complexes have been prepared using a two-steps pathway involved the activation of [Re(CO)3Cl(bipy)] with triflate silver salts in the presence of acetonitrile followed by the thermally activated substitution of the acetonitrile adduct by commercially available substituted pyridine derivatives. They have been prepared from modest to good yields, fully characterized by means of NMR, IR and mass spectrometry, and their photophysical properties have been investigated. Upon excitation into the MLCT band of each complex (absorption band at ca. 300 nm), three of them exhibit a bright green luminescence centered at c.a. 494 nm, with a quantum yield of 0.60% in acetonitrile. These interesting photophysical features make them potential fluorescent cellular imaging agents. Moreover, thank to their ancillary ligand, they could be also considered as interesting scaffolds for the preparation of dual-imaging heterobimetallic species.В данной работе представлены результаты исследований пяти новых разнолигандных трис-карбонильных комплексов рения(I) на основе пиридинтриазольных производных, так называемых pyta. Такие катионные комплексы общей формулы [Re(CO)3(pyta-COOMe)L] (L = производные пиридина) сочетают в себе карбоксилатную функциональную группу для дальнейшего биомолекулярного связывания с хелатированным металлсодержащим фрагментом – на основе pyta-трискарбонильных комплексных частиц, которые могут выступать в качестве флуоресцентного центра. Комплексы были получены двухстадийной реакцией, основанной на активации [Re(CO)3Cl(bipy)] трифлатом серебра в присутствии ацетонитрила с дальнейшим взаимодействием термически активированного ацетонитрильного аддукта с коммерчески доступными замещенными пиридинпроизводными. Координационные соединения были получены с разными выходами, исследованы методами ЯМР-, ИК- и масс-спектроскопии и изучены их фотофизические свойства. При использовании длины волны возбуждения, соответствующей центру полосы переноса заряда металл-лиганд (MLCT) для каждого комплекса (полоса поглощения ~ 300 нм), три из них проявляют ярко-зеленую люминесценцию в ацетонитриле с центром ~ 494 нм и квантовым выходом 0,60%. Такие фотофизические особенности делают их потенциальными флуоресцентными биовизуализирующими агентами. Кроме того, благодаря дополнительным лигандам они могут быть использованы как основа для получения гетеробиметаллических частиц для двойственной визуализации.В даній публікації представлені результати досліджень п’яти нових різнолігандних трис-карбонільних комплексів ренію(I) на основі піридинтриазольних похідних, так званих pyta. Такі катіонні комплекси загальної формули [Re(CO)3(pyta-COOMe)L] (L = похідні піридину) поєднують карбоксилатну функціональну групу, яка може бути використана для подальшого біомолекулярного зв’язування з хелатованим металовмісним фрагментом на основі pyta-трис-карбонільних комплексних часточок, які можуть виступати в якості флуоресцентного центру. Комплекси були отримані двостадійною реакцією, заснованою на активації [Re(CO)3Cl(bipy)] трифлатом срібла в присутності ацетонітрилу з подальшою взаємодією термічно активованого ацетонітрильного аддукту з комерційно доступними заміщеними піридинпохідними. Координаційні сполуки були отримані з різними виходами, охарактеризовані методами ЯМР-, ІЧ- та мас-спектроскопії і досліджені їх фотофізичні властивості. При використанні довжини хвилі збудження, яка відповідає центру смуги переносу заряду метал-ліганд (MLCT) для кожного комплексу (смуга поглинання ~300 нм), три з них виявляють яскраво-червону люмінесценцію в ацетонітрилі з центром ~494 нм та квантовим виходом 0,60%. Такі фотофізичні особливості роблять їх потенційними флуоресцентними біовізуалізуючими агентами. До того ж, завдяки додатковим лігандам вони можуть бути використані як основа для створення гетеробіметалічних часточок для подвійної візуалізації

A second wind for the cholinergic system in Alzheimer’s therapy:

Notwithstanding tremendous research efforts, the cause of Alzheimer’s disease (AD) remains elusive and there is no curative treatment. The cholinergic hypothesis presented 35 years ago was the first major evidence-based hypothesis regarding AD etiology. It proposed that the depletion of brain acetylcholine was a primary cause of cognitive decline in advanced age and AD. It relied on a series of observations obtained in aged animals, elderly and AD patients which pointed to dysfunctions of cholinergic basal forebrain, similarities between cognitive impairments induced by anticholinergic drugs and those found in advanced age and AD, and beneficial effects of drugs stimulating cholinergic activity. This review comes back on these major results to show how this hypothesis provided the drive for the development of anticholinesterase inhibitor-based therapies of AD, the almost exclusive approved treatment in use despite transient and modest efficacy. New ideas for improving cholinergic therapies are also compared and discussed in light of the current revival of the cholinergic hypothesis based on two sets of evidence from new animal models and refined imagery techniques in humans. First, human and animal studies agree on detecting signs of cholinergic dysfunctions much earlier than initially thought. Second, alterations of the cholinergic system are deeply intertwined with its reactive responses providing the brain with efficient compensatory mechanisms to delay the conversion to AD. Active research in this field should give new insight to develop multi-therapies incorporating cholinergic manipulation, as well as early biomarkers of AD allowing earlier diagnostics. This is of prime importance to counteract a disease that is now recognized to start early in adult life

Extraction of the Bacterial Extracellular Polysaccharide FucoPol by Membrane-Based Methods: Efficiency and Impact on Biopolymer Properties

LA/P/0140/2020In this study, membrane-based methods were evaluated for the recovery of FucoPol, the fucose-rich exopolysaccharide (EPS) secreted by the bacterium Enterobacter A47, aiming at reducing the total water consumption and extraction time, while keeping a high product recovery, thus making the downstream procedure more sustainable and cost-effective. The optimized method involved ultrafiltration of the cell-free supernatant using a 30 kDa molecular weight cut-off (MWCO) membrane that allowed for a 37% reduction of the total water consumption and a 55% reduction of the extraction time, compared to the previously used method (diafiltration-ultrafiltration with a 100 kDa MWCO membrane). This change in the downstream procedure improved the product’s recovery (around 10% increase) and its purity, evidenced by the lower protein (8.2 wt%) and inorganic salts (4.0 wt%) contents of the samples (compared to 9.3 and 8.6 wt%, respectively, for the previously used method), without impacting FucoPol’s sugar and acyl groups composition, molecular mass distribution or thermal degradation profile. The biopolymer’s emulsion-forming and stabilizing capacity was also not affected (emulsification activity (EA) with olive oil, at a 2:3 ratio, of 98 ± 0% for all samples), while the rheological properties were improved (the zero-shear viscosity increased from 8.89 ± 0.62 Pa·s to 17.40 ± 0.04 Pa·s), which can be assigned to the higher purity degree of the extracted samples. These findings demonstrate a significant improvement in the downstream procedure raising FucoPol’s recovery, while reducing water consumption and operation time, key criteria in terms of process economic and environmental sustainability. Moreover, those changes improved the biopolymer’s rheological properties, known to significantly impact FucoPol’s utilization in cosmetic, pharmaceutical or food products.publishersversionpublishe