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Search Results: 1 - 10 of 142648 matches for " Karl K. Weitz "
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Proteomic and Physiological Responses of Kineococcus radiotolerans to Copper
Christopher E. Bagwell,Kim K. Hixson,Charles E. Milliken,Daniel Lopez-Ferrer,Karl K. Weitz
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012427
Abstract: Copper is a highly reactive, toxic metal; consequently, transport of this metal within the cell is tightly regulated. Intriguingly, the actinobacterium Kineococcus radiotolerans has been shown to not only accumulate soluble copper to high levels within the cytoplasm, but the phenotype also correlated with enhanced cell growth during chronic exposure to ionizing radiation. This study offers a first glimpse into the physiological and proteomic responses of K. radiotolerans to copper at increasing concentration and distinct growth phases. Aerobic growth rates and biomass yields were similar over a range of Cu(II) concentrations (0–1.5 mM) in complex medium. Copper uptake coincided with active cell growth and intracellular accumulation was positively correlated with Cu(II) concentration in the growth medium (R2 = 0.7). Approximately 40% of protein coding ORFs on the K. radiotolerans genome were differentially expressed in response to the copper treatments imposed. Copper accumulation coincided with increased abundance of proteins involved in oxidative stress and defense, DNA stabilization and repair, and protein turnover. Interestingly, the specific activity of superoxide dismutase was repressed by low to moderate concentrations of copper during exponential growth, and activity was unresponsive to perturbation with paraquot. The biochemical response pathways invoked by sub-lethal copper concentrations are exceptionally complex; though integral cellular functions are preserved, in part, through the coordination of defense enzymes, chaperones, antioxidants and protective osmolytes that likely help maintain cellular redox. This study extends our understanding of the ecology and physiology of this unique actinobacterium that could potentially inspire new biotechnologies in metal recovery and sequestration, and environmental restoration.
A Method to Determine Lysine Acetylation Stoichiometries
Ernesto S. Nakayasu,Si Wu,Michael A. Sydor,Anil K. Shukla,Karl K. Weitz,Ronald J. Moore,Kim K. Hixson,Jong-Seo Kim,Vladislav A. Petyuk,Matthew E. Monroe,Ljiljiana Pasa-Tolic,Wei-Jun Qian,Richard D. Smith,Joshua N. Adkins,Charles Ansong
International Journal of Proteomics , 2014, DOI: 10.1155/2014/730725
Abstract: Lysine acetylation is a common protein posttranslational modification that regulates a variety of biological processes. A major bottleneck to fully understanding the functional aspects of lysine acetylation is the difficulty in measuring the proportion of lysine residues that are acetylated. Here we describe a mass spectrometry method using a combination of isotope labeling and detection of a diagnostic fragment ion to determine the stoichiometry of protein lysine acetylation. Using this technique, we determined the modification occupancy for ~750 acetylated peptides from mammalian cell lysates. Furthermore, the acetylation on N-terminal tail of histone H4 was cross-validated by treating cells with sodium butyrate, a potent deacetylase inhibitor, and comparing changes in stoichiometry levels measured by our method with immunoblotting measurements. Of note we observe that acetylation stoichiometry is high in nuclear proteins, but very low in mitochondrial and cytosolic proteins. In summary, our method opens new opportunities to study in detail the relationship of lysine acetylation levels of proteins with their biological functions. 1. Introduction Lysine acetylation (KAc) of proteins is a ubiquitous posttranslational modification (PTM) that controls many cellular processes. The dynamic regulation of KAc by lysine acetyltransferases (KATs) and deacetylases (KDACs) modulates many important cellular functions, such as cell metabolism and gene expression [1, 2]. Recent advances in mass spectrometry combined with immunoaffinity purification are enabling the identification and relative quantification of thousands of acetylation sites in a single experiment [3–5]. These new data have boosted the discovery of regulatory functions of KAc for many proteins, including a variety of metabolic enzymes [2]. Although significant progress has been made, a major remaining hurdle in the field is the determination of acetylation stoichiometry on proteins. The knowledge of KAc stoichiometry is considered essential to better understand the mechanism and impact of this modification on the control protein functions, such as enzymatic activity [2, 6]. Indeed, this problem is not exclusive to KAc as there are almost no systematic determinations of the stoichiometry of PTMs. This has remained a challenge because methods to determine stoichiometry of PTMs are not compatible with enrichment procedures, since both modified and unmodified versions of polypeptides need to be present in the sample. Global studies have been successfully performed to determine the stoichiometries
Galois-module theory for wildly ramified covers of curves over finite fields
Helena Fischbacher-Weitz,Bernhard K?ck
Mathematics , 2014,
Abstract: Given a Galois cover of curves over a finite field, we relate epsilon constants appearing in functional equations of Artin L-functions to an equivariant Euler characteristic. Our main theorem generalises a result of Chinburg from the tamely to the weakly ramified case. We furthermore apply Chinburg's result to obtain a `weak' relation in the general case.
Metabolic Reprogramming during Purine Stress in the Protozoan Pathogen Leishmania donovani
Jessica L. Martin equal contributor,Phillip A. Yates equal contributor,Radika Soysa,Joshua F. Alfaro,Feng Yang,Kristin E. Burnum-Johnson,Vladislav A. Petyuk,Karl K. Weitz,David G. Camp II,Richard D. Smith,Phillip A. Wilmarth,Larry L. David,Gowthaman Ramasamy,Peter J. Myler,Nicola S. Carter
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1003938
Abstract: The ability of Leishmania to survive in their insect or mammalian host is dependent upon an ability to sense and adapt to changes in the microenvironment. However, little is known about the molecular mechanisms underlying the parasite response to environmental changes, such as nutrient availability. To elucidate nutrient stress response pathways in Leishmania donovani, we have used purine starvation as the paradigm. The salvage of purines from the host milieu is obligatory for parasite replication; nevertheless, purine-starved parasites can persist in culture without supplementary purine for over three months, indicating that the response to purine starvation is robust and engenders parasite survival under conditions of extreme scarcity. To understand metabolic reprogramming during purine starvation we have employed global approaches. Whole proteome comparisons between purine-starved and purine-replete parasites over a 6–48 h span have revealed a temporal and coordinated response to purine starvation. Purine transporters and enzymes involved in acquisition at the cell surface are upregulated within a few hours of purine removal from the media, while other key purine salvage components are upregulated later in the time-course and more modestly. After 48 h, the proteome of purine-starved parasites is extensively remodeled and adaptations to purine stress appear tailored to deal with both purine deprivation and general stress. To probe the molecular mechanisms affecting proteome remodeling in response to purine starvation, comparative RNA-seq analyses, qRT-PCR, and luciferase reporter assays were performed on purine-starved versus purine-replete parasites. While the regulation of a minority of proteins tracked with changes at the mRNA level, for many regulated proteins it appears that proteome remodeling during purine stress occurs primarily via translational and/or post-translational mechanisms.
Equivariant Riemann-Roch theorems for curves over perfect fields
Helena B. Fischbacher-Weitz,Bernhard K?ck
Mathematics , 2007,
Abstract: We prove an equivariant Riemann-Roch formula for divisors on algebraic curves over perfect fields. By reduction to the known case of curves over algebraically closed fields, we first show a preliminary formula with coefficients in Q. We then prove and shed some further light on a divisibility result that yields a formula with integral coefficients. Moreover, we give variants of the main theorem for equivariant locally free sheaves of higher rank.
Between professional autonomy and economic orientation — The medical profession in a changing health care system
K?lble, Karl
GMS Psycho-Social-Medicine , 2005,
Abstract: The current discussions surrounding the German health care system are being determined and defined by the concepts of "profitability", "efficiency" and "saving". These concepts also determine the demands made on this system and have had an effect on the medical profession. The economy's growing influence on physicians' decision-making and the increasing necessity to look at and regulate services under economic aspects arising from the need to save costs are seen by the medical profession as a threat to its autonomous conduct and freedom to make decisions, in other words it sees it as a danger to its medical orientation. Conflicts between medical autonomy and economic orientation in physicians' conduct are therefore already foreseeable, as are conflicts between medicine and economy in regards to who has the power to define the terms of the public health system.Objective: This article will outline the area of conflict based on the available literature. It will discuss how the political and economic regulatory attempts affect the medical profession's autonomous conduct. It will also discuss which conflicts of conduct emerge for physicians, what types of solutions the medical profession tends to develop as a reaction, and whether or not this tension between medical and economic orientation can be resolved in an acceptable way.Methodology: This article should first outline the changed economic and political basic conditions and the attempts to reform the German health care system, using this as a starting point. Following this, it will explore the significance professional autonomy acquires within the concept of profession from the point of view of the sociology of professions. With this in mind, the third part of this article will describe and analyze the effects of advanced economization on the medical profession's autonomous conduct, which has long been regarded as uncontested. This part of the article will also describe and analyze the medical profession's strategies it uses to defend its autonomy. Finally, this article will discuss whether or not a stronger integration of medical and economic responsibility is possible.Conclusion and summary: The conclusion that will be drawn from this discussion is that the medical profession can only avoid the pending loss of its autonomy (deprofessionalization) if it is able to combine cost efficiency and quality (and integrate economic aspects into its actions). If it is unable to do so, it will lose more and more control over the public health system to the state, economy, and management.
Molecular Assembly and Biosynthesis of Acetylcholinesterase in Brain and Muscle: the Roles of t-peptide, FHB Domain, and N-linked Glycosylation
Karl W. K. Tsim
Frontiers in Molecular Neuroscience , 2011, DOI: 10.3389/fnmol.2011.00036
Abstract: Acetylcholinesterase (AChE) is responsible for the hydrolysis of the neurotransmitter, acetylcholine, in the nervous system. The functional localization and oligomerization of AChE T variant are depending primarily on the association of their anchoring partners, either collagen tail (ColQ) or proline-rich membrane anchor (PRiMA). Complexes with ColQ represent the asymmetric forms (A12) in muscle, while complexes with PRiMA represent tetrameric globular forms (G4) mainly found in brain and muscle. Apart from these traditional molecular forms, a ColQ-linked asymmetric form and a PRiMA-linked globular form of hybrid cholinesterases (ChEs), having both AChE and BChE catalytic subunits, were revealed in chicken brain and muscle. The similarity of various molecular forms of AChE and BChE raises interesting question regarding to their possible relationship in enzyme assembly and localization. The focus of this review is to provide current findings about the biosynthesis of different forms of ChEs together with their anchoring proteins.
Countering the Somali Pirates: Harmonizing the International Response
Richard Weitz
Journal of Strategic Security , 2009,
Abstract: The growing threat to international shipping in the Gulf of Aden and neighboring regions from pirates operating off the shores of lawless Somalia has engendered an unparalleled global response. Over the past year, numerous international security organizations as well as national governments have organized many separate multilateral and single-country maritime security operations in the Horn of Africa region. Despite the unprecedented extent of this effort, this mishmash of ad hoc multinational and national initiatives has had only a limited effect. These various contingents typically have conflicting mandates and rules of engagement. They have also become fixated on responding to immediate problems rather than organizing a robust regional maritime structure, which could replace the foreign fleets when they inevitably withdraw.
An Improvement on Ranks of Explicit Tensors
Benjamin Weitz
Computer Science , 2011,
Abstract: We give constructions of n^k x n^k x n tensors of rank at least 2n^k - O(n^(k-1)). As a corollary we obtain an [n]^r shaped tensor with rank at least 2n^(r/2) - O(n^(r/2)-1) when r is odd. The tensors are constructed from a simple recursive pattern, and the lower bounds are proven using a partitioning theorem developed by Brockett and Dobkin. These two bounds are improvements over the previous best-known explicit tensors that had ranks n^k and n^(r/2) respectively
Towards the Synthesis of Inosine Building Blocks for the Preparation of Oligonucleotides with Hydrophobic Alkyl Chains Between the Nucleotide Units
Karl K?stler,Helmut Rosemeyer
Molecules , 2009, DOI: 10.3390/molecules14114326
Abstract: The scientific objective of the research reported in this manuscript was the synthesis of novel phosphoramidite building blocks for the preparation of lipophilic oligonucleotides. Reaction of inosine (4) with 4-oxopentyl-4-methylbenzoate (2c) in the presence of triethyl orthoformate and 4M HCl in 1,4-dioxane gave a diastereoisomeric mixture of the ketals 5. Subsequent 4,4’-dimethoxytritylation at the 5’-hydroxyl afforded (R)-6 + (S)-6 which could be separated chromatographically. Detoluoylation gave compounds (R)-7 and (S)-7. Phosphitylation of a diastereoisomeric mixture of 7 led to a mixture of four diastereoisomers of the corresponding 2-cyanoethylphosphoramidites 8.
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