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Rube tube : CBS and rural comedy in the sixties
\"Historian Sara Eskridge examines television's rural comedy boom in the 1960s and the political, social, and economic factors that made these shows a perfect fit for CBS. The network, nicknamed the Communist Broadcasting System during the Red Scare of the 1940s, saw its image hurt again in the 1950s with the quiz show scandals and a campaign against violence in westerns. When a rival network introduced rural-themed programs to cater to the growing southern market, CBS latched onto the trend and soon reestablished itself as the Country Broadcasting System. Its rural comedies dominated the ratings throughout the decade, attracting viewers from all parts of the country. With fascinating discussions of The Andy Griffith Show, The Beverly Hillbillies, Petticoat Junction, and other shows, Eskridge reveals how the southern image was used to both entertain and reassure Americans in the turbulent 1960s\"-- Provided by publisher.
Book
Tau PET imaging in neurodegenerative tauopathies—still a challenge
The accumulation of pathological misfolded tau is a feature common to a collective of neurodegenerative disorders known as tauopathies, of which Alzheimer’s disease (AD) is the most common. Related tauopathies include progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), Down’s syndrome (DS), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). Investigation of the role of tau pathology in the onset and progression of these disorders is now possible due the recent advent of tau-specific ligands for use with positron emission tomography (PET), including first- (e.g., [18F]THK5317, [18F]THK5351, [18F]AV1451, and [11C]PBB3) and second-generation compounds [namely [18F]MK-6240, [18F]RO-948 (previously referred to as [18F]RO69558948), [18F]PI-2620, [18F]GTP1, [18F]PM-PBB3, and [18F]JNJ64349311 ([18F]JNJ311) and its derivative [18F]JNJ-067)]. In this review we describe and discuss findings from in vitro and in vivo studies using both initial and new tau ligands, including their relation to biomarkers for amyloid-β and neurodegeneration, and cognitive findings. Lastly, methodological considerations for the quantification of in vivo ligand binding are addressed, along with potential future applications of tau PET, including therapeutic trials.
Journal Article
The Non-Essential Amino Acid Cysteine Becomes Essential for Tumor Proliferation and Survival
The non-essential amino acid cysteine is used within cells for multiple processes that rely on the chemistry of its thiol group. Under physiological conditions, many non-transformed tissues rely on glutathione, circulating cysteine, and the de novo cysteine synthesis (transsulfuration) pathway as sources of intracellular cysteine to support cellular processes. In contrast, many cancers require exogeneous cystine for proliferation and viability. Herein, we review how the cystine transporter, xCT, and exogenous cystine fuel cancer cell proliferation and the mechanisms that regulate xCT expression and activity. Further, we discuss the potential contribution of additional sources of cysteine to the cysteine pool and what is known about the essentiality of these processes in cancer cells. Finally, we discuss whether cyst(e)ine dependency and associated metabolic alterations represent therapeutically targetable metabolic vulnerabilities.
Journal Article
Structure and Physiological Regulation of AMPK
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric αβγ complex that functions as a central regulator of energy homeostasis. Energy stress manifests as a drop in the ratio of adenosine triphosphate (ATP) to AMP/ADP, which activates AMPK’s kinase activity, allowing it to upregulate ATP-generating catabolic pathways and to reduce energy-consuming catabolic pathways and cellular programs. AMPK senses the cellular energy state by competitive binding of the three adenine nucleotides AMP, ADP, and ATP to three sites in its γ subunit, each, which in turn modulates the activity of AMPK’s kinase domain in its α subunit. Our current understanding of adenine nucleotide binding and the mechanisms by which differential adenine nucleotide occupancies activate or inhibit AMPK activity has been largely informed by crystal structures of AMPK in different activity states. Here we provide an overview of AMPK structures, and how these structures, in combination with biochemical, biophysical, and mutational analyses provide insights into the mechanisms of adenine nucleotide binding and AMPK activity modulation.
Journal Article
Folate gene polymorphisms CBS 844ins68 and RFC1 A80G and risk of Down syndrome offspring in young Iranian women: A cross-sectional study
Background: Cytogenetics and association studies showed that folate gene polymorphisms can increase the risk of chromosomal nondisjunction and aneuploidies. The folate-metabolizing gene polymorphisms in Down syndrome mothers (DSM) have been assessed in a variety of populations. Reduced folate carrier 1 (RFC1) and cystathionine beta-synthase (CBS) are key enzymes in folate metabolism. Objective: 2 common polymorphisms, CBS 844ins68 and RFC1 A80G, were analyzed to determine their probable risk for having Down syndrome (DS) babies in young mothers of Khuzestan province, Iran. Materials and Methods: This study was conducted on 100 mothers who had trisomy 21 DS children. 100 age- and ethnic-matched mothers with at least 2 healthy children and no history of abnormal pregnancies were considered as control. The samples were collected from all the mothers from June 2019 to April 2021. Genomic DNA was extracted from peripheral blood. The CBS-844ins68 and RFC1-A80G were genotyped using polymerase chain reaction-electrophoresis and restriction fragment length polymorphism, respectively. Results: The frequency of RFC1 AG and GG genotypes in DSM was significantly higher than the control mothers (odds ratio [OR] of 2.38 and 3.07, respectively). The heterozygote genotype of CBS 844ins68 was significantly more prevalent among DSM than the control (OR: 2.419). The OR was significantly increased to 6.667 when the homozygote of both variants was found together. Conclusion: Studying polymorphisms possibly increases the susceptibility of having a DS child. However, ethnicity, nutrition, and epistatic interactions are considerable factors to be evaluated in future studies. Key words: Down syndrome, Folic acid, Polymorphism, CBS, RFC1.
Journal Article
Painlevé analysis for a new integrable equation combining the modified Calogero–Bogoyavlenskii–Schiff (MCBS) equation with its negative-order form
A new integrable equation is constructed by combining the recursion operator of the modified Calogero–Bogoyavlenskii–Schiff equation and its inverse recursion operator. The Painlevé is performed to demonstrate the complete integrability of the newly developed equation. Multiple-soliton solutions are depicted as manifestation of the integrability. We further show that this equation enjoys a variety of soliton solutions that include kinks, peakon, cuspon.
Journal Article
A variety of completely integrable Calogero–Bogoyavlenskii–Schiff equations with time-dependent coefficients
PurposeThe purpose of this paper is to introduce a variety of new completely integrable Calogero–Bogoyavlenskii–Schiff (CBS) equations with time-dependent coefficients. The author obtains multiple soliton solutions and multiple complex soliton solutions for each of the developed models.Design/methodology/approachThe newly developed models with time-dependent coefficients have been handled by using the simplified Hirota’s method. Moreover, multiple complex soliton solutions are derived by using complex Hirota’s criteria.FindingsThe developed models exhibit complete integrability, for specific determined functions, by investigating the compatibility conditions for each model.Research limitations/implicationsThe paper presents an efficient algorithm for handling integrable equations with analytic time-dependent coefficients.Practical implicationsThe work presents new integrable equations with a variety of time-dependent coefficients. The author showed that integrable equations with time-dependent coefficients give real and complex soliton solutions.Social implicationsThis study presents useful algorithms for finding and studying integrable equations with time-dependent coefficients.Originality/valueThe paper gives new integrable CBS equations which appear in propagation of waves and provide a variety of multiple real and complex soliton solutions.
Journal Article
Stereoselective reduction of enantiopure α-l-amino-β-keto esters using oxazaborolidine catalysts for the synthesis of statine analogues
An efficient diastereoselective synthesis of Boc-protected 4-amino 3-hydroxy esters starting from natural amino acids is described. The key synthetic strategy involves diastereoselective reduction of α-L-amino-β-keto esters in the presence of enantiopure R and S-2-Methyl-CBS-oxazaborolidine catalysts using borane as hydride source. The product diastereoselectivity depends upon the use of (R)or (S)enantiomer of 2-Methyl-CBS-oxazaborolidine. A reasonable mechanism is included which explains the diastereoselectivity of the reactions with the use of different enantiomers of 2-Methyl-CBS-oxazaborolidine. Furthermore, the resulting diastereomeric mixture of the reduced products can be separated by column chromatography to gain access to the single pure diastereomers.
Journal Article
Unimolecular reaction of acetone oxide and its reaction with water in the atmosphere
Criegee intermediates (i.e., carbonyl oxides with two radical sites) are known to be important atmospheric reagents; however, our knowledge of their reaction kinetics is still limited. Although experimental methods have been developed to directly measure the reaction rate constants of stabilized Criegee intermediates, the experimental results cover limited temperature ranges and do not completely agree well with one another. Here we investigate the unimolecular reaction of acetone oxide [(CH₃)₂COO] and its bimolecular reaction with H₂O to obtain rate constants with quantitative accuracy comparable to experimental accuracy. We do this by using CCSDT(Q)/CBS//CCSD(T)-F12a/DZ-F12 benchmark results to select and validate exchange-correlation functionals, which are then used for direct dynamics calculations by variational transition state theory with small-curvature tunneling and torsional and high-frequency anharmonicity. We find that tunneling is very significant in the unimolecular reaction of (CH₃)₂COO and its bimolecular reaction with H₂O. We show that the atmospheric lifetimes of (CH₃)₂COO depend on temperature and that the unimolecular reaction of (CH₃)₂COO is the dominant decay mode above 240 K, while the (CH₃)₂COO + SO₂ reaction can compete with the corresponding unimolecular reaction below 240 K when the SO₂ concentration is 9 × 1010 molecules per cubic centimeter. We also find that experimental results may not be sufficiently accurate for the unimolecular reaction of (CH₃)₂COO above 310 K. Not only does the present investigation provide insights into the decay of (CH₃)₂COO in the atmosphere, but it also provides an illustration of how to use theoretical methods to predict quantitative rate constants of medium-sized Criegee intermediates.
Journal Article
Involvement of B-aat1 and Cbs in regulating mantle pigmentation in the Pacific oyster (Crassostrea gigas)
Background
Shell color formation is an important physiological process in bivalves, the molecular genetic basis has potential application in bivalve aquaculture, but there is still remaining unclear about this issue. The cystine/glutamate transporter (
Slc7a11
) and cystathionine beta-synthase (
Cbs
) are integral genes in pheomelanin synthesis pathway, which is vital to skin pigmentation.
Methods and results
Here, the sequences of b (0, +) -type amino acid transporter 1 (
B-aat1
) and
Cbs
in Pacific oyster (
Crassostrea gigas
) (
CgB-aat1
,
CgCbs
) were characterized
.
Phylogenetically, the deduced amino acid sequences of
CgB-aat1
and
CgCbs
both possessed conserved features. Genes were both ubiquitously expressed in six tested tissues with more abundant expression level in central mantle. Besides, the polyclonal antibodies of
CgB-aat1
,
CgCbs
,
CgTyr
, and
CgTyrp2
were successfully prepared. Immunofluorescence analysis revealed that
CgB-aat1
and
CgCbs
proteins were both expressed in gill rudiments of eyed-larvae and concentrated mainly in cytoplasm of epithelial cell and nerve axons in mantle. Additionally, after
CgB-aat1
or
CgCbs
silencing, expressions at mRNA and protein levels of
CgB-aat1
and
CgCbs
involved in pheomelanin synthesis were significantly suppressed, and
CgTyr
,
CgTyrp1
and
CgTyrp2
related to eumelanin synthesis were also down-regulated but no apparent differences, respectively. Moreover, micrographic examination found less brown-granules at mantle edge in
CgB-aat1
interference group.
Conclusion
These results implied that pheomelanin synthesis was possible induced by
CgB-aat1-CgTyr-CgCbs
axis, and it played an essential role on mantle pigmentation in the oysters. These findings provide the useful genetic knowledge and enrich the physiological information for the shell color formation in bivalve aquaculture.
Journal Article