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Human Evolution and Fantastic Victorian Fiction, by Anna Neill; pp. xi + 170. New York and London: Routledge, 2021, $128.00, $39.16 ebook. Anna Neill's Human Evolution and Victorian Fantastic Fiction [...]

Fibrosis can affect any organ and is responsible for up to 45% of all deaths in the industrialized world. It has long been thought to be relentlessly progressive and irreversible, but both preclinical models and clinical trials in various organ systems have shown that fibrosis is a highly dynamic process. This has clear implications for therapeutic interventions that are designed to capitalize on this inherent plasticity. However, despite substantial progress in our understanding of the pathobiology of fibrosis, a translational gap remains between the identification of putative antifibrotic targets and conversion of this knowledge into effective treatments in humans. Here we discuss the transformative experimental strategies that are being leveraged to dissect the key cellular and molecular mechanisms that regulate fibrosis, and the translational approaches that are enabling the emergence of precision medicine-based therapies for patients with fibrosis. This review discusses how single-cell profiling and other technological advances are increasing our understanding of the mechanisms of fibrosis, thereby accelerating the discovery, development and testing of new treatments., Author(s): Neil C. Henderson [sup.1] [sup.2] , Florian Rieder [sup.3] [sup.4] , Thomas A. Wynn [sup.5] Author Affiliations: (1) University of Edinburgh Centre for Inflammation Research, The Queen's Medical Research [...]

A Master Scholar Pays a Debt of Gratitude. Jack Zipes. Ernst Bloch: The Pugnacious Philosopher of Hope. Palgrave MacMillan, 2019. xvii + 213 pp. ISBN 978-3-03-021173-8. $83.40 hc. The interest [...]

New Items in the Archive of Early Sf. Mary Ellis Gibson, editor. Science Fiction in Colonial India 1835-1905: Five Tales of Speculation, Resistance and Rebellion. Anthem Press, 2019. 172 pp. [...]

Patient perceptions of the causes of preoperative symptoms, expected impact of surgery on symptoms and anticipated timeline of recovery are likely to affect the risk of readmission following elective surgical procedures. However, these perceptions have not been studied. A qualitative study was designed to explore these perceptions, using the common-sense model of self-regulation (CSM) as the conceptual framework. CSM is grounded in illness representations, describing how patients make sense of changes in physical well-being (e.g. symptoms) and develop and assess management plans. It also establishes a broader framework for examining patients' a priori expectations and timelines for outcomes based on comparisons to prior experiences and underlying self-prototypes, or 'Self as Anchor'. A convenience sample of 14 patients aged 56-81 who underwent elective surgery was recruited. Semi-structured interviews informed by the CSM were completed on the day of discharge. Content analysis with deductive coding was used, and emerging themes were fit to components of the CSM, including the five domains of Illness Representations-identity, cause, timeline, control, and consequences. Two additional themes, outlook (toward the health care system, providers and recovery efforts), and motivation (external or internal for recovering), relate to self-prototypes, expectations for outcomes, and search for coherence. Misattribution of symptoms, unrealistic expectations for outcomes (e.g. expecting complete resolution of symptoms unrelated to the surgical procedure) and timelines for recovery (unrealistically short), and the (baseline) 'normal healthy self' as distinct from the (temporarily) 'sick self' were recurrent themes. Findings suggest that patient perceptions and the actual recovery process may be misaligned. The results underscore the importance of assessing patients' perceptions and expectations, actively engaging patients in their own healthcare, and providing adequate support during the transition to home., Author(s): Michael B. Gehring [sup.1] [sup.2] , Stacee Lerret [sup.2] , Jonette Johnson [sup.1] [sup.2] , Julie Rieder [sup.1] [sup.2] , David Nelson [sup.2] , Laurel Copeland [sup.4] , Ashley [...]

This article reads Albert Wendt's theorization and practice of 'postcolonial' writing in opposition to the project of constructing a unitary theory of 'World SF,' which I argue is a misguided effort that, in spite of its good intentions, carries with it some unfortunate colonial baggage. The article focuses on two long narratives by Albert Wendt, the most celebrated and influential Oceanian writer of the past half century. In contrast to understanding Wendt's work as a 'semi-peripheral' success at forging a 'structural compromise' between Western and Indigenous forms, I argue for using Ngugi wa Thiong'o's theory of 'globalectics' to describe how Wendt's 'synthesis forged in resistance' articulates Indigenous and Western traditions. To flesh out this theoretical intervention, the article proceeds to a reading of how Black Rainbow and The Adventures of Vela bring the dynamics of identity, recognition, and ignorance to bear upon the legacy and ongoing effects of colonialism., In 'World Systems and World Science Fiction,' which leads off a 2014 issue of Paradoxa titled SF Now, Andrew Milner proposes mapping SF onto a scheme borrowed from economic historian [...]

Diverse Perspectives on Literature and the Posthuman. Bruce Clarke and Manuela Rossini, editors. The Cambridge Companion to Literature and the Posthuman. Cambridge: Cambridge UP, 2017. xxxiv + 231 pp. ISBN [...]

A History of Ideas. Mark C. Jerng. Racial Worldmaking: The Power of Popular Fiction. New York: Fordham UP, 2018. vii + 284 pp. ISBN 978-0-82-327777-3. $30 pbk. Reviewed by John [...]

IL-36 is a member of the IL-1 superfamily and consists of three agonists and one receptor antagonist (IL-36Ra). The three endogenous agonists, IL-36[alpha], -[beta], and -[gamma], act primarily as proinflammatory cytokines, and their signaling through the IL-36 receptor (IL-36R) promotes immune cell infiltration and secretion of inflammatory and chemotactic molecules. However, IL-36 signaling also fosters secretion of profibrotic soluble mediators, suggesting a role in fibrotic disorders. IL-36 isoforms and IL-36 have been implicated in inflammatory diseases including psoriasis, arthritis, inflammatory bowel diseases, and allergic rhinitis. Moreover, IL-36 has been connected to fibrotic disorders affecting the kidney, lung, and intestines. This review summarizes the expression, cellular source, and function of IL-36 in inflammation and fibrosis in various organs, and proposes that IL-36 modulation may prove valuable in preventing or treating inflammatory and fibrotic diseases and may reveal a mechanistic link between inflammation and fibrosis., Introduction First identified in 1988 as a member of the IL-1 superfamily, interleukin-36 (IL-36) plays a role in the initiation and progression of inflammatory and fibrotic diseases (1-7). In fact, [...]

We consider the problem of minimizing a certainty equivalent of the total or discounted cost over a finite and an infinite time horizon that is generated by a partially observable Markov decision process (POMDP). In contrast to a risk-neutral decision maker, this optimization criterion takes the variability of the cost into account. It contains as a special case the classical risk-sensitive optimization criterion with an exponential utility. We show that this optimization problem can be solved by embedding the problem into a completely observable Markov decision process with extended state space and give conditions under which an optimal policy exists. The state space has to be extended by the joint conditional distribution of current unobserved state and accumulated cost. In case of an exponential utility, the problem simplifies considerably and we rediscover what in previous literature has been named information state. However, since we do not use any change of measure techniques here, our approach is simpler. A simple example, namely, a risk-sensitive Bayesian house selling problem, is considered to illustrate our results. Keywords: partially observable Markov decision problem * certainty equivalent * exponential utility * updating operator * value iteration, 1. Introduction In this work, we consider partially observable Markov decision processes (POMDP) under a general risk-sensitive optimization criterion for problems with finite and infinite time horizon. This is a [...]

Timely Intersections of Sf and Race. Isiah Lavender III, ed. Black and Brown Planets: The Politics of Race in Science Fiction. Jackson: University Press of Mississippi, 2014. viii + 250 [...]

In Wilson disease (WD), functional loss of ATPase copper-transporting p (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration- and European Medicines Agency-approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD., Introduction Wilson disease (WD) is an autosomal recessively inherited disorder of copper metabolism caused by ATPase copper-transporting β (ATP7B) gene mutations (1-3). ATP7B is a copper-transporting ATPase that mediates copper [...]

We investigate the problem of minimizing a certainty equivalent of the total or discounted cost over a finite and an infinite horizon that is generated by a Markov decision process [...]

Byline: William. Coutinho, Paulo. Vieira, Fernanda. Kutchak, Alexandre. Dias, Marcelo. Rieder, Luiz. Forgiarini Context: Cough assist (CA) is a device to improve bronchial hygiene of patients with secretion in the [...]

Statins are prescribed widely to lower plasma low-density lipoprotein (LDL) concentrations and cardiovascular disease risk (1) and have been shown to have beneficial effects in a broad range of patients (2, 3). However, statins are associated with an increased risk, albeit small, of clinical myopathy (4) and type 2 diabetes (5). Despite evidence for substantial genetic influence on LDL concentrations (6), pharmacogenomic trials have failed to identify genetic variations with large effects on either statin efficacy (7-9) or toxicity (10), and have produced little information regarding mechanisms that modulate statin response. Here we identify a downstream target of statin treatment by screening for the effects of invitrostatin exposure on genetic associations with gene expression levels in lymphoblastoid cell lines derived from 480 participants of a clinical trial of simvastatin treatment (7). This analysis identified six expression quantitative trait loci (eQTLs) that interacted with simvastatin exposure, including rs9806699, a cis-eQTL for the gene glycine amidinotransferase (GATM) that encodes the rate-limiting enzyme in creatine synthesis. We found this locus to be associated with incidence of statin-induced myotoxicity in two separate populations (meta-analysis odds ratio = 0.60). Furthermore, we found that GATM knockdown in hepatocyte-derived cell lines attenuated transcriptional response to sterol depletion, demonstrating that GATM may act as a functional linkbetween statin-mediated lowering of cholesterol and susceptibility to statin-induced myopathy., Analysis of individual variation in transcriptional response to drug treatment has successfully identified regulatory genetic variants that interact with treatment in model organisms (11) and human tissues (12-15). Cellular transcriptional [...]

It is well established that autism spectrum disorders (ASD) have a strong genetic component; however, for at least 70% of cases, the underlying genetic cause is unknown (1). Under the hypothesis that de novo mutations underlie a substantial fraction of the risk for developing ASD in families with no previous history of ASD or related phenotypes--so-called sporadic or simplex families (2,3)--we sequenced all coding regions of the genome (the exome) for parent-child trios exhibiting sporadic ASD, including 189 new trios and 20 that were previously reported (4). Additionally, we also sequenced the exomes of 50 unaffected siblings corresponding to these new (n = 31) and previously reported trios (n = 19) (4), for a total of 677 individual exomes from 209 families. Here we show that de novo point mutations are overwhelmingly paternal in origin (4:1 bias) and positively correlated with paternal age, consistent with the modest increased risk for children of older fathers to develop ASD (5). Moreover, 39% (49 of 126) of the most severe or disruptive de novo mutations map to a highly interconnected β-catenin/chromatin remodelling protein network ranked significantly for autism candidate genes. In proband exomes, recurrent protein-altering mutations were observed in two genes: CHD8 and NTNG1. Mutation screening of six candidate genes in 1,703 ASD probands identified additional de novo, protein-altering mutations in GRIN2B, LAMC3 and SCN1A. Combined with copy number variant (CNV) data, these results indicate extreme locus heterogeneity but also provide a target for future discovery, diagnostics and therapeutics., We selected 189 autism trios from the Simons Simplex Collection (SSC) (6), which included males significantly impaired with autism and intellectual disability (n = 47), a female sample set (n [...]

Colour sidedness is a dominantly inherited phenotype of cattle characterized by the polarization of pigmented sectors on the flanks, snout and ear tips1. It is also referred to as 'lineback' or 'witrik' (which means white back), as colour-sided animals typically display a white band along their spine. Colour sidedness is documented at least since the Middle Ages and is presently segregating in several cattle breeds around the globe, including in Belgian blue and brown Swiss (1,2). Here we report that colour sidedness is determined by a first allele on chromosome 29 ([Cs.sub.29]), which results from the translocation of a 492-kilobase chromosome 6 segment encompassing KIT to chromosome 29, and a second allele on chromosome 6 ([CS.sub.6]), derived from the first by repatriation of fused 575-kilobase chromosome 6 and 29 sequences to the KIT locus. We provide evidence that both translocation events involved circular intermediates. This is the first example, to our knowledge, of a phenotype determined by homologous yet non-syntenic alleles that result from a novel copy-number-variant-generating mechanism., To gain insights into the molecular basis of colour sidedness (Fig. 1), we genotyped 21 colour-sided and 30 control Belgian blue animals with a custom-made 50K single nucleotide polymorphism (SNP) [...]

Ifosfamide-induced nephrotoxicity is a serious adverse effect in children undergoing chemotherapy. Our previous cell and rodent models have shown that the antioxidant N-acetylcysteine (NAC), used extensively as an antidote for acetaminophen poisoning, protects renal tubular cells from ifosfamide-induced nephrotoxicity at a clinically relevant concentration. For the use of NAC to be clinically relevant in preventing ifosfamide nephrotoxicity, we must ensure there is no effect of NAC on the antitumor activity of ifosfamide. Common pediatric tumors that are sensitive to ifosfamide, human neuroblastoma SK-N-BE(2) and rhabdomyosarcoma RD114-B cells, received either no pretreatment or pretreatment with 400 µmol/L of NAC, followed by concurrent treatment with NAC and either ifosfamide or the active agent ifosfamide mustard. Ifosfamide mustard significantly decreased the growth of both cancer cell lines in a dose-dependent manner (p < 0.001). The different combined treatments of NAC alone, sodium 2-mercaptoethanesulfonate alone, or NAC plus sodium 2-mercaptoethanesulfonate did not significantly interfere with the tumor cytotoxic effect of ifosfamide mustard. These observations suggest that NAC may improve the risk/benefit ratio of ifosfamide by decreasing ifosfamide-induced nephrotoxicity without interfering with its antitumor effect in cancer cells clinically treated with ifosfamide. Key words: ifosfamide, N-acetylcysteine, nephrotoxicity, pediatric tumors, antitumor activity. La nephrotoxicite induite par l'ifosfamide est un effet indesirable grave chez les enfants sous chimiotherapie. Nos modeles cellulaires et murins anterieurs ont montre que la N-acetylcysteine (NAC) antioxydante, largement utilisee comme antidote de l'intoxication a l'acetaminophene, protege les cellules tabulaires renales contre la nephrotoxicite induite par l'ifosfamide a une concentration cliniquement significative. Pour que la NAC previenne efficacement la nephrotoxicite induite par l'ifosfamide, elle ne doit pas avoir d'effet sur l'activite antitumorale de celle-ci. Pour nos experiences, des tumeurs pediatriques communes sensibles a l'ifosfamide, les cellules humaines SK-N-BE(2) de neuroblastome et RD114-B de rhabdomyosarcome, n'ont ete soumises a aucun pretraitement, ou ont ete pretraitees avec 400 µmol/L de NAC, puis soumises a un traitement concomitant avec la NAC et avec soit l'ifosfamide, soit la forme active moutarde de l'ifosfamide. La forme active moutarde a diminue considerablement la croissance des deux lignees de cellules cancereuses en fonction de la dose utilisee (p < 0,001). Les differents traitements, NAC uniquement, ou 2-mercaptoethanolsulfonate sodium uniquement, ou NAC plus 2-mercaptoethanolsulfonate sodium, n'ont pas montre d'interference significative avec l'effet cytotoxique tumoral de l'ifosfamide moutarde. Ces observations donnent a penser que NAC pourrait ameliorer le rapport benefice/risque de l'ifosfamide en diminuant la nephrotoxicite induite par celle-ci sans interferer avec son effet antitumoral dans ces cellules cancereuses. Mots-cles : ifosfamide, N-acetylcysteine, nephrotoxicite, tumeurs pediatriques, activite antitumorale. [Traduit par la Redaction], Introduction Improved therapy for pediatric cancers has resulted in a remarkable increase in the number of long-term survivors of childhood cancer (Oeffinger et al. 2006). However, many of these survivors [...]

[gamma][delta] T cells present in epithelia[ tissues provide a crucial first line of defense against environmental insults, including infection, trauma, and malignancy, yet the molecular events surrounding their activation remain poorly defined. Here we identify an epithelial [gamma][delta] T cell--specific costimulatory molecule, junctional adhesion molecule--like protein (JAML). Binding of JAML to its ligand Coxsackie and adenovirus receptor (CAR) provides costimulation leading to cellular proliferation and cytokine and growth factor production. Inhibition of JAML costimulation leads to diminished [gamma][delta] T cell activation and delayed wound closure akin to that seen in the absence of [gamma][delta] T cells. Our results identify JAML as a crucial component of epithelial [gamma][delta] T cell biology and have broader implications for CAR and JAML in tissue homeostasis and repair. 10.1126/science.1192698

Exposure of esophageal mueosa to hydrochloric acid (HC1) is a crucial factor in the pathogenesis of reflux disease. We examined supernatant of HC1-exposed rabbit mucosa for inflammatory mediators enhancing migration of leukocytes and production of [H.sub.2][O.sub.2] as an indicator of leukocyte activation. A tubular segment of rabbit esophageal mucosa was tied at both ends to form a sac, which was filled with HC1-acidified Krebs buffer at pH 5 (or plain Krebs buffer as control) and kept oxygenated at 37[degrees]C. The medium around the sac (supernatant) was collected after 3 h. Rabbit peripheral blood leukocytes (PBL) were isolated, and sac supernatant was used to investigate PBL migration and [H.sub.2][O.sub.2] production. HCl-exposed esophageal mucosa released substance P (SP), CGRP, platelet-activating factor (PAF), and IL-8 into the supernatant. PBL migration increased in response to IL-8 or to supernatant of the HCl-filled mucosal sac. Supernatant-induced PBL migration was inhibited by IL-8 antibodies and by antagonists for PAF (CV3988) or neurokinin 1 (i.e., SP), but not by a CGRP antagonist. Supernatant of the HCl-filled mucosal sac increased [H.sub.2][O.sub.2] release by PBL that was significantly reduced by CV3988 and by a SP antagonist but was not affected by IL-8 antibodies or by a CGRP antagonist. We conclude that IL-8, PAF, and SP are important inflammatory mediators released by esophageal mucosa in response to acid that promote PBL migration. In addition, PAF and SP induce production of [H.sub.2][O.sub.2] by PBL. These findings provide a direct link between acid exposure and recruitment and activation of immune cells in esophageal mucosa. PAF; substance P; IL-8; gastroesophageal reflux doi: 10.1152/ajpgi.00160.2010.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tips.2010.05.006 Byline: Mitzi Nagarkatti, Sadiye Amcaoglu Rieder, Venkatesh L. Hegde, Shunsuke Kanada, Prakash Nagarkatti Abstract: Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties. Significant clinical and experimental data on the use of cannabinoids as anti-inflammatory agents exist in many autoimmune disease settings, but virtually no studies have been undertaken on their potential role in transplant rejection. Here we suggest a theoretical role for the use of cannabinoids in preventing allograft rejection. The psychotropic properties of CB1 agonists limit their clinical use, but CB2 agonists may offer a new avenue to selectively target immune cells involved in allograft rejection. Moreover, development of mixed CB1/CB2 agonists that cannot cross the blood-brain barrier may help prevent their undesired psychotropic properties. In addition, manipulation of endocannabinoids in vivo by activating their biosynthesis and inhibiting cellular uptake and metabolism may offer another pathway to regulate immune response during allograft rejection. Author Affiliation: Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, USA

The importance of Jules Verne's voyages extraordinaires for any construction of the history of science fiction seems beyond dispute. As James Gunn put it in a recent roundtable discussion of [...]

7-Aminomethyl-7-deazaguanine (pre[Q.sub.1]) sensitive mRNA domains belong to the smallest riboswitches known to date. Although recent efforts have revealed the three-dimensional architecture of the ligand-aptamer complex less is known about the molecular details of the ligand-induced response mechanism that modulates gene expression. We present an in vitro investigation on the ligand-induced folding process of the pre[Q.sub.1] responsive RNA element from Fusobacterium nucleatum using biophysical methods, including fluorescence and NMR spectroscopy of site-specifically labeled riboswitch variants. We provide evidence that the full-length riboswitch domain adopts two different coexisting stem-loop structures in the expression platform. Upon addition of pre[Q.sub.1], the equilibrium of the competing hairpins is significantly shifted. This system therefore, represents a finely tunable antiterminator/terminator interplay that impacts the in vivo cellular response mechanism. A model is presented how a riboswitch that provides no obvious overlap between aptamer and terminator stem-loop solves this communication problem by involving bistable sequence determinants. RNA | chemical synthesis | labeling | bistable structures I riboswitches doi/ 10.1073/pnas.0914925107

Gastroesophageal reflux disease (GERD) is one of the most common problems in clinical practice today. It is widely believed that functional and structural abnormalities of the gastroesophageal junction as well as an abnormal exposure to gastroduodenal contents are the main contributors to its pathogenesis. Novel findings of the inflammatory process in GERD suggest a far more complex process involving multifaceted inflammatory mechanisms. This review summarizes knowledge about the expression of inflammatory mediators in GERD and their potential cellular sources and provides an integrated concept of disease pathogenesis. In addition we evaluate the contribution of inflammatory mediators to well-known complications of GERD, namely motility abnormalities, fibrosis, and carcinogenesis. Novel findings regarding the pathophysiology of esophageal inflammation should enhance our understanding of GERD and its complications and provide new treatment insights. cytokines; motility; stricture; stenosis doi: 10.1152/ajpgi.00454.2009.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.forsciint.2009.12.040 Byline: R. Gow (a), S. Thomson (b), M. Rieder (b)(c), S. Van Uum (b), G. Koren (a)(b)(d)(e) Keywords: Hair; Cortisol; Chronic stress; Hypothalamic-pituitary-adrenal axis Abstract: Hair analyses for exogenous compounds, specifically drugs of abuse, have been a useful tool in detecting long-term drug exposure. More recently, studies have delved into the exposure of endogenous compounds in hair. Cortisol is synthesized in the adrenal cortex in response to stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis. While catecholamines generally indicate acute stress, cortisol can be used as an indicator for sub-acute and chronic stress. Studies on the effects of chronic stress are most often subjective in nature, relying on questionnaires asking the participant to recall on past stressors. This can lead to the issue of recall and reporting bias. A new objective measure of chronic stress is needed for a more accurate understanding of the effects of chronic stress on the body. This review uses emerging evidence to describe the usefulness of hair analysis for cortisol and discusses the current methods used. Author Affiliation: (a) Department of Physiology and Pharmacology, University of Western Ontario, Canada (b) Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, Canada (c) CIHR-GSK Chair in Pediatric Clinical Pharmcology, Children's Health Research Institute, London, Ontario, Canada (d) Ivey Chair in Molecular Toxicology, University of Western Ontario, Canada (e) Department of Clinical Pharmacology/Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada Article History: Received 12 June 2009; Accepted 2 September 2009

It's a Franchise! Nicholas Michaud, ed. Frankenstein and Philosophy: The Shocking Truth. Chicago: Open Court, 2013. 302 pp. ISBN 9780812698367. $19.95 pbk. To many scholars and students of science fiction, [...]

To determine why the duration of mitosis (DM) is less in Taxol than in nocodazole or Eg5 inhibitors we studied the relationship between Taxol concentration, the DM, and the mitotic checkpoint. We found that unlike for other spindle poisons, in Taxol the DM becomes progressively shorter as the concentration surpasses ~0.5 [micro]M. Studies on RPE1 and PtK2 expressing GFP/ cyclin B or YFP/Mad2 revealed that cells ultimately satisfy the checkpoint in Taxol and do so faster at concentrations >0.5 [micro]M. Inhibiting the aurora-B kinase in Taxol-treated RPE1 cells accelerates checkpoint satisfaction by stabilizing syntelic kinetochore attachments and reduces the DM to ~1.5 h regardless of drug concentration. A similar stabilization of syntelic attachments by Taxol itself appears responsible for accelerated checkpoint satisfaction at concentrations >0.5 [micro]M. Our results provide a novel conceptual framework for how Taxol prolongs mitosis and caution against using it in checkpoint studies. They also offer an explanation for why some cells are more sensitive to lower versus higher Taxol concentrations.

Introduction: The needs and issues of rural women regarding pharmacologic information and therapy are rarely explored. We sought to explore the needs and issues of rural women in Canada regarding [...]

When the spindle assembly checkpoint (SAC) cannot be satisfied, cells exit mitosis via mitotic slippage. In microtubule (MT) poisons, slippage requires cyclin B proteolysis, and it appears to be accelerated in drug concentrations that allow some MT assembly. To determine if MTs accelerate slippage, we followed mitosis in human RPE-1 cells exposed to various spindle poisons. At 37[degrees]C, the duration of mitosis in nocodazole, colcemid, or vinblastine concentrations that inhibit MT assembly varied from 20 to 30 h, revealing that different MT poisons differentially depress the cyclin B destruction rate during slippage. The duration of mitosis in Eg5 inhibitors, which induce monopolar spindles without disrupting MT dynamics, was the same as in cells lacking MTs. Thus, in the presence of numerous unattached kinetochores, MTs do not accelerate slippage. Finally, compared with cells lacking MTs, exit from mitosis is accelerated over a range of spindle poison concentrations that allow MT assembly because the SAC becomes satisfied on abnormal spindles and not because slippage is accelerated.

Crystalline CsAlSi[O.sub.4] was synthesized from a stoichiometric mixture of [Al.sub.2][O.sub.3] + Si[O.sub.2] + [Cs.sub.2]O (plus excess water) in Ag-capsules at hydrostatic pressure of 0.1 GPa and temperature of 695 [degrees]C. The duration of synthesis was 46 h. The crystal structure of CsAlSi[O.sub.4] was investigated by single-crystal X-ray diffraction. The structure is orthorhombic with Pc[2.sub.1]n space group and lattice parameters: a = 9.414(1), b = 5.435(1), and c = 8.875(1) [Angstrom]. Because of the orthohexagonal relation between b and a (a [approximately equal to] b[square root of 3]), within the standard uncertainty on the lattice parameters, a hexagonal superlattice exists, which is responsible for twinning. The crystals are twinned by reflection, with twin planes (110) and (310): twinning in both cases is by reticular merohedry with twin index 2 and hexagonal twin lattice ([L.sub.T]). The transformation from the lattice of the individual ([L.sub.ind]) to [L.sub.T] is given by: [a.sub.T] = [a.sub.ind] - [b.sub.ind,] [b.sub.T] = [2b.sub.ind] , and [c.sub.T] = [c.sub.ind]. The refinement was initiated using the previously published atomic coordinates for RbAlSi[O.sub.4]. The final least-square cycles were conducted with anisotropic displacement parameters. [R.sub.1] = 3.04% for 66 parameters and 2531 unique reflections. For a more reliable crystallographic comparison the crystal structure of RbAlSi[O.sub.4] is reinvestigated here adopting the same data collection and least-squares refinement strategy as for CsAlSi[O.sub.4]. The crystal structure of the CsAlSi[O.sub.4] feldspathoid is built on an ABW framework type, showing a fully ordered Si/Al-distribution in the tetrahedral framework. The only extra-framework site is occupied by Cs, lying off-center in the 8mR-channels. CsAlSi[O.sub.4] is more likely to retain Cs when immersed in a fluid phase, relative to several other Cs-bearing zeolites. The topological configuration of the Cs-polyhedron (and its bonding environment), the small dimension of the pores and the high flexibility of the ABW framework type would imply a better thermal and elastic stability of CsAlSi[O.sub.4] than those of the zeolitic Cs-aluminosilicates. In this light, CsAlSi[O.sub.4] can be considered as a functional material potentially usable for fixation and deposition of radioactive isotopes of Cs and can also be considered as a potential solid host for a [sup.137]Cs [gamma]-radiation source to be used in sterilization applications. Keywords: CsAlSi[O.sub.4], RbAlSi[O.sub.4], ABW framework type, feldspathoid, crystal structure, nuclear waste disposal phase

Background Tuberculosis (TB) remains a significant global health problem, responsible for an estimated 1.7 million deaths per year worldwide [1 ]. Resistance to anti-tuberculosis drugs is an important threat to [...]

Empire as thought experiment. Patricia Kerslake. Science Fiction and Empire. Liverpool: Liverpool university press, 2007. 217 pp. $75 hdbk. 'We are all products of the historical imperial project,' writes Patricia [...]

Several studies are conducted to study the association between the common polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1[alpha] and plasma C-reactive protein (CRP) concentration. The two discussed phenomenon are shown to be completely related and dependent on each other.

Byline: Mary Alm, PhD (Department of Pediatrics and Adolescent Health, University of Minnesota, Minneapolis, Minnesota, almx0002@umn.edu); Nafisseh Soroudi, PhD (Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts); Judith Wylie-Rosett, EdD, [...]