bluuebunny/crossref_metadata_2025 huggingface dataset:
Suspected zoonotic transmission of rotavirus group A in Danish adults
Authors: MIDGLEY S. E. , HJULSAGER C. K. , LARSEN L. E. , FALKENHORST G. , BÖTTIGER B.
Published: September 2011

Group A rotaviruses infect humans and a variety of animals. In July 2006 a rare rotavirus strain with G8P[14] specificity was identified in the stool samples of two adult patients with diarrheoa, who lived in the same geographical area in Denmark. Nucleotide sequences of the VP7, VP4, VP6, and NSP4 genes of the identified strains were identical. Phylogenetic analyses showed that both Danish G8P[14] strains clustered with rotaviruses of animal, mainly, bovine and caprine, origin. The high genetic relatedness to animal rotaviruses and the atypical epidemiological features suggest that these human G8P[14] strains were acquired through direct zoonotic transmission events.
Kant, Intervention and the ‘Failed State’
Authors: Cavallar Georg , Reinisch August
Published: September 2011

Nowadays Kant's practical philosophy (including his political philosophy) is as highly regarded as his theoretical philosophy. This is an important development since the more constructive side of Kant's philosophy is to be found in his moral and political works. The main task of theCritique of Pure Reasonis to clarify its concepts and to get rid of basic errors, and thus only ‘negative’. The moral and political writings, on the other hand, try to expand the scope of reason ‘for practical purposes’ (‘in praktischer Absicht’). Establishing principles of moral and political conduct, their main objective is not negative, but constructive.
Pleasure and Fit in Kant's Aesthetics
Authors: Rogerson Kenneth F.
Published: September 2011

In the third Critique Kant shifts the focus in his enquiry from the status of factual statements in the Critique of Pure Reason and the grounding of moral imperatives in the Critique of Practical Reason to investigating two methods of considering the world which go beyond the strictly verifiable. This is a move from evaluating the interplay of a ‘determinate’ set of facts and intellectual preconditions to forming what Kant calls ‘reflective’ judgements on these facts. There are two major questions which the Critique of Judgement tackles. On the one hand Kant ambitiously considers how we might properly interpret a set of facts as comprising a larger teleological system and, on the other hand, he is interested in the seemingly quite separate issue of the appreciation of objects as beautiful. It is this latter issue which shall concern us here. Consistent with the reflective stand in the third Critique, Kant argues from the very outset that beauty is not an empirical concept with which we might describe the world. Beauty is not objective in the sense that size, colour or weight might be. Objective properties of this kind belong to the world of scientific understanding. Instead, he holds that judgements of aesthetic merit should be based upon the subjective pleasure we take in experiencing works of art and natural objects.
The Place of Punishment in Kant's Rechtslehre
Authors: Gorner Paul
Published: September 2011

If Kant had never written the section of the Rechtslehre on punishment we would still have known from the Critique of Practical Reason that he held a strongly retributive view of punishment. But it is not a view which we could have inferred from the rest of the Rechtslehre. Despite its intuitive appeal, Kant's justification of judicial punishment simply does not fit the account of right he gives in the Rechtslehre. According to this account the only justification for coercion is that it constitutes a ‘hindering of a hindrance’ to freedom. But there is no way in which this requires punishment to be retributive.
HOPE AND MEMORY IN THE THOUGHT OF JUDITH SHKLAR
Authors: FORRESTER KATRINA
Published: September 2011

Current interpretations of the political theory of Judith Shklar focus to a disabling extent on her short, late article “The Liberalism of Fear” (1989); commentators take this late essay as representative of her work as a whole and thus characterize her as an anti-totalitarian, Cold War liberal. Other interpretations situate her political thought alongside followers of John Rawls and liberal political philosophy. Challenging the centrality of fear in Shklar's thought, this essay examines her writings on utopian and normative thought, the role of history in political thinking and her notions of ordinary cruelty and injustice. In particular, it shifts emphasis away from an exclusive focus on her late writings in order to consider works published throughout her long career at Harvard University, from 1950 until her death in 1992. By surveying the range of Shklar's critical standpoints and concerns, it suggests that postwar American liberalism was not as monolithic as many interpreters have assumed. Through an examination of her attitudes towards her forebears and contemporaries, it shows why the dominant interpretations of Shklar—as anti-totalitarian émigré thinker, or normative liberal theorist—are flawed. In fact, Shklar moved restlessly between these two categories, and drew from each tradition. By thinking about both hope and memory, she bridged the gap between two distinct strands of postwar American liberalism.
Catholicism, Rawlsian Political Liberalism, and Reciprocity: Insights from the Travails of Bishop Henry of Calgary
Authors: Soroski John
Published: September 2011

John Rawls contended that an overlapping consensus for “political liberalism” could be found in different ways across the range of comprehensive systems of value in western societies. Three recent conflicts concerning the relationship of church and state in Canada involving the Catholic Bishop of Calgary, Frederick Henry, provide an opportunity to consider Rawls' ideas in a specific societal context. The first of these conflicts — Henry's call for the excommunication of Catholic Prime Minister Paul Martin for legalizing same-sex marriage — suggests that the resources for a Rawlsian overlapping consensus may be difficult to find in Catholicism. The refusal of the Calgary Catholic School Board to obey Henry's order to end the use of gambling related school fund-raising, the second of the Bishop's “travails,” undercuts that conclusion, but the moral emptiness of the vocabulary of cultural liberalism, which the Board deployed in its self-justifications, suggests that too much liberalism might be almost as regrettable as too little. Henry's third travail — a call before the Human Rights Commission to answer charges of “discriminatory public speech” for his public criticisms of homosexuality — suggests the merit of recognizing an alternative to overlapping consensus as the source of Catholic recognition of Rawlsian political liberalism: reciprocity.
Perception of Health, Suicidal Ideation, and Suicide Attempt Among Adults in the Community
Authors: Goodwin Renee D. , Marusic Andrej
Published: September 2011

Background: There is a well-known association between perception of poor physical health and higher rates of physical and psychological morbidity. However, little is known about the possible link between perception of health and suicidality. Aims: The study examines the relationship between perception of poor health and suicidal ideation and suicide attempt among adults in the community. Methods: Data were drawn from the National Comorbidity Survey (n = 5,877), a representative sample of individuals 15–54 years of age in the United States. Multiple logistic regression analyses were used to determine the relationship between perception of poor health and the likelihood of suicidal ideation and suicide attempt. Sociodemographic characteristics, comorbid mental disorders, and physical illnesses were adjusted for in the final model. Results: Perception of poor health was associated with a significantly increased likelihood of suicidal ideation (OR = 2.14 (1.36, 3.35) and suicide attempt (OR = 2.03 (1.06, 3.91)), which persisted after adjusting for differences in sociodemographic characteristics, mental disorders, and self-reported physical illnesses. Conclusions: Our findings provide initial evidence that perception of poor health is associated with a significantly increased likelihood of suicidal ideation and suicide attempt among adults in the community.
Early Adolescence and Suicidal Ideations in Croatia
Authors: Franić Tomislav , Dodig Goran , Kardum Goran , Marčinko Darko , Ujević Ante , Biluić Marijo
Published: September 2011

Background/Aims: Suicidal ideations (SI) indicate and predict psychological distress. We examined the prevalence of SI among early adolescents and its association with parental war participation, personal, behavioral, and sociodemographic characteristics. Methods: We performed a cross-sectional questionnaire study on 803 12-year-old adolescents. Data were collected using a sociodemographic questionnaire, the Junior Eysenck Personality Questionnaire and Children Depression Inventory. Unintentional injuries, physical fighting, and involvement in bullying behavior were assessed using questions from the World Health Organization (WHO) survey Health Behavior in School-aged Children. Suicidal ideations were assessed with three dichotomous items. Results: There were no gender differences in SI prevalence. SI in males were associated with lower maternal education, crowded families, birth order, parental war participation, physical fighting, being bullied, and substance use. In females, we found associations with lower parental educational level, number of brothers, lower perception of the relationship with parents, parental relationship, family cohesion and parental control, negative attitude toward school, rare church attendance, fighting, and being bully or bullied. Depressive symptoms and SI were associated in both genders. Conclusions: SI showed gender-specific associations that may partially be explained with parental war involvement. These findings may have potentially important clinical and preventive implications.
IL‐22 and non‐ELR‐CXC chemokine expression in chronic hepatitis B virus‐infected liver
Authors: Xiang Xiaogang , Gui Honglian , King Nicholas JC , Cole Louise , Wang Hui , Xie Qing , Bao Shisan
Published: September 2011

Hepatitis B virus infection is still a major global health problem, despite decades of research. Interleukin (IL)‐22 induces acute phase reactants and chemokines, favors anti‐microbial defence and protects tissues from damage. IL‐22 is important in chronic skin inflammation, but its role in chronic hepatitis B (CHB) is unclear. This study explores the association between intra‐hepatic IL‐22 expression, its relevant associated cytokines and the severity of liver inflammation/fibrosis in CHB patients. IL‐22, IL‐17, IL‐10, IL‐6, non‐ELR‐CXC chemokines (CXCL‐9, CXCL‐10, CXCL‐11), fibroblast growth factors and Kupffer cell (KC) numbers were measured in patients with CHB (n=65), acute hepatitis B (AHB; n=4), chronic hepatitis C (CHC; n=14) and non‐viral hepatitis (n=23), using immunohistochemistry. Expression of IL‐22, IL‐17, IL‐10, IL‐6, non‐ELR‐CXC chemokines and number of KCs in liver tissues were substantially higher in AHB patients than others. In CHB patients, the expression of IL‐22, IL‐6, CXCL‐9 and CXCL‐10 were significantly higher with alanine aminotransferase (ALT) levels ⩽twice the upper limit of normal (ULN), compared with those with ALT levels >twice the ULN, whereas IL‐10 and IL‐17 showed a reverse pattern. IL‐22 was inversely (P<0.01), but IL‐17 was positively (P<0.05), correlated with the histological activity index) in these patients, and a significant negative correlation between the fibrosis stage and IL‐22 or non‐ELR‐CXC chemokines was observed. Furthermore, immunofluorescent labeling demonstrated a close spatial association of IL‐22, CXCL‐9, ‐10 or ‐11 in the CHB liver. We speculate that IL‐22 and non‐ELR‐CXC chemokines synergistically may provide protection in liver inflammation/fibrosis during CHB infection.
In vivo accumulation of T cells in response to IL‐2/anti‐IL‐2 mAb complexes is dependent in part on the TNF family ligand 4‐1BBL
Authors: Lin Gloria H Y , Stone John C , Surh Charles D , Watts Tania H
Published: September 2011

Immune complexes combining IL‐2 with particular anti‐IL‐2 antibodies can be used to selectively expand regulatory T cells or memory T cells. Combining IL‐2 with anti‐IL‐2 (Clone S4B6) greatly enhances the biological potency of IL‐2 in vivo leading to selective expansion of CD8 memory T cells and NK cells compared with regulatory T cells. Here we show that in vivo administration of IL‐2/anti‐IL‐2 mAb (IL‐2/mAb) complexes induces 4‐1BB expression on both adoptively transferred antigen‐specific memory CD8 T cells as well as on endogenous memory phenotype cells. Remarkably, the accumulation of adoptively transferred memory CD8 T cells following in vivo IL‐2/mAb‐complex treatment was found to be dependent in part on the presence of 4‐1BBL in the host. These effects were independent of IL‐2‐induced cell division, suggesting that 4‐1BBL‐induced survival signals contribute to IL‐2/mAb‐complex‐induced T‐cell accumulation in vivo.
Haem oxygenase-1: non-canonical roles in physiology and pathology
Authors: Grochot-Przeczek Anna , Dulak Jozef , Jozkowicz Alicja
Published: September 2011

HO-1 (haem oxygenase-1) is a ubiquitously expressed inducible enzyme degrading haem to CO, biliverdin and Fe2+. Its activation reduces oxidative stress in cells and inhibits inflammation, both due to removal of haem and because of the biological activity of HO-1 products. CO may act similarly to NO, activating soluble guanylate cyclase and elevating cGMP production. It inhibits platelet aggregation, reduces leucocyte adhesion, decreases apoptosis and lowers the production of some pro-inflammatory cytokines. Biliverdin is converted into bilirubin by biliverdin reductase, and both compounds are potent antioxidants, free radical scavengers and inhibitors of the complement cascade. Iron ions can be potentially toxic, increasing the generation of hydroxyl radicals, but simultaneous induction of ferritin and activation of the Fe-ATPase iron transporter protects cells from oxidative stress. Importantly, basal and induced expression of HO-1 is very variable in the human population because of the highly polymorphic (GT)n fragment in the promoter, which may have clinical relevance. The recognized roles of HO-1 are far beyond cytoprotection. The enzyme is important in the regulation of cell proliferation, differentiation and apoptosis. Its activity improves neovascularization, attenuates inflammation and modulates the immune response, thereby influencing carcinogenesis, wound healing, transplant survival and the progression of cardiovascular diseases. Recent results indicate that HO-1 may also act through the regulation of microRNAs, which suggests a much broader involvement of HO-1 in the modulation of cell functions and offers a potential explanation for some well-known activities whose mechanism has hitherto been unclear.
Tree preserving embedding
Authors: Shieh Albert D. , Hashimoto Tatsunori B. , Airoldi Edoardo M.
Published: September 2011

The goal of dimensionality reduction is to embed high-dimensional data in a low-dimensional space while preserving structure in the data relevant to exploratory data analysis such as clusters. However, existing dimensionality reduction methods often either fail to separate clusters due to the crowding problem or can only separate clusters at a single resolution. We develop a new approach to dimensionality reduction: tree preserving embedding. Our approach uses the topological notion of connectedness to separate clusters at all resolutions. We provide a formal guarantee of cluster separation for our approach that holds for finite samples. Our approach requires no parameters and can handle general types of data, making it easy to use in practice and suggesting new strategies for robust data visualization.
Random phase detection in multidimensional NMR
Authors: Maciejewski Mark W. , Fenwick Matthew , Schuyler Adam D. , Stern Alan S. , Gorbatyuk Vitaliy , Hoch Jeffrey C.
Published: September 2011

Despite advances in resolution accompanying the development of high-field superconducting magnets, biomolecular applications of NMR require multiple dimensions in order to resolve individual resonances, and the achievable resolution is typically limited by practical constraints on measuring time. In addition to the need for measuring long evolution times to obtain high resolution, the need to distinguish the sign of the frequency constrains the ability to shorten measuring times. Sign discrimination is typically accomplished by sampling the signal with two different receiver phases or by selecting a reference frequency outside the range of frequencies spanned by the signal and then sampling at a higher rate. In the parametrically sampled (indirect) time dimensions of multidimensional NMR experiments, either method imposes an additional factor of 2 sampling burden for each dimension. We demonstrate that by using a single detector phase at each time sample point, but randomly altering the phase for different points, the sign ambiguity that attends fixed single-phase detection is resolved. Random phase detection enables a reduction in experiment time by a factor of 2 for each indirect dimension, amounting to a factor of 8 for a four-dimensional experiment, albeit at the cost of introducing sampling artifacts. Alternatively, for fixed measuring time, random phase detection can be used to double resolution in each indirect dimension. Random phase detection is complementary to nonuniform sampling methods, and their combination offers the potential for additional benefits. In addition to applications in biomolecular NMR, random phase detection could be useful in magnetic resonance imaging and other signal processing contexts.
Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2
Authors: MacLauchlan Susan , Yu Jun , Parrish Marcus , Asoulin Tara A. , Schleicher Michael , Krady Marie M. , Zeng Jianmin , Huang Paul L. , Sessa William C. , Kyriakides Themis R.
Published: September 2011

Injury- and ischemia-induced angiogenesis is critical for tissue repair and requires nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS). We present evidence that NO induces angiogenesis by modulating the level of the angiogenesis inhibitor thrombospondin 2 (TSP2). TSP2 levels were higher than WT in eNOS KO tissues in hind-limb ischemia and cutaneous wounds. In vitro studies confirmed that NO represses TSP2 promoter activity. Moreover, double-eNOS/TSP2 KO mice were generated and found to rescue the phenotype of eNOS KO mice. Studies in mice with knock-in constitutively active or inactive eNOS on the Akt-1 KO background showed that eNOS activity correlates with TSP2 levels. Our observations of NO-mediated regulation of angiogenesis via the suppression of TSP2 expression provide a description of improved eNOS KO phenotype by means other than restoring NO signaling.
Examining the dynamics of chromosomal passenger complex (CPC)-dependent phosphorylation during cell division
Authors: Tan Lei , Kapoor Tarun M.
Published: September 2011

The dynamic cellular reorganization needed for successful mitosis requires regulatory cues that vary across microns. The chromosomal passenger complex (CPC) is a conserved regulator involved in key mitotic events such as chromosome–microtubule attachment and spindle midzone formation. Recently, spatial phosphorylation gradients have been reported for CPC substrates, raising the possibility that CPC-dependent signaling establishes order on the micron-length scale in dividing cells. However, this hypothesis has not been tested, largely because of incomplete characterization of the CPC-dependent phosphorylation dynamics. Without these data it is difficult to evaluate perturbations of CPC signaling and select one that alters the spatial organization of substrate phosphorylation at a particular stage of mitosis, without changing overall phosphorylation levels. Here we examine the spatiotemporal dynamics of CPC-dependent phosphorylation along microtubules throughout mitosis using a Förster resonance energy transfer-based sensor. We find that a CPC substrate phosphorylation gradient, with highest phosphorylation levels between the two spindle poles, emerges when a cell enters mitosis. Interestingly, this gradient becomes undetectable at metaphase, but can be revealed by partially suppressing CPC activity, suggesting that high substrate phosphorylation levels can mask persistent CPC-dependent spatial patterning. After anaphase onset, the gradient emerges and persists until cell cleavage. Selective mislocalization of the CPC during anaphase suppresses gradient formation, but overall substrate phosphorylation levels remain unchanged. Under these conditions, the spindle midzone fails to organize and function properly. Our findings suggest a model in which the CPC establishes phosphorylation gradients to coordinate the spatiotemporal dynamics needed for error-free cell division.
MHC genotypes associate with resistance to a frog-killing fungus
Authors: Savage Anna E. , Zamudio Kelly R.
Published: September 2011

The emerging amphibian disease chytridiomycosis is caused by the fungal pathogenBatrachochytrium dendrobatidis(Bd). Amphibian populations and species differ in susceptibility toBd, yet we know surprisingly little about the genetic basis of this natural variation. MHC loci encode peptides that initiate acquired immunity in vertebrates, making them likely candidates for determining disease susceptibility. However, MHC genes have never been characterized in the context of chytridiomycosis. Here, we performed experimentalBdinfections in laboratory-reared frogs collected from five populations that show natural variation inBdsusceptibility. We found that alleles of an expressed MHC class IIB locus associate with survival followingBdinfection. Across populations, MHC heterozygosity was a significant predictor of survival. Within populations, MHC heterozygotes and individuals bearing MHC allele Q had a significantly reduced risk of death, and we detected a significant signal of positive selection along the evolutionary lineage leading to allele Q. Our findings demonstrate that immunogenetic variation affects chytridiomycosis survival under controlled experimental conditions, confirming that host genetic polymorphisms contribute to chytridiomycosis resistance.
Exome sequencing identifies a spectrum of mutation frequencies in advanced and lethal prostate cancers
Authors: Kumar Akash , White Thomas A. , MacKenzie Alexandra P. , Clegg Nigel , Lee Choli , Dumpit Ruth F. , Coleman Ilsa , Ng Sarah B. , Salipante Stephen J. , Rieder Mark J. , Nickerson Deborah A. , Corey Eva , Lange Paul H. , Morrissey Colm , Vessella Robert L. , Nelson Peter S. , Shendure Jay
Published: September 2011

To catalog protein-altering mutations that may drive the development of prostate cancers and their progression to metastatic disease systematically, we performed whole-exome sequencing of 23 prostate cancers derived from 16 different lethal metastatic tumors and three high-grade primary carcinomas. All tumors were propagated in mice as xenografts, designated the LuCaP series, to model phenotypic variation, such as responses to cancer-directed therapeutics. Although corresponding normal tissue was not available for most tumors, we were able to take advantage of increasingly deep catalogs of human genetic variation to remove most germline variants. On average, each tumor genome contained ∼200 novel nonsynonymous variants, of which the vast majority was specific to individual carcinomas. A subset of genes was recurrently altered across tumors derived from different individuals, including TP53, DLK2, GPC6, and SDF4. Unexpectedly, three prostate cancer genomes exhibited substantially higher mutation frequencies, with 2,000–4,000 novel coding variants per exome. A comparison of castration-resistant and castration-sensitive pairs of tumor lines derived from the same prostate cancer highlights mutations in the Wnt pathway as potentially contributing to the development of castration resistance. Collectively, our results indicate that point mutations arising in coding regions of advanced prostate cancers are common but, with notable exceptions, very few genes are mutated in a substantial fraction of tumors. We also report a previously undescribed subtype of prostate cancers exhibiting “hypermutated” genomes, with potential implications for resistance to cancer therapeutics. Our results also suggest that increasingly deep catalogs of human germline variation may challenge the necessity of sequencing matched tumor-normal pairs.
Inference of seed bank parameters in two wild tomato species using ecological and genetic data
Authors: Tellier Aurélien , Laurent Stefan J. Y. , Lainer Hilde , Pavlidis Pavlos , Stephan Wolfgang
Published: September 2011

Seed and egg dormancy is a prevalent life-history trait in plants and invertebrates whose storage effect buffers against environmental variability, modulates species extinction in fragmented habitats, and increases genetic variation. Experimental evidence for reliable differences in dormancy over evolutionary scales (e.g., differences in seed banks between sister species) is scarce because complex ecological experiments in the field are needed to measure them. To cope with these difficulties, we developed an approximate Bayesian computation (ABC) framework that integrates ecological information on population census sizes in the priors of the parameters, along with a coalescent model accounting simultaneously for seed banks and spatial genetic structuring of populations. We collected SNP data at seven nuclear loci (over 300 SNPs) using a combination of three spatial sampling schemes: population, pooled, and species-wide samples. We provide evidence for the existence of a seed bank in two wild tomato species (
Solanum chilense
and
Solanum peruvianum
) found in western South America. Although accounting for uncertainties in ecological data, we infer for each species (
i
) the past demography and (
ii
) ecological parameters, such as the germination rate, migration rates, and minimum number of demes in the metapopulation. The inferred difference in germination rate between the two species may reflect divergent seed dormancy adaptations, in agreement with previous population genetic analyses and the ecology of these two sister species: Seeds spend, on average, a shorter time in the soil in the specialist species (
S. chilense
) than in the generalist species (
S. peruvianum
).
UBLCP1 is a 26S proteasome phosphatase that regulates nuclear proteasome activity
Authors: Guo Xing , Engel James L. , Xiao Junyu , Tagliabracci Vincent S. , Wang Xiaorong , Huang Lan , Dixon Jack E.
Published: September 2011

Protein degradation by the 26S proteasome is a fundamental process involved in a broad range of cellular activities, yet how proteasome activity is regulated remains poorly understood. We report here that ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) is a 26S proteasome phosphatase that regulates nuclear proteasome activity. UBLCP1 directly interacts with the proteasome via its UBL domain and is exclusively localized in the nucleus. UBLCP1 dephosphorylates the 26S proteasome and inhibits proteasome activity in vitro. Knockdown of UBLCP1 in cells promotes 26S proteasome assembly and selectively enhances nuclear proteasome activity. Our results describe the first identified proteasome-specific phosphatase and uncover a unique mechanism for phosphoregulation of the proteasome.
Replacement of histone H3 with CENP-A directs global nucleosome array condensation and loosening of nucleosome superhelical termini
Authors: Panchenko Tanya , Sorensen Troy C. , Woodcock Christopher L. , Kan Zhong-yuan , Wood Stacey , Resch Michael G. , Luger Karolin , Englander S. Walter , Hansen Jeffrey C. , Black Ben E.
Published: September 2011

Centromere protein A (CENP-A) is a histone H3 variant that marks centromere location on the chromosome. To study the subunit structure and folding of human CENP-A-containing chromatin, we generated a set of nucleosomal arrays with canonical core histones and another set with CENP-A substituted for H3. At the level of quaternary structure and assembly, we find that CENP-A arrays are composed of octameric nucleosomes that assemble in a stepwise mechanism, recapitulating conventional array assembly with canonical histones. At intermediate structural resolution, we find that CENP-A-containing arrays are globally condensed relative to arrays with the canonical histones. At high structural resolution, using hydrogen-deuterium exchange coupled to mass spectrometry (H/DX-MS), we find that the DNA superhelical termini within each nucleosome are loosely connected to CENP-A, and we identify the key amino acid substitution that is largely responsible for this behavior. Also the C terminus of histone H2A undergoes rapid hydrogen exchange relative to canonical arrays and does so in a manner that is independent of nucleosomal array folding. These findings have implications for understanding CENP-A-containing nucleosome structure and higher-order chromatin folding at the centromere.
Inhibitory interneurons in a cortical column form hot zones of inhibition in layers 2 and 5A
Authors: Meyer Hanno S. , Schwarz Daniel , Wimmer Verena C. , Schmitt Arno C. , Kerr Jason N. D. , Sakmann Bert , Helmstaedter Moritz
Published: September 2011

Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in cortical columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a column contains ∼2,200 INs (11.5% of ∼19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The “hot zones” of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.
Speed limit of protein folding evidenced in secondary structure dynamics
Authors: Lin Milo M. , Mohammed Omar F. , Jas Gouri S. , Zewail Ahmed H.
Published: September 2011

As the simplest and most prevalent motif of protein folding, α-helix initiation is the starting point of macromolecular complexity. In this work, helix initiation was directly measured via ultrafast temperature-jump spectroscopy on the smallest possible helix nucleus for which only the first turn is formed. The rate’s dependence on sequence, length, and temperature reveals the fastest possible events in protein folding dynamics, and it was possible to separate the rate-limiting torsional (conformational) diffusion from the fast annealing of the helix. An analytic coarse-grained model for this process, which predicts the initiation rate as a function of temperature, confirms this picture. Moreover, the stipulations of the model were verified by ensemble-converging all-atom molecular dynamics simulations, which reproduced both the picosecond annealing and the nanosecond diffusion processes observed experimentally.
Complex genetic architecture of
Drosophila
aggressive behavior
Authors: Zwarts Liesbeth , Magwire Michael M. , Carbone Mary Anna , Versteven Marijke , Herteleer Liesbet , Anholt Robert R. H. , Callaerts Patrick , Mackay Trudy F. C.
Published: September 2011

Epistasis and pleiotropy feature prominently in the genetic architecture of quantitative traits but are difficult to assess in outbred populations. We performed a diallel cross among coisogenic
Drosophila P
-element mutations associated with hyperaggressive behavior and showed extensive epistatic and pleiotropic effects on aggression, brain morphology, and genome-wide transcript abundance in head tissues. Epistatic interactions were often of greater magnitude than homozygous effects, and the topology of epistatic networks varied among these phenotypes. The transcriptional signatures of homozygous and double heterozygous genotypes derived from the six mutations imply a large mutational target for aggressive behavior and point to evolutionarily conserved genetic mechanisms and neural signaling pathways affecting this universal fitness trait.
Tumor suppressor protein (p)53, is a regulator of NF-κB repression by the glucocorticoid receptor
Authors: Murphy Samantha H. , Suzuki Kotaro , Downes Michael , Welch Genevieve L. , De Jesus Paul , Miraglia Loren J. , Orth Anthony P. , Chanda Sumit K. , Evans Ronald M. , Verma Inder M.
Published: September 2011

Glucocorticoids can inhibit inflammation by abrogating the activity of NF-κB, a family of transcription factors that regulates the production of proinflammatory cytokines. To understand the molecular mechanism of repression of NF-κB activity by glucocorticoids, we performed a high-throughput siRNA oligo screen to identify novel genes involved in this process. Here, we report that loss of p53, a tumor suppressor protein, impaired repression of NF-κB target gene transcription by glucocorticoids. Additionally, loss of p53 also impaired transcription of glucocorticoid receptor (GR) target genes, whereas upstream NF-κB and glucocorticoid receptor signaling cascades remained intact. We further demonstrate that p53 loss severely impaired glucocorticoid rescue of death in a mouse model of LPS shock. Our findings unveil a new role for p53 in the repression of NF-κB by glucocorticoids and suggest important implications for treatment of the proinflammatory microenvironments found in tumors with aberrant p53 activity.
Segregation distortion and its effect on genetic mapping in plants
Authors: Xian-Liang Song , Xue-Zhen Sun , Tian-Zhen Zhang
Published: September 2011

Segregation distortion, identified as a strong evolutionary force, is common in genetic mapping research. In plants, the percentage, degree, origin and genetic effects of segregation distortion vary significantly with species, population types, crosses and marker types. The exhibition, common features, causes, methods of mapping segregation distortion loci, effects of segregation distortion on map construction and corresponding mapping strategies in plants, mainly in crops, are reviewed in this paper.
Advances in genetic mapping of the sorghum genome
Authors: Zhi-Ben Yi , Yi Sun , Xiao-Hong Liang , Wei-Jun Zhao , Min Yan , Li-Xia Cui
Published: September 2011

The construction of the sorghum (Sorghum bicolorL. Moench) molecular genetic linkage map started in the early 1990s. Molecular genetic maps with a high density of markers covering almost the entire sorghum genome have been completed and integration of a sorghum genetic and physical map is under way. The correlation between genetic linkage groups and relevant chromosomes was established and the locations of the important structures of chromosomes, such as centromeres, long and short arms, nucleolus organizer region (NOR), etc., have been identified on the linkage groups. Molecular cytogenetic mapping of each chromosome has been advanced substantially. With continuing progress in the field, sequencing of the full sorghum genome and study of sorghum functional genomics will be initiated soon.
Three Drops of Blood
Authors: Hedayat Sadeq
Published: September 2011

Yesterdays they changed my room. Am I completely cured now? Will I be free to leave next week as the superintendent promised? Have I been sick at all? For one year, they wouldn't give me a pen and paper which I wanted more than anything else. I always thought about the many things I would write once they gave me a pen and paper. Yesterday, without asking, they brought me paper and a pen...something I longed for so much...something I waited for so long. But what's the use? Since yesterday, I have been able to write nothing, no matter how hard I try. It's as though someone were holding me back, as though my arm were paralysed. Now, as I read over the garbled lines which are etched into the paper, the only words I can make out are... “three drops of blood.”
The Economic History of Iran, 1800–1914, and Its Political Impact an Overview
Authors: Keddie Nikki R.
Published: September 2011

The economic history of Iran is a subject that has barely begun to receive the attention it deserves. Articles and parts of books on particular aspects of the subject appeared as early as the nineteenth century, but it is only since World War II that there have been extensive and serious studies in English, and these are still few and far between. Prof. Lambton's book Landlord and Peasant in Persia deserves to be singled out as a major pioneering study, and recently there has appeared Professor Charles Issawi's edited volume, The Economic History of Iran 1800-1914 (Chicago: University of Chicago Press, 1971). This book brings together an outstanding collection of articles, excerpts, and sources, many of them translated from Persian, French, German, Russian, and Italian, that provide a basis for an understanding of the economic history of Iran in the nineteenth century.
The Memoirs of Ḥaydar Khān ᶜAmū Ughlū
Authors: Sheikholeslami A. Reza , Wilson Dunning
Published: September 2011

In 1946 a short autobiographical account of Ḥaydar Khān ᶜAmū Ughlū, the Caucasian revolutionary who participated in the Iranian Constitutional movement, 1905-1909, appeared in the Persian monthly journal, Yādigār. The article, which was accompanied by an introduction as well as by some concluding remarks, was unsigned. The editorial policies of the journal, however, indicate that unsigned articles were written by ᶜAbbās Iqbāl, the editor. Iqbāl does not attempt to establish the authenticity of this account, nor do other historians who have used it in their research. While in the absence of the document its authenticity cannot be established, it is possible to make some comments concerning the probability that this may be authentic and that the events mentioned in the autobiography took place, the role Ḥaydar Khān played in these events, and the significance of these events for the Iranian political structure.
cAbbās Mīrzā's will
Authors: Pakdaman Homa , Royce William
Published: September 2011

The document translated below is a will written by cAbbās Mīrzā, the Heir Apparent, in July, 1830, three years before his death in Khurasan. This will is important because of its style and content. Written in a hasty manner, and originally in Persian, in some places it gives the impression of having been translated from Āzarī Turkish. The author has paid little attention to grammatical rules and literary embellishments. The force of the document derives from the author's deep feelings of hope (for future military success), sorrow (for past defeats), and uncertainty and worry (for the destiny of his children). References are made to the political events and personalities of the times, not directly, but in connection with the author's personal concerns. On the whole, cAbbās Mīrzā's major preoccupations in this document are to justify past errors, to be buried as a man of God, and to be remembered as a national hero.
Some Observations on Religion in Safavid Persia
Authors: Algar Hamid
Published: September 2011

It is indisputable that the religious history both of the Safavid period and of the two centuries that preceded it remains inadequately explored. There existed in Transoxania and Anatolia, as well as the Iranian plateau, a plethora of groups and individuals with diverse tendencies and aspirations that it is difficult, in our present state of knowledge, to synthesize into a comprehensible whole. There are however a number of minor observations on Professor Nasr's presentation that I wish to make. The first is an expression of respectful disagreement, and the others are intended to direct attention to matters not mentioned in his otherwise comprehensive paper.

Professor Nasr's contention that Sufism owes its essential origin to Shiᶜism, and that therefore its suppression in the Safavid period ought to be regarded as a return to the womb that bore it, is highly contestable.
Observations Sur L'architecture Civile D'ispahan
Authors: Zander Giuseppe
Published: September 2011

Avant d'essayer de tracer un exposé des valeurs de l'architecture safavide, il est utile d'analyser les formes géomètriques des voûtes et les systèmes constructifs. Ensuite quelques exemples significatifs de palais et de maisons seront choisis, soit en rapport avec la dialectique de l'ancien et du nouveau, soit dans les relations entre les ouvrages auliques et les demeures bourgeoises, soit dans la recherche d'une relation rationnelle entre la forme et la structure. Enfin se posera le problème irrésolu de la formation culturelle des architectes de l'âge safavide.

Le bois. Le bois, le chanār ou platanus orientalis, est depuis toujours largement employé dans l'architecture persane pour le soutien des terrasses horizontales. Les couvertures en forme de toit se trouvent rarement ẹt tout au plus aux époques qājār tardive ou moderne. On voit encore dans certaines formes modernes spontanées et paysannes des systèmes à structures de ligne homogènes, d'ascendance notoirement achéménide, par exemple dans certains ṭālārs rustiques du Mazandaran, comme celui publié par André Godard.
Minorities of Isfahan: The Armenian Community of Isfahan 1587–1722
Authors: Gregorian Vartan
Published: September 2011

In their “recreation of the Persian nationality” and their proclamation of Shiᶜite Islam as the official state religion of Persia, the Safavids performed a crucial historical role. They formalized, institutionalized, intensified and politicized the Sunni-Shiᶜite doctrinal and regional schism within the Islamic world. Coming in the wake of the four centuries of Turko-Mongol invasions which had already helped to “harden the division of the Muslim lands into separate Arabic, Persian and Turkish regions between which literary communication was confined to the restricted circles of the educated,“ the triumph of the Shiᶜite revolution in Persia formalized the division of Islamic Asia into three major Muslim political entities: Ottoman, Safavid and Mughal. Safavid Persia drove wedges between the Sunni Ottoman empire, the Mughal empire and Central Asia. Safavid and shicite Persia, however, was not a monolith. It was an ethnic, linguistic, and religious mosaic.
Elites and Classes: Confrontation or Integration
Authors: Bill James A.
Published: September 2011

Scholars of society and politics have over the years developed a large number of theoretical approaches to assist them in understanding their subject matter. These methodological orientations necessarily affect research findings and results. Social scientists have not always been known for their toleration of any approach that differs substantially from their own. Some, therefore, harden their own approaches into doctrines while those developed by others are treated as heresies. Dogmatism triumphs over open-mindedness.

Practitioners of the elite approach are as prone to this malady as are any other group of theoreticians. And for some very understandable reasons. In American political science, those who adopt an elite perspective have been unfairly but consistently attacked by the “pluralists,” i.e., those who adopt a group approach and in so doing disavow the existence and/or importance of elites. The attack takes on a nasty normative slant whereby elite scholars are insidiously identified as proponents of the phenomenon they study.
The Constitutional Ideas of a Shi'ite Mujtahid: Muhammad Husayn Na'ini
Authors: Nouraie Fereshte M.
Published: September 2011

The Iranian constitutional movement of the early twentieth century involved various segments of Iranian society. Intellectuals, enlightened members of the bureaucracy, religious leaders, merchants and the urban population, each to a greater or lesser extent participated in this reform movement. Naturally their political attitudes, objectives, and interests differed. The intellectuals, who were secular in outlook and influenced by liberal Western ideas, hoped for the establishment of a constitutional form of government. A small group of reformers in the government sympathized with these men and were in close contact with them. Indeed, it is difficult to distinguish between the former and the latter since most of the intelligentsia were also a part of the ruling class. Perhaps one of the best examples is Mīrzā Malkam Khān Nāẓim al-Dawlah (1834-1908), who represents the attitude of a liberal thinker as well as a reformist member of the bureaucracy.
What is (Iranian) National Character? A Sociolinguistic Approach
Authors: Beeman William O.
Published: September 2011

It is surprising, somehow, to witness the degree to which the concept of national character doggedly maintains its intuitive appeal in the social sciences. Despite widespread criticism of the use of the concept as the basis for studying human societies, few researchers find themselves able to deny that different societies seem to have a distinctive “feel” to them, and it is a rare field worker indeed who doesn't speak, informally at least, of the members of a society in which he has worked in terms of collective “psychological” characteristics. Widely used anthropological concepts such as “ethos,” “value system,” and even “culture” itself reflect this feeling in differing degrees. The inherent intuitive appeal of the national character concept persists, then, despite our best efforts to repudiate it.

In trying to understand this phenomenon, it seems a vain effort to return once again to the question: “Do national characters exist?”. In place of this well-worked exercise, I feel it more profitable to turn away from the natives and focus on the epistemology of the observer.
Seeking Absolution
Authors: Hedayat Sadegh
Published: September 2011

The scorching wind mingled the dirt and sand, blowing it in the pilgrims’ faces. The sun burned and shrivelled everything. The camels stepped to the monotonous melody of iron and brass bells, their necks swaying rhythmically, their frowning snouts and hanging muzzles revealing their dissatisfaction with their fate.

Through the dust, the caravan moved slowly in the middle of the grey dirt road. The ash-colored, dry, sandy desert stretched as far as the eye could see, shimmering in the heat and at times forming a series of low mounds at the side of the road. For miles not even a date palm relieved the monotony. Wherever there was a handful of stagnant water in a ditch a family had pitched a shelter. The air burned everything, taking one's breath away. It was like stepping into the corridor of hell.

The caravan had been on the road for thirty-six days. Their mouths dry, their bodies weak, their pockets empty, the pilgrims had watched their money supply diminish like snow under the hot Arabian sun.