bluuebunny/crossref_metadata_2025 huggingface dataset:
The Religious Affiliation of Representatives and Support for Funding the Iraq War
Authors: Collins Todd A. , Wink Kenneth A. , Guth James L. , Livingston C. Don
Published: September 2011

In this article, we add to the evolving literature examining the importance of religious orientation and political elite behavior. We use data on the religious affiliations of United States House of Representative members to test the influence of religion on military funding for the “War on Terror.” Our findings indicate that, even after controlling for traditional political factors, such as ideology and partisanship, representatives' religious backgrounds often played a role in support for this bill. Roman Catholics, African-American Protestants, and those of other religions and the non-religious were more strongly opposed to funding for military intervention than mainline Protestants, even after controlling for other factors. This article provides a further look at the influence of religion and suggests that factors outside the traditional political dynamics may also be important in examining elite behaviors.
Cylindrical near-field far-field transformation in a half-space with conditions of dielectric and lossy ground
Authors: Payet Nicolas , Darces Muriel , Hélier Marc , Montmagnon Jean-Louis , Jangal Florent
Published: September 2011

The direct measurement of the radiation pattern of an antenna is often unreachable. A near-field sampling followed by a near-field/far-field (NF/FF) transformation is therefore substituted. This process is, in most cases, applied to antennas placed in free-space or over a perfect electric conductor. On the contrary, few results concern real environment conditions. Nevertheless, it is well known that the nature of the soil can drastically change the radiating characteristic of an antenna. The lack of information about the behavior of the antenna in real conditions can give rise to substantial errors in the evaluation of the performances of electromagnetic devices. The aim of this paper is then to propose a new NF/FF transformation able to reliably supply the field radiated by an antenna placed over a plane, homogeneous, dielectric, and lossy interface. The method is based on the cylindrical-wave expansion of the electric field. The real soil is taken into account by means of its reflection coefficients. First results are given for simple antennas and for both transverse magnetic and transverse electric polarizations.
Best Practice Elements of Multilevel Suicide Prevention Strategies
Authors: van der Feltz-Cornelis Christina M. , Sarchiapone Marco , Postuvan Vita , Volker Daniëlle , Roskar Saska , Grum Alenka Tančič , Carli Vladimir , McDaid David , O’Connor Rory , Maxwell Margaret , Ibelshäuser Angela , Van Audenhove Chantal , Scheerder Gert , Sisask Merike , Gusmão Ricardo , Hegerl Ulrich
Published: September 2011

Background: Evidence-based best practices for incorporation into an optimal multilevel intervention for suicide prevention should be identifiable in the literature. Aims: To identify effective interventions for the prevention of suicidal behavior. Methods: Review of systematic reviews found in the Pubmed, Cochrane, and DARE databases. Steps include risk-of-bias assessment, data extraction, summarization of best practices, and identification of synergistic potentials of such practices in multilevel approaches. Results: Six relevant systematic reviews were found. Best practices identified as effective were as follows: training general practitioners (GPs) to recognize and treat depression and suicidality, improving accessibility of care for at-risk people, and restricting access to means of suicide. Although no outcomes were reported for multilevel interventions or for synergistic effects of multiple interventions applied together, indirect support was found for possible synergies in particular combinations of interventions within multilevel strategies. Conclusions: A number of evidence-based best practices for the prevention of suicide and suicide attempts were identified. Research is needed on the nature and extent of potential synergistic effects of various preventive activities within multilevel interventions.
GPS radio occultation for climate monitoring and change detection
Authors: Steiner A. K. , Lackner B. C. , Ladstädter F. , Scherllin‐Pirscher B. , Foelsche U. , Kirchengast G.
Published: September 2011

Observation of the atmospheric climate and detection of changes require high quality data. Radio Occultation (RO) using Global Positioning System (GPS) signals is based on time measurements with precise atomic clocks. It provides a long‐term stable and consistent data record with global coverage and favorable error characteristics. Highest quality and vertical resolution is given in the upper troposphere and lower stratosphere (UTLS). RO data exist from the GPS/Met mission within 1995–1997, and continuous observations are available since 2001. We give a review on studies using RO data for climate monitoring and change detection in the UTLS and discuss RO characteristics and error estimates, climate change indicators, trend detection, and comparison to conventional upper‐air data. These studies showed that RO parameters cover the whole UTLS with useful indicators of climate change, being most robust in the tropics. Refractivity is most sensitive in the lower stratosphere (LS) and tropopause region, pressure/geopotential height and temperature over the UTLS region. An emerging climate change signal in the RO record can be detected for geopotential height of pressure levels and for temperature, reflecting warming of the troposphere and cooling of the LS. The results are in agreement with trends in radiosonde and ERA‐Interim records. Climate model trends basically agree as well but they show less warming/cooling contrast across the tropical tropopause. (Advanced) Microwave Sounding Unit LS bulk temperature anomalies show significant differences to RO. Overall, the quality of RO climate records is suitable to fulfill the requirements of a global climate change monitoring system.
Validation of tropospheric slant path delays derived from single and dual frequency GPS receivers
Authors: Deng Zhiguo , Bender Michael , Zus Florian , Ge Maorong , Dick Galina , Ramatschi Markus , Wickert Jens , Löhnert Ulrich , Schön Steffen
Published: September 2011

In order to increase the spatial resolution of tropospheric delays derived from GPS observations, existing GPS networks assembled from dual frequency (DF) receivers must be densified. For economic reasons, low‐cost single‐frequency (SF) receivers are considered for the densification. The Satellite‐specific Epoch‐differenced Ionospheric Delay model (SEID) was developed at the German Research Centre for Geosciences (GFZ) to derive the ionospheric corrections for SF GPS receivers. Those corrections allow synthesizing a L2 observable for SF receivers, and existing GPS processing packages can analyze the resulting observables (L1 and synthesized L2) using the same methodology as with DF receivers. The SEID model has already been successfully applied to tropospheric Zenith Total Delay (ZTD) and station coordinates estimation. To assess the possibility of densifying an existing GPS network with low‐cost SF GPS receivers, observations from 258 German DF GPS stations are treated as observations from SF GPS stations (only L1 GPS observations are used). While in a previous study ZTD products were validated, in this study Slant Total Delay (STD) and Slant Water Vapor (SWV) products, derived from SF data and the SEID model, are validated using tropospheric products derived from DF data, a Water Vapor Radiometer (WVR) and a numerical weather model.
Embryo - maternal communication: signalling before and during placentation in cattle and pig
Authors: Østrup Esben , Hyttel Poul , Østrup Olga
Published: September 2011

Communication during early pregnancy is essential for successful reproduction. In this review we address the beginning of the communication between mother and developing embryo; including morphological and transcriptional changes in the endometrium as well as epigenetic regulation mechanisms directing the placentation. An increasing knowledge of the embryo–maternal communication might not only help to improve the fertility of our farm animals but also our understanding of human health and reproduction.
A whole-genome RNAi screen identifies an 8q22 gene cluster that inhibits death receptor-mediated apoptosis
Authors: Dompe Nicholas , Rivers Celina Sanchez , Li Li , Cordes Shaun , Schwickart Martin , Punnoose Elizabeth A. , Amler Lukas , Seshagiri Somasekar , Tang Jerry , Modrusan Zora , Davis David P.
Published: September 2011

Deregulation of apoptosis is a common occurrence in cancer, for which emerging oncology therapeutic agents designed to engage this pathway are undergoing clinical trials. With the aim of uncovering strategies to activate apoptosis in cancer cells, we used a pooled shRNA screen to interrogate death receptor signaling. This screening approach identified 16 genes that modulate the sensitivity to ligand induced apoptosis, with several genes exhibiting frequent overexpression and/or copy number gain in cancer. Interestingly, two of the top hits, EDD1 and GRHL2, are found 50 kb apart on chromosome 8q22, a region that is frequently amplified in many cancers. By using a series of silencing and overexpression studies, we show that EDD1 and GRHL2 suppress death-receptor expression, and that EDD1 expression is elevated in breast, pancreas, and lung cancer cell lines resistant to death receptor-mediated apoptosis. Supporting the relevance of EDD1 and GRHL2 as therapeutic candidates to engage apoptosis in cancer cells, silencing the expression of either gene sensitizes 8q22-amplified breast cancer cell lines to death receptor induced apoptosis. Our findings highlight a mechanism by which cancer cells may evade apoptosis, and therefore provide insight in the search for new targets and functional biomarkers for this pathway.
Inhibition recruitment in prefrontal cortex during sleep spindles and gating of hippocampal inputs
Authors: Peyrache Adrien , Battaglia Francesco P. , Destexhe Alain
Published: September 2011

During light slow-wave sleep, the thalamo-cortical network oscillates in waxing-and-waning patterns at about 7 to 14 Hz and lasting for 500 ms to 3 s, called spindles, with the thalamus rhythmically sending strong excitatory volleys to the cortex. Concurrently, the hippocampal activity is characterized by transient and strong excitatory events, Sharp-Waves-Ripples (SPWRs), directly affecting neocortical activity—in particular the medial prefrontal cortex (mPFC)—which receives monosynaptic fibers from the ventral hippocampus and subiculum. Both spindles and SPWRs have been shown to be strongly involved in memory consolidation. However, the dynamics of the cortical network during natural sleep spindles and how prefrontal circuits simultaneously process hippocampal and thalamo-cortical activity remain largely undetermined. Using multisite neuronal recordings in rat mPFC, we show that during sleep spindles, oscillatory responses of cortical cells are different for different cell types and cortical layers. Superficial neurons are more phase-locked and tonically recruited during spindle episodes. Moreover, in a given layer, interneurons were always more modulated than pyramidal cells, both in firing rate and phase, suggesting that the dynamics are dominated by inhibition. In the deep layers, where most of the hippocampal fibers make contacts, pyramidal cells respond phasically to SPWRs, but not during spindles. Similar observations were obtained when analyzing γ-oscillation modulation in the mPFC. These results demonstrate that during sleep spindles, the cortex is functionnaly “deafferented” from its hippocampal inputs, based on processes of cortical origin, and presumably mediated by the strong recruitment of inhibitory interneurons. The interplay between hippocampal and thalamic inputs may underlie a global mechanism involved in the consolidation of recently formed memory traces.
Whole-genome nucleotide diversity, recombination, and linkage disequilibrium in the model legume
Medicago truncatula
Authors: Branca Antoine , Paape Timothy D. , Zhou Peng , Briskine Roman , Farmer Andrew D. , Mudge Joann , Bharti Arvind K. , Woodward Jimmy E. , May Gregory D. , Gentzbittel Laurent , Ben Cécile , Denny Roxanne , Sadowsky Michael J. , Ronfort Joëlle , Bataillon Thomas , Young Nevin D. , Tiffin Peter
Published: September 2011

Medicago truncatula
is a model for investigating legume genetics, including the genetics and evolution of legume–rhizobia symbiosis. We used whole-genome sequence data to identify and characterize sequence polymorphisms and linkage disequilibrium (LD) in a diverse collection of 26
M. truncatula
accessions. Our analyses reveal that
M. truncatula
harbors both higher diversity and less LD than soybean (
Glycine max
) and exhibits patterns of LD and recombination similar to
Arabidopsis thaliana
. The population-scaled recombination rate is approximately one-third of the mutation rate, consistent with expectations for a species with a high selfing rate. Linkage disequilibrium, however, is not extensive, and therefore, the low recombination rate is likely not a major constraint to adaptation. Nucleotide diversity in 100-kb windows was negatively correlated with gene density, which is expected if diversity is shaped by selection acting against slightly deleterious mutations. Among putative coding regions, members of four gene families harbor significantly higher diversity than the genome-wide average. Three of these families are involved in resistance against pathogens; one of these families, the nodule-specific, cysteine-rich gene family, is specific to the galegoid legumes and is involved in control of rhizobial differentiation. The more than 3 million SNPs that we detected, approximately one-half of which are present in more than one accession, are a valuable resource for genome-wide association mapping of genes responsible for phenotypic diversity in legumes, especially traits associated with symbiosis and nodulation.
Valuation of plug-in vehicle life-cycle air emissions and oil displacement benefits
Authors: Michalek Jeremy J. , Chester Mikhail , Jaramillo Paulina , Samaras Constantine , Shiau Ching-Shin Norman , Lave Lester B.
Published: September 2011

We assess the economic value of life-cycle air emissions and oil consumption from conventional vehicles, hybrid-electric vehicles (HEVs), plug-in hybrid-electric vehicles (PHEVs), and battery electric vehicles in the US. We find that plug-in vehicles may reduce or increase externality costs relative to grid-independent HEVs, depending largely on greenhouse gas and SO2emissions produced during vehicle charging and battery manufacturing. However, even if future marginal damages from emissions of battery and electricity production drop dramatically, the damage reduction potential of plug-in vehicles remains small compared to ownership cost. As such, to offer a socially efficient approach to emissions and oil consumption reduction, lifetime cost of plug-in vehicles must be competitive with HEVs. Current subsidies intended to encourage sales of plug-in vehicles with large capacity battery packs exceed our externality estimates considerably, and taxes that optimally correct for externality damages would not close the gap in ownership cost. In contrast, HEVs and PHEVs with small battery packs reduce externality damages at low (or no) additional cost over their lifetime. Although large battery packs allow vehicles to travel longer distances using electricity instead of gasoline, large packs are more expensive, heavier, and more emissions intensive to produce, with lower utilization factors, greater charging infrastructure requirements, and life-cycle implications that are more sensitive to uncertain, time-sensitive, and location-specific factors. To reduce air emission and oil dependency impacts from passenger vehicles, strategies to promote adoption of HEVs and PHEVs with small battery packs offer more social benefits per dollar spent.
Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling
Authors: Beirowski Bogdan , Gustin Jason , Armour Sean M. , Yamamoto Hiroyasu , Viader Andreu , North Brian J. , Michán Shaday , Baloh Robert H. , Golden Judy P. , Schmidt Robert E. , Sinclair David A. , Auwerx Johan , Milbrandt Jeffrey
Published: September 2011

The formation of myelin by Schwann cells (SCs) occurs via a series of orchestrated molecular events. We previously used global expression profiling to examine peripheral nerve myelination and identified the NAD+-dependent deacetylase Sir-two-homolog 2 (Sirt2) as a protein likely to be involved in myelination. Here, we show that Sirt2 expression in SCs is correlated with that of structural myelin components during both developmental myelination and remyelination after nerve injury. Transgenic mice lacking or overexpressing Sirt2 specifically in SCs show delays in myelin formation. In SCs, we found that Sirt2 deacetylates Par-3, a master regulator of cell polarity. The deacetylation of Par-3 by Sirt2 decreases the activity of the polarity complex signaling component aPKC, thereby regulating myelin formation. These results demonstrate that Sirt2 controls an essential polarity pathway in SCs during myelin assembly and provide insights into the association between intracellular metabolism and SC plasticity.
Hypoxia-induced transcriptional repression of the melanoma-associated oncogene
MITF
Authors: Feige Erez , Yokoyama Satoru , Levy Carmit , Khaled Mehdi , Igras Vivien , Lin Richard J. , Lee Stephen , Widlund Hans R. , Granter Scott R. , Kung Andrew L. , Fisher David E.
Published: September 2011

Microphthalmia-associated transcription factor (MITF) regulates normal melanocyte development and is also a lineage-selective oncogene implicated in melanoma and clear-cell sarcoma (i.e., melanoma of soft parts). We have observed that MITF expression is potently reduced under hypoxic conditions in primary melanocytes and melanoma and clear cell sarcoma cells through hypoxia inducible factor 1 (HIF1)-mediated induction of the transcriptional repressor differentially expressed in chondrocytes protein 1 (DEC1) (BHLHE40), which subsequently binds and suppresses the promoter of
M-MITF
(melanocyte-restricted MITF isoform). Correspondingly, hypoxic conditions or HIF1α stabilization achieved by using small-molecule prolyl-hydroxylase inhibitors reduced M-MITF expression, leading to melanoma cell growth arrest that was rescued by ectopic expression of M-MITF in vitro. Prolyl hydroxylase inhibition also potently suppressed melanoma growth in a mouse xenograft model. These studies illuminate a physiologic hypoxia response in pigment cells leading to M-MITF suppression, one that suggests a potential survival advantage mechanism for MITF amplification in metastatic melanoma and offers a small-molecule strategy for suppression of the MITF oncogene in vivo.
Critical thresholds and tangible targets for ecosystem-based management of coral reef fisheries
Authors: McClanahan Tim R. , Graham Nicholas A. J. , MacNeil M. Aaron , Muthiga Nyawira A. , Cinner Joshua E. , Bruggemann J. Henrich , Wilson Shaun K.
Published: September 2011

Sustainably managing ecosystems is challenging, especially for complex systems such as coral reefs. This study develops critical reference points for sustainable management by using a large empirical dataset on the coral reefs of the western Indian Ocean to investigate associations between levels of target fish biomass (as an indicator of fishing intensity) and eight metrics of ecosystem state. These eight ecological metrics each exhibited specific thresholds along a continuum of fishable biomass ranging from heavily fished sites to old fisheries closures. Three thresholds lay above and five below a hypothesized window of fishable biomass expected to produce a maximum multispecies sustainable yield (BMMSY). Evaluating three management systems in nine countries, we found that unregulated fisheries often operate below theBMMSY, whereas fisheries closures and, less frequently, gear-restricted fisheries were within or above this window. These findings provide tangible management targets for multispecies coral reef fisheries and highlight key tradeoffs required to achieve different fisheries and conservation goals.
Grafted human-induced pluripotent stem-cell–derived neurospheres promote motor functional recovery after spinal cord injury in mice
Authors: Nori Satoshi , Okada Yohei , Yasuda Akimasa , Tsuji Osahiko , Takahashi Yuichiro , Kobayashi Yoshiomi , Fujiyoshi Kanehiro , Koike Masato , Uchiyama Yasuo , Ikeda Eiji , Toyama Yoshiaki , Yamanaka Shinya , Nakamura Masaya , Okano Hideyuki
Published: September 2011

Once their safety is confirmed, human-induced pluripotent stem cells (hiPSCs), which do not entail ethical concerns, may become a preferred cell source for regenerative medicine. Here, we investigated the therapeutic potential of transplanting hiPSC-derived neurospheres (hiPSC-NSs) into nonobese diabetic (NOD)-severe combined immunodeficient (SCID) mice to treat spinal cord injury (SCI). For this, we used a hiPSC clone (201B7), established by transducing four reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc) into adult human fibroblasts. Grafted hiPSC-NSs survived, migrated, and differentiated into the three major neural lineages (neurons, astrocytes, and oligodendrocytes) within the injured spinal cord. They showed both cell-autonomous and noncell-autonomous (trophic) effects, including synapse formation between hiPSC-NS–derived neurons and host mouse neurons, expression of neurotrophic factors, angiogenesis, axonal regrowth, and increased amounts of myelin in the injured area. These positive effects resulted in significantly better functional recovery compared with vehicle-treated control animals, and the recovery persisted through the end of the observation period, 112 d post-SCI. No tumor formation was observed in the hiPSC-NS–grafted mice. These findings suggest that hiPSCs give rise to neural stem/progenitor cells that support improved function post-SCI and are a promising cell source for its treatment.
Essential role of Mediator subunit Med1 in invariant natural killer T-cell development
Authors: Yue Xiaojing , Izcue Ana , Borggrefe Tilman
Published: September 2011

CD1d-restricted invariant NKT (iNKT) cells are a unique lineage of T lymphocytes that regulate both innate and adaptive immunity. The Mediator complex forms the bridge between transcriptional activators and the general transcription machinery. Med1/TRAP220 (also called DRIP205) is a key component of Mediator that interacts with ligand-bound hormone receptors, such as the vitamin D receptor. Here, we show that T-cell–specific Med1 deficiency results in a specific block in iNKT cell development but the development of conventional αβ T cells remains grossly normal. The defect is cell-intrinsic and depends neither on apoptosis, cell-cycle control, nor on CD1d expression of CD4+CD8+double-positive thymocytes. Surprisingly, ectopic expression of a Vα14-Jα18 T-cell receptor transgene completely rescues the defect caused by Med1 deficiency. At the molecular level, thymic iNKT cells in Med1−/−animals display reduced levels of IL-2Rβ and T-bet expression and could not complete terminal maturation. Thus, Med1 is essential for a complete intrathymic development of iNKT cells.
Ancient host specificity within a single species of brood parasitic bird
Authors: Spottiswoode Claire N. , Stryjewski Katherine Faust , Quader Suhel , Colebrook-Robjent John F. R. , Sorenson Michael D.
Published: September 2011

Parasites that exploit multiple hosts often experience diversifying selection for host-specific adaptations. This can result in multiple strains of host specialists coexisting within a single parasitic species. A long-standing conundrum is how such sympatric host races can be maintained within a single parasitic species in the face of interbreeding among conspecifics specializing on different hosts. Striking examples are seen in certain avian brood parasites such as cuckoos, many of which show host-specific differentiation in traits such as host egg mimicry. Exploiting a Zambian egg collection amassed over several decades and supplemented by recent fieldwork, we show that the brood parasitic Greater HoneyguideIndicator indicatorexhibits host-specific differentiation in both egg size and egg shape. Genetic analysis of honeyguide eggs and chicks show that two highly divergent mitochondrial DNA lineages are associated with ground- and tree-nesting hosts, respectively, indicating perfect fidelity to two mutually exclusive sets of host species for millions of years. Despite their age and apparent adaptive diversification, however, these ancient lineages are not cryptic species; a complete lack of differentiation in nuclear genes shows that mating between individuals reared by different hosts is sufficiently frequent to prevent speciation. These results indicate that host specificity is maternally inherited, that host-specific adaptation among conspecifics can be maintained without reproductive isolation, and that host specificity can be remarkably ancient in evolutionary terms.
Rumi functions as both a protein
O
-glucosyltransferase and a protein
O
-xylosyltransferase
Authors: Takeuchi Hideyuki , Fernández-Valdivia Rodrigo C. , Caswell Devin S. , Nita-Lazar Aleksandra , Rana Nadia A. , Garner Thomas P. , Weldeghiorghis Thomas K. , Macnaughtan Megan A. , Jafar-Nejad Hamed , Haltiwanger Robert S.
Published: September 2011

Mutations in
rumi
result in a temperature-sensitive loss of Notch signaling in
Drosophila
.
Drosophila
Rumi is a soluble, endoplasmic reticulum-retained protein with a CAP10 domain that functions as a protein
O
-glucosyltransferase. In human and mouse genomes, three potential Rumi homologues exist: one with a high degree of identity to
Drosophila
Rumi (52%), and two others with lower degrees of identity but including a CAP10 domain (KDELC1 and KDELC2). Here we show that both mouse and human Rumi, but not KDELC1 or KDELC2, catalyze transfer of glucose from UDP-glucose to an EGF repeat from human factor VII. Similarly, human Rumi, but not KDELC1 or KDELC2, rescues the
Notch
phenotypes in
Drosophila rumi
clones. During characterization of the Rumi enzymes, we noted that, in addition to protein
O
-glucosyltransferase activity, both mammalian and
Drosophila
Rumi also showed significant protein
O
-xylosyltransferase activity. Rumi transfers Xyl or glucose to serine 52 in the
O
-glucose consensus sequence (

) of factor VII EGF repeat. Surprisingly, the second serine (S53) facilitates transfer of Xyl, but not glucose, to the EGF repeat by Rumi. EGF16 of mouse Notch2, which has a diserine motif in the consensus sequence (

), is also modified with either
O
-Xyl or
O
-glucose glycans in cells. Mutation of the second serine (S590A) causes a loss of
O
-Xyl but not
O
-glucose at this site. Altogether, our data establish dual substrate specificity for the glycosyltransferase Rumi and provide evidence that amino acid sequences of the recipient EGF repeat significantly influence which donor substrate (UDP-glucose or UDP-Xyl) is used.
HSP90 functions in the circadian clock through stabilization of the client F-box protein ZEITLUPE
Authors: Kim Tae-sung , Kim Woe Yeon , Fujiwara Sumire , Kim Jeongsik , Cha Joon-Yung , Park Jin Ho , Lee Sang Yeol , Somers David E.
Published: September 2011

The autoregulatory loops of the circadian clock consist of feedback regulation of transcription/translation circuits but also require finely coordinated cytoplasmic and nuclear proteostasis. Although protein degradation is important to establish steady-state levels, maturation into their active conformation also factors into protein homeostasis. HSP90 facilitates the maturation of a wide range of client proteins, and studies in metazoan clocks implicate HSP90 as an integrator of input or output. Here we show that the
Arabidopsis
circadian clock-associated F-box protein ZEITLUPE (ZTL) is a unique client for cytoplasmic HSP90. The HSP90-specific inhibitor geldanamycin and RNAi-mediated depletion of cytoplasmic HSP90 reduces levels of ZTL and lengthens circadian period, consistent with
ztl
loss-of-function alleles. Transient transfection of artificial microRNA targeting cytoplasmic HSP90 genes similarly lengthens period. Proteolytic targets of SCF
ZTL
, TOC1 and PRR5, are stabilized in geldanamycin-treated seedlings, whereas the levels of closely related clock proteins, PRR3 and PRR7, are unchanged. An in vitro holdase assay, typically used to demonstrate chaperone activity, shows that ZTL can be effectively bound, and aggregation prevented, by HSP90. GIGANTEA, a unique stabilizer of ZTL, may act in the same pathway as HSP90, possibly linking these two proteins to a similar mechanism. Our findings establish maturation of ZTL by HSP90 as essential for proper function of the
Arabidopsis
circadian clock. Unlike metazoan systems, HSP90 functions here within the core oscillator. Additionally, F-box proteins as clients may place HSP90 in a unique and more central role in proteostasis.
Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer cell growth and proliferation
Authors: Benod Cindy , Vinogradova Maia V. , Jouravel Natalia , Kim Grace E. , Fletterick Robert J. , Sablin Elena P.
Published: September 2011

An essential regulator of gene transcription, nuclear receptor liver receptor homologue 1 (LRH-1) controls cell differentiation in the developing pancreas and maintains cholesterol homeostasis in adults. Recent genome-wide association studies linked mutations in the LRH-1 gene and its up-stream regulatory regions to development of pancreatic cancer. In this work, we show that LRH-1 transcription is activated up to 30-fold in human pancreatic cancer cells compared to normal pancreatic ductal epithelium. This activation correlates with markedly increased LRH-1 protein expression in human pancreatic ductal adenocarcinomas in vivo. Selective blocking of LRH-1 by receptor specific siRNA significantly inhibits pancreatic cancer cell proliferation in vitro. The inhibition is tracked in part to the attenuation of the receptor’s transcriptional targets controlling cell growth, proliferation, and differentiation. Previously, LRH-1 was shown to contribute to formation of intestinal tumors. This study demonstrates the critical involvement of LRH-1 in development and progression of pancreatic cancer, suggesting the LRH-1 receptor as a plausible therapeutic target for treatment of pancreatic ductal adenocarcinomas.
Basic peptide-morpholino oligomer conjugate that is very effective in killing bacteria by gene-specific and nonspecific modes
Authors: Wesolowski Donna , Tae Hyun Seop , Gandotra Neeru , Llopis Paula , Shen Ning , Altman Sidney
Published: September 2011

Basic peptides covalently linked to nucleic acids, or chemically modified nucleic acids, enable the insertion of such a conjugate into bacteria grown in liquid medium and mammalian cells in tissue culture. A unique peptide, derived from human T cells, has been employed in a chemical synthesis to make a conjugate with a morpholino oligonucleotide. This new conjugate is at least 10- to 100-fold more effective than previous peptides used in altering the phenotype of host bacteria if the external guide sequence methodology is employed in these experiments. Bacteria with target genes expressing chloramphenicol resistance, penicillin resistance, or gyrase A function can effectively be reduced in their expression and the host cells killed. Several bacteria are susceptible to this treatment, which has a broad range of potency. The loss in viability of bacteria is not due only to complementarity with a target RNA and the action of RNase P, but also to a non-gene-specific tight binding of the complexed nontargeted RNA to the basic polypeptide-morpholino oligonucleotide.
Specificity and detection of insulin-reactive CD4+T cells in type 1 diabetes in the nonobese diabetic (NOD) mouse
Authors: Crawford Frances , Stadinski Brian , Jin Niyun , Michels Aaron , Nakayama Maki , Pratt Philip , Marrack Philippa , Eisenbarth George , Kappler John W.
Published: September 2011

In the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D), an insulin peptide (B:9–23) is a major target for pathogenic CD4+T cells. However, there is no consensus on the relative importance of the various positions or “registers” this peptide can take when bound in the groove of the NOD MHCII molecule, IAg7. This has hindered structural studies and the tracking of the relevant T cells in vivo with fluorescent peptide-MHCII tetramers. Using mutated B:9–23 peptides and methods for trapping the peptide in particular registers, we show that most, if not all, NOD CD4+T cells react to B:9–23 bound in low-affinity register 3. However, these T cells can be divided into two types depending on whether their response is improved or inhibited by substituting a glycine for the B:21 glutamic acid at the p8 position of the peptide. On the basis of these findings, we constructed a set of fluorescent insulin-IAg7tetramers that bind to most insulin-specific T-cell clones tested. A mixture of these tetramers detected a high frequency of B:9–23-reactive CD4+T cells in the pancreases of prediabetic NOD mice. Our data are consistent with the idea that, within the pancreas, unique processing of insulin generates truncated peptides that lack or contain the B:21 glutamic acid. In the thymus, the absence of this type of processing combined with the low affinity of B:9–23 binding to IAg7in register 3 may explain the escape of insulin-specific CD4+T cells from the mechanisms that usually eliminate self-reactive T cells.
TrkB signaling in parvalbumin-positive interneurons is critical for gamma-band network synchronization in hippocampus
Authors: Zheng Kang , An Juan Ji , Yang Feng , Xu Weifeng , Xu Zhi-Qing David , Wu Jianyoung , Hökfelt Tomas G. M. , Fisahn André , Xu Baoji , Lu Bai
Published: September 2011

Although brain-derived neurotrophic factor (BDNF) is known to regulate circuit development and synaptic plasticity, its exact role in neuronal network activity remains elusive. Using mutant mice (TrkB-PV
−/−
) in which the gene for the BDNF receptor, tyrosine kinase B receptor (
trkB
), has been specifically deleted in parvalbumin-expressing, fast-spiking GABAergic (PV+) interneurons, we show that TrkB is structurally and functionally important for the integrity of the hippocampal network. The amplitude of glutamatergic inputs to PV+ interneurons and the frequency of GABAergic inputs to excitatory pyramidal cells were reduced in the TrkB-PV
−/−
mice. Functionally, rhythmic network activity in the gamma-frequency band (30–80 Hz) was significantly decreased in hippocampal area CA1. This decrease was caused by a desynchronization and overall reduction in frequency of action potentials generated in PV+ interneurons of TrkB-PV
−/−
mice. Our results show that the integration of PV+ interneurons into the hippocampal microcircuit is impaired in TrkB-PV
−/−
mice, resulting in decreased rhythmic network activity in the gamma-frequency band.
Regulatory elements required for the activation and repression of the protocadherin-α gene cluster
Authors: Kehayova Polina , Monahan Kevin , Chen Weisheng , Maniatis Tom
Published: September 2011

The mouse protocadherin (
Pcdh
) -α, -β, and -γ gene clusters encode more than 50 protein isoforms, the combinatorial expression of which generates vast single-cell diversity in the brain. At present, the mechanisms by which this diversity is expressed are not understood. Here we show that two transcriptional enhancer elements, HS5-1 and HS7, play a critical role in
Pcdh
α gene expression in mice. We show that the HS5-1 element functions as an enhancer in neurons and a silencer in nonneuronal cells. The enhancer activity correlates with the binding of zinc finger DNA binding protein CTCF to the target promoters, and the silencer activity requires the binding of the REST/NRSF repressor complex in nonneuronal cells. Thus, the HS5-1 element functions as a neuron-specific enhancer and nonneuronal cell repressor. In contrast, the HS7 element functions as a
Pcdh
α cluster-wide transcription enhancer element. These studies reveal a complex organization of regulatory elements required for generating single cell Pcdh diversity.
SCAR molecular markers of the B biotype and two non-B populations of the whitefly, Bemisia tabaci (Hemiptera: Aleyrodidae)
Authors: Lian-Sheng Zang , Tong Jiang , Jing Xu , Shu-Sheng Liu , You-Jun Zhang
Published: September 2011

Random amplified polymorphic DNA (RAPD) analyses were performed with random primer H16 for the B biotype and two non-B populations of Bemisia tabaci collected from Zhejiang (China). The specific sequence fragments containing 446, 390 and 1317 nucleotides were amplified for the B biotype, ZHJ-1, ZHJ-2 populations, respectively. The three specific fragments were cloned and sequenced, and three pairs of SCAR primers were designed according to the sequences determined. With improvement of the conditions of the polymerase chain reaction (PCR), the specific fragments of B biotype, ZHJ-1 and ZHJ-2 populations, namely 439, 366 and 1238 nucleotides, respectively, were amplified with the sequence characterized amplified region (SCAR) primer of the corresponding population, while specific fragments of the other populations of B. tabaci or Trialeurodes vaporariorum could not be amplified.
Musical Acculturation in Iran
Authors: Klitz Brian , Cherlin Norma
Published: September 2011

Acculturation has been accomplished traditionally when a society has absorbed foreign elements originally superimposed by invasion or acquired through excursions and study in other countries. These traditional means have been supplemented more recently by modern forms of communication and rapid travel, which tend to aggravate the natural imbalance of acculturation and to raise the specter of a cultural imperialism attended by a decline in quality or a reduction in number of indigenous cultural undertakings.

In Iran, with respect to musical acculturation, this hazard has been recognized for some time. For instance, Tehran's Conservatory for National Music was formally established by the Ministry of Culture and Art in 1949 with the specific objectives of systematically restoring national music and reviving the original Iranian instruments, and, in 1968, a High Commission of Culture and Art was formed to consider, among other matters, the question of acculturation.
Bahār in the Context of Persian Constitutional Revolution
Authors: Loraine Michael B.
Published: September 2011

Bahār provides an unusual example of a writer belonging to different periods of Persian literature. He began writing early and lived long enough to pass through several admittedly rapid stages in modern Persian history. Thus he is known as one of the poets of the Constitutional period, whose poems were chanted and recited by the overthrowers of the old autocracy, even more by those who counteracted the Lesser Autocracy of Muḥammad ˓Alī Shāh, as well as the poet, journalist, scholar and teacher of the restored constitution, the reign of Riā Shāh and just after.

A close look at the Dīvān reveals a third period, less important from the literary point of view, but which preceded the others and gave Bahār a stamp he was never wholly to lose, even though he was acutely sensitive to the rapid changes Persian society and culture were to undergo during his life.
Les Caravanserais Routiers Safavids
Authors: Siroux Maxime
Published: September 2011

A la fin du quinzieme sifècle et à l'aube du seizième l'Iran était déchiré par des guerres intestines résultant de l'émiettement du pouvoir des Timurides. Le pays, sur le chemin de sa perte, subissait au nord comme à l'est, les terribles pressions de belliqueuses tribus.

En ce chaos, il appartint au futur fondateur de la dynastie des Safavides, Shāh Ismāᶜīl I (règne de 1499 à 1524 A.D.), de s'imposer, grâce à l'appui d'une faction turque, établie par sa famille dans la province caspienne du Gilan.

D'un sang illustre, puisque descendant du septième imam, Mūsā al-Kāzim, ce personnage, guerrier énergique et intelligent, héritait également des vertus combattives de ses ascendants de la tribu Ak Koyunlu et de la finesse de sa grand'mère, princesse grecque. En l'absence d'un rival de même valeur, ce prince chiite, alors que les populations partageaient en grande partie la même foi, fut sans difficulté reconnu comme roi.
Aspects of the Safavid Ensemble at Isfahan
Authors: Wilber Donald
Published: September 2011

Any effort to relate the plan and the structures of the royal ensemble of Shāh ᶜAbbās and his successors with the existing remains must draw on the observations of the French jeweler Chardin who was in Persia between 1666 and 1670 and between 1671 and 1677. His first stay coincided with the last years of the reign of ᶜAbbās II and his second with the early years of the reign of Sulayman I. In 1666 he and a friend, Herbert Diager, “Chef du Commerce des Hollandais,” resolved to produce an account of Isfahan, “ou rien ne fut omis de ce que feroit digne d'être sû.” Aided by two local mullas, they piled up voluminous notes, and in 1676 Chardin abridged this material to some eighty pages.

According to Chardin, “La beauté d'Ispahan consiste particulièrement dans un grand nombre de Palais magnifiques, de Maisons gaies & riantes, de Caravanserais spacieux, de fort beaux Bazars, & de Canaux & de Ruës, dont les côtez sont couverts de haut platanes.“
Hafez's “Turk of Shiraz” Again
Authors: Hillmann Michael C.
Published: September 2011

The most familiar of Hafez's poems in the English-speaking world is the so-called “Turk of Shiraz” ghazal, a much translated and frequently discussed poem that has been called a number of things which it isn't: A great poem, a grand philosophical utterance, a unified composition and a typical Hafezian ghazal. And it hasn't been called something which it may well be: a verse-song intended for recital with musical accompaniment.
Recent Economic Changes in Boir Ahmad: Regional Growth without Development
Authors: Loeffler Reinhold L.
Published: September 2011

I concluded my previous paper on this subject with the remark that the people of Boir Ahmad, faced with the depletion of their pastures, the unavailability of new land, the difficulty of obtaining higher education, and the low wages earned from migrant labor, were looking toward the future trusting a merciful God to open, as they say, five doors for each one that was closed. That was in 1971. Since then, doors have indeed been opening up for the people of Boir Ahmad, a process which is filling them with new expectations for the future, but which is also changing basically the structure of their traditional way of life. These changes are most pronounced in the western and eastern parts of Boir Ahmad, i.e., in the nearer and farther environs of the administrative centers of Yasuj and Deh Dasht. In the present paper I shall describe these changes, using as an example a village 36 kilometers to the northwest of Yasuj, the Deh Bozorg Sisakht, commonly called Sisakht, the largest village of Boir Ahmad (pop. in 1976: 2596).
Iran's Migration of Skilled Labor to the United States
Authors: Askari Hossein , Cummings John T. , Izbudak Mehmet
Published: September 2011

The growth of Iran's economy, like that of any developing country, is dependent not only on how its natural resources are used, but also its human resources. The two together can lead to increases in both the quantity and quality of physical capital. This process does not require absolutely synchronous improvements in the way both natural and human resources are employed, but certainly changes must be parallel.

If, on the other hand, exploitation of natural resources moves forward much more rapidly, considerable physical capital can be acquired in a short time. But without ample supplies of skilled labor, capital goods may then be used inefficiently or even stand idle. This problem can be partly overcome in the short run if it is possible to hire foreigners to supplement the domestic labor in sufficient amounts and with the proper skills. On the other hand, if a nation's growing educational system turns out skilled people at rates faster than the growth in available jobs, then employment, underemployment, or migration are the immediate choices facing many workers and their families.
The Strange Death of Ibrahim Khalil Khan of Qarabagh
Authors: Atkin Muriel
Published: September 2011

Ibrahim Khalil Khan, the octogenarian ruler of Qarabagh in the southern Caucasus, was shot by Russian soldiers on the night of June 14, 1806. In one sense, there is nothing mysterious about the khan's death. Qarabaghi, Russian, and Iranian sources agree that he was killed for having sided with Iran against Russia's attempt to take control of his khanate and all the lands between the High Caucasus and the Aras River. However, this explanation raises more important questions which have gone unanswered. For years Ibrahim Khalil had sided with Georgia and then Russia against Iran. What made him switch sides in time of war? Russia did not plan to supplant rule by khan in Qarabagh and did not kill every ruler it deposed. Why then did the Russians kill this khan? How was it possible for the execution of Russian policy to slip out of St. Petersburg's control?
Between the Old and the New: The Protocols of the Elders of Zion in Communist Poland
Authors: Rozenbaum Wlodzimierz
Published: September 2011

Jean-Paul Sartre once observed that “contrary to a wide spread opinion, it is not the Jewish character that provokes anti-Semitism but, rather, that it is the anti-Semite who creates the New.” This statement seems to have particular validity in regard to communist Poland, where in the years 1967–1968 the authorities carried out a large-scale campaign against the small Jewish minority, numbering less than 30,000, most of whom had long been assimilated.
Bangladesh-the Struggle for Cultural Independence
Authors: Coates Jenefer
Published: September 2011

The major part of this article was completed before the recent war between India and Pakistan and the establishment of an independent state of Bangladesh. Its aim was to gather evidence about one of the principal bones of contention between the east and west wings of Pakistan, the conflict of two cultures, and to show how a specific assault was made on Bengali culture and the Bengali intellectuals as part of a wider political and military assault on the people of East Pakistan. Events during the last days of the recent war have tragically confirmed the author's thesis and a postscript has been added dealing with the final massacre of intellectuals in Dacca. The names of witnesses have not been disclosed at their request. Editor.
The Ordeal of Natalya Gorbanevskaya
Authors: Weissbort Daniel
Published: September 2011

Natalya Gorbanevskaya was released from detention in a psychiatric hospital on 24 February this year.
I can't complain
Authors: Vaculík Ludvík
Published: September 2011

This is the full text of an interview given to the Swiss Journalist, Friedrich Rentsch, last winter by the Czech novelist Ludvík Vaculík, and published in the Hamburg newspaper Die Zeit on 12 January 1973. Vaculík is perhaps best known in the West as the chief author of the famous ‘Two Thousand Words’ manifesto on democratic socialism, which was published by a group of Czech writers in the summer of 1968 at the height of the Dubĉek government's crisis. He has also written two highly praised novels, The Axe ( published in Czechoslovakia in 1966) and The Guinea-pigs, published abroad in 1971 and shortly to appear in English (see the extract that appeared in INDEX 2/1972 pp. 153-9). Vaculík is at present living in Prague and is still writing, but since his name is still on the black list of writers issued by the present government (see INDEX 2/1972, p. 45) his works cannot be published in Czechoslovakia.