bluuebunny/crossref_metadata_2025 huggingface dataset:
Punctuation and syntax of the RNA polymerase II CTD code in fission yeast
Authors: Schwer Beate , Sanchez Ana M. , Shuman Stewart
Published: October 2012

The primary structure and phosphorylation pattern of the tandem Y
1
S
2
P
3
T
4
S
5
P
6
S
7
repeats of the RNA polymerase II carboxyl-terminal domain (CTD) convey information about the transcription apparatus—a CTD code—to a large ensemble of CTD-binding receptor proteins. Four of the seven coding “letters” of the fission yeast CTD (Tyr1, Pro3, Ser5, Pro6) are essential in vivo, but the grammatical rules of the code are obscure. Here we show that the minimal fission yeast CTD coding unit is a decapeptide Y
1
S
2
P
3
T
4
S
5
P
6
S
7
Y
1
S
2
P
3
and the spacing between coding units is flexible; the coding unit must contain two Tyr1 residues and the spacing between consecutive tyrosines is important; Ser5-PO
4
-Pro6 comprises an essential two-letter code “word” that is read by the mRNA capping apparatus; and a threshold number of Ser5-PO
4
-Pro6 words are needed to comprise a readable “sentence” of CTD information. Bypassing the essentiality of the Ser5 and Pro6 letters by fusion of capping enzymes to the CTD helped reveal how CTD phosphorylation circuits are wired in vivo. We found that the Ser2-PO
4
mark is independent of Ser5, Pro6, Ser7, and Thr4, whereas the Ser5-PO
4
mark is independent of Ser2, Ser7, and Thr4. These results provide unique insights to the reading and writing of the CTD code.
Controlled biosynthesis of odd-chain fuels and chemicals via engineered modular metabolic pathways
Authors: Tseng Hsien-Chung , Prather Kristala L. J.
Published: October 2012

Microbial systems are being increasingly developed as production hosts for a wide variety of chemical compounds. Broader adoption of microbial synthesis is hampered by a limited number of high-yielding natural pathways for molecules with the desired physical properties, as well as the difficulty in functionally assembling complex biosynthetic pathways in heterologous hosts. Here, we address both of these challenges by reporting the adaptation of the butanol biosynthetic pathway for the synthesis of odd-chain molecules and the development of a complementary modular toolkit to facilitate pathway construction, characterization, and optimization in engineered
Escherichia coli
. The modular feature of our pathway enables multientry and multiexit biosynthesis of various odd-chain compounds at high efficiency. By varying combinations of the pathway and toolkit enzymes, we demonstrate controlled production of propionate, trans-2-pentenoate, valerate, and pentanol, compounds with applications that include biofuels, antibiotics, biopolymers, and aroma chemicals. Importantly, and in contrast to a previously used method to identify limitations in heterologous amorphadiene production, our bypass strategy was effective even without the presence of freely membrane-diffusible substrates. This approach should prove useful for optimization of other pathways that use CoA-derivatized intermediates, including fatty acid β-oxidation and the mevalonate pathway for isoprenoid synthesis.
IL-10–induced microRNA-187 negatively regulates TNF-α, IL-6, and IL-12p40 production in TLR4-stimulated monocytes
Authors: Rossato Marzia , Curtale Graziella , Tamassia Nicola , Castellucci Monica , Mori Laura , Gasperini Sara , Mariotti Barbara , De Luca Mariacristina , Mirolo Massimiliano , Cassatella Marco A. , Locati Massimo , Bazzoni Flavia
Published: October 2012

IL-10 is a potent anti-inflammatory molecule that, in phagocytes, negatively targets cytokine expression at transcriptional and posttranscriptional levels. Posttranscriptional checkpoints also represent the specific target of a recently discovered, evolutionary conserved class of small silencing RNAs known as “microRNAs” (miRNAs), which display the peculiar function of negatively regulating mRNA processing, stability, and translation. In this study, we report that activation of primary human monocytes up-regulates the expression of miR-187 both in vitro and in vivo. Accordingly, we identify miR-187 as an IL-10–dependent miRNA playing a role in IL-10–mediated suppression of TNF-α, IL-6, and the p40 subunit of IL-12 (IL-12p40) produced by primary human monocytes following activation of Toll-like receptor 4 (TLR4). Ectopic expression of miR-187 consistently and selectively reduces TNFα, IL-6, and IL-12p40 produced by LPS-activated monocytes. Conversely, the production of LPS-induced TNF-α, IL-6, and IL-12p40 is increased significantly when miR-187 expression is silenced. Our data demonstrate that miR-187 directly targets TNF-α mRNA stability and translation and indirectly decreases IL-6 and IL-12p40 expression via down-modulation of IκBζ, a master regulator of the transcription of these latter two cytokines. These results uncover an miRNA-mediated pathway controlling cytokine expression and demonstrate a central role of miR-187 in the physiological regulation of IL-10–driven anti-inflammatory responses.
Atomic resolution structure of human α-tubulin acetyltransferase bound to acetyl-CoA
Authors: Taschner Michael , Vetter Melanie , Lorentzen Esben
Published: October 2012

Acetylation of lysine residues is an important posttranslational modification found in all domains of life. α-tubulin is specifically acetylated on lysine 40, a modification that serves to stabilize microtubules of axons and cilia. Whereas histone acetyltransferases have been extensively studied, there is no structural and mechanistic information available on α-tubulin acetyltransferases. Here, we present the structure of the human α-tubulin acetyltransferase catalytic domain bound to its cosubstrate acetyl-CoA at 1.05 Å resolution. Compared with other lysine acetyltransferases of known structure, α-tubulin acetyltransferase displays a relatively well-conserved cosubstrate binding pocket but is unique in its active site and putative α-tubulin binding site. Using acetylation assays with structure-guided mutants, we map residues important for acetyl-CoA binding, substrate binding, and catalysis. This analysis reveals a basic patch implicated in substrate binding and a conserved glutamine residue required for catalysis, demonstrating that the family of α-tubulin acetyltransferases uses a reaction mechanism different from other lysine acetyltransferases characterized to date.
Structure of the α-tubulin acetyltransferase, αTAT1, and implications for tubulin-specific acetylation
Authors: Friedmann David R. , Aguilar Andrea , Fan Jiayi , Nachury Maxence V. , Marmorstein Ronen
Published: October 2012

Protein acetylation is an important posttranslational modification with the recent identification of new substrates and enzymes, new links to disease, and modulators of protein acetylation for therapy. α-tubulin acetyltransferase (αTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes. Here, we present the X-ray crystal structure of the human αTAT1/acetyl-CoA complex. Together with structure-based mutagenesis, enzymatic analysis, and functional studies in cells, we elucidate the catalytic mechanism and mode of tubulin-specific acetylation. We find that αTAT1 has an overall fold similar to the Gcn5 histone acetyltransferase but contains a relatively wide substrate binding groove and unique structural elements that play important roles in α-tubulin–specific acetylation. Conserved aspartic acid and cysteine residues play important catalytic roles through a ternary complex mechanism. αTAT1 mutations have analogous effects on tubulin acetylation in vitro and in cells, demonstrating that it is the central determining factor of α-tubulin K40 acetylation levels in vivo. Together, these studies provide general insights into distinguishing features between histone and tubulin acetyltransferases, and they have specific implications for understanding the molecular basis of tubulin acetylation and for developing small molecule modulators of microtubule acetylation for therapy.
Enhanced top soil carbon stocks under organic farming
Authors: Gattinger Andreas , Muller Adrian , Haeni Matthias , Skinner Colin , Fliessbach Andreas , Buchmann Nina , Mäder Paul , Stolze Matthias , Smith Pete , Scialabba Nadia El-Hage , Niggli Urs
Published: October 2012

It has been suggested that conversion to organic farming contributes to soil carbon sequestration, but until now a comprehensive quantitative assessment has been lacking. Therefore, datasets from 74 studies from pairwise comparisons of organic vs. nonorganic farming systems were subjected to metaanalysis to identify differences in soil organic carbon (SOC). We found significant differences and higher values for organically farmed soils of 0.18 ± 0.06% points (mean ± 95% confidence interval) for SOC concentrations, 3.50 ± 1.08 Mg C ha
−1
for stocks, and 0.45 ± 0.21 Mg C ha
−1
y
−1
for sequestration rates compared with nonorganic management. Metaregression did not deliver clear results on drivers, but differences in external C inputs and crop rotations seemed important. Restricting the analysis to zero net input organic systems and retaining only the datasets with highest data quality (measured soil bulk densities and external C and N inputs), the mean difference in SOC stocks between the farming systems was still significant (1.98 ± 1.50 Mg C ha
−1
), whereas the difference in sequestration rates became insignificant (0.07 ± 0.08 Mg C ha
−1
y
−1
). Analyzing zero net input systems for all data without this quality requirement revealed significant, positive differences in SOC concentrations and stocks (0.13 ± 0.09% points and 2.16 ± 1.65 Mg C ha
−1
, respectively) and insignificant differences for sequestration rates (0.27 ± 0.37 Mg C ha
−1
y
−1
). The data mainly cover top soil and temperate zones, whereas only few data from tropical regions and subsoil horizons exist. Summarizing, this study shows that organic farming has the potential to accumulate soil carbon.
Homogeneous record of Atlantic hurricane surge threat since 1923
Authors: Grinsted Aslak , Moore John C. , Jevrejeva Svetlana
Published: October 2012

Detection and attribution of past changes in cyclone activity are hampered by biased cyclone records due to changes in observational capabilities. Here we construct an independent record of Atlantic tropical cyclone activity on the basis of storm surge statistics from tide gauges. We demonstrate that the major events in our surge index record can be attributed to landfalling tropical cyclones; these events also correspond with the most economically damaging Atlantic cyclones. We find that warm years in general were more active in all cyclone size ranges than cold years. The largest cyclones are most affected by warmer conditions and we detect a statistically significant trend in the frequency of large surge events (roughly corresponding to tropical storm size) since 1923. In particular, we estimate that Katrina-magnitude events have been twice as frequent in warm years compared with cold years (
P
< 0.02).
Peptide toxin glacontryphan-M is present in the wings of the butterfly
Hebomoia glaucippe
(Linnaeus, 1758) (Lepidoptera: Pieridae)
Authors: Bae Narkhyun , Li Lin , Lödl Martin , Lubec Gert
Published: October 2012

Protein profiling has revealed the presence of glacontryphan-M, a peptide toxin identified only in the sea snail genus
Conus
, in the wings of
Hebomoia glaucippe
(HG). The wings and body of HG were homogenized and the proteins were extracted and analyzed by 2D gel electrophoresis with subsequent in-gel digestion. Posttranslational protein modifications were detected and analyzed by nano–LC-MS/MS. An antibody was generated against glacontryphan-M, and protein extracts from the wings of HG samples from Malaysia, Indonesia, and the Philippines were tested by immunoblotting. Glacontryphan-M was unambiguously identified in the wings of HG containing the following posttranslational protein modifications: monoglutamylation at E55, methylation at E53, quinone modification at W61, cyanylation at C56, and amidation of the C terminus at G63. Immunoblotting revealed the presence of the toxin in the wings of HG from all origins, showing a single band for glacontryphan-M in HG samples from Malaysia and Philippines and a double band in HG samples from Indonesia. Intriguingly, sequence analysis indicated that the
Conus
glacontryphan is identical to that of HG. The toxin may function as a defense against diverse predators, including ants, mantes, spiders, lizards, green frogs, and birds.
Crystal structure of the human PRMT5:MEP50 complex
Authors: Antonysamy Stephen , Bonday Zahid , Campbell Robert M. , Doyle Brandon , Druzina Zhanna , Gheyi Tarun , Han Bomie , Jungheim Louis N. , Qian Yuewei , Rauch Charles , Russell Marijane , Sauder J. Michael , Wasserman Stephen R. , Weichert Kenneth , Willard Francis S. , Zhang Aiping , Emtage Spencer
Published: October 2012

Protein arginine methyltransferases (PRMTs) play important roles in several cellular processes, including signaling, gene regulation, and transport of proteins and nucleic acids, to impact growth, differentiation, proliferation, and development. PRMT5 symmetrically di-methylates the two-terminal ω-guanidino nitrogens of arginine residues on substrate proteins. PRMT5 acts as part of a multimeric complex in concert with a variety of partner proteins that regulate its function and specificity. A core component of these complexes is the WD40 protein MEP50/WDR77/p44, which mediates interactions with binding partners and substrates. We have determined the crystal structure of human PRMT5 in complex with MEP50 (methylosome protein 50), bound to an S-adenosylmethionine analog and a peptide substrate derived from histone H4. The structure of the surprising hetero-octameric complex reveals the close interaction between the seven-bladed β-propeller MEP50 and the N-terminal domain of PRMT5, and delineates the structural elements of substrate recognition.
Serine phosphorylation by SYK is critical for nuclear localization and transcription factor function of Ikaros
Authors: Uckun Fatih M. , Ma Hong , Zhang Jian , Ozer Zahide , Dovat Sinisa , Mao Cheney , Ishkhanian Rita , Goodman Patricia , Qazi Sanjive
Published: October 2012

Ikaros is a zinc finger-containing DNA-binding protein that plays a pivotal role in immune homeostasis through transcriptional regulation of the earliest stages of lymphocyte ontogeny and differentiation. Functional deficiency of Ikaros has been implicated in the pathogenesis of acute lymphoblastic leukemia, the most common form of childhood cancer. Therefore, a stringent regulation of Ikaros activity is considered of paramount importance, but the operative molecular mechanisms responsible for its regulation remain largely unknown. Here we provide multifaceted genetic and biochemical evidence for a previously unknown function of spleen tyrosine kinase (SYK) as a partner and posttranslational regulator of Ikaros. We demonstrate that SYK phoshorylates Ikaros at unique C-terminal serine phosphorylation sites S358 and S361, thereby augmenting its nuclear localization and sequence-specific DNA binding activity. Mechanistically, we establish that SYK-induced Ikaros activation is essential for its nuclear localization and optimal transcription factor function.
Low intravascular pressure activates endothelial cell TRPV4 channels, local Ca
2+
events, and IK
Ca
channels, reducing arteriolar tone
Authors: Bagher Pooneh , Beleznai Timea , Kansui Yasuo , Mitchell Ray , Garland Christopher J. , Dora Kim A.
Published: October 2012

Endothelial cell (EC) Ca
2+
-activated K channels (SK
Ca
and IK
Ca
channels) generate hyperpolarization that passes to the adjacent smooth muscle cells causing vasodilation. IK
Ca
channels focused within EC projections toward the smooth muscle cells are activated by spontaneous Ca
2+
events (Ca
2+
puffs/pulsars). We now show that transient receptor potential, vanilloid 4 channels (TRPV4 channels) also cluster within this microdomain and are selectively activated at low intravascular pressure. In arterioles pressurized to 80 mmHg, ECs generated low-frequency (∼2 min
−1
) inositol 1,4,5-trisphosphate receptor-based Ca
2+
events. Decreasing intraluminal pressure below 50 mmHg increased the frequency of EC Ca
2+
events twofold to threefold, an effect blocked with the TRPV4 antagonist RN1734. These discrete events represent both TRPV4-sparklet- and nonsparklet-evoked Ca
2+
increases, which on occasion led to intracellular Ca
2+
waves. The concurrent vasodilation associated with increases in Ca
2+
event frequency was inhibited, and basal myogenic tone was increased, by either RN1734 or TRAM-34 (IK
Ca
channel blocker), but not by apamin (SK
Ca
channel blocker). These data show that intraluminal pressure influences an endothelial microdomain inversely to alter Ca
2+
event frequency; at low pressures the consequence is activation of EC IK
Ca
channels and vasodilation, reducing the myogenic tone that underpins tissue blood-flow autoregulation.
Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques
Authors: Olinger Gene Garrard , Pettitt James , Kim Do , Working Cara , Bohorov Ognian , Bratcher Barry , Hiatt Ernie , Hume Steven D. , Johnson Ashley K. , Morton Josh , Pauly Michael , Whaley Kevin J. , Lear Calli M. , Biggins Julia E. , Scully Corinne , Hensley Lisa , Zeitlin Larry
Published: October 2012

Filovirus infections can cause a severe and often fatal disease in humans and nonhuman primates, including great apes. Here, three anti-Ebola virus mouse/human chimeric mAbs (c13C6, h-13F6, and c6D8) were produced in Chinese hamster ovary and in whole plant (
Nicotiana benthamiana
) cells. In pilot experiments testing a mixture of the three mAbs (MB-003), we found that MB-003 produced in both manufacturing systems protected rhesus macaques from lethal challenge when administered 1 h postinfection. In a pivotal follow-up experiment, we found significant protection (
P
< 0.05) when MB-003 treatment began 24 or 48 h postinfection (four of six survived vs. zero of two controls). In all experiments, surviving animals that received MB-003 experienced little to no viremia and had few, if any, of the clinical symptoms observed in the controls. The results represent successful postexposure in vivo efficacy by a mAb mixture and suggest that this immunoprotectant should be further pursued as a postexposure and potential therapeutic for Ebola virus exposure.
Human mortality improvement in evolutionary context
Authors: Burger Oskar , Baudisch Annette , Vaupel James W.
Published: October 2012

Life expectancy is increasing in most countries and has exceeded 80 in several, as low-mortality nations continue to make progress in averting deaths. The health and economic implications of mortality reduction have been given substantial attention, but the observed malleability of human mortality has not been placed in a broad evolutionary context. We quantify the rate and amount of mortality reduction by comparing a variety of human populations to the evolved human mortality profile, here estimated as the average mortality pattern for ethnographically observed hunter-gatherers. We show that human mortality has decreased so substantially that the difference between hunter-gatherers and today’s lowest mortality populations is greater than the difference between hunter-gatherers and wild chimpanzees. The bulk of this mortality reduction has occurred since 1900 and has been experienced by only about 4 of the roughly 8,000 human generations that have ever lived. Moreover, mortality improvement in humans is on par with or greater than the reductions in mortality in other species achieved by laboratory selection experiments and endocrine pathway mutations. This observed plasticity in age-specific risk of death is at odds with conventional theories of aging.
Oxidized quinones signal onset of darkness directly to the cyanobacterial circadian oscillator
Authors: Kim Yong-Ick , Vinyard David J. , Ananyev Gennady M. , Dismukes G. Charles , Golden Susan S.
Published: October 2012

Synchronization of the circadian clock in cyanobacteria with the day/night cycle proceeds without an obvious photoreceptor, leaving open the question of its specific mechanism. The circadian oscillator can be reconstituted in vitro, where the activities of two of its proteins, KaiA and KaiC, are affected by metabolites that reflect photosynthetic activity: KaiC phosphorylation is directly influenced by the ATP/ADP ratio, and KaiA stimulation of KaiC phosphorylation is blocked by oxidized, but not reduced, quinones. Manipulation of the ATP/ADP ratio can reset the timing of KaiC phosphorylation peaks in the reconstituted in vitro oscillator. Here, we show that pulses of oxidized quinones reset the cyanobacterial circadian clock both in vitro and in vivo. Onset of darkness causes an abrupt oxidation of the plastoquinone pool in vivo, which is in contrast to a gradual decrease in the ATP/ADP ratio that falls over the course of hours until the onset of light. Thus, these two metabolic measures of photosynthetic activity act in concert to signal both the onset and duration of darkness to the cyanobacterial clock.
From adverb to conjunction and back
Authors: Rutten Gijsbert
Published: October 2012

In late Middle Dutch, the temporal adverb dan “then” grammaticalized into an adversative coordinator (“but”), which remained in use up to the nineteenth century. This paper investigates how adversative dan can be deduced from earlier usages and why it later disappeared. The paper’s first part discusses how temporal dan developed an exclusive function (“except”), from which the adversative use is derived. Semantic maps are used to represent the development, and to make clear similarities and differences with German and English cognates of dan (dann/denn and than/then respectively). The second part reports corpus studies of seventeenth and eighteenth-century letters and diaries, showing text type and frequency effects on the use of adversative dan, which led to its disappearance. This will be interpreted as a peculiar case of degrammaticalization, lacking semantic enrichment and syntactic flexibilization which normally accompany degrammaticalization. The case of dan suggests that text type and frequency are important factors in (de)grammaticalization.
Contact-induced restructuring of pronominal morphosyntax in Umpithamu (Cape York Peninsula, Australia)
Authors: Verstraete Jean-Christophe
Published: October 2012

This paper analyses the morphosyntactic status of pronouns in Umpithamu, a language from Cape York Peninsula (Australia). The analysis shows that pronominal morphosyntax in Umpithamu deviates from what can be expected historically and typologically, and attributes this to restructuring under the influence of intensive contact with Lamalamic languages, to which it is not closely related. The evidence for contact-induced restructuring combines a clear linguistic case involving a rare morphosyntactic pattern with a rare function, with a well-documented anthropological case for long-standing language contact. The outcome of the process is morphologically hybrid, combining the external structure of enclitic forms with the internal structure of free forms, which testifies to the abrupt nature of the process that was involved.
“Who knows best?”
Authors: Sidnell Jack
Published: October 2012

This essay reviews current work in conversation analysis with an eye to what it might contribute to the study of evidentiality and epistemic asymmetry. After a brief review of some aspects of the interactional organization of conversation, I turn to consider the way in which participants negotiate relative epistemic positioning through the use of particular practices of speaking. The analytic focus here is on agreements and confirmations especially in assessment sequences. In conclusion, I consider a single case in which various practices are employed to convey a delicate balance of knowledge and simultaneously to attend to a range of other, non-epistemic, interactional issues.
A Direct‐Gradient Multivariate Index of Biotic Condition
Authors: Miranda L. E. , Aycock J. N. , Killgore K. J.
Published: October 2012

Multimetric indexes constructed by summing metric scores have been criticized despite many of their merits. A leading criticism is the potential for investigator bias involved in metric selection and scoring. Often there is a large number of competing metrics equally well correlated with environmental stressors, requiring a judgment call by the investigator to select the most suitable metrics to include in the index and how to score them. Data‐driven procedures for multimetric index formulation published during the last decade have reduced this limitation, yet apprehension remains. Multivariate approaches that select metrics with statistical algorithms may reduce the level of investigator bias and alleviate a weakness of multimetric indexes. We investigated the suitability of a direct‐gradient multivariate procedure to derive an index of biotic condition for fish assemblages in oxbow lakes in the Lower Mississippi Alluvial Valley. Although this multivariate procedure also requires that the investigator identify a set of suitable metrics potentially associated with a set of environmental stressors, it is different from multimetric procedures because it limits investigator judgment in selecting a subset of biotic metrics to include in the index and because it produces metric weights suitable for computation of index scores. The procedure, applied to a sample of 35 competing biotic metrics measured at 50 oxbow lakes distributed over a wide geographical region in the Lower Mississippi Alluvial Valley, selected 11 metrics that adequately indexed the biotic condition of five test lakes. Because the multivariate index includes only metrics that explain the maximum variability in the stressor variables rather than a balanced set of metrics chosen to reflect various fish assemblage attributes, it is fundamentally different from multimetric indexes of biotic integrity with advantages and disadvantages. As such, it provides an alternative to multimetric procedures.
Homophobia or sexism? A systematic review of prejudice against nonheterosexual orientation in Brazil
Authors: Costa Angelo Brandelli , Peroni Rodrigo Oliva , Bandeira Denise Ruschel , Nardi Henrique Caetano
Published: October 2012

Since it was coined in the 1970s, in the United States, the term “homophobia” has been invoked to define the prejudice against nonheterosexual orientation. Besides the US, the phenomenon has been detected in many contemporary societies, including Brazil. Prejudice against nonheterosexual orientation is strongly associated with the historical and social contexts in which it is embedded, which means that the term should not be used without a clear definition of its local specificities. This applies to the recent debate around homophobia in the Brazilian context. In an attempt to identify existing studies of prejudice against nonheterosexual orientations in Brazil, a systematic review was conducted in SciELO indexes, PubMed, PsycINFO, SCOPUS, and Web of Science. The articles were collected using the keyword “homophobia” and related terms, and “Brazil”, in the languages ⁣⁣of the databases. The search returned 355 articles. Of these, 247 were removed because they were duplicates. The abstracts of 109 studies published between 1973 and 2011were analyzed. Thirty‐one articles were identified as relevant. The reviewed studies indicate that prejudice against nonheterosexual orientations is an evident and widespread phenomenon that is prevalent in various populations and contexts. Nevertheless, prejudice in Brazil is not homogeneous, and particular attention is necessary to the inequality of gender relations (sexism) and prejudice against gender nonconformity, which seem to explain, if not cause, most of the prejudice against nonheterosexual orientations. Although theoretically there is a clear distinction between sexual orientation and gender expression, from the standpoint of manifestation of prejudice that distinction seems to be more tenuous.
Bases of social power, leadership styles, and organizational commitment
Authors: Pierro Antonio , Raven Bertram H. , Amato Clara , Bélanger Jocelyn J.
Published: October 2012

Affective organizational commitment reflects the extent to which organizational members are loyal and willing to work toward organizational objectives (Meyer & Allen, 1997). In particular, affective organizational commitment holds very important implications at all organizational levels (e.g., turnover rates, performance, and citizenship behavior). Whereas previous research has evinced the positive influence of transformational and charismatic leadership styles on affective commitment toward the organization (Bass & Avolio, 1994), little is known with regard to the nature of this relationship. In line with the interpersonal power/interaction model, the present investigation aimed to investigate the mechanism at play between transformational leadership style and affective organizational commitment. Specifically, we hypothesized that transformational leadership style would increase affective organizational commitment through its effect on willingness to comply with soft bases of power. In two studies, we subjected the foregoing hypotheses to empirical scrutiny. In Study 1, the proposed mediation model was empirically supported with Italian employees in the public sector. Attesting to the robustness of our findings, Study 2 replicated the findings of Study 1 with Italian employees from the public and private sectors. In addition, Study 2 replicated Study 1 using a different measure of transformational leadership. Both Study 1 and Study 2 provided results consistent with our hypotheses. Specifically, the present paper reports empirical evidence that (1) the more participants report having a transformational leader, the more willing they become to comply with soft (but not harsh) power bases, (2) in turn, greater willingness to comply with soft (but not harsh) power bases increases one's affective organizational commitment. These findings provide additional support for the interpersonal power/interaction model and pave the way for new research directions.
Elevated Streamflows Increase Dam Passage by Juvenile Coho Salmon during Winter: Implications of Climate Change in the Pacific Northwest
Authors: Kock Tobias J. , Liedtke Theresa L. , Rondorf Dennis W. , Serl John D. , Kohn Mike , Bumbaco Karin A.
Published: October 2012

A 4-year evaluation was conducted to determine the proportion of juvenile coho salmon Oncorhynchus kisutch passing Cowlitz Falls Dam, on the Cowlitz River, Washington, during winter. River and reservoir populations of coho salmon parr were monitored using radiotelemetry to determine if streamflow increases resulted in increased downstream movement and dam passage. This was of interest because fish that pass downstream of Cowlitz Falls Dam become landlocked in Riffe Lake and are lost to the anadromous population. Higher proportions of reservoir-released fish (0.391–0.480) passed Cowlitz Falls Dam than did river-released fish (0.037–0.119). Event-time analyses demonstrated that streamflow increases were important predictors of dam passage rates during the study. The estimated effect of increasing streamflows on the risk of dam passage varied annually and ranged from 9% to 75% for every 28.3 m3/s increase in streamflow. These results have current management implications because they demonstrate the significance of dam passage by juvenile coho salmon during winter months when juvenile fish collection facilities are typically not operating. The results also have future management implications because climate change predictions suggest that peak streamflow timing for many watersheds in the Pacific Northwest will shift from late spring and early summer to winter. Increased occurrence of intense winter flood events is also expected. Our results demonstrate that juvenile coho salmon respond readily to streamflow increases and initiate downstream movements during winter months, which could result in increased passage at dams during these periods if climate change predictions are realized in the coming decades.

Received February 7, 2012; accepted July 31, 2012
Inhibition of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension
Authors: Hameed Abdul G. , Arnold Nadine D. , Chamberlain Janet , Pickworth Josephine A. , Paiva Claudia , Dawson Sarah , Cross Simon , Long Lu , Zhao Lan , Morrell Nicholas W. , Crossman David C. , Newman Christopher M.H. , Kiely David G. , Francis Sheila E. , Lawrie Allan
Published: October 2012

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the progressive narrowing and occlusion of small pulmonary arteries. Current therapies fail to fully reverse this vascular remodeling. Identifying key pathways in disease pathogenesis is therefore required for the development of new-targeted therapeutics. We have previously reported tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) immunoreactivity within pulmonary vascular lesions from patients with idiopathic PAH and animal models. Because TRAIL can induce both endothelial cell apoptosis and smooth muscle cell proliferation in the systemic circulation, we hypothesized that TRAIL is an important mediator in the pathogenesis of PAH. We demonstrate for the first time that TRAIL is a potent stimulus for pulmonary vascular remodeling in human cells and rodent models. Furthermore, antibody blockade or genetic deletion of TRAIL prevents the development of PAH in three independent rodent models. Finally, anti-TRAIL antibody treatment of rodents with established PAH reverses pulmonary vascular remodeling by reducing proliferation and inducing apoptosis, improves hemodynamic indices, and significantly increases survival. These preclinical investigations are the first to demonstrate the importance of TRAIL in PAH pathogenesis and highlight its potential as a novel therapeutic target to direct future translational therapies.
Identification of Axl as a downstream effector of TGF-β1 during Langerhans cell differentiation and epidermal homeostasis
Authors: Bauer Thomas , Zagórska Anna , Jurkin Jennifer , Yasmin Nighat , Köffel René , Richter Susanne , Gesslbauer Bernhard , Lemke Greg , Strobl Herbert
Published: October 2012

Transforming growth factor-β1 (TGF-β1) is a fundamental regulator of immune cell development and function. In this study, we investigated the effects of TGF-β1 on the differentiation of human Langerhans cells (LCs) and identified Axl as a key TGF-β1 effector. Axl belongs to the TAM (Tyro3, Axl, and Mer) receptor tyrosine kinase family, whose members function as inhibitors of innate inflammatory responses in dendritic cells and are essential to the prevention of lupus-like autoimmunity. We found that Axl expression is induced by TGF-β1 during LC differentiation and that LC precursors acquire Axl early during differentiation. We also describe prominent steady-state expression as well as inflammation-induced activation of Axl in human epidermal keratinocytes and LCs. TGF-β1–induced Axl enhances apoptotic cell (AC) uptake and blocks proinflammatory cytokine production. The antiinflammatory role of Axl in the skin is reflected in a marked impairment of the LC network preceding spontaneous skin inflammation in mutant mice that lack all three TAM receptors. Our findings highlight the importance of constitutive Axl expression to tolerogenic barrier immunity in the epidermis and define a mechanism by which TGF-β1 enables silent homeostatic clearing of ACs to maintain long-term self-tolerance.
Basis for allosteric open-state stabilization of voltage-gated potassium channels by intracellular cations
Authors: Goodchild Samuel J. , Xu Hongjian , Es-Salah-Lamoureux Zeineb , Ahern Christopher A. , Fedida David
Published: October 2012

The open state of voltage-gated potassium (Kv) channels is associated with an increased stability relative to the pre-open closed states and is reflected by a slowing of OFF gating currents after channel opening. The basis for this stabilization is usually assigned to intrinsic structural features of the open pore. We have studied the gating currents of Kv1.2 channels and found that the stabilization of the open state is instead conferred largely by the presence of cations occupying the inner cavity of the channel. Large impermeant intracellular cations such as N-methyl-d-glucamine (NMG+) and tetraethylammonium cause severe slowing of channel closure and gating currents, whereas the smaller cation, Cs+, displays a more moderate effect on voltage sensor return. A nonconducting mutant also displays significant open state stabilization in the presence of intracellular K+, suggesting that K+ ions in the intracellular cavity also slow pore closure. A mutation in the S6 segment used previously to enlarge the inner cavity (Kv1.2-I402C) relieves the slowing of OFF gating currents in the presence of the large NMG+ ion, suggesting that the interaction site for stabilizing ions resides within the inner cavity and creates an energetic barrier to pore closure. The physiological significance of ionic occupation of the inner cavity is underscored by the threefold slowing of ionic current deactivation in the wild-type channel compared with Kv1.2-I402C. The data suggest that internal ions, including physiological concentrations of K+, allosterically regulate the deactivation kinetics of the Kv1.2 channel by impairing pore closure and limiting the return of voltage sensors. This may represent a primary mechanism by which Kv channel deactivation kinetics is linked to ion permeation and reveals a novel role for channel inner cavity residues to indirectly regulate voltage sensor dynamics.
What Language Dependence Problem? A Reply for Joyce to Fitelson on Joyce
Authors: Pedersen Arthur Paul , Glymour Clark
Published: October 2012

In an essay recently published in this journal, Branden Fitelson argues that a variant of Miller's argument for the language dependence of the accuracy of predictions can be applied to Joyce's notion of accuracy of credences formulated in terms of scoring rules, resulting in a general potential problem for Joyce's argument for probabilism. We argue that no relevant problem of the sort Fitelson supposes arises since his main theorem and his supporting arguments presuppose the validity of nonlinear transformations of credence functions that Joyce's theory, charitably construed, would identify as invalid on the basis of the principle of simple dominance.
Rescuing Reflection
Authors: Park Ilho
Published: October 2012

In this article, I suggest an argument that seems to show a conflict between the reflection principle and conditionalization. In particular, I show that when the reflection principle is formulated in a standard way, the principle conflicts with Jeffrey conditionalization. And it is argued that the source of the conflict resides in an ambiguity of the standard formulation. Furthermore, I attempt to rescue the principle using Bayes factors. That is, I suggest a new formulation of the principle so as to avoid the conflict.
The Joint Account of Mechanistic Explanation
Authors: Bonnie Fagan Melinda
Published: October 2012

Many explanations in molecular biology, neuroscience, and other fields of experimental biology describe mechanisms underlying phenomena of interest. These mechanistic explanations (MEx) account for higher-level phenomena in terms of causally active parts and their spatiotemporal organization. What makes such a mechanistic description explanatory? The best-developed answer, Craver's causal-mechanical account, has several weaknesses. It does not fully explicate the target of explanation, interlevel relation, or interactive nonmodular character of many biological mechanisms as we understand them. An alternative account of MEx, emphasizing interdependence among a mechanism's components (‘jointness’), remedies these difficulties.
A numerical and experimental investigation of an axially symmetric RF plasma
Authors: Sutton Yvonne C , Johnson Peter C , Naidis George V , Sharp David , Braithwaite Nicholas St J
Published: October 2012

The characteristics of an atmospheric pressure, RF discharge in air were determined and compared with a 2D numerical model adapted from that used for a dc glow discharge. For a 15 mm discharge, the RF plasma's electrical and optical characteristics show a close correlation to several equivalent dc plasmas and to the results calculated from the adapted model. For an rms conduction current range of 11–30 mA, the rotational temperature varies between 2800 and 3200 K; the vibrational temperature shows a change of 3500–4000 K with near equilibrium conditions to the rotational state occuring in the central region of the discharge. Spatial measurements and modelling of nitrogen emission spectra identify the changes in the temperatures and dimensions along the vertical z-axis as well as the spatial dependence on the atomic and molecular species generated in the discharge.
Shape evolution of MBE grown Si1−xGex structures on high-index Si(5 5 12) surfaces: a temperature dependent study
Authors: Dash J K , Rath A , Juluri R R , Satyam P V
Published: October 2012

The morphological evolution and the effect of growth temperature on size, orientation and composition of molecular beam epitaxy grown Ge–Si islands on Si(5 5 12) surfaces have been investigated in the temperature range from room temperature to 800 °C. Two modes of substrate heating, i.e. radiative heating (RH) and direct current heating (DH) have been used. The post-growth characterization was carried out ex situ by scanning electron microscopy, cross-sectional transmission electron microscopy and Rutherford backscattering spectrometry. In the RH case, we found spherical island structures at 600 °C with a bimodal distribution and upon increasing temperature, the structures got faceted at 700 °C. At 800 °C thick (∼122 nm) dome-like structures are formed bounded by facets. While in the case of dc heating, after the optimum critical temperature 600 °C, well aligned trapezoidal Si1−x
Ge
x
structures with a graded composition starts forming along the step edges. Interestingly, these aligned structures have been found only around 600 °C, neither at low temperature nor at higher temperatures.
Convex rationally connected varieties
Authors: Pandharipande R.
Published: October 2012

We prove that all nonsingular, convex, rationally connected, complete intersections in projective space are homogeneous.
Surgical Outcome of Percutaneous Endoscopic Interlaminar Lumbar Discectomy for Highly Migrated Disk Herniation
Authors: Kim Chi H. , Chung Chun K. , Woo Ji W.
Published: October 2012

Study Design:

Technical report.

Objective:

To present a detailed surgical technique for percutaneous endoscopic interlaminar discectomy (PEID) for highly migrated disk herniation.

Summary of Background Data:

Percutaneous lumbar endoscopic discectomy for highly migrated disk herniation is still challenging even for an experienced surgeon. Because of the risk of failure and technical difficulty, open discectomy is recommended for a high-grade migration. However, past reports focused on the transforaminal approach (percutaneous endoscopic transforaminal discectomy) and may give a biased impression. We may overlook the merit of PEID. The surgical procedure for PEID is similar to a traditional open discectomy and the range of approach could be widened by the inclined introduction and pivoting motion of an endoscope.

Methods:

Eighteen consecutive patients (M:F=12:6; age, 56±15 y) with highly migrated disk herniation were enrolled for the present study. The disk material was migrated superiorly in 7 patients (L4–5, 4; L5–S1, 2; L2–3, 1) and inferiorly in 11 patients (L4–5, 6; L3–4, 4; L5–S1, 1). PEID was applied in 17 patients and PETD was performed for L2–3 disk herniation. The follow-up period was 16±12 months. The outcome was graded using the MacNab criteria.

Results:

Complete removal of the disk material was confirmed with magnetic resonance imaging in 16 patients (success rate 89%). Revision operation was necessary in 2 patients with inferior migration from L4–5. The residual disk was removed through the L5–S1 laminar window 2 days after surgery with excellent outcome at the last follow-up. The outcome at the last follow-up was excellent in 12 patients, good in 3, fair in 2, and poor in 1. Dural tear was suspected in 1 patient without any further problems and there was no recurrence during follow-up.

Conclusions:

PEID may be applied comfortably even for less-experienced surgeons because of the familiar anatomy with open surgery.
Comparison of Direct Pars Repair Techniques of Spondylolysis in Pediatric and Adolescent Patients
Authors: Karatas Ali F. , Dede Ozgur , Atanda Alfred A. , Holmes Larry , Rogers Kenneth , Gabos Peter , Shah Suken A.
Published: October 2012

Study Design:

Retrospective clinical cohort study.

Objective:

To compare the clinical and radiographic outcomes of patients who were treated with intrasegmental pars fixation by either laminar compression screw (LS) or a pedicle screw, rod, and laminar hook (PSRH) construct.

Summary of Background Data:

Spondylolysis is a nonunion defect of the pars interarticularis. In symptomatic spondylolysis, direct repair of the pars interarticularis defect can preserve motion and prevent abnormal stresses at the adjacent levels.

Methods:

Sixteen patients who failed nonoperative treatment and underwent direct pars repair by using LS (n=9) or PSRH (n=7) constructs were included in the study. Clinical outcome was assessed by using the MacNab criteria. Radiologic fusion and complications were evaluated using plain radiographs or computed tomography images and patient charts.

Results:

The healing rate was 100% after 6 months. The healing time was similar in both the groups: LS, 6.5 months; PSRH, 6.2 months. Patients with PSRH (5.9 mo) were more likely to return to sports earlier relative to patients with LS (7.7 mo). There were no complications in the LS group; in the PSRH group, 1 patient had mild sensory deficit and 2 had superficial wound infections. The MacNab criteria for pain assessment showed an excellent or good outcome in 8 of 9 patients in LS group and 6 of 7 patients in PSRH group. Relative to LS patients, there was a significant increase in surgical time and estimated blood loss among PSRH patients.

Conclusions:

Either of the mentioned 2 techniques appears to produce acceptable results. Biplanar fluoroscopy and navigation systems could minimize the risk of screw misplacement with LS construct. Familiarity with the various fixation techniques will allow the surgeon to select the most appropriate surgical technique.
Double-Grating Displacement Structure for Improving the Light Extraction Efficiency of LEDs
Authors: Wang Zhibin , Hao Yang , Wang Zhongdong , Liu Xian , Zhang Qian , Zhu Dandan
Published: October 2012

To improve the light extraction efficiency of light-emitting diodes (LEDs), grating patterns were etched on GaN and silver film surfaces. The grating-patterned surface etching enabled the establishment of an LED model with a double-grating displacement structure that is based on the surface plasmon resonance principle. A numerical simulation was conducted using the finite difference time domain method. The influence of different grating periods for GaN surface and silver film thickness on light extraction efficiency was analyzed. The light extraction efficiency of LEDs was highest when the grating period satisfied grating coupling conditions. The wavelength of the highest value was also close to the light wavelength of the medium. The plasmon resonance frequencies on both sides of the silver film were affected by silver film thickness. With increasing film thickness, plasmon resonance frequency tended toward the same value and light extraction efficiency reached its maximum. When the grating period for the GaN surface was 365 nm and the silver film thickness was 390 nm, light extraction efficiency reached a maximum of 55%.