bluuebunny/crossref_metadata_2025 huggingface dataset:
Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice
Authors: Sester David P. , Sagulenko Vitaliya , Thygesen Sara J. , Cridland Jasmyn A. , Loi Yen Siew , Cridland Simon O. , Masters Seth L. , Genske Ulrich , Hornung Veit , Andoniou Christopher E. , Sweet Matthew J. , Degli-Esposti Mariapia A. , Schroder Kate , Stacey Katryn J.
Published: June 2015

Inflammasomes are protein complexes that promote caspase activation, resulting in processing of IL-1β and cell death, in response to infection and cellular stresses. Inflammasomes have been anticipated to contribute to autoimmunity. The New Zealand Black (NZB) mouse develops anti-erythrocyte Abs and is a model of autoimmune hemolytic anemia. These mice also develop anti-nuclear Abs typical of lupus. In this article, we show that NZB macrophages have deficient inflammasome responses to a DNA virus and fungal infection. Absent in melanoma 2 (AIM2) inflammasome responses are compromised in NZB by high expression of the AIM 2 antagonist protein p202, and consequently NZB cells had low IL-1β output in response to both transfected DNA and mouse CMV infection. Surprisingly, we also found that a second inflammasome system, mediated by the NLR family, pyrin domain containing 3 (NLRP3) initiating protein, was completely lacking in NZB cells. This was due to a point mutation in an intron of the Nlrp3 gene in NZB mice, which generates a novel splice acceptor site. This leads to incorporation of a pseudoexon with a premature stop codon. The lack of full-length NLRP3 protein results in NZB being effectively null for Nlrp3, with no production of bioactive IL-1β in response to NLRP3 stimuli, including infection with Candida albicans. Thus, this autoimmune strain harbors two inflammasome deficiencies, mediated through quite distinct mechanisms. We hypothesize that the inflammasome deficiencies in NZB alter the interaction of the host with both microflora and pathogens, promoting prolonged production of cytokines that contribute to development of autoantibodies.
mTOR Complex Signaling through the SEMA4A–Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells
Authors: Ito Daisuke , Nojima Satoshi , Nishide Masayuki , Okuno Tatsusada , Takamatsu Hyota , Kang Sujin , Kimura Tetsuya , Yoshida Yuji , Morimoto Keiko , Maeda Yohei , Hosokawa Takashi , Toyofuku Toshihiko , Ohshima Jun , Kamimura Daisuke , Yamamoto Masahiro , Murakami Masaaki , Morii Eiichi , Rakugi Hiromi , Isaka Yoshitaka , Kumanogoh Atsushi
Published: June 2015

Mammalian target of rapamycin (mTOR) plays crucial roles in activation and differentiation of diverse types of immune cells. Although several lines of evidence have demonstrated the importance of mTOR-mediated signals in CD4+ T cell responses, the involvement of mTOR in CD8+ T cell responses is not fully understood. In this study, we show that a class IV semaphorin, SEMA4A, regulates CD8+ T cell activation and differentiation through activation of mTOR complex (mTORC) 1. SEMA4A−/− CD8+ T cells exhibited impairments in production of IFN-γ and TNF-α and induction of the effector molecules granzyme B, perforin, and FAS-L. Upon infection with OVA-expressing Listeria monocytogenes, pathogen-specific effector CD8+ T cell responses were significantly impaired in SEMA4A−/− mice. Furthermore, SEMA4A−/− CD8+ T cells exhibited reduced mTORC1 activity and elevated mTORC2 activity, suggesting that SEMA4A is required for optimal activation of mTORC1 in CD8+ T cells. IFN-γ production and mTORC1 activity in SEMA4A−/− CD8+ T cells were restored by administration of recombinant Sema4A protein. In addition, we show that plexin B2 is a functional receptor of SEMA4A in CD8+ T cells. Collectively, these results not only demonstrate the role of SEMA4A in CD8+ T cells, but also reveal a novel link between a semaphorin and mTOR signaling.
Codelivery of Envelope Protein in Alum with MVA Vaccine Induces CXCR3-Biased CXCR5+ and CXCR5− CD4 T Cell Responses in Rhesus Macaques
Authors: Iyer Smita S. , Gangadhara Sailaja , Victor Blandine , Gomez Rosy , Basu Rahul , Hong Jung Joo , Labranche Celia , Montefiori David C. , Villinger Francois , Moss Bernard , Amara Rama Rao
Published: June 2015

The goal of an HIV vaccine is to generate robust and durable protective Ab. Vital to this goal is the induction of CD4+ T follicular helper (TFH) cells. However, very little is known about the TFH response to HIV vaccination and its relative contribution to magnitude and quality of vaccine-elicited Ab titers. In this study, we investigated these questions in the context of a DNA/modified vaccinia virus Ankara SIV vaccine with and without gp140 boost in aluminum hydroxide in rhesus macaques. In addition, we determined the frequency of vaccine-induced CD4+ T cells coexpressing chemokine receptor, CXCR5 (facilitates migration to B cell follicles) in blood and whether these responses were representative of lymph node TFH responses. We show that booster modified vaccinia virus Ankara immunization induced a distinct and transient accumulation of proliferating CXCR5+ and CXCR5− CD4 T cells in blood at day 7 postimmunization, and the frequency of the former but not the latter correlated with TFH and B cell responses in germinal centers of the lymph node. Interestingly, gp140 boost induced a skewing toward CXCR3 expression on germinal center TFH cells, which was strongly associated with longevity, avidity, and neutralization potential of vaccine-elicited Ab response. However, CXCR3+ cells preferentially expressed the HIV coreceptor CCR5, and vaccine-induced CXCR3+CXCR5+ cells showed a moderate positive association with peak viremia following SIV251 infection. Taken together, our findings demonstrate that vaccine regimens that elicit CXCR3-biased TFH cell responses favor Ab persistence and avidity but may predispose to higher acute viremia in the event of breakthrough infections.
Dissecting CD8+ NKT Cell Responses to Listeria Infection Reveals a Component of Innate Resistance
Authors: Seregin Sergey S. , Chen Grace Y. , Laouar Yasmina
Published: June 2015

A small pool of NK1.1+ CD8+ T cells is harbored among the conventional CD8+ T cell compartment. Conclusions drawn from the analysis of immune responses mediated by cytotoxic CD8+ T cells are often based on the total population, which includes these contaminating NK1.1+ CD8+ T cells. An unresolved question is whether NK1.1+ CD8+ cells are conventional T cells that acquire NK1.1 expression upon activation or delineation into memory phenotype or whether they are a distinct cell population that induces immune responses in a different manner than conventional T cells. To address this question, we used the Listeria monocytogenes model of infection and followed CD8+ NK1.1+ T cells and NK1.1− CD8+ T cells during each phase of the immune response: innate, effector, and memory. Our central finding is that CD8+ NK1.1+ cells and conventional NK1.1− CD8+ T cells both contribute to the adaptive immune response to Listeria, but only CD8+ NK1.1+ cells were equipped with the ability to provide a rapid innate immune response, as demonstrated by early and Ag-independent IFN-γ production, granzyme B expression, and degranulation. More importantly, purified conventional CD8+ T cells alone, in the absence of any contaminating CD8+ NK1.1+ cells, were not sufficient to provide early protection to lethally infected mice. These results highlight the role of CD8+ NK1.1+ T cells in mounting early innate responses that are important for host defense and support the therapeutic potential of this subset to improve the effectiveness of protective immunity.
Julian of Norwich and the Sin of Forgetfulness
Authors: Tracy Kisha G.
Published: June 2015

This essay considers how memory is pervasive in Julian of Norwich's Revelations and why recollection and forgetfulness are essential to her experiences even from the beginning of the short version. She defines a certain type of forgetfulness, that which causes a separation between her and God, as sinful, and this perception of sin influences the analysis and composition of her visions. By recollecting in specific ways, she attempts to provide a remedy for her “sin of forgetfulness.”
Pedagogy, Devotion, and Marginalia:
Authors: Hill Gabriel
Published: June 2015

This article examines manuscripts containing The Pore Caitif, a late fourteenth-century Middle English devotional manual. Whereas most studies of The Pore Caitif have focused either on the Wycliffite ideas and sources the tracts contain or on devotional material drawn from influential mystical texts, this study examines the patterns of marginalia that appear in these manuscripts in order to study what elements of the text attracted the attention of fifteenth-century users. While individuals could have used the work in a variety of ways, the marginalia indicate that many users focused on passages that teach basic catechetical details and ignored the elements that have attracted modern scholars to The Pore Caitif.
H2A histone-fold and DNA elements in nucleosome activate SWR1-mediated H2A.Z replacement in budding yeast
Authors: Ranjan Anand , Wang Feng , Mizuguchi Gaku , Wei Debbie , Huang Yingzi , Wu Carl
Published: June 2015

The histone variant H2A.Z is a universal mark of gene promoters, enhancers, and regulatory elements in eukaryotic chromatin. The chromatin remodeler SWR1 mediates site-specific incorporation of H2A.Z by a multi-step histone replacement reaction, evicting histone H2A-H2B from the canonical nucleosome and depositing the H2A.Z-H2B dimer. Binding of both substrates, the canonical nucleosome and the H2A.Z-H2B dimer, is essential for activation of SWR1. We found that SWR1 primarily recognizes key residues within the α2 helix in the histone-fold of nucleosomal histone H2A, a region not previously known to influence remodeler activity. Moreover, SWR1 interacts preferentially with nucleosomal DNA at superhelix location 2 on the nucleosome face distal to its linker-binding site. Our findings provide new molecular insights on recognition of the canonical nucleosome by a chromatin remodeler and have implications for ATP-driven mechanisms of histone eviction and deposition.
Hydraulic and sediment transport properties of autogenic avulsion cycles on submarine fans with supercritical distributaries
Authors: Hamilton Paul B. , Strom Kyle B. , Hoyal David C. J. D.
Published: June 2015

Submarine fans, like other distributive systems, are built by repeated avulsion cycles. However, relative to deltas and alluvial fans, much less is known about avulsions in subaqueous settings. In this study, we ran a set of subaqueous fan experiments to investigate the mechanics associated with autogenic avulsion cycles of self‐formed channels and lobe deposits on steep slopes. The experiments used saline density currents with crushed plastic to emulate sustained turbidity currents and bed load transport. We collected detailed hydraulic and bathymetric measurements and made use of a 1‐D laterally expanding density current model to better understand different aspects of the avulsion cycle. Our results reveal three major components of the avulsion cycles: (1) distributary channel incision, extension, and stagnation; (2) mouth bar aggradation and hydraulic jump initiation; and (3) hydraulic jump sedimentation and upstream retreat. Interestingly, in all but one experiment, the avulsion cycles led to fans that remained perched above the basin slope break. Experimental data and hydraulic theory were used to unravel actual mechanics associated with cycles. We found that channels stopped extending into the basin due to a decay in sediment transport capacity relative to sediment supply and that the reduction in capacity was primarily an outcome of expansion‐driven velocity reduction; dilution played a secondary role. Once channel extension ceased, mouth bar deposits aggraded to a thickness approximately equal to the critical step height needed to create a choked flow condition. The choke then initiated a hydraulic jump on the upstream side of the bar. Once formed, the jump detained a majority of the incoming sediment and forced the channel‐to‐lobe transition upstream, filling the channel with steep backset bedding and capping the entire channel with a mounded lobate deposit. These intrinsic processes repeated through multiple avulsion cycles to build the fan.
Turbulence‐induced thermal signatures over evaporating bare soil surfaces
Authors: Haghighi Erfan , Or Dani
Published: June 2015

Soil wetness and airflow turbulence are key factors affecting surface energy balance components thereby influencing surface skin temperature. Turbulent eddies interacting with evaporating surfaces often induce localized and intermittent evaporative and sensible heat fluxes that leave distinct thermal signatures. These surface thermal fluctuations observable by infrared thermography (IRT) offer a means for characterization of overlaying turbulent airflows and remote quantification of surface wetness. We developed a theoretical and experimental methodology for using rapid IR surface temperature measurements to deduce surface wetness and evaporative fluxes from smooth bare soils. The mechanistic model provides theoretical links between surface thermal fluctuations, soil, and aerodynamic properties enabling thermal inferences of soil wetness with explicit consideration of soil thermal capacity and airflow turbulence effects. The method potentially improves accuracy of soil wetness assessment by IRT‐based techniques whose performance is strongly influenced by surface‐turbulence interactions and offers new ways for quantifying fluxes directly at their origin.
Seasonal controls of canopy chlorophyll content on forest carbon uptake: Implications for GPP modeling
Authors: Croft H. , Chen J. M. , Froelich N. J. , Chen B. , Staebler R. M.
Published: June 2015

Forested ecosystems represent an important part of the global carbon cycle, with accurate estimates of gross primary productivity (GPP) crucial for understanding ecosystem response to environmental controls and improving global carbon models. This research investigated the relationships between leaf area index (LAI) and leaf chlorophyll content (ChlLeaf) with forest carbon uptake. Ground measurements of LAI and ChlLeaf were taken approximately every 9 days across the 2013 growing season from day of year (DOY) 130 to 290 at Borden Forest, Ontario. These biophysical measurements were supported by on‐site eddy covariance flux measurements. Differences in the temporal development of LAI and ChlLeaf were considerable, with LAI reaching maximum values within approximately 10 days of bud burst at DOY 141. In contrast, ChlLeaf accumulation only reached maximum values at DOY 182. This divergence has important implications for GPP models which use LAI to represent the fraction of light absorbed by a canopy (fraction of absorbed photosynthetic active radiation (fAPAR)). Daily GPP values showed the strongest relationship with canopy chlorophyll content (ChlCanopy; R2 = 0.69, p < 0.001), with the LAI and GPP relationship displaying nonlinearity at the start and end of the growing season (R2 = 0.55, p < 0.001). Modeled GPP derived from LAI × PAR and ChlCanopy × PAR was tested against measured GPP, giving R2 = 0.63, p < 0.001 and R2 = 0.82, p < 0.001, respectively. This work demonstrates the importance of considering canopy pigment status in deciduous forests, with models that use fAPARLAI rather than fAPARChl neglecting to account for the importance of leaf photosynthetic potential.
Estimating self‐clutter of the multiple‐pulse technique
Authors: Reimer A. S. , Hussey G. C.
Published: June 2015

Autocorrelation function (ACF) estimates from voltage data measured by high‐frequency ionospheric radar systems that utilize the multiple‐pulse technique of Farley (1972) are susceptible to interference from self‐clutter. Self‐clutter is caused by simultaneous returns from multiple transmitted pulses echoing from unwanted, or ambiguous ranges. Without accurate estimates of self‐clutter it is impossible to account for all the uncertainty in estimates of the radar ACF. Voltage‐ and power‐based self‐clutter estimators are presented and evaluated using a modified version of the radar data simulator of Ribeiro et al. (2013a) and data from the Super Dual Auroral Radar Network (SuperDARN). It is shown that self‐clutter caused by ambiguous ranges filled with ground scatter can be accurately estimated using a voltage‐based self‐clutter estimator but that for ionospheric origin self‐clutter a maximal estimator must be used. Two maximal self‐clutter estimators are discussed and verified using the radar data simulator. A discussion of the application of the self‐clutter estimator as it is applied to ACFs obtained with Saskatoon SuperDARN radar is also presented.
Wave Optics
Authors: Dallas William J.
Published: June 2015

Narrowly interpreted, the term wave optics encompasses propagation, diffraction, and interference. Under a broader interpretation, wave optics includes those areas of optics governed by the electromagnetic wave equation. We begin with a brief review of the wave equation as it is built on the foundation of Maxwell's equations including some interaction of light with materials. We then look at polarization and chromatic composition in wave‐optical terms. Next is a translation of the wave equation into propagation relations organized under linear systems theory. We examine the propagation of optical waves from curved surfaces. An interesting and useful aspect of propagation is the existence of helical light; light that twists as it travels. We move on to interference and then diffraction. The hologram serves as an important example of interference, while the computer‐generated hologram is an example of control over diffraction. The Talbot effect, or Fourier self‐imaging, is a stunning example of the richness of propagation from diffractive optical elements. Finally, we discuss the subject of phase retrieval from irradiance distributions on multiple surfaces.
Pure H2 production through hollow fiber hydrogen‐selective MFI zeolite membranes using steam as sweep gas
Authors: Zhang Yuting , Sun Qi , Gu Xuehong
Published: June 2015

Hollow fiber MFI zeolite membranes were modified by catalytic cracking deposition of methyldiethoxysilane to enhance their H2/CO2 separation performance and further used in high temperature water gas shift membrane reactor. Steam was used as the sweep gas in the MR for the production of pure H2. Extensive investigations were conducted on MR performance by variations of temperature, feed pressure, sweep steam flow rate, and steam‐to‐CO ratio. CO conversion was obviously enhanced in the MR as compared with conventional packed‐bed reactor (PBR) due to the coupled effects of H2 removal as well as counter‐diffusion of sweep steam. Significant increment in CO conversion for MR vs. PBR was obtained at relatively low temperature and steam‐to‐CO ratio. A high H2 permeate purity of 98.2% could be achieved in the MR swept by steam. Moreover, the MR exhibited an excellent long‐term operating stability for 100 h in despite of the membrane quality. © 2015 American Institute of Chemical Engineers AIChE J, 61: 3459–3469, 2015
Droplets sliding over shearing surfaces studied by molecular dynamics
Authors: Derksen J. J.
Published: June 2015

Through molecular dynamics, the sliding motion of a liquid drop embedded in another liquid over a substrate as a result of a shear flow is studied. The two immiscible Lennard‐Jones liquids have the same density and viscosity. The system is isothermal. Viscosity, surface tension, and static contact angles follow from calibration simulations. Sliding speeds and drop deformations (in terms of dynamic contact angles) are determined as a function of the shear rate. The latter is nondimensionalized as a capillary number (Ca) that has been varied in the range 0.02–0.64. For Ca up to 0.32, sliding speeds are approximately linear in Ca. For larger Ca, very strong droplet deformations are observed. © 2015 American Institute of Chemical Engineers AIChE J, 61: 4020–4027, 2015
Estimation of chimpanzee community size and genetic diversity in Kahuzi‐Biega National Park, Democratic Republic of Congo
Authors: Basabose Augustin K. , Inoue Eiji , Kamungu Sebulimbwa , Murhabale Bertin , Akomo‐Okoue Etienne‐Francois , Yamagiwa Juichi
Published: June 2015

A small chimpanzee habitat in the montane forest of Kahuzi‐Biega National Park, Democratic Republic of Congo, is connected with the lowland forest of this park through a corridor, which is affected by human encroachment. To assess the conservation status of the chimpanzee population in this small habitat, we estimated the size of the community and evaluated its genetic diversity by using 279 fecal samples collected in the montane forest of Kahuzi. Using autosomal microsatellite (or short tandem repeat, STR) loci, we identified 32 individuals, comprising 19 females and 13 males. Samples from 24 individuals were collected at least twice and a genetic mark‐recapture analysis estimated that the community size was 36 (range: 32–42). Data on nest site sharing confirmed that all the samples belonged to the same community. Nest site sharing information may be useful in population studies of unhabituated chimpanzees. The genetic structure and diversity of the 32 genotyped individuals was assessed using Y‐chromosomal short tandem repeat (Y‐STR) loci and mitochondrial D‐loops. One dominant Y‐STR haplotype was found, whereas there was no dominant haplotype in the mitochondrial region, reflecting a female‐biased dispersal pattern, which is typical of chimpanzees. The genetic diversity for three markers in Kahuzi chimpanzees was comparable to that in other eastern chimpanzee populations. A relatively high heterozygosity and negative inbreeding coefficient (FIS) for STR loci suggests that the study community belongs to an outbreeding chimpanzee population. These findings suggest that individuals of the study community may have reproductive contact with other chimpanzee individuals from neighboring communities in Kahuzi‐Biega National Park, at least in the recent past. Am. J. Primatol. 77:1015–1025, 2015. © 2015 Wiley Periodicals, Inc.
Characteristics of alpha males in Nepal gray langurs
Authors: Borries Carola , Perlman Rachel F. , Koenig Andreas
Published: June 2015

In species with strong male‐male competition, access to females in multimale‐multifemale groups is usually regulated via a dominance hierarchy. The highest ranking (alpha) male often has priority of access and sires most offspring. The alpha male can change in three basic ways: (i) a recent immigrant or a resident challenges and becomes the new alpha; (ii) formation of a new group; (iii) succession—becoming alpha after higher ranking males have left. When, in a given primate population, the alpha male changes in different ways, two questions arise: (a) which is the most successful tactic and (b) do male attributes, such as age, aggressiveness or propensity to commit infanticide, affect the outcome? We examined these questions in the seasonally breeding Nepal gray langurs (Semnopithecus schistaceus) at Ramnagar, where new alpha males were either recent immigrants or residents. Success was measured as alpha tenure, residency duration, and the number of offspring sired (paternity exclusion based on DNA analysis, 28 infants). We documented 12 alpha‐male tenures across two multimale‐multifemale groups between 1991 and 1997. The predominant mode of change was the immigrant tactic. Age had no effect perhaps because alpha males were among the youngest adult males in their group. As expected, infanticidal males performed similarly to non‐infanticidal ones. Alpha tenure was highly variable and longer for immigrant alphas and hyper‐aggressive ones. However, none of the tactics or attributes examined resulted in significantly longer residencies or more offspring, likely because of the timing of immigrations and stochastic effects (i.e., the number of conceptions occurring per alpha tenure). The influence of female mate choice on male reproductive success requires further investigation. Furthermore, it remains to be examined why resident alpha males—with their presumed better knowledge of their opponents —performed so poorly. Am. J. Primatol. 79:e22437, 2017. © 2015 Wiley Periodicals, Inc.
Need for speed: Sexual maturation precedes social maturation in gray mouse lemurs
Authors: Hohenbrink Sarah , Zimmermann Elke , Radespiel Ute
Published: June 2015

The life history of mammals underlies a fast–slow continuum, ranging from “slow” species with large body size, delayed sexual maturation, low fertility, and long lifespan, to “fast” species showing the opposite traits. Primates fall into the “slow” category, considering their relatively low offspring numbers and delayed juvenile development. However, social and sexual maturation processes do not necessarily have to be completed simultaneously. The comparison of the timeframes for sexual and social maturation is largely lacking for primates, with the prominent exception of humans. Here, we compare both maturation processes in a basal primate, the gray mouse lemur, which ranges in many aspects at the fast end of the slow–fast life history continuum among primates. We compared the patterns and frequencies of various social and solitary behaviors in young adults (YA, 12–13 months old) and older individuals (A, ≥2 years) of both sexes outside estrus. Observations were conducted during mix‐sexed dyadic encounter experiments under controlled captive conditions (eight dyads per age class). Results indicate that although all young adults were sexually mature, social maturation was not yet completed in all behavioral domains: Age‐dependent differences were found in the number of playing dyads, female marking behavior, female aggression, and social tolerance. Thus, this study provides a first indication that social maturation lags behind sexual maturation in an ancestral nocturnal primate model, indicating that these two developmental schemes may have been decoupled early and throughout the primate lineage. Am. J. Primatol. 77:1049–1059, 2015. © 2015 Wiley Periodicals, Inc.
Die Chemie der Redox‐Flow‐Batterien
Authors: Noack Jens , Roznyatovskaya Nataliya , Herr Tatjana , Fischer Peter
Published: June 2015

Aufgrund der besonderen Eigenschaft der getrennten Skalierbarkeit von Energie und Leistung und der damit verbundenen potenziell niedrigen Energiespeicherkosten haben sich die Entwicklungen von unterschiedlichen Redox‐Flow‐Batterien zur Speicherung für fluktuierende erneuerbare Energien in den letzten Jahren intensiviert, was zu einem deutlichen Zuwachs an wissenschaftlicher Literatur geführt hat. Aus diesem Grund wird, anhand einer streng systematischen Einteilung und einem Fokus auf die Chemie der Elektrolyte, ein umfassender und kritischer Überblick über die Eigenschaften dieser Batterien und ihr zukünftiges Entwicklungspotenzial gegeben.
Metal‐Mediated Production of Isocyanates, R3ENCO from Dinitrogen, Carbon Dioxide, and R3ECl
Authors: Keane Andrew J. , Farrell Wesley S. , Yonke Brendan L. , Zavalij Peter Y. , Sita Lawrence R.
Published: June 2015

A highly efficient and versatile chemical cycle has been developed for the production of isocyanates through the molecular fixation of N2, CO2 and R3ECl (E=C, Si, and Ge). Key steps include a ‘one‐pot’ photolytic NN bond cleavage of a Group 6 dinuclear dinitrogen complex with in situ trapping by R3ECl to provide a metal terminal imido complex that can engage in simultaneous nitrene‐group transfer and oxygen‐atom transfer to generate an intermediate metal terminal oxo complex with release of the isocyanate product. Reaction of the oxo complex with additional equivalents of R3ECl regenerates a metal dichloride that is the precursor for dinuclear dinitrogen starting material.
Diastereodivergente asymmetrische 1,4‐Addition von Oxindolen an Nitroolefine durch polyfunktionelle Nickel‐H‐Brücken‐Azolium‐ Katalysatoren
Authors: Mechler Melanie , Peters René
Published: June 2015

Diastereodivergenz ist eine Herausforderung für die katalytische asymmetrische Synthese. Für viele Reaktionstypen ist die Bildung eines Diastereomers inhärent bevorzugt, während das andere Diastereomer nicht direkt und effizient zugänglich ist, sondern umständliche Syntheseumwege erfordert. Das Umgehen dieser natürlichen Präferenz mithilfe eines Katalysators erfordert die räumliche Kontrolle über beide Reaktionspartner. Wir stellen einen neuartigen, polyfunktionellen Katalysator vor, in dem eine NiII‐Bis(phenoxyimin)‐Einheit, freie Hydroxygruppen und ein axial‐chiraler Bisimidazolium‐Baustein an der Stereokontrolle der direkten 1,4‐Addition von Oxindolen an Nitroolefine beteiligt sind. Beide Epimere des 1,4‐Adduktes sind nach Belieben durch Variation der Konstitution und Konfiguration des Liganden zugänglich. Wie bereits berichtet wurde, sind die Produkte wertvolle Vorstufen für Indolalkaloide, und die vorliegende Methode sollte somit den Zugang zu den epimeren Derivaten eröffnen.
Kontakt zwischen den β1‐ und β2‐Segmenten von α‐Synuclein inhibiert die Amyloidbildung
Authors: Shaykhalishahi Hamed , Gauhar Aziz , Wördehoff Michael M. , Grüning Clara S. R. , Klein Antonia N. , Bannach Oliver , Stoldt Matthias , Willbold Dieter , Härd Torleif , Hoyer Wolfgang
Published: June 2015

Die Umwandlung des intrinsisch ungeordneten Proteins α‐Synuclein (α‐syn) in Amyloidaggregate ist ein Schlüsselprozess der Parkinson‐Krankheit. Die Sequenzregion 35–59 enthält die β‐Strangsegmente β1 und β2 aus Strukturmodellen von α‐syn‐Amyloidfibrillen sowie die Mehrzahl der bekannten krankheitsassoziierten Mutationen. β1 und β2 gehen miteinander transiente Interaktionen in monomerem α‐syn ein. Hier untersuchen wir die Folgen von β1‐β2‐Kontakten mittels Disulfid‐Engineering, biophysikalischen Techniken und Zellviabilitäts‐Assays. Die Doppelcystein‐Mutante α‐synCC mit einer Disulfidbrücke zwischen β1 und β2 bildet keine Aggregate und inhibiert die Aggregation und Toxizität von Wildtyp‐α‐syn. Wir zeigen, dass α‐syn die Aggregation des Amyloid‐β‐Peptids und des Inselamyloid‐Polypeptids inhibiert, ein Effekt, der in der α‐synCC‐Mutante verstärkt ist. Tertiäre Interaktionen in der β1‐β2‐Region von α‐syn beeinträchtigen die Nukleation der Amyloidbildung. Ein therapeutischer Ansatz wäre folglich die Förderung solcher Interaktionen.
Hoch effiziente C‐SeCF3‐Kupplung von Aryliodiden durch einen luftbeständigen zweikernigen PdI‐Katalysator
Authors: Aufiero Marialuisa , Sperger Theresa , Tsang Althea S.‐K. , Schoenebeck Franziska
Published: June 2015

Aufbauend auf unseren jüngsten Entdeckungen bei zweikernigen PdI‐Komplexen beschreiben wir hier die Anwendung dieses Konzeptes zur Realisierung der ersten katalytischen Umwandlung von Aryliodiden zu ArSeCF3‐Verbindungen. Durch die Verwendung eines luft‐, feuchtigkeits‐ und temperaturbeständigen PdI‐Zweikernkomplexes konnte die hoch effiziente C‐SeCF3‐Kupplung einer Reihe von Aryliodiden erreicht werden. Ein neuer SeCF3‐verbrückter zweikerniger PdI‐Komplex 3 wurde isoliert, auf seine katalytische Kompetenz untersucht und als Katalysator wiederverwendet. Sowohl experimentelle als auch berechnete Resultate lassen auf einen Zweikern‐PdI‐Katalysemodus schließen.
Vier‐ und sechsfache Tandem‐Dominoreaktionen zur Synthese von dimeren tetrasubstituierten Alkenen als molekulare Doppelschalter
Authors: Tietze Lutz F. , Waldecker Bernd , Ganapathy Dhandapani , Eichhorst Christoph , Lenzer Thomas , Oum Kawon , Reichmann Sven O. , Stalke Dietmar
Published: June 2015

Es wurde eine hocheffiziente Palladium‐katalysierte vierfache Tandem‐Dominoreaktion entwickelt, die zwei Carbopalladierungen und zwei C‐H‐Aktivierungen umfasst. Dabei wurden die helical‐chiralen tetrasubstituierten Alkene 3 und 6 ausgehend von den Substraten 1 und 4 erhalten. Die für den Aufbau der Ausgangsverbindung erforderliche Sonogashira‐Reaktion lässt sich zudem im Sinne einer sechsfachen Tandem‐Dominoreaktion integrieren. Es wurden 20 Verbindungen mit unterschiedlichen Substitutionsmustern in Ausbeuten von bis zu 97 % synthetisiert, und die helicale Chiralität der Verbindungen wurde durch Röntgenstrukturanalyse nachgewiesen. Photophysikalische Untersuchungen zeigen einen sehr schnellen lichtinduzierten Wechsel der stereochemischen Konfiguration.
Highly Robust Palladium(II) α‐Diimine Catalysts for Slow‐Chain‐Walking Polymerization of Ethylene and Copolymerization with Methyl Acrylate
Authors: Dai Shengyu , Sui Xuelin , Chen Changle
Published: June 2015

A series of sterically demanding α‐diimine ligands bearing electron‐donating and electron‐withdrawing substituents were synthesized by an improved synthetic procedure in high yield. Subsequently, the corresponding Pd complexes were prepared and isolated by column chromatography. These Pd complexes demonstrated unique properties in ethylene polymerization, including high thermal stability and high activity, thus generating polyethylene with a high molecular weight and very low branching density. Similar properties were observed for ethylene/methyl acrylate copolymerization. Because of the high molecular weight and low branching density, the generated polyethylene and ethylene/methyl acrylate copolymer were semicrystalline solids. The (co)polymers had unique microstructures originating from the unique slow‐chain‐walking activity of these Pd complexes.
Mehrdimensionaler Entwurf von Antikrebspeptiden
Authors: Lin Yen‐Chu , Lim Yi Fan , Russo Erica , Schneider Petra , Bolliger Lea , Edenharter Adriana , Altmann Karl‐Heinz , Halin Cornelia , Hiss Jan A. , Schneider Gisbert
Published: June 2015

Wir stellen hier den rechnergestützten Entwurf und die Optimierung von Peptiden vor, die selektiv Krebszellen zerstören können. Der Designprozess ermöglichte die Verschmelzung von Eigenschaften bekannter Antikrebs‐, zellpenetrierender und Tumor‐adressierender Peptide. Dabei identifizierten maschinelle Lernverfahren vollautomatisch neue Peptide mit den vorhergesagten Eigenschaften. Ausgehend von einer als Vorlage fungierenden Aminosäuresequenz haben wir systematisch die Toxizität der Peptide gegen eine Reihe von Krebszelllinien optimiert, während gleichzeitig die Aktivität gegen primäre humane Endothelzellen reduziert wurde. Die vom Computer generierten Peptide zeigten verbesserte Krebszellpenetration, lösten Apoptose aus und waren in der Lage, die zytotoxisch wirksame Konzentration von gleichzeitig verabreichten Chemotherapeutika in vitro zu reduzieren. Diese Studie demonstriert das Potenzial mehrdimensionaler maschineller Lernverfahren, innerhalb kurzer Zeit neue Peptide mit den gewünschten Eigenschaften zu erhalten.
The Chemistry of Redox‐Flow Batteries
Authors: Noack Jens , Roznyatovskaya Nataliya , Herr Tatjana , Fischer Peter
Published: June 2015

The development of various redox‐flow batteries for the storage of fluctuating renewable energy has intensified in recent years because of their peculiar ability to be scaled separately in terms of energy and power, and therefore potentially to reduce the costs of energy storage. This has resulted in a considerable increase in the number of publications on redox‐flow batteries. This was a motivation to present a comprehensive and critical overview of the features of this type of batteries, focusing mainly on the chemistry of electrolytes and introducing a thorough systematic classification to reveal their potential for future development.
Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes
Authors: Pelay‐Gimeno Marta , Glas Adrian , Koch Oliver , Grossmann Tom N.
Published: June 2015

Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics. Herein, we introduce a new classification of peptidomimetics (classes A–D) that enables a clear assignment of available approaches. Based on this classification, the Review summarizes strategies that have been applied for the structure‐based design of PPI inhibitors through stabilizing or mimicking turns, β‐sheets, and helices.
Contact between the β1 and β2 Segments of α‐Synuclein that Inhibits Amyloid Formation
Authors: Shaykhalishahi Hamed , Gauhar Aziz , Wördehoff Michael M. , Grüning Clara S. R. , Klein Antonia N. , Bannach Oliver , Stoldt Matthias , Willbold Dieter , Härd Torleif , Hoyer Wolfgang
Published: June 2015

Conversion of the intrinsically disordered protein α‐synuclein (α‐syn) into amyloid aggregates is a key process in Parkinson’s disease. The sequence region 35–59 contains β‐strand segments β1 and β2 of α‐syn amyloid fibril models and most disease‐related mutations. β1 and β2 frequently engage in transient interactions in monomeric α‐syn. The consequences of β1–β2 contacts are evaluated by disulfide engineering, biophysical techniques, and cell viability assays. The double‐cysteine mutant α‐synCC, with a disulfide linking β1 and β2, is aggregation‐incompetent and inhibits aggregation and toxicity of wild‐type α‐syn. We show that α‐syn delays the aggregation of amyloid‐β peptide and islet amyloid polypeptide involved in Alzheimer’s disease and type 2 diabetes, an effect enhanced in the α‐synCC mutant. Tertiary interactions in the β1–β2 region of α‐syn interfere with the nucleation of amyloid formation, suggesting promotion of such interactions as a potential therapeutic approach.
Biosensing by Tandem Reactions of Structure Switching, Nucleolytic Digestion, and DNA Amplification of a DNA Assembly
Authors: Liu Meng , Zhang Wenqing , Zhang Qiang , Brennan John D. , Li Yingfu
Published: June 2015

ϕ29 DNA polymerase (ϕ29DP) is able to carry out repetitive rounds of DNA synthesis using a circular DNA template by rolling circle amplification (RCA). It also has the ability to execute 3′–5′ digestion of single‐stranded but not double‐stranded DNA. A biosensor engineering strategy is presented that takes advantage of these two properties of ϕ29DP coupled with structure‐switching DNA aptamers. The design employs a DNA assembly made of a circular DNA template, a DNA aptamer, and a pre‐primer. The DNA assembly is unable to undergo RCA in the absence of cognate target owing to the formation of duplex structures. The presence of the target, however, triggers a structure‐switching event that causes nucleolytic conversion of the pre‐primer by ϕ29DP into a mature primer to facilitate RCA. This method relays target detection by the aptamer to the production of massive DNA amplicons, giving rise to dramatically enhanced detection sensitivity.
Plasmonic Colloidosomes as Three‐Dimensional SERS Platforms with Enhanced Surface Area for Multiphase Sub‐Microliter Toxin Sensing
Authors: Phan‐Quang Gia Chuong , Lee Hiang Kwee , Phang In Yee , Ling Xing Yi
Published: June 2015

Colloidosomes are robust microcapsules attractive for molecular sensing because of their characteristic micron size, large specific surface area, and dual‐phase stability. However, current colloidosome sensors are limited to qualitative fluorogenic receptor‐based detection, which restrict their applicability to a narrow range of molecules. Here, we introduce plasmonic colloidosome constructed from Ag nanocubes as an emulsion‐based 3D SERS platform. The colloidosomes exhibit excellent mechanical robustness, flexible size tunability, versatility to merge, and ultrasensitivity in SERS quantitation of food/industrial toxins down to sub‐femtomole levels. Using just 0.5 μL of sample volumes, our plasmonic colloidosomes exhibit >3000‐fold higher SERS sensitivity over conventional suspension platform. Notably, we demonstrate the first high‐throughput multiplex molecular sensing across multiple liquid phases.
Reversible Switching of Redox‐Active Molecular Orbitals and Electron Transfer Pathways in CuA Sites of Cytochrome c Oxidase
Authors: Zitare Ulises , Alvarez‐Paggi Damián , Morgada Marcos N. , Abriata Luciano A. , Vila Alejandro J. , Murgida Daniel H.
Published: June 2015

The CuA site of cytochrome c oxidase is a redox hub that participates in rapid electron transfer at low driving forces with two redox cofactors in nearly perpendicular orientations. Spectroscopic and electrochemical characterizations performed on first and second‐sphere mutants have allowed us to experimentally detect the reversible switching between two alternative electronic states that confer different directionalities to the redox reaction. Specifically, the M160H variant of a native CuA shows a reversible pH transition that allows to functionally probe both states in the same protein species. Alternation between states exerts a dramatic impact on the kinetic redox parameters, thereby suggesting this effect as the mechanism underlying the efficiency and directionality of CuA electron transfer in vivo. These findings may also prove useful for the development of molecular electronics.
Teachers as health workers: Patterns and imperatives of Australian teachers’ work
Authors: Rossi Tony , Pavey Amanda , Macdonald Doune , McCuaig Louise
Published: June 2015

With increasing cross‐sectoral relationships and partnerships and the blurring of the boundaries of the various service sectors, the membrane that is assumed to separate education and health in terms of young people's wellbeing looks thinner than ever. In this project we are concerned to know what teachers do in terms of young people's health, how much time they spend doing it and to what extent this work might be considered as health work? The paper is informed by a Likert style survey and semi‐structured interview data collected from a large cohort of teachers employed in different school sectors across Queensland, Australia and is framed by ideas concerning field, practice and doxa. The data suggest that teachers, often with a minimum of training, undertake work that might be categorised as health work and do so with a high degree of commitment and with a growing sense of urgency but with concerns related to their competence. We consider it important to understand the reasons why and the extent to which teachers engage in work that might be more readily associated with public health and to ask “are teachers health workers?”
PdHx Entrapped in a Covalent Triazine Framework Modulates Selectivity in Glycerol Oxidation
Authors: Chan‐Thaw Carine E. , Villa Alberto , Wang Di , Santo Vladimiro Dal , Orbelli Biroli Alessio , Veith Gabriel M. , Thomas Arne , Prati Laura
Published: June 2015

Pd nanoparticles within a nitrogen‐containing covalent triazine framework (CTF) material are investigated to understand if the highly tunable CTF chemistry mediates the catalytic properties of the Pd nanoparticles. Surprisingly, our results demonstrate that the CTF stabilizes the formation of 2.6 nm PdHx particles within the pores. These confined PdHx particles are very active for the liquid‐phase oxidation of glycerol and promote CC cleavage, probably connected with the enhanced in situ formation of H2O2. During recycling tests, the confined particles are transformed progressively to very stable Pd0 particles. This stability has been attributed mainly to a confinement effect as nanoparticles trapped outside the pores lose activity rapidly. These results indicate that there is a potential to tune CTF chemistry to modify the chemistry of the catalytic metals significantly.
Galactose Oxidase Variants for the Oxidation of Amino Alcohols in Enzyme Cascade Synthesis
Authors: Herter Susanne , McKenna Shane M. , Frazer Andrew R. , Leimkühler Silke , Carnell Andrew J. , Turner Nicholas J.
Published: June 2015

The use of selected engineered galactose oxidase (GOase) variants for the oxidation of amino alcohols to aldehydes under mild conditions in aqueous systems is reported. GOase variant F2 catalyses the regioselective oxidation of N‐carbobenzyloxy (Cbz)‐protected 3‐amino‐1,2‐propanediol to the corresponding α‐hydroxyaldehyde which was then used in an aldolase reaction. Another variant, M3–5, was found to exhibit activity towards free and N‐Cbz‐protected aliphatic and aromatic amino alcohols allowing the synthesis of lactams such as 3,4‐dihydronaphthalen‐1(2H)‐one, 2‐pyrrolidone and valerolactam in one‐pot tandem reactions with xanthine dehydrogenase (XDH) or aldehyde oxidase (PaoABC).
Recent Developments in Palladium‐Based Bimetallic Catalysts
Authors: Liao Fenglin , Lo Tsz Woon Benedict , Tsang Shik Chi Edman
Published: June 2015

As one of the alternative metals to platinum, which supports a wide range of applications in chemistry and catalysis in industry, palladium increasingly receives attention because of its similar physicochemical properties. However, Pd is generally less expensive than Pt and has a richer natural reserve. Herein, some recently developed techniques for the preparation and characterization of Pd‐based bimetallic catalysts are reviewed. The impact on catalytic reactions of interest, including hydrogenation, dehydrogenation, hydrogenolysis, reforming, the oxygen reduction reaction, and hydrodesulfurization are also discussed. It is shown that the catalytic performance of Pd‐based bimetallic catalysts is strongly dependent on the geometric and electronic states of Pd, which can be significantly affected by blended foreign element(s). Rationalization of the structure–activity relationship can provide useful guidelines to the fine tuning of these important catalytic reactions.
Versatile Relay and Cooperative Palladium(0) N‐Heterocyclic Carbene/Copper(I) N‐Heterocyclic Carbene Catalysis for the Synthesis of Tri‐ and Tetrasubstituted Alkenes
Authors: Lesieur Mathieu , Bidal Yannick D. , Lazreg Faïma , Nahra Fady , Cazin Catherine S. J.
Published: June 2015

Two new and efficient dual catalytic procedures for the synthesis of tri‐ and tetrasubstituted alkenes using aryl bromides and chlorides are reported. The formation of these vinyl arenes occurs independently in a one‐pot relay and a one‐pot cooperative procedure using well‐defined Pd and Cu N‐heterocyclic carbene (NHC) complexes. Mechanistic studies were performed to elucidate the key role of the solvent in each procedure as well as the formation of the key intermediate, [Cu(alkenylboron)(NHC)], which allows transmetalation with the Pd‐NHC co‐catalyst in the cooperative catalysis.
Design of Carbon‐Encapsulated Fe3O4 Nanocatalyst with Enhanced Performance for Fischer–Tropsch Synthesis
Authors: Tu Jun‐ling , Ding Ming‐yue , Zhang Qian , Zhang Yu‐lan , Wang Chen‐guang , Wang Tie‐jun , Ma Long‐long , Li Xin‐jun
Published: June 2015

Fischer–Tropsch synthesis (FTS), an important process for the production of liquid fuels and chemicals from syngas derived from coal and biomass, is receiving renewed interest for both industrial and academic applications. Adjusting the product distribution of hydrocarbons is the focus of research in this field. Herein, a novel carbon‐encapsulated Fe3O4 nanocatalyst was synthesized by a simple one‐step solvothermal method without calcination. The catalyst exhibited excellent catalytic activity and higher selectivity for C5–12 hydrocarbons (gasoline range products) than the traditional Fe2O3 catalyst. A 45.25 % C5–12 selectivity was obtained for Fe3O4@C, which is close to the maximum value from the Anderson–Schulz–Flory distribution.