bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhomogeneous linewidth broadening and radiative lifetime dispersion of size dependent direct bandgap radiation in Si quantum dot
Authors: Wu Chung-Lun , Lin Gong-Ru
Published: November 2012

The SiOx (SiOx:Si-QDs) with buried Si quantum dots (Si-QDs) is synthesized by plasma-enhanced chemical vapor deposition (PECVD), and the size-dependent wave-function of Si-QDs embedded in Si-rich SiO2 matrix is experimentally and theoretically analyzed to reformulate its bandgap energy as Eg(d) = 1.12+5.83/d1.78. The photoluminescent lifetime of Si-QDs is dominated by the non-phonon assisted radiative recombination. Shrinking the Si-QD size from 4.3 to 1.9 nm increases the overlapping probability of electron-hole wave-functions in Si-QD to shorten the non-phonon assisted radiative lifetime from 6.3 μs to 83 ns. Fitting the time-resolved photoluminescence trace with a stretched exponential decay function reveals a lifetime dispersion factor. The lifetime dispersion greatly reduced from 0.8 to 0.39 by enlarging the size distribution of Si-QDs from 0.2 to 1.1 nm, which elucidates the inhomogeneous linewidth broadening feature of Si-QDs. Based on the simulation of non-phonon assisted recombination process, the full-band stretched exponential decay analysis confirms the correlation between inhomogeneous linewidth broadening and lifetime dispersion in Si-QDs.
Monitoring metal contamination of silicon by multiwavelength room temperature photoluminescence spectroscopy
Authors: Jian Shiu-Ko Jang , Jeng Chih-Cherng , Yoo Woo Sik
Published: November 2012

Thin thermal oxide film (∼36 nm) was grown on p--Si (100) wafers in a vertical furnace at 950 °C for 90 min in 1 atm dry O2 as a vehicle for monitoring metal contamination. They are annealed in separate vertical furnaces at 1100°C for 120 min in N2 and tested for metal contamination using multiwavelength room temperature photoluminescence (RTPL), inductively coupled plasma mass spectroscopy (ICP-MS) and secondary ion mass spectroscopy (SIMS). Significant RTPL intensity and spectral variations, corresponding to the degree of metal contamination, were observed. Nondestructive wafer mapping and virtual depth profiling capabilities of RTPL is a very attractive metal contamination monitoring technique.
A Multi-Step Continuous Flow Process for the N-Demethylation of Alkaloids
Authors: Nakano Yuji , Savage G. Paul , Saubern Simon , Scammells Peter J. , Polyzos Anastasios
Published: November 2012

Dextromethorphan was N-demethylated using the non-classical Polonovski reaction under continuous flow conditions, in two steps: initial N-oxidation with m-chloroperbenzoic acid followed by iron-catalysed N-demethylation of the resulting N-oxide.
Impact of industrial-age climate change on the relationship between water uptake and tissue nitrogen in eucalypt seedlings
Authors: Sherwin Gyro L. , George Laurel , Kannangara Kamali , Tissue David T. , Ghannoum Oula
Published: November 2012

This study explored reductions in tissue nitrogen concentration ([N]) at elevated CO2 concentrations ([CO2]), and changes in plant water and N uptake. Eucalyptus saligna Sm. seedlings were grown under three [CO2] levels (preindustrial (280 μL L–1), current (400 μL L–1) or projected (640 μL L–1)) and two air temperatures (current, (current + 4°C)). Gravimetric water use, leaf gas exchange and tissue dry mass and %N were determined. Solid-state 15N-NMR spectroscopy was used for determining the partitioning of N chemical groups in the dry matter fractions. Water use efficiency (WUE) improved with increasing [CO2] at ambient temperature, but strong leaf area and weak reductions in transpiration rates led to greater water use at elevated [CO2]. High temperature increased plant water use, such that WUE was not significantly stimulated by increasing [CO2] at high temperature. Total N uptake increased with increasing [CO2] but not temperature, less than the increase recorded for plant biomass. Tissue [N] decreased with rising [CO2] and at high temperature, but N use efficiency increased with rising [CO2]. Total N uptake was positively correlated with total water use and root biomass under all treatments. Growth [CO2] and temperature did not affect the partitioning of 15N among the N chemical groups. The reductions of tissue [N] with [CO2] and temperature were generic, not specific to particular N compounds. The results suggest that reductions in tissue [N] are caused by changes in root N uptake by mass flow due to altered transpiration rates at elevated [CO2] and temperature.
Prevalence and predictors of high-grade anal intraepithelial neoplasia in a community-based sample of homosexual men
Authors: Hillman Richard J. , van Leeuwen Marina T. , Vajdic Claire M. , McHugh Leo , Prestage Garrett P. , Botes Leon P. , Zablotska Iryna , Medley Gabriele , Tabrizi Sepehr N. , Grulich Andrew E. , Jin Fengyi
Published: November 2012

Background We report the prevalence and predictors for high-grade anal intraepithelial neoplasia (HGAIN) in community-based cohorts of HIV-negative and HIV-positive homosexual men in Sydney, Australia. Methods: A cross-sectional study of consecutive participants in both cohorts was performed in 2005 (204 HIV-negative and 128 HIV-positive men). Anal swabs collected by a research nurse underwent cytological analysis, using the ThinPrep procedure, and human papillomavirus (HPV) testing. Participants who had cytological abnormalities other than low-grade squamous epithelial lesions (SIL) were referred for high resolution anoscopy (HRA). Results: A total of 114 men had cytological abnormalities (24.3% of HIV-negative and 57.5% of HIV-positive men, odds ratio (OR) = 4.21, 95% confidence interval (CI) 2.57–6.90). However, only three (2.3%) HIV-positive men and no HIV-negative men had high-grade SIL on anal cytology. Seventy-seven men were referred for HRA, of whom 63 (81.8%) attended. Histologically confirmed HGAIN was detected in 21 (33.3%). The prevalence of HGAIN was higher in HIV-positive men (10.8%) than in HIV-negative men (5.0%, OR = 2.29, 95% CI 0.93–5.63, P = 0.071). HGAIN was not related to age but was strongly associated with the detection of high-risk types of anal HPV (OR = 10.1, 95% CI 1.33–76.2) rather than low-risk types (OR = 1.97, 95% CI 0.74–5.25). Conclusion: HGAIN was prevalent in homosexual men across all age groups and was more than twice as common in HIV-positive men compared with HIV-negative men. The presence of high-risk anal HPV was highly predictive of HGAIN.
The epidemiology and natural history of anal human papillomavirus infection in men who have sex with men
Authors: Machalek Dorothy A. , Grulich Andrew E. , Jin Fengyi , Templeton David J. , Poynten I. Mary
Published: November 2012

Studies on the epidemiology and natural history of anal human papillomavirus (HPV) infection are essential to understand the significance of this virus in the aetiology of anal cancer in men who have sex with men (MSM). This paper presents a review of studies on anal HPV in MSM. For this review, a Medline search was performed to identify English-language articles published in peer-reviewed journals on the epidemiology, natural history and risk factors for anal HPV infection in MSM. Anal HPV prevalence is high in MSM and infection with multiple HPV types is common. The available prospective data suggest detection of new anal HPV infections may also be common. However, with limited epidemiological data available on infection dynamics and associated behavioural risk factors, it is difficult to draw conclusions on how persistent anal HPV infection is in this population.
Why a special issue on anal cancer and what is in it?
Authors: Fairley Christopher K. , Brotherton Julia M. L. , Hillman Richard , Grulich Andrew E.
Published: November 2012

This editorial describes the contents of this special issue of Sexual Health devoted to anal cancer. The aim of the issue is to provide readers with information to assist them in making decisions about what to do about detecting anal cancer early in men who have sex with men with HIV. Should they be advocating screening? It discusses the epidemiology of HPV infection, anal intraepithelial neoplasia, and anal cancer in MSM, heterosexual men and women; anal cancer screening and treatment of anal cancer. And most importantly, what should be done about vaccinating boys with the HPV vaccine.
Time for a strategic research response to anal cancer
Authors: Grulich Andrew E. , Hillman Richard , Brotherton Julia M. L. , Fairley Christopher K.
Published: November 2012

Anal cancer was until recently regarded as a rare cancer of little consequence. The articles in this special edition of Sexual Health clearly demonstrate that anal cancer is increasing in incidence and, in some populations, it has become an urgent public health priority. In this summary paper, we will review the data presented in this issue and elsewhere on the magnitude of the issue, the means of prevention and treatment, and suggest a way forward.
Telomere- and telomerase-interacting protein that unfolds telomere G-quadruplex and promotes telomere extension in mammalian cells
Authors: Wang Feng , Tang Ming-liang , Zeng Zhi-xiong , Wu Ren-yi , Xue Yong , Hao Yu-hua , Pang Dai-Wen , Zhao Yong , Tan Zheng
Published: November 2012

Telomere extension by telomerase is essential for chromosome stability and cell vitality. Here, we report the identification of a splice variant of mammalian heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), hnRNP A2*, which binds telomeric DNA and telomerase in vitro. hnRNP A2* colocalizes with telomerase in Cajal bodies and at telomeres. In vitro assays show that hnRNP A2* actively unfolds telomeric G-quadruplex DNA, exposes 5 nt of the 3′ telomere tail and substantially enhances the catalytic activity and processivity of telomerase. The expression level of hnRNP A2* in tissues positively correlates with telomerase activity, and overexpression of hnRNP A2* leads to telomere elongation in vivo. Thus, hnRNP A2* plays a positive role in unfolding telomere G-quadruplexes and in enhancing telomere extension by telomerase.
Aneuploidy-induced delaminating cells drive tumorigenesis in
Drosophila
epithelia
Authors: Dekanty Andrés , Barrio Lara , Muzzopappa Mariana , Auer Herbert , Milán Marco
Published: November 2012

Genomic instability has been observed in essentially all sporadic carcinomas. Here we use
Drosophila
epithelial cells to address the role of chromosomal instability in cancer development as they have proved useful for elucidating the molecular mechanisms underlying tumorigenic growth. We first show that chromosomal instability leads to an apoptotic response. Interestingly, this response is p53 independent, as opposed to mammalian cells, and depends on the activation of the c-Jun N-terminal kinase (JNK) signaling cascade. When prevented from undergoing programmed cell death (PCD), chromosomal instability induces neoplasic overgrowth. These tumor-like tissues are able to grow extensively and metastasize when transplanted into the abdomen of adult hosts. Detailed analysis of the tumors allows us to identify a delaminating cell population as the critical one in driving tumorigenesis. Cells loose their apical–basal polarity, mislocalize DE-cadherin, and delaminate from the main epithelium. A JNK-dependent transcriptional program is activated specifically in delaminating cells and drives nonautonomous tissue overgrowth, basement membrane degradation, and invasiveness. These findings unravel a general and rapid tumorigenic potential of genomic instability, as opposed to its proposed role as a source of mutability to select specific tumor-prone aneuploid cells, and open unique avenues toward the understanding of the role of genomic instability in human cancer.
Na
+
/K
+
-ATPase E960 and phospholemman F28 are critical for their functional interaction
Authors: Khafaga Mounir , Bossuyt Julie , Mamikonian Luiza , Li Joseph C. , Lee Linda L. , Yarov-Yarovoy Vladimir , Despa Sanda , Bers Donald M.
Published: November 2012

Na
+
-K
+
-ATPase (NKA) establishes the transmembrane [Na
+
] gradient in cells. In heart, phospholemman (PLM) inhibits NKA activity by reducing its apparent Na
+
affinity, an effect that is relieved by PLM phosphorylation. The NKA crystal structure suggests regions of PLM–NKA interaction, but the sites important for functional effects in live cells are not known. We tested wild type (WT) and CFP–NKA-α1 point mutants (alanine substitution at F956, E960, L964, and F967) for fluorescence resonance energy transfer (FRET) with WT–PLM–YFP in HEK293 cells. NKA–PLM FRET was unaltered with F956A or F967A, reduced with L964A, and nearly abolished with E960A. Mutating the PLM site (F28A) identified by structural analysis to interact with E960-NKA also nearly abolished NKA–PLM FRET. In contrast, NKA–PLM coimmunoprecipitation was only slightly reduced by E960A–NKA or F28A–PLM mutants, consistent with an additional interaction site. FRET titrations indicate that the additional site has higher affinity than that between E960–NKA and F28–PLM. To test whether the FRET-preventing mutations also prevent PLM functional effects, we measured NKA-mediated Na
+
-transport in intact cells. For WT–NKA, PLM reduced apparent Na
+
-affinity of NKA and PLM phosphorylation reversed the effect. In contrast, for E960A–NKA the apparent Na
+
-affinity was unaltered by either PLM or forskolin-induced PLM phosphorylation. We conclude that E960 on NKA and F28 on PLM are critical for PLM effects on both NKA function and NKA–PLM FRET, but also there is at least one additional site that is critical for tethering PLM to NKA.
Microbial life at −13 °C in the brine of an ice-sealed Antarctic lake
Authors: Murray Alison E. , Kenig Fabien , Fritsen Christian H. , McKay Christopher P. , Cawley Kaelin M. , Edwards Ross , Kuhn Emanuele , McKnight Diane M. , Ostrom Nathaniel E. , Peng Vivian , Ponce Adrian , Priscu John C. , Samarkin Vladimir , Townsend Ashley T. , Wagh Protima , Young Seth A. , Yung Pung To , Doran Peter T.
Published: November 2012

The permanent ice cover of Lake Vida (Antarctica) encapsulates an extreme cryogenic brine ecosystem (−13 °C; salinity, 200). This aphotic ecosystem is anoxic and consists of a slightly acidic (pH 6.2) sodium chloride-dominated brine. Expeditions in 2005 and 2010 were conducted to investigate the biogeochemistry of Lake Vida’s brine system. A phylogenetically diverse and metabolically active
Bacteria
dominated microbial assemblage was observed in the brine. These bacteria live under very high levels of reduced metals, ammonia, molecular hydrogen (H
2
), and dissolved organic carbon, as well as high concentrations of oxidized species of nitrogen (i.e., supersaturated nitrous oxide and ∼1 mmol⋅L
−1
nitrate) and sulfur (as sulfate). The existence of this system, with active biota, and a suite of reduced as well as oxidized compounds, is unusual given the millennial scale of its isolation from external sources of energy. The geochemistry of the brine suggests that abiotic brine-rock reactions may occur in this system and that the rich sources of dissolved electron acceptors prevent sulfate reduction and methanogenesis from being energetically favorable. The discovery of this ecosystem and the in situ biotic and abiotic processes occurring at low temperature provides a tractable system to study habitability of isolated terrestrial cryoenvironments (e.g., permafrost cryopegs and subglacial ecosystems), and is a potential analog for habitats on other icy worlds where water-rock reactions may cooccur with saline deposits and subsurface oceans.
Hubs of brain functional networks are radically reorganized in comatose patients
Authors: Achard Sophie , Delon-Martin Chantal , Vértes Petra E. , Renard Félix , Schenck Maleka , Schneider Francis , Heinrich Christian , Kremer Stéphane , Bullmore Edward T.
Published: November 2012

Human brain networks have topological properties in common with many other complex systems, prompting the following question: what aspects of brain network organization are critical for distinctive functional properties of the brain, such as consciousness? To address this question, we used graph theoretical methods to explore brain network topology in resting state functional MRI data acquired from 17 patients with severely impaired consciousness and 20 healthy volunteers. We found that many global network properties were conserved in comatose patients. Specifically, there was no significant abnormality of global efficiency, clustering, small-worldness, modularity, or degree distribution in the patient group. However, in every patient, we found evidence for a radical reorganization of high degree or highly efficient “hub” nodes. Cortical regions that were hubs of healthy brain networks had typically become nonhubs of comatose brain networks and vice versa. These results indicate that global topological properties of complex brain networks may be homeostatically conserved under extremely different clinical conditions and that consciousness likely depends on the anatomical location of hub nodes in human brain networks.
Acquisition of 1,000 eubacterial genes physiologically transformed a methanogen at the origin of Haloarchaea
Authors: Nelson-Sathi Shijulal , Dagan Tal , Landan Giddy , Janssen Arnold , Steel Mike , McInerney James O. , Deppenmeier Uwe , Martin William F.
Published: November 2012

Archaebacterial halophiles (Haloarchaea) are oxygen-respiring heterotrophs that derive from methanogens—strictly anaerobic, hydrogen-dependent autotrophs. Haloarchaeal genomes are known to have acquired, via lateral gene transfer (LGT), several genes from eubacteria, but it is yet unknown how many genes the Haloarchaea acquired in total and, more importantly, whether independent haloarchaeal lineages acquired their genes in parallel, or as a single acquisition at the origin of the group. Here we have studied 10 haloarchaeal and 1,143 reference genomes and have identified 1,089 haloarchaeal gene families that were acquired by a methanogenic recipient from eubacteria. The data suggest that these genes were acquired in the haloarchaeal common ancestor, not in parallel in independent haloarchaeal lineages, nor in the common ancestor of haloarchaeans and methanosarcinales. The 1,089 acquisitions include genes for catabolic carbon metabolism, membrane transporters, menaquinone biosynthesis, and complexes I–IV of the eubacterial respiratory chain that functions in the haloarchaeal membrane consisting of diphytanyl isoprene ether lipids. LGT on a massive scale transformed a strictly anaerobic, chemolithoautotrophic methanogen into the heterotrophic, oxygen-respiring, and bacteriorhodopsin-photosynthetic haloarchaeal common ancestor.
Alternative bacterial two-component small heat shock protein systems
Authors: Bepperling Alexander , Alte Ferdinand , Kriehuber Thomas , Braun Nathalie , Weinkauf Sevil , Groll Michael , Haslbeck Martin , Buchner Johannes
Published: November 2012

Small heat shock proteins (sHsps) are molecular chaperones that prevent the aggregation of nonnative proteins. The sHsps investigated to date mostly form large, oligomeric complexes. The typical bacterial scenario seemed to be a two-component sHsps system of two homologous sHsps, such as the
Escherichia coli
sHsps IbpA and IbpB. With a view to expand our knowledge on bacterial sHsps, we analyzed the sHsp system of the bacterium
Deinococcus radiodurans
, which is resistant against various stress conditions.
D. radiodurans
encodes two sHsps, termed Hsp17.7 and Hsp20.2. Surprisingly, Hsp17.7 forms only chaperone active dimers, although its crystal structure reveals the typical α-crystallin fold. In contrast, Hsp20.2 is predominantly a 36mer that dissociates into smaller oligomeric assemblies that bind substrate proteins stably. Whereas Hsp20.2 cooperates with the ATP-dependent bacterial chaperones in their refolding, Hsp17.7 keeps substrates in a refolding-competent state by transient interactions. In summary, we show that these two sHsps are strikingly different in their quaternary structures and chaperone properties, defining a second type of bacterial two-component sHsp system.
Integrative analysis of the zinc finger transcription factor Lame duck in the
Drosophila
myogenic gene regulatory network
Authors: Busser Brian W. , Huang Di , Rogacki Kevin R. , Lane Elizabeth A. , Shokri Leila , Ni Ting , Gamble Caitlin E. , Gisselbrecht Stephen S. , Zhu Jun , Bulyk Martha L. , Ovcharenko Ivan , Michelson Alan M.
Published: November 2012

Contemporary high-throughput technologies permit the rapid identification of transcription factor (TF) target genes on a genome-wide scale, yet the functional significance of TFs requires knowledge of target gene expression patterns, cooperating TFs, and
cis
-regulatory element (CRE) structures. Here we investigated the myogenic regulatory network downstream of the
Drosophila
zinc finger TF Lame duck (Lmd) by combining both previously published and newly performed genomic data sets, including ChIP sequencing (ChIP-seq), genome-wide mRNA profiling, cell-specific expression patterns of putative transcriptional targets, analysis of histone mark signatures, studies of TF cooccupancy by additional mesodermal regulators, TF binding site determination using protein binding microarrays (PBMs), and machine learning of candidate CRE motif compositions. Our findings suggest that Lmd orchestrates an extensive myogenic regulatory network, a conclusion supported by the identification of Lmd-dependent genes, histone signatures of Lmd-bound genomic regions, and the relationship of these features to cell-specific gene expression patterns. The heterogeneous cooccupancy of Lmd-bound regions with additional mesodermal regulators revealed that different transcriptional inputs are used to mediate similar myogenic gene expression patterns. Machine learning further demonstrated diverse combinatorial motif patterns within tissue-specific Lmd-bound regions. PBM analysis established the complete spectrum of Lmd DNA binding specificities, and site-directed mutagenesis of Lmd and additional newly discovered motifs in known enhancers demonstrated the critical role of these TF binding sites in supporting full enhancer activity. Collectively, these findings provide insights into the transcriptional codes regulating muscle gene expression and offer a generalizable approach for similar studies in other systems.
Prefrontal D1 dopamine signaling is required for temporal control
Authors: Narayanan Nandakumar S. , Land Benjamin B. , Solder John E. , Deisseroth Karl , DiLeone Ralph J.
Published: November 2012

Temporal control, or how organisms guide movements in time to achieve behavioral goals, depends on dopamine signaling. The medial prefrontal cortex controls many goal-directed behaviors and receives dopaminergic input primarily from the midbrain ventral tegmental area. However, this system has never been linked with temporal control. Here, we test the hypothesis that dopaminergic projections from the ventral tegmental area to the prefrontal cortex influence temporal control. Rodents were trained to perform a fixed-interval timing task with an interval of 20 s. We report several results: first, that decreasing dopaminergic neurotransmission using virally mediated RNA interference of tyrosine hydroxylase impaired temporal control, and second that pharmacological disruption of prefrontal D1 dopamine receptors, but not D2 dopamine receptors, impaired temporal control. We then used optogenetics to specifically and selectively manipulate prefrontal neurons expressing D1 dopamine receptors during fixed-interval timing performance. Selective inhibition of D1-expressing prefrontal neurons impaired fixed-interval timing, whereas stimulation made animals more efficient during task performance. These data provide evidence that ventral tegmental dopaminergic projections to the prefrontal cortex influence temporal control via D1 receptors. The results identify a critical circuit for temporal control of behavior that could serve as a target for the treatment of dopaminergic diseases.
Circadian regulation of olfaction and an evolutionarily conserved, nontranscriptional marker in
Caenorhabditis elegans
Authors: Olmedo Maria , O’Neill John S. , Edgar Rachel S. , Valekunja Utham K. , Reddy Akhilesh B. , Merrow Martha
Published: November 2012

Circadian clocks provide a temporal structure to processes from gene expression to behavior in organisms from all phyla. Most clocks are synchronized to the environment by alternations of light and dark. However, many organisms experience only muted daily environmental cycles due to their lightless spatial niches (e.g., caves or soil). This has led to speculation that they may dispense with the daily clock. However, recent reports contradict this notion, showing various behavioral and molecular rhythms in
Caenorhabditis elegans
and in blind cave fish. Based on the ecology of nematodes, we applied low-amplitude temperature cycles to synchronize populations of animals through development. This entrainment regime reveals rhythms on multiple levels: in olfactory cued behavior, in RNA and protein abundance, and in the oxidation state of a broadly conserved peroxiredoxin protein. Our work links the nematode clock with that of other clock model systems; it also emphasizes the importance of daily rhythms in sensory functions that are likely to impact on organism fitness and population structure.
Capturing reaction paths and intermediates in Cre-
loxP
recombination using single-molecule fluorescence
Authors: Pinkney Justin N. M. , Zawadzki Pawel , Mazuryk Jaroslaw , Arciszewska Lidia K. , Sherratt David J. , Kapanidis Achillefs N.
Published: November 2012

Site-specific recombination plays key roles in microbe biology and is exploited extensively to manipulate the genomes of higher organisms. Cre is a well studied site-specific recombinase, responsible for establishment and maintenance of the P1 bacteriophage genome in bacteria. During recombination, Cre forms a synaptic complex between two 34-bp DNA sequences called
loxP
after which a pair of strand exchanges forms a Holliday junction (HJ) intermediate; HJ isomerization then allows a second pair of strand exchanges and thus formation of the final recombinant product. Despite extensive work on the Cre-
loxP
system, many of its mechanisms have remained unclear, mainly due to the transient nature of complexes formed and the ensemble averaging inherent to most biochemical work. Here, we address these limitations by introducing tethered fluorophore motion (TFM), a method that monitors large-scale DNA motions through reports of the diffusional freedom of a single fluorophore. We combine TFM with Förster resonance energy transfer (FRET) and simultaneously observe both large- and small-scale conformational changes within single DNA molecules. Using TFM–FRET, we observed individual recombination reactions in real time and analyzed their kinetics. Recombination was initiated predominantly by exchange of the “bottom-strands” of the DNA substrate. In productive complexes we used FRET distributions to infer rapid isomerization of the HJ intermediates and that a rate-limiting step occurs after this isomerization. We also observed two nonproductive synaptic complexes, one of which was structurally distinct from conformations in crystals. After recombination, the product synaptic complex was extremely stable and refractory to subsequent rounds of recombination.
Climate impacts on human settlement and agricultural activities in northern Norway revealed through sediment biogeochemistry
Authors: D’Anjou Robert M. , Bradley Raymond S. , Balascio Nicholas L. , Finkelstein David B.
Published: November 2012

Disentangling the effects of climate change and anthropogenic activities on the environment is a major challenge in paleoenvironmental research. Here, we used fecal sterols and other biogeochemical compounds in lake sediments from northern Norway to identify both natural and anthropogenic signals of environmental change during the late Holocene. The area was first occupied by humans and their grazing animals at ∼2,250 ± 75 calendar years before 1950 AD (calendar years before present). The arrival of humans is indicated by an abrupt increase in coprostanol (and its epimer epicoprostanol) in the sediments and an associated increase in 5β-stigmastanol (and 5β-epistigmastanol), which resulted from human and animal feces washing into the lake. Human settlement was accompanied by an abrupt increase in landscape fires (indicated by the rise in pyrolytic polycyclic aromatic hydrocarbons) and a decline in woodland (registered by a change in
n
-alkane chain lengths from leaf waxes), accelerating a process that began earlier in the Holocene. Human activity and associated landscape changes in the region over the last two millennia were mainly driven by summer temperatures, as indicated by independent tree-ring reconstructions, although there were periods when socioeconomic factors played an equally important role. In this study, fecal sterols in lake sediments have been used to provide a record of human occupancy through time. This approach may be useful in many archeological studies, both to confirm the presence of humans and grazing animals, and to distinguish between anthropogenic and natural factors that have influenced the environment in the past.
Serial population extinctions in a small mammal indicate Late Pleistocene ecosystem instability
Authors: Brace Selina , Palkopoulou Eleftheria , Dalén Love , Lister Adrian M. , Miller Rebecca , Otte Marcel , Germonpré Mietje , Blockley Simon P. E. , Stewart John R. , Barnes Ian
Published: November 2012

The Late Pleistocene global extinction of many terrestrial mammal species has been a subject of intensive scientific study for over a century, yet the relative contributions of environmental changes and the global expansion of humans remain unresolved. A defining component of these extinctions is a bias toward large species, with the majority of small-mammal taxa apparently surviving into the present. Here, we investigate the population-level history of a key tundra-specialist small mammal, the collared lemming (
Dicrostonyx torquatus
), to explore whether events during the Late Pleistocene had a discernible effect beyond the large mammal fauna. Using ancient DNA techniques to sample across three sites in North-West Europe, we observe a dramatic reduction in genetic diversity in this species over the last 50,000 y. We further identify a series of extinction-recolonization events, indicating a previously unrecognized instability in Late Pleistocene small-mammal populations, which we link with climatic fluctuations. Our results reveal climate-associated, repeated regional extinctions in a keystone prey species across the Late Pleistocene, a pattern likely to have had an impact on the wider steppe-tundra community, and one that is concordant with environmental change as a major force in structuring Late Pleistocene biodiversity.
Structural basis for Marburg virus VP35–mediated immune evasion mechanisms
Authors: Ramanan Parameshwaran , Edwards Megan R. , Shabman Reed S. , Leung Daisy W. , Endlich-Frazier Ariel C. , Borek Dominika M. , Otwinowski Zbyszek , Liu Gai , Huh Juyoung , Basler Christopher F. , Amarasinghe Gaya K.
Published: November 2012

Filoviruses,
marburgvirus
(MARV) and
ebolavirus
(EBOV), are causative agents of highly lethal hemorrhagic fever in humans. MARV and EBOV share a common genome organization but show important differences in replication complex formation, cell entry, host tropism, transcriptional regulation, and immune evasion. Multifunctional filoviral viral protein (VP) 35 proteins inhibit innate immune responses. Recent studies suggest double-stranded (ds)RNA sequestration is a potential mechanism that allows EBOV VP35 to antagonize retinoic-acid inducible gene-I (RIG-I) like receptors (RLRs) that are activated by viral pathogen–associated molecular patterns (PAMPs), such as double-strandedness and dsRNA blunt ends. Here, we show that MARV VP35 can inhibit IFN production at multiple steps in the signaling pathways downstream of RLRs. The crystal structure of MARV VP35 IID in complex with 18-bp dsRNA reveals that despite the similar protein fold as EBOV VP35 IID, MARV VP35 IID interacts with the dsRNA backbone and not with blunt ends. Functional studies show that MARV VP35 can inhibit dsRNA-dependent RLR activation and interferon (IFN) regulatory factor 3 (IRF3) phosphorylation by IFN kinases TRAF family member-associated NFkb activator (TANK) binding kinase-1 (TBK-1) and IFN kB kinase e (IKKe) in cell-based studies. We also show that MARV VP35 can only inhibit RIG-I and melanoma differentiation associated gene 5 (MDA5) activation by double strandedness of RNA PAMPs (coating backbone) but is unable to inhibit activation of RLRs by dsRNA blunt ends (end capping). In contrast, EBOV VP35 can inhibit activation by both PAMPs. Insights on differential PAMP recognition and inhibition of IFN induction by a similar filoviral VP35 fold, as shown here, reveal the structural and functional plasticity of a highly conserved virulence factor.
Compression of the DNA substrate by a viral packaging motor is supported by removal of intercalating dye during translocation
Authors: Dixit Aparna Banerjee , Ray Krishanu , Black Lindsay W.
Published: November 2012

Viral genome packaging into capsids is powered by high-force-generating motor proteins. In the presence of all packaging components, ATP-powered translocation in vitro expels all detectable tightly bound YOYO-1 dye from packaged short dsDNA substrates and removes all aminoacridine dye from packaged genomic DNA in vivo. In contrast, in the absence of packaging, the purified T4 packaging ATPase alone can only remove up to
∼
1/3 of DNA-bound intercalating YOYO-1 dye molecules in the presence of ATP or ATP-γ-S. In sufficient concentration, intercalating dyes arrest packaging, but rare terminase mutations confer resistance. These distant mutations are highly interdependent in acquiring function and resistance and likely mark motor contact points with the translocating DNA. In stalled Y-DNAs, FRET has shown a decrease in distance from the phage T4 terminase C terminus to portal consistent with a linear motor, and in the Y-stem DNA compression between closely positioned dye pairs. Taken together with prior FRET studies of conformational changes in stalled Y-DNAs, removal of intercalating compounds by the packaging motor demonstrates conformational change in DNA during normal translocation at low packaging resistance and supports a proposed linear “DNA crunching” or torsional compression motor mechanism involving a transient grip-and-release structural change in B form DNA.
Architecture of a flagellar apparatus in the fast-swimming magnetotactic bacterium MO-1
Authors: Ruan Juanfang , Kato Takayuki , Santini Claire-Lise , Miyata Tomoko , Kawamoto Akihiro , Zhang Wei-Jia , Bernadac Alain , Wu Long-Fei , Namba Keiichi
Published: November 2012

The bacterial flagellum is a motility organelle that consists of a rotary motor and a helical propeller. The flagella usually work individually or by forming a loose bundle to produce thrust. However, the flagellar apparatus of marine bacterium MO-1 is a tight bundle of seven flagellar filaments enveloped in a sheath, and it has been a mystery as to how the flagella rotate smoothly in coordination. Here we have used electron cryotomography to visualize the 3D architecture of the sheathed flagella. The seven filaments are enveloped with 24 fibrils in the sheath, and their basal bodies are arranged in an intertwined hexagonal array similar to the thick and thin filaments of vertebrate skeletal muscles. This complex and exquisite architecture strongly suggests that the fibrils counter-rotate between flagella in direct contact to minimize the friction of high-speed rotation of individual flagella in the tight bundle within the sheath to enable MO-1 cells to swim at about 300 µm/s.
Wnt7a treatment ameliorates muscular dystrophy
Authors: von Maltzahn Julia , Renaud Jean-Marc , Parise Gianni , Rudnicki Michael A.
Published: November 2012

Duchenne muscular dystrophy (DMD) is a devastating genetic muscular disorder of childhood marked by progressive debilitating muscle weakness and wasting, and ultimately death in the second or third decade of life. Wnt7a signaling through its receptor Fzd7 accelerates and augments regeneration by stimulating satellite stem cell expansion through the planar cell polarity pathway, as well as myofiber hypertrophy through the AKT/mammalian target of rapamycin (mTOR) anabolic pathway. We investigated the therapeutic potential of the secreted factor Wnt7a for focal treatment of dystrophic DMD muscles using the
mdx
mouse model, and found that Wnt7a treatment efficiently induced satellite cell expansion and myofiber hypertrophy in treated mucles in
mdx
mice. Importantly, Wnt7a treatment resulted in a significant increase in muscle strength, as determined by generation of specific force. Furthermore, Wnt7a reduced the level of contractile damage, likely by inducing a shift in fiber type toward slow-twitch. Finally, we found that Wnt7a similarly induced myotube hypertrophy and a shift in fiber type toward slow-twitch in human primary myotubes. Taken together, our findings suggest that Wnt7a is a promising candidate for development as an ameliorative treatment for DMD.
Herpesvirus entry mediator is a serotype specific determinant of pathogenesis in ocular herpes
Authors: Karaba Andrew H. , Kopp Sarah J. , Longnecker Richard
Published: November 2012

Infection with herpes simplex virus type 1 (HSV-1) and HSV-2 is initiated by viral glycoprotein D (gD) binding to a receptor on the host cell. Two receptors, herpesvirus entry mediator (HVEM) and nectin-1, mediate entry in murine models of HSV-1 and HSV-2. HVEM is dispensable for HSV-2 infection of the vagina and brain, but is required for WT pathogenesis of HSV-1 infection of the cornea. By challenging WT and HVEM KO mice with multiple strains of HSV-1 and HSV-2, we demonstrate that without HVEM, all HSV-1 strains tested do not replicate well in the cornea and infection does not result in severe symptoms, as observed in WT mice. In contrast, all HSV-2 strains tested had no requirement for HVEM to replicate to WT levels in the cornea and still cause severe disease. These findings imply that HSV-2 does not require HVEM to cause disease regardless of route of entry, but HVEM must be present for HSV-1 to cause full pathogenesis in the eye. These findings uncover a unique role for HVEM in mediating HSV-1 infection in an area innervated by the trigeminal ganglion and may explain why the presence of HVEM can lead to severe inflammation in the cornea. Thus, the dependence on HVEM is a dividing point between HSV-1 and HSV-2 that evolved to infect areas innervated by different sensory ganglia.
Type II
1
factors satisfying the spatial isomorphism conjecture
Authors: Cameron Jan , Christensen Erik , Sinclair Allan M. , Smith Roger R. , White Stuart A. , Wiggins Alan D.
Published: November 2012

This paper addresses a conjecture in the work by Kadison and Kastler [Kadison RV, Kastler D (1972)
Am J Math
94:38–54] that a von Neumann algebra
M
on a Hilbert space

should be unitarily equivalent to each sufficiently close von Neumann algebra
N
, and, moreover, the implementing unitary can be chosen to be close to the identity operator. This conjecture is known to be true for amenable von Neumann algebras, and in this paper, we describe classes of nonamenable factors for which the conjecture is valid. These classes are based on tensor products of the hyperfinite II
1
factor with crossed products of abelian algebras by suitably chosen discrete groups.
Amygdala lesions disrupt modulation of functional MRI activity evoked by facial expression in the monkey inferior temporal cortex
Authors: Hadj-Bouziane Fadila , Liu Ning , Bell Andrew H. , Gothard Katalin M. , Luh Wen-Ming , Tootell Roger B. H. , Murray Elisabeth A. , Ungerleider Leslie G.
Published: November 2012

Significance

Successful social interaction depends on the ability to recognize others, evaluate their mental states (e.g. intentions, desires, and beliefs), and “read” their emotional states. Here, we show that, in monkeys, damage to the amygdala, a brain structure that is central to the expression of emotion, significantly disrupts the processing of emotional facial expression in high-level visual cortical areas involved in face recognition. These findings suggest that the projections of the amygdala to visual cortical areas likely enhance the sensory processing of biologically important signals, including those related to potential environmental threats and social contexts.
Carbon source-dependent expansion of the genetic code in bacteria
Authors: Prat Laure , Heinemann Ilka U. , Aerni Hans R. , Rinehart Jesse , O’Donoghue Patrick , Söll Dieter
Published: November 2012

Despite the fact that the genetic code is known to vary between organisms in rare cases, it is believed that in the lifetime of a single cell the code is stable. We found
Acetohalobium arabaticum
cells grown on pyruvate genetically encode 20 amino acids, but in the presence of trimethylamine (TMA),
A. arabaticum
dynamically expands its genetic code to 21 amino acids including pyrrolysine (Pyl).
A. arabaticum
is the only known organism that modulates the size of its genetic code in response to its environment and energy source. The gene cassette
pylTSBCD
, required to biosynthesize and genetically encode UAG codons as Pyl, is present in the genomes of 24 anaerobic archaea and bacteria. Unlike archaeal Pyl-decoding organisms that constitutively encode Pyl, we observed that
A. arabaticum
controls Pyl encoding by down-regulating transcription of the entire Pyl operon under growth conditions lacking TMA, to the point where no detectable Pyl-tRNA
Pyl
is made in vivo. Pyl-decoding archaea adapted to an expanded genetic code by minimizing TAG codon frequency to typically ∼5% of ORFs, whereas Pyl-decoding bacteria (∼20% of ORFs contain in-frame TAGs) regulate Pyl-tRNA
Pyl
formation and translation of UAG by transcriptional deactivation of genes in the Pyl operon. We further demonstrate that Pyl encoding occurs in a bacterium that naturally encodes the Pyl operon, and identified Pyl residues by mass spectrometry in
A. arabaticum
proteins including two methylamine methyltransferases.
Hydrodynamic turbulence as a problem in nonequilibrium statistical mechanics
Authors: Ruelle David P.
Published: November 2012

The problem of hydrodynamic turbulence is reformulated as a heat flow problem along a chain of mechanical systems describing units of fluid of smaller and smaller spatial extent. These units are macroscopic but have a few degrees of freedom, and they can be studied by the methods of (microscopic) nonequilibrium statistical mechanics. The fluctuations predicted by statistical mechanics correspond to the intermittency observed in turbulent flows. Specifically, we obtain the formula

for the exponents of the structure functions (

). The meaning of the adjustable parameter
κ
is that when an eddy of size
r
has decayed to eddies of size

, their energies have a thermal distribution. The above formula, with

is in good agreement with experimental data. This lends support to our physical picture of turbulence, a picture that can thus also be used in related problems.
Capturing microRNA targets using an RNA-induced silencing complex (RISC)-trap approach
Authors: Cambronne Xiaolu A. , Shen Rongkun , Auer Paul L. , Goodman Richard H.
Published: November 2012

Identifying targets is critical for understanding the biological effects of microRNA (miRNA) expression. The challenge lies in characterizing the cohort of targets for a specific miRNA, especially when targets are being actively down-regulated in miRNA– RNA-induced silencing complex (RISC)–messengerRNA (mRNA) complexes. We have developed a robust and versatile strategy called RISCtrap to stabilize and purify targets from this transient interaction. Its utility was demonstrated by determining specific high-confidence target datasets for miR-124, miR-132, and miR-181 that contained known and previously unknown transcripts. Two previously unknown miR-132 targets identified with RISCtrap, adaptor protein CT10 regulator of kinase 1 (CRK1) and tight junction-associated protein 1 (TJAP1), were shown to be endogenously regulated by miR-132 in adult mouse forebrain. The datasets, moreover, differed in the number of targets and in the types and frequency of microRNA recognition element (MRE) motifs, thus revealing a previously underappreciated level of specificity in the target sets regulated by individual miRNAs.
Endogenously produced nitric oxide mitigates sensitivity of melanoma cells to cisplatin
Authors: Godoy Luiz C. , Anderson Chase T. M. , Chowdhury Rajdeep , Trudel Laura J. , Wogan Gerald N.
Published: November 2012

Melanoma patients experience inferior survival after biochemotherapy when their tumors contain numerous cells expressing the inducible isoform of NO synthase (iNOS) and elevated levels of nitrotyrosine, a product derived from NO. Although several lines of evidence suggest that NO promotes tumor growth and increases resistance to chemotherapy, it is unclear how it shapes these outcomes. Here we demonstrate that modulation of NO-mediated S-nitrosation of cellular proteins is strongly associated with the pattern of response to the anticancer agent cisplatin in human melanoma cells in vitro. Cells were shown to express iNOS constitutively, and to generate sustained nanomolar levels of NO intracellularly. Inhibition of NO synthesis or scavenging of NO enhanced cisplatin-induced apoptotic cell death. Additionally, pharmacologic agents disrupting S-nitrosation markedly increased cisplatin toxicity, whereas treatments favoring stabilization of S-nitrosothiols (SNOs) decreased its cytotoxic potency. Activity of the proapoptotic enzyme caspase-3 was higher in cells treated with a combination of cisplatin and chemicals that decreased NO/SNOs, whereas lower activity resulted from cisplatin combined with stabilization of SNOs. Constitutive protein S-nitrosation in cells was detected by analysis with biotin switch and reduction/chemiluminescence techniques. Moreover, intracellular NO concentration increased significantly in cells that survived cisplatin treatment, resulting in augmented S-nitrosation of caspase-3 and prolyl-hydroxylase-2, the enzyme responsible for targeting the prosurvival transcription factor hypoxia-inducible factor-1α for proteasomal degradation. Because activities of these enzymes are inhibited by S-nitrosation, our data thus indicate that modulation of intrinsic intracellular NO levels substantially affects cisplatin toxicity in melanoma cells. The underlying mechanisms may thus represent potential targets for adjuvant strategies to improve the efficacy of chemotherapy.
GENERATION IN ITSELF OR FOR ITSELF?
Authors: May Christina
Published: November 2012

The concept of welfare generation and the idea of possible conflicts between generations have been discussed frequently in the context of pension systems. In order to form interest groups that could engage in such a conflict, the generations in question would have to form clear collectives with strong agendas. This article shows that the concept of generation is rather vague and that it is not possible to define a generational collective characterised by its experiences with and attitudes towards the welfare state or the pension system. Pensioner cohorts have so far been identified mainly on the basis of financial transactions. If other resources and characteristics are taken into account, the seemingly clear-cut differences between generations get blurred. Apart from these external factors, there is also no evidence to be found for specific generations perceiving themselves as winners or losers, nor do they show an outspoken conflict potential that would mark them as actors in generational disputes.