bluuebunny/crossref_metadata_2025 huggingface dataset:
Making Yourself at Home on an Island: The First 1000 Years (+?) of the Irish Mesolithic
Authors: Woodman Peter
Published: April 2013

This paper is based on the 2009 Europa lecture which concentrated on the issues surrounding the Early Holocene colonisation of Ireland and placed it both in a broader European context as well as asking why the initial settlement of Ireland should take place so late. It also reconsidered the reasons why there was a significant change in technology within the Irish Mesolithic. This paper suggests that over-emphasis has been placed on the Irish ‘Early’–Later Mesolithic change which had been thought to take place at a very specific point in time. Instead it is suggested that changes began to take place soon after settlement began in Ireland and that many of the classic Mesolithic type fossils, most notably microliths, began to vanish, perhaps around or just after 9000 years calbp. It seems preferable to redefine the chronology of the Irish Mesolithic into two main phases the EARLIER and LATER Mesolithic with an, as yet undefined, chronological boundary between 8800 and 8600 calbp. At the same time it recognises that there are significant changes (facies) within each of the major phases, some of which could even be regional. It should also be noted that not all of the facies need necessarily be associated with a distinct range of obvious type fossils.
Pits and Place-making: Neolithic Habitation and Deposition Practices in East Yorkshirec. 4000–2500 BC
Authors: Carver Genevieve
Published: April 2013

This article presents the findings of a study which sought to explore the nature of Neolithic habitation practices in east Yorkshire, primarily using evidence from pits. The morphology of pits and material deposited into them were examined in order to discern the kinds of activities taking place close by, and the possible motivation behind pits being dug. The temporality, spatial organisation, and landscape distribution of pits was considered in conjunction with information from domestic features, artefact spreads, and monumental and funerary features in order to create a coherent image of the ways in which people lived in and exploited the landscape.

It is argued that, given the scarcity of direct evidence for residential contexts, the information from pits can tell us about occupation practices. Viewed in conjunction with evidence for changing subsistence practices and an increasingly monumentalised landscape from the Early Neolithic onwards, the deposition of domestic material in pits is interpreted as part of cycles of renewal that created more permanent connections between people and their homes.
GIFTING PAIN: THE PLEASURES OF LIBERAL GUILT INLONDON, A PILGRIMAGEANDSTREET LIFE IN LONDON
Authors: Ghosh Tanushree
Published: April 2013

In 1872, Blanchard Jerrold and Gustave Dorébegan publishing their lavish travelogue,London, a Pilgrimage. Much renowned for his illustrations ofDivine Comedy,Don Quixote,Paradise Lost,Idylls of the King, and other significant literary texts, Doré's considerable reputation as an artist fetched him a staggering sum of ten thousand pounds as payment for his work inLondon, a Pilgrimage. Jerrold, responsible for conceptualizing the project, was an established liberal playwright and journalist, often contributing pieces to theDaily News,Illustrated London News, andAthenaeum.Looking for interesting material, Jerrold and Doré traveled all over London; Doré often made notes on the spot and finished the illustrations later. Seeking to situate their work within the field of social exploration, Jerrold and Doré referenced Henry Mayhew's reformist journalistic series,London Labour and the London Poor. Jerrold claimed that their social investigation would reproduce for contemporary readers Mayhew's categories of “those who work, those who cannot, [and] those who won't work” (“Frontmatter”). Volumes ofLondon, a Pilgrimage, however, were reviewed as gift-books in various periodicals; theExaminer, for example, reviewed it in the “Christmas-Books” section, indicating that these volumes, which contained pictures of lower-class shanties and miserable, under-fed people, were being gifted and enjoyed (“Christmas-Books”).
Psychometric Properties of the 44-Item Version of Ryff’s Psychological Well-Being Scale
Authors: Kállay Éva , Rus Claudia
Published: April 2013

This study examined the factorial validity and reliability (Ωw) of the nonreversed, 44-item version of Ryff’s Psychological Well-Being Scale (PWBS; Ryff, 1989 ) on a Romanian convenience sample of 664 participants from the general population. The results showed that the correlated six-factor model presented a relatively good fit, χ²(887) = 2922.85, p < .001, RMSEA = .059, RMSEA 90% CI = [.056; .062], SRMR = .048, CFI = .973, compared to single-factor and independent six-factor models. Based on the ΔCFI value, we found no significant differences between the correlated six-factor and the hierarchical model. Although the correlated six-factor model had a relatively good fit, the high correlations between the six latent factors suggest a high overlap among them. Our results indicate that well-being can be conceptualized as a second-order factor encompassing six dimensions, represented by autonomy, positive relations, environmental mastery, personal growth, purpose in life, and self-acceptance. The value of the Ωwreliability coefficient of the six subscales as well as the whole instrument was above .70. The present study has a practical implication by highlighting the factorial validity of a shorter (44-item) instrument, thus shortening the time necessary for data collection.
Psychological Resilience
Authors: Fletcher David , Sarkar Mustafa
Published: April 2013

The purpose of this paper is to review and critique the variety of definitions, concepts, and theories of psychological resilience. To this end, the narrative is divided into three main sections. The first considers how resilience has been defined in the psychology research literature. Despite the construct being operationalized in a variety of ways, most definitions are based around two core concepts: adversity and positive adaptation. A substantial body of evidence suggests that resilience is required in response to different adversities, ranging from ongoing daily hassles to major life events, and that positive adaptation must be conceptually appropriate to the adversity examined in terms of the domains assessed and the stringency of criteria used. The second section examines the conceptualization of resilience as either a trait or a process, and explores how it is distinct from a number of related terms. Resilience is conceptualized as the interactive influence of psychological characteristics within the context of the stress process. The final section reviews the theories of resilience and critically examines one theory in particular that is commonly cited in the resilience literature. Future theories in this area should take into account the multiple demands individuals encounter, the meta-cognitive and -emotive processes that affect the resilience-stress relationship, and the conceptual distinction between resilience and coping. The review concludes with implications for policy, practice, and research including the need to carefully manage individuals’ immediate environment, and to develop the protective and promotive factors that individuals can proactively use to build resilience.
Pentamerisation of a scFv directed against TRAIL receptor 2 increases its antitumour efficacy
Authors: Wang Wei , He Wen , Wang Lei , Zhang Ge , Gao Bin
Published: April 2013

Single‐chain variable fragments (scFvs) have been considered as promising therapeutic drugs. However, their low affinity and rapid clearance from the blood have limited their wider application clinically. In this study, we aimed to improve scFv antibodies by multimerising a scFv against the death receptor 5 (DR5, TNFR10B) through fusion with a coiled‐coil domain of human cartilage oligomeric matrix protein 48. By forming a pentamer, nick‐named a combody, the avidity of the scFv increased 104‐fold and combody was more effective than its monomeric counterpart for antitumour activity in both in vitro and in vivo experiments.
Targeted disruption of MCPIP1/Zc3h12a results in fatal inflammatory disease
Authors: Miao Ruidong , Huang Shengping , Zhou Zhou , Quinn Tim , Van Treeck Benjamin , Nayyar Tehreem , Dim Daniel , Jiang Zhisheng , Papasian Christopher J , Eugene Chen Y , Liu Gang , Fu Mingui
Published: April 2013

Previous studies using MCP‐induced protein 1 (MCPIP1)/Zc3h12a‐deficient mice suggest that MCPIP1 is an important regulator of inflammation and immune homeostasis. However, the characterization of the immunological phenotype of MCPIP1‐deficient mice has not been detailed. In this study, we performed evaluation through histological, flow cytometric, enzyme‐linked immunosorbent assay and real‐time PCR analysis and found that targeted disruption of MCPIP1 gene leads to fatal, highly aggressive and widespread immune‐related lesions. In addition to previously observed growth retardation, splenomegaly, lymphoadenopathy, severe anemia and premature death, MCPIP1‐deficient mice showed disorganization of lymphoid organs, including spleen, lymph nodes and thymus, and massive infiltration of lymphocytes, macrophages and neutrophils into many other non‐lymphoid organs, primarily in lungs and liver. Flow cytometric analysis found significant increase in activated and differentiated T cells in peripheral blood and spleen of MCPIP1‐deficient mice. Moreover, heightened production of inflammatory cytokines from activated macrophages and T cells were observed in MCPIP1‐deficient mice. Interestingly, treatment of MCPIP1‐deficient mice with antibiotics resulted in significant improvement of life span and a decrease in inflammatory syndrome. Taken together, these results suggest a prominent role for MCPIP1 in the control of inflammation and immune homeostasis.
The synergy in cytokine production through MyD88‐TRIF pathways is co‐ordinated with ERK phosphorylation in macrophages
Authors: Ting Tan Rebecca Suet , Lin Bin , Liu Qian , Tucker‐Kellogg Lisa , Ho Bow , Leung Bernard PL , Ding Jeak Ling
Published: April 2013

Although specific single Toll‐like receptor (TLR) ligands are known to drive the development of Th1 or Th2 immunity, the outcome of different combinations of TLR ligands on innate immunity is not well defined. Spatiotemporal dynamics are critical in determining the specificity of the immune response, but the mechanisms underlying combinatorial TLR stimulation remain unclear. Here, we tested pairwise combinations of TLR ligands separated by different time intervals for their effect on cytokine production in macrophages. We observed that stimulation via a combination of MyD88‐ and TRIF‐utilizing adaptors leads to a highly synergistic cytokine response. On a timescale of 4–24 h, macrophages pretreated with poly(I:C) (TLR3 ligand) are cross‐primed to a second stimulation with R848 (TLR7 ligand) and vice versa, and each condition exhibits different optimal time windows of synergistic response for each cytokine. We show that the synergy resulting from combinatorial stimuli (poly(I:C) and R848 is also regulated by the order and dosage of the TLR agonists. Secondary response genes, which depend on new protein synthesis for transcription, show greater synergy than primary response genes, and such enhancement is abolished when new protein synthesis is inhibited. Synergistic cytokine production appears concordant with sustained ERK phosphorylation, suggesting that the de novo factors act via inhibition of ERK dephosphorylation, for example, by the downregulation of dual specificity phosphatase 6. Taken together, our findings illustrate a checkpoint in the innate immune system, where the synchronization of timing of both MyD88 and TRIF pathways is required for a maximal cytokine response and potential memory effect in macrophages.
ABCA8 stimulates sphingomyelin production in oligodendrocytes
Authors: Kim Woojin Scott , Hsiao Jen-Hsiang T. , Bhatia Surabhi , Glaros Elias N. , Don Anthony S. , Tsuruoka Shuichi , Shannon Weickert Cynthia , Halliday Glenda M.
Published: April 2013

Members of the ABCA (ATP-binding cassette subfamily A) family are characterized by their ability to transport lipids across cellular membranes and regulate lipid homoeostasis in the brain and peripheral tissues. ABCA8 is a little-known member of this subfamily that was originally cloned from human brain libraries and has no known function. In an effort to elucidate the role of ABCA8 in the brain we first undertook a comprehensive analysis of its expression in the human brain. ABCA8 was differentially expressed in multiple regions of adult human brains with significantly higher expression in oligodendrocyte-enriched white matter regions compared with grey matter cortical regions. We then assessed the impact of ABCA8 on sphingomyelin production in oligodendrocyte and showed that ABCA8 was able to significantly stimulate both sphingomyelin synthase 1 expression and sphingomyelin production. Furthermore, ABCA8 expression in the prefrontal cortex across the human life span correlated strongly with age-associated myelination, and the myelinating gene p25α was significantly up-regulated with ABCA8. The present study represents the first extensive expression and functional study of ABCA8 in the human brain and the results strongly suggest that ABCA8 regulates lipid metabolism in oligodendrocytes and potentially plays a role in myelin formation and maintenance.
Structural and functional interactions of the prostate cancer suppressor protein NKX3.1 with topoisomerase I
Authors: Song Liang-Nian , Bowen Cai , Gelmann Edward P.
Published: April 2013

NKX3.1 (NK3 homeobox 1) is a prostate tumour suppressor protein with a number of activities that are critical for its role in tumour suppression. NKX3.1 mediates the cellular response to DNA damage by interacting with ATM (ataxia telangiectasia mutated) and by activation of topoisomerase I. In the present study we characterized the interaction between NKX3.1 and topoisomerase I. The NKX3.1 homeodomain binds to a region of topoisomerase I spanning the junction between the core and linker domains. Loss of the topoisomerase I N-terminal domain, a region for frequent protein interactions, did not affect binding to NKX3.1 as was shown by the activation of Topo70 (N-terminal truncated topoisomerase I) in vitro. In contrast, NKX3.1 interacts with the enzyme reconstituted from peptide fragments of the core and linker active site domains, but inhibits the DNA-resolving activity of the reconstituted enzyme in vitro. The effect of NKX3.1 on both Topo70 and the reconstituted enzyme was seen in the presence and absence of camptothecin. Neither NKX3.1 nor CPT (camptothecin) had an effect on the interaction of the other with topoisomerase I. Therefore the interactions of NKX3.1 and CPT with the linker domain of topoisomerase I are mutually exclusive. However, in cells the effect of NKX3.1 on topoisomerase binding to DNA sensitized the cells to cellular toxicity and the induction of apoptosis by low doses of CPT. Lastly, topoisomerase I is important for the effect of NKX3.1 on cell survival after DNA damage as topoisomerase knockdown blocked the effect of NKX3.1 on clonogenicity after DNA damage. Therefore NKX3.1 and topoisomerase I interact in vitro and in cells to affect the CPT sensitivity and DNA-repair functions of NKX3.1.
Ube2W conjugates ubiquitin to α-amino groups of protein N-termini
Authors: Tatham Michael H. , Plechanovová Anna , Jaffray Ellis G. , Salmen Helena , Hay Ronald T.
Published: April 2013

The covalent attachment of the protein ubiquitin to intracellular proteins by a process known as ubiquitylation regulates almost all major cellular systems, predominantly by regulating protein turnover. Ubiquitylation requires the co-ordinated action of three enzymes termed E1, E2 and E3, and typically results in the formation of an isopeptide bond between the C-terminal carboxy group of ubiquitin and the ϵ-amino group of a target lysine residue. However, ubiquitin is also known to conjugate to the thiol of cysteine residue side chains and the α-amino group of protein N-termini, although the enzymes responsible for discrimination between different chemical groups have not been defined. In the present study, we show that Ube2W (Ubc16) is an E2 ubiquitin-conjugating enzyme with specific protein N-terminal mono-ubiquitylation activity. Ube2W conjugates ubiquitin not only to its own N-terminus, but also to that of the small ubiquitin-like modifier SUMO (small ubiquitin-related modifier) in a manner dependent on the SUMO-targeted ubiquitin ligase RNF4 (RING finger protein 4). Furthermore, N-terminal mono-ubiquitylation of SUMO-2 primes it for poly-ubiquitylation by the Ubc13–UEV1 (ubiquitin-conjugating enzyme E2 variant 1) heterodimer, showing that N-terminal ubiquitylation regulates protein fate. The description in the present study is the first of an E2-conjugating enzyme with N-terminal ubiquitylation activity, and highlights the importance of E2 enzymes in the ultimate outcome of E3-mediated ubiquitylation.
Genetic effects of polymorphisms in the prolactin receptor gene on chicken reproductive traits
Authors: Li D. Y. , Zhang L. , Trask J. S. , Xu H. L. , Yin H. D. , Zhu Q.
Published: April 2013

Prolactin receptor (PRLR) is a single transmembrane protein through which prolactin plays a wide variety of physiological roles in vertebrates. Markers of alleles for the PRLR gene were assessed for the association with six reproductive traits (bodyweight at first egg; egg weight at first egg; age at first egg; number of eggs at 300 days of age; bodyweight at 300 days of age; and egg weight at 300 days of age) in a single generation of the Erlang Mountain Chicken. Five single-nucleotide polymorphisms were detected in the PRLR gene by sequencing pooled DNA samples. Genotypes were identified using PCR-single strand conformational polymorphism and direct PCR-sequencing methods. The GLM procedure was used to estimate the association between genotypes and reproductive traits. The results showed that at the P1 locus, individuals with genotype TT had shorter age at first egg and greater number of eggs at 300 days of age than those with genotype CC (P < 0.01). Our findings suggest that the single-nucleotide polymorphism g.-14A > G at P1 locus could be a potential genetic marker for age at first egg and number of eggs at 300 days of age in the Erlang Mountain Chicken and haplotype ATGTT might be advantageous for reproductive traits.
Purification and characterisation of a phosphatidylcholine-binding protein from duck Biceps femoris muscle
Authors: Wang D. Y. , Zhang M. H. , Liu F. , Zhu Y. Z. , Xu W. M.
Published: April 2013

The interaction between protein and phospholipids is a widespread phenomenon involving several physiological events in postmortem muscle. We hereby report a method for one-step purification of a phosphatidylcholine-binding (PC-binding) protein from duck Biceps femoris muscle with relatively high purity and yield using ion-exchange chromatography. This PC-binding protein has an inhibitory effect on the activity of phospholipase A2 (PLA2). A decrease (~62.3%) in PLA2 activity was observed. It had a strong affinity to bind PC at pH range of 6.2–6.8 with a peak at pH 6.6 (13.36 ± 0.48 g PC/g protein); in addition, raising ATP content from 1 to 5 μmol/mL enhanced the binding capacity. The PC-binding protein plays a potential role in the integrity of membrane and meat quality.
Bentonite can decrease ammonia volatilisation losses from poultry litter: laboratory studies
Authors: Redding M. R.
Published: April 2013

Ammonia volatilisation from manure materials within poultry sheds can adversely affect production, and also represents a loss of fertiliser value from the spent litter. This study sought to compare the ability of alum and bentonite to decrease volatilisation losses of ammonia from spent poultry litter. An in-vessel volatilisation trial with air flushing, ammonia collection, and ammonia analysis was conducted over 64 days to evaluate the mitigation potential of these two materials. Water-saturated spent litter was incubated at 25°C in untreated condition (control) or with three treatments: an industry-accepted rate of alum [4% Al2(SO4)3·18H2O by dry mass of litter dry mass; ALUM], air-dry bentonite (127% by dry mass; BENT), or water-saturated bentonite (once again at 127% by dry mass; SATBENT). A high proportion of the nitrogen contained in the untreated spent litter was volatilised (62%). Bentonite additions were superior to alum additions at retaining spent litter ammonia (nitrogen losses: 15%, SATBENT; 34%, BENT; 54%, ALUM). Where production considerations favour comparable high rates of bentonite addition (e.g. where the litter is to be re-formulated as a fertiliser), this clay has potential to decrease ammonia volatilisation either in-shed or in spent litter stockpiles or formulated products, without the associated detrimental effect of alum on phosphorus availability.
Iron nodules in ferric soils of the Fraser Coast, Australia: relicts of laterisation or features of contemporary weathering and pedogenesis?
Authors: Löhr S. C. , Grigorescu M. , Cox M. E.
Published: April 2013

The genesis of ferruginous nodules and pisoliths in soils and weathering profiles of coastal southern and eastern Australia has long been debated. It is not clear whether iron (Fe) nodules are redox accumulations, residues of Miocene laterite duricrust, or the products of contemporary weathering of Fe-rich sedimentary rocks. This study combines a catchment-wide survey of Fe nodule distribution in Poona Creek catchment (Fraser Coast, Queensland) with detailed investigations of a representative ferric soil profile to show that Fe nodules are derived from Fe-rich sandstones. Where these crop out, they are broken down, transported downslope by colluvial processes, and redeposited. Chemical and physical weathering transforms these eroded rock fragments into non-magnetic Fe nodules. Major features of this transformation include lower hematite/goethite and kaolinite/gibbsite ratios, increased porosity, etching of quartz grains, and development of rounded morphology and a smooth outer cortex. Iron nodules are commonly concentrated in ferric horizons. We show that these horizons form as the result of differential biological mixing of the soil. Bioturbation gradually buries nodules and rock fragments deposited at the surface of the soil, resulting in a largely nodule-free ‘biomantle’ over a ferric ‘stone line’. Maghemite-rich magnetic nodules are a prominent feature of the upper half of the profile. These are most likely formed by the thermal alteration of non-magnetic nodules located at the top of the profile during severe bushfires. They are subsequently redistributed through the soil profile by bioturbation. Iron nodules occurring in the study area are products of contemporary weathering of Fe-rich rock units. They are not laterite duricrust residues nor are they redox accumulations, although redox-controlled dissolution/re-precipitation is an important component of post-depositional modification of these Fe nodules.
Differential principal component analysis of ChIP-seq
Authors: Ji Hongkai , Li Xia , Wang Qian-fei , Ning Yang
Published: April 2013

We propose differential principal component analysis (dPCA) for analyzing multiple ChIP- sequencing datasets to identify differential protein–DNA interactions between two biological conditions. dPCA integrates unsupervised pattern discovery, dimension reduction, and statistical inference into a single framework. It uses a small number of principal components to summarize concisely the major multiprotein synergistic differential patterns between the two conditions. For each pattern, it detects and prioritizes differential genomic loci by comparing the between-condition differences with the within-condition variation among replicate samples. dPCA provides a unique tool for efficiently analyzing large amounts of ChIP-sequencing data to study dynamic changes of gene regulation across different biological conditions. We demonstrate this approach through analyses of differential chromatin patterns at transcription factor binding sites and promoters as well as allele-specific protein–DNA interactions.
Notch1 modulates oxidative stress induced cell death through suppression of apoptosis signal-regulating kinase 1
Authors: Mo Jung-Soon , Yoon Ji-Hye , Ann Eun-Jung , Ahn Ji-Seon , Baek Hyeong-Jin , Lee Hye-Jin , Kim Seol-Hee , Kim Yeong-Dae , Kim Mi-Yeon , Park Hee-Sae
Published: April 2013

Notch1 genes encode receptors for a signaling pathway that regulates various aspects of cell growth and differentiation; however, the role of Notch1 signaling in p38 mitogen-activated protein kinase (MAPK) signaling pathway is still not well defined. In this study, we found that Notch1 intracellular domain (Notch1-IC) prevents oxidative stress-induced cell death through the suppression of the Apoptosis signal-regulating kinase (ASK) 1 signaling pathway. Notch1-IC inhibited H
2
O
2
-induced activation of ASK1 and the activation of downstream kinases in the p38 MAPK signaling cascade. The results of both in vivo binding and kinase studies have revealed that ASK1 is the direct target of Notch1-IC, whereas it produced no effect on either MAP kinase kinase (MKK) 3 or p38 MAPK. Notch1-IC blocked both the homooligomerization of ASK1 and inhibited ASK1 activity. Furthermore, Notch1-IC facilitated the translocation of activated ASK1 toward the nucleus. Notch1 knockdown was determined to be highly susceptible to oxidative stress-induced activation of ASK1-MKK3/MKK6-p38 MAPK signaling cascade and cell death. Taken together, our findings suggest that Notch1-IC may act as a negative regulator in ASK1 signaling cascades.
Climate change, wine, and conservation
Authors: Hannah Lee , Roehrdanz Patrick R. , Ikegami Makihiko , Shepard Anderson V. , Shaw M. Rebecca , Tabor Gary , Zhi Lu , Marquet Pablo A. , Hijmans Robert J.
Published: April 2013

Climate change is expected to impact ecosystems directly, such as through shifting climatic controls on species ranges, and indirectly, for example through changes in human land use that may result in habitat loss. Shifting patterns of agricultural production in response to climate change have received little attention as a potential impact pathway for ecosystems. Wine grape production provides a good test case for measuring indirect impacts mediated by changes in agriculture, because viticulture is sensitive to climate and is concentrated in Mediterranean climate regions that are global biodiversity hotspots. Here we demonstrate that, on a global scale, the impacts of climate change on viticultural suitability are substantial, leading to possible conservation conflicts in land use and freshwater ecosystems. Area suitable for viticulture decreases 25% to 73% in major wine producing regions by 2050 in the higher RCP 8.5 concentration pathway and 19% to 62% in the lower RCP 4.5. Climate change may cause establishment of vineyards at higher elevations that will increase impacts on upland ecosystems and may lead to conversion of natural vegetation as production shifts to higher latitudes in areas such as western North America. Attempts to maintain wine grape productivity and quality in the face of warming may be associated with increased water use for irrigation and to cool grapes through misting or sprinkling, creating potential for freshwater conservation impacts. Agricultural adaptation and conservation efforts are needed that anticipate these multiple possible indirect effects.
Antagonistic self-sensing and mate-sensing signaling controls antibiotic-resistance transfer
Authors: Chatterjee Anushree , Cook Laura C. C. , Shu Che-Chi , Chen Yuqing , Manias Dawn A. , Ramkrishna Doraiswami , Dunny Gary M. , Hu Wei-Shou
Published: April 2013

Conjugation is one of the most common ways bacteria acquire antibiotic resistance, contributing to the emergence of multidrug-resistant “superbugs.” Bacteria of the genus
Enterococcus faecalis
are highly antibiotic-resistant nosocomial pathogens that use the mechanism of conjugation to spread antibiotic resistance between resistance-bearing donor cells and resistance-deficient recipient cells. Here, we report a unique quorum sensing-based communication system that uses two antagonistic signaling molecules to regulate conjugative transfer of tetracycline-resistance plasmid pCF10 in
E. faecalis
. A “mate-sensing” peptide sex pheromone produced by recipient cells is detected by donor cells to induce conjugative genetic transfer. Using mathematical modeling and experimentation, we show that a second antagonistic “self-sensing” signaling peptide, previously known to suppress self-induction of donor cells, also serves as a classic quorum-sensing signal for donors that functions to reduce antibiotic-resistance transfer at high donor density. This unique form of quorum sensing may provide a means of limiting the spread of the plasmid and present opportunities to control antibiotic-resistance transfer through manipulation of intercellular signaling, with implications in the clinical setting.
Abrupt drainage cycles of the Fennoscandian Ice Sheet
Authors: Soulet Guillaume , Ménot Guillemette , Bayon Germain , Rostek Frauke , Ponzevera Emmanuel , Toucanne Samuel , Lericolais Gilles , Bard Edouard
Published: April 2013

Continental ice sheets are a key component of the Earth’s climate system, but their internal dynamics need to be further studied. Since the last deglaciation, the northern Eurasian Fennoscandian Ice Sheet (FIS) has been connected to the Black Sea (BS) watershed, making this basin a suitable location to investigate former ice-sheet dynamics. Here, from a core retrieved in the BS, we combine the use of neodymium isotopes, high-resolution elemental analysis, and biomarkers to trace changes in sediment provenance and river runoff. We reveal cyclic releases of meltwater originating from Lake Disna, a proglacial lake linked to the FIS during Heinrich Stadial 1. Regional interactions within the climate–lake–FIS system, linked to changes in the availability of subglacial water, led to abrupt drainage cycles of the FIS into the BS watershed. This phenomenon raised the BS water level by ∼100 m until the sill of the Bosphorus Strait was reached, flooding the vast northwestern BS shelf and deeply affecting the hydrology and circulation of the BS and, probably, of the Marmara and Aegean Seas.
Microstructure and rheology of a flow-induced structured phase in wormlike micellar solutions
Authors: Cardiel Joshua J. , Dohnalkova Alice C. , Dubash Neville , Zhao Ya , Cheung Perry , Shen Amy Q.
Published: April 2013

Surfactant molecules can self-assemble into various morphologies under proper combinations of ionic strength, temperature, and flow conditions. At equilibrium, wormlike micelles can transition from entangled to branched and multiconnected structures with increasing salt concentration. Under certain flow conditions, micellar structural transitions follow different trajectories. In this work, we consider the flow of two semidilute wormlike micellar solutions through microposts, focusing on their microstructural and rheological evolutions. Both solutions contain cetyltrimethylammonium bromide and sodium salicylate. One is weakly viscoelastic and shear thickening, whereas the other is strongly viscoelastic and shear thinning. When subjected to strain rates of ∼10
3
s
−1
and strains of ∼10
3
, we observe the formation of a stable flow-induced structured phase (FISP), with entangled, branched, and multiconnected micellar bundles, as evidenced by electron microscopy. The high stretching and flow alignment in the microposts enhance the flexibility and lower the bending modulus of the wormlike micelles. As flexible micelles flow through the microposts, it becomes energetically favorable to minimize the number of end caps while concurrently promoting the formation of cross-links. The presence of spatial confinement and extensional flow also enhances entropic fluctuations, lowering the energy barrier between states, thus increasing transition frequencies between states and enabling FISP formation. Whereas the rheological properties (zero-shear viscosity, plateau modulus, and stress relaxation time) of the shear-thickening precursor are smaller than those of the FISP, those of the shear-thinning precursor are several times larger than those of the FISP. This rheological property variation stems from differences in the structural evolution from the precursor to the FISP.
Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model
Authors: Danielsson Frida , Skogs Marie , Huss Mikael , Rexhepaj Elton , O’Hurley Gillian , Klevebring Daniel , Pontén Fredrik , Gad Annica K. B. , Uhlén Mathias , Lundberg Emma
Published: April 2013

The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a four-stage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that ∼6% (
n
= 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.
Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy
Authors: Yang Yonghua , Fiskus Warren , Yong Bao , Atadja Peter , Takahashi Yoshinori , Pandita Tej K. , Wang Hong-Gang , Bhalla Kapil N.
Published: April 2013

Autophagy is a stress-induced catabolic process in which cytoplasmic components, sequestered in double-membrane autophagic vesicles (AVs) or autophagosomes, are delivered to lysosomes for degradation and recycling [Kroemer G, Mariño G, Levine B (2010)
Mol Cell
40(2):280–293]. Activity of the class III phosphatidylinositol-3-OH-kinase (PI3K) vacuolar protein-sorting (Vps) 34, bound to coiled-coil moesin-like B-cell lymphoma 2 (Bcl-2)–interacting protein Beclin-1, is required for phosphoinositide generation, essential for AV formation in autophagy [Cuervo AM (2010)
Nat Cell Biol
12(8):735–737]. However, how autophagy-inducing stress regulates Vps34 activity has not been fully elucidated. Our findings demonstrate that autophagy-inducing stress increases intracellular levels of acetylated inducible heat shock protein (hsp) 70, which binds to the Beclin-1–Vps34 complex. Acetylated hsp70 also recruits E3 ligase for SUMOylation, KRAB–ZFP-associated protein 1 (KAP1), inducing Lys840 SUMOylation and increasing Vps34 activity bound to Beclin 1. Knockdown of hsp70 abolished the Beclin-1–Vps34 complex formation, as well as inhibited KAP1 binding to Vps34 and AV formation. Notably, autophagy-inducing stress due to histone deacetylase inhibitor treatment induced AV formation in the wild-type but not hsp70.1/3 knockout mouse embryonic fibroblasts MEFs. These findings highlight a regulatory mechanism of Vps34 activity, which involves acetylated hsp70 and KAP1-dependent SUMOylation of Vps34 bound to Beclin 1.
Cyclin-dependent kinase inhibitor p20 controls circadian cell-cycle timing
Authors: Laranjeiro Ricardo , Tamai T. Katherine , Peyric Elodie , Krusche Peter , Ott Sascha , Whitmore David
Published: April 2013

Specific stages of the cell cycle are often restricted to particular times of day because of regulation by the circadian clock. In zebrafish, both mitosis (M phase) and DNA synthesis (S phase) are clock-controlled in cell lines and during embryo development. Despite the ubiquitousness of this phenomenon, relatively little is known about the underlying mechanism linking the clock to the cell cycle. In this study, we describe an evolutionarily conserved cell-cycle regulator, cyclin-dependent kinase inhibitor 1d (20 kDa protein, p20), which along with
p21,
is a strongly rhythmic gene and directly clock-controlled. Both p20 and p21 regulate the G1/S transition of the cell cycle. However, their expression patterns differ, with
p20
predominant in developing brain and peak expression occurring 6 h earlier than
p21
.
p20
expression is also p53-independent in contrast to
p21
regulation. Such differences provide a unique mechanism whereby S phase is set to different times of day in a tissue-specific manner, depending on the balance of these two inhibitors.
Anisotropic particles align perpendicular to the flow direction in narrow microchannels
Authors: Trebbin Martin , Steinhauser Dagmar , Perlich Jan , Buffet Adeline , Roth Stephan V. , Zimmermann Walter , Thiele Julian , Förster Stephan
Published: April 2013

The flow orientation of anisotropic particles through narrow channels is of importance in many fields, ranging from the spinning and molding of fibers to the flow of cells and proteins through thin capillaries. It is commonly assumed that anisotropic particles align parallel to the flow direction. When flowing through narrowed channel sections, one expects the increased flow rate to improve the parallel alignment. Here, we show by microfocus synchrotron X-ray scattering and polarized optical microscopy that anisotropic colloidal particles align perpendicular to the flow direction after passing a narrow channel section. We find this to be a general behavior of anisotropic colloids, which is also observed for disk-like particles. This perpendicular particle alignment is stable, extending downstream throughout the remaining part of the channel. We show by microparticle image velocimetry that the particle reorientation in the expansion zone after a narrow channel section occurs in a region with considerable extensional flow. This extensional flow is promoted by shear thinning, a typical property of complex fluids. Our discovery has important consequences when considering the flow orientation of polymers, micelles, fibers, proteins, or cells through narrow channels, pipes, or capillary sections. An immediate consequence for the production of fibers is the necessity for realignment by extension in the flow direction. For fibrous proteins, reorientation and stable plug flow are likely mechanisms for protein coagulation.
Conserved MIP receptor–ligand pair regulates
Platynereis
larval settlement
Authors: Conzelmann Markus , Williams Elizabeth A. , Tunaru Sorin , Randel Nadine , Shahidi Réza , Asadulina Albina , Berger Jürgen , Offermanns Stefan , Jékely Gáspár
Published: April 2013

Life-cycle transitions connecting larval and juvenile stages in metazoans are orchestrated by neuroendocrine signals including neuropeptides and hormones. In marine invertebrate life cycles, which often consist of planktonic larval and benthic adult stages, settlement of the free-swimming larva to the sea floor in response to environmental cues is a key life cycle transition. Settlement is regulated by a specialized sensory–neurosecretory system, the larval apical organ. The neuroendocrine mechanisms through which the apical organ transduces environmental cues into behavioral responses during settlement are not yet understood. Here we show that myoinhibitory peptide (MIP)/allatostatin-B, a pleiotropic neuropeptide widespread among protostomes, regulates larval settlement in the marine annelid
Platynereis dumerilii
. MIP is expressed in chemosensory–neurosecretory cells in the annelid larval apical organ and signals to its receptor, an orthologue of the
Drosophila
sex peptide receptor, expressed in neighboring apical organ cells. We demonstrate by morpholino-mediated knockdown that MIP signals via this receptor to trigger settlement. These results reveal a role for a conserved MIP receptor–ligand pair in regulating marine annelid settlement.
Neo-sex chromosomes and adaptive potential in tortricid pests
Authors: Nguyen Petr , Sýkorová Miroslava , Šíchová Jindra , Kůta Václav , Dalíková Martina , Čapková Frydrychová Radmila , Neven Lisa G. , Sahara Ken , Marec František
Published: April 2013

Changes in genome architecture often have a significant effect on ecological specialization and speciation. This effect may be further enhanced by involvement of sex chromosomes playing a disproportionate role in reproductive isolation. We have physically mapped the Z chromosome of the major pome fruit pest, the codling moth,Cydia pomonella(Tortricidae), and show that it arose by fusion between an ancestral Z chromosome and an autosome corresponding to chromosome 15 in theBombyx morireference genome. We further show that the fusion originated in a common ancestor of the main tortricid subfamilies, Olethreutinae and Tortricinae, comprising almost 700 pest species worldwide. The Z–autosome fusion brought two major genes conferring insecticide resistance and clusters of genes involved in detoxification of plant secondary metabolites under sex-linked inheritance. We suggest that this fusion significantly increased the adaptive potential of tortricid moths and thus contributed to their radiation and subsequent speciation.
Intercellular trafficking of the nuclear oncoprotein DEK
Authors: Saha Anjan K. , Kappes Ferdinand , Mundade Amruta , Deutzmann Anja , Rosmarin David M. , Legendre Maureen , Chatain Nicolas , Al-Obaidi Zeina , Adams Barbara S. , Ploegh Hidde L. , Ferrando-May Elisa , Mor-Vaknin Nirit , Markovitz David M.
Published: April 2013

DEK is a biochemically distinct, conserved nonhistone protein that is vital to global heterochromatin integrity. In addition, DEK can be secreted and function as a chemotactic, proinflammatory factor. Here we show that exogenous DEK can penetrate cells, translocate to the nucleus, and there carry out its endogenous nuclear functions. Strikingly, adjacent cells can take up DEK secreted from synovial macrophages. DEK internalization is a heparan sulfate-dependent process, and cellular uptake of DEK into DEK knockdown cells corrects global heterochromatin depletion and DNA repair deficits, the phenotypic aberrations characteristic of these cells. These findings thus unify the extracellular and intracellular activities of DEK, and suggest that this paracrine loop involving DEK plays a role in chromatin biology.
Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration
Authors: Karunarathne W. K. Ajith , Giri Lopamudra , Patel Anilkumar K. , Venkatesh Kareenhalli V. , Gautam N.
Published: April 2013

Significance

Here we used a visual blue opsin to induce asymmetric signaling in a cell. The opsin recruited endogenous G proteins and allowed immune cell migration to be optically steered with directional precision. Using this approach, cellular and molecular response dynamics were quantitated to facilitate computational modeling of migration. We identified an ultrasensitive switch-like signaling response that explains how immune cells filter background fluctuations in signals and respond decisively to persistent stimuli. This approach can be widely applied to understand G-protein–coupled receptor-stimulated signaling network control of other cell behaviors and potentially to control cell movements in whole animals.
On the role of surface diffusion in determining the shape or morphology of noble-metal nanocrystals
Authors: Xia Xiaohu , Xie Shuifen , Liu Maochang , Peng Hsin-Chieh , Lu Ning , Wang Jinguo , Kim Moon J. , Xia Younan
Published: April 2013

Controlling the shape or morphology of metal nanocrystals is central to the realization of their many applications in catalysis, plasmonics, and electronics. In one of the approaches, the metal nanocrystals are grown from seeds of certain crystallinity through the addition of atomic species. In this case, manipulating the rates at which the atomic species are added onto different crystallographic planes of a seed has been actively explored to control the growth pattern of a seed and thereby the shape or morphology taken by the final product. Upon deposition, however, the adsorbed atoms (adatoms) may not stay at the same sites where the depositions occur. Instead, they can migrate to other sites on the seed owing to the involvement of surface diffusion, and this could lead to unexpected deviations from a desired growth pathway. Herein, we demonstrated that the growth pathway of a seed is indeed determined by the ratio between the rates for atom deposition and surface diffusion. Our result suggests that surface diffusion needs to be taken into account when controlling the shape or morphology of metal nanocrystals.
Thymoproteasome subunit-β5T generates peptide-MHC complexes specialized for positive selection
Authors: Xing Yan , Jameson Stephen C. , Hogquist Kristin A.
Published: April 2013

Cortical thymic epithelial cells (cTECs) express a unique thymoproteasome subunit-β5T that plays an essential role in the development of CD8 T cells. In contrast, the immunoproteasome subunit-β5i is expressed in other thymic antigen-presenting cells (APCs). The thymoproteasome may generate peptides that are specialized for positive selection, or it may simply serve to generate peptides that are distinct from other APCs that cause negative selection, thereby promoting an overall larger number of surviving clones to mature and function in the immune system. To distinguish these models, we genetically engineered mice to express distinct peptide repertoires in cTECs vs. other APCs without expressing β5T, by generating
β5t

5i

knockin mice, in which β5i replaced β5T in cTECs. When such animals were crossed to
β5i

−/−

mice, β5i was exclusively expressed in cTECs, whereas β5 was expressed in other cells. However, this mouse did not support normal positive selection, suggesting that β5T generates peptides that are intrinsically better for positive selection (i.e., β5i could not replace β5T) and not merely because these peptides are distinct from peptides presented by other APCs. Finally, using an
Nur77

GFP

reporter, we show that the T cells generated in the absence of β5T have higher reactivity to self, generating predominantly CD44
hi
memory phenotype peripheral CD8
+
T cells. Altogether, our results suggest that the thymoproteasome supports positive selection by generating peptides that are optimized for the selection of weakly self-reactive, naïve T-cell clones.