bluuebunny/crossref_metadata_2025 huggingface dataset:
Fire responses to postglacial climate change and human impact in northern Patagonia (41–43°S)
Authors: Iglesias Virginia , Whitlock Cathy
Published: December 2014

Significance

Fire is a key ecological process affecting ecosystem dynamics and services. Fire frequency, intensity, and size reflect complex climate–vegetation–human interactions and their evolution through time. The long-term history of these interactions provides insights into the variability of the ecosystem and a context for future environmental change. We use paleoenvironmental data from the Patagonian forest/steppe border and introduce generalized additive models as trend-detection tools in paleoecology to assess the relative influence of climate, vegetation, and humans in shaping the fire regime. Our results suggest that for the last 18,000 y, fires have been predominantly limited by fuel discontinuity rather than by suitable climate conditions. In contrast to extensive present-day anthropogenic impact, Patagonian ecosystems evolved with minimal human influence prior to European settlement.
Structural basis and dynamics of multidrug recognition in a minimal bacterial multidrug resistance system
Authors: Habazettl Judith , Allan Martin , Jensen Pernille Rose , Sass Hans-Jürgen , Thompson Charles J. , Grzesiek Stephan
Published: December 2014

Significance

Multidrug recognition is an important phenomenon that is not well understood. TipA, a bacterial transcriptional regulator, constitutes a minimal multidrug resistance system against numerous thiopeptide antibiotics. We show that motions in the millisecond to microsecond time range form the basis of the TipA multidrug recognition mechanism. This may be common to many multidrug recognition systems. The discovery that the structural antibiotic motifs essential for binding to TipA and to the ribosome are identical makes the multidrug recognition mechanism of TipA a useful model for ribosomal thiopeptide binding and current antibiotic drug development.
Structural and functional studies of Bud23–Trm112 reveal 18S rRNA
N
7
-G1575 methylation occurs on late 40S precursor ribosomes
Authors: Létoquart Juliette , Huvelle Emmeline , Wacheul Ludivine , Bourgeois Gabrielle , Zorbas Christiane , Graille Marc , Heurgué-Hamard Valérie , Lafontaine Denis L. J.
Published: December 2014

Significance

Ribosomes are essential cellular nanomachines responsible for all protein synthesis in vivo. Efficient and faithful ribosome biogenesis requires a plethora of assembly factors whose precise role and timing of action remains to be established. Here we determined the crystal structure of Bud23–Trm112, which is required for efficient pre-rRNA processing steps leading to 18S rRNA synthesis and methylation of 18S rRNA at position G1575. For the first time, to our knowledge, we identified where on Bud23–Trm112 the contacts with precursor ribosomes occur. We further report that the essential helicase Dhr1 interacts directly with Bud23–Trm112, proposing a concerted action of these proteins in ribosome assembly. Finally, we reveal that the methyltransferase activity of Bud23–Trm112 and its requirement for pre-rRNA processing are disconnected in time.
Robust scaling of strength and elastic constants and universal cooperativity in disordered colloidal micropillars
Authors: Strickland Daniel J. , Huang Yun-Ru , Lee Daeyeon , Gianola Daniel S.
Published: December 2014

Significance

The mechanical response of glassy materials is important in numerous technological and natural processes, yet the link between the embryonic stages of plastic deformation and macroscopic mechanical failure remains elusive. The incipient inelastic rearrangements are believed to be highly cooperative and characterized by a scaling of yield strength and elastic constants. Whether this behavior transcends the nature of bonding is still an open question. Here, we show that disordered colloidal micropillars spanning the spectrum of glassy packing also demonstrate a robust scaling of elastic and plastic properties. Our measured relationship and deduced cooperative rearrangement strains bear striking resemblance to other glassy systems with disparate bonding, implying a universal building block for macroscopic flow.
Wireless gas detection with a smartphone via rf communication
Authors: Azzarelli Joseph M. , Mirica Katherine A. , Ravnsbæk Jens B. , Swager Timothy M.
Published: December 2014

Significance

This paper describes the first example of an adaption of near-field communication (NFC) technology—in 0.5 billion modern smartphones and mobile devices installed in 2014—toward portable, wireless, non-line-of-sight gas phase chemical sensing. We demonstrate the ability to convert inexpensive commercial NFC tags into chemical sensors that detect and discriminate analytes at part-per-thousand and part-per-million concentrations. This effort merges rational design of conductive nanostructured materials for selective chemical sensing with portable and widely distributed NFC technology to deliver a new method of acquiring chemical information about an NFC tag’s local environment. This paper introduces a concept for distributed chemical sensing by the growing number of people that carry NFC-enabled smartphones, tablets, and other smart devices.
Mechanisms of NDV-3 vaccine efficacy in MRSA skin versus invasive infection
Authors: Yeaman Michael R. , Filler Scott G. , Chaili Siyang , Barr Kevin , Wang Huiyuan , Kupferwasser Deborah , Hennessey John P. , Fu Yue , Schmidt Clint S. , Edwards John E. , Xiong Yan Q. , Ibrahim Ashraf S.
Published: December 2014

Significance

Staphylococcus aureus
is an opportunistic pathogen of the normal human flora. It is among the most frequent causes of cutaneous abscesses, leading to life-threatening invasive infection. Incomplete understanding of host defenses against
S. aureus
skin or invasive infection has hindered development of effective vaccines to address these issues. NDV-3 is a unique cross-kingdom vaccine targeting
S. aureus
and
Candida albicans
. The present studies offer important new evidence: (
i
) NDV-3 protects against methicillin-resistant
S. aureus
skin and skin structure infection largely through IL-22– and IL-17A–mediated host defense peptide and neutrophil induction, (
ii
) vaccine-mediated IL-22 and IL-17A play distinct roles in protection against cutaneous versus invasive infection, and (
iii
) NDV-3 vaccine efficacy in this model involves a coordinated induction of innate and adaptive immunity.
Impact of an immune modulator fingolimod on acute ischemic stroke
Authors: Fu Ying , Zhang Ningnannan , Ren Li , Yan Yaping , Sun Na , Li Yu-Jing , Han Wei , Xue Rong , Liu Qiang , Hao Junwei , Yu Chunshui , Shi Fu-Dong
Published: December 2014

Significance

In patients with acute ischemic stroke (AIS), the abrupt and massive influx of lymphocytes from the periphery to the ischemic region orchestrates focal inflammatory responses, catalyzes tissue death, and worsens clinical outcomes. In this early phase clinical study, we reduced lymphocyte migration to the brain during the first 72 h of AIS via oral administration of three doses of fingolimod. This administration led to a significant reduction of secondary lesion enlargement, microvascular permeability, and better clinical outcomes during the acute phase and 3-mo follow-up visit. This study will provoke new investigations on the efficacy of modulation of brain inflammation in AIS.
Fibroblasts secrete Slit2 to inhibit fibrocyte differentiation and fibrosis
Authors: Pilling Darrell , Zheng Zhichao , Vakil Varsha , Gomer Richard H.
Published: December 2014

Significance

A key question in fibrosing diseases is why monocytes do not become fibrocytes in healthy tissues but can become fibrocytes in fibrotic lesions. We show that fibroblasts secrete a signal that inhibits the differentiation of monocytes into fibrocytes. We identify the signal as Slit2 and show that Slit2 levels are low in fibrotic lesions. We also show that injection of Slit2 prevents fibrosis in a mouse model of lung fibrosis. The identification of Slit2 as a key signal in normal tissues that prevents entering monocytes from becoming fibrocytes represents a major advance in our understanding of the regulation of the innate immune system and how fibrosis propagates, as well as a potential novel therapeutic for fibrosis.
Context-dependent incremental timing cells in the primate hippocampus
Authors: Sakon John J. , Naya Yuji , Wirth Sylvia , Suzuki Wendy A.
Published: December 2014

Significance

Episodic memory refers to the ability to recall specifics of past events in our lives. An essential aspect of events is timing when things occur during an episode. A number of recent studies have shown that the hippocampus, a structure known to be essential to form episodic memories, possesses neurons that explicitly mark moments in time. We add a previously unidentified finding to this work by showing that individual primate hippocampal neurons not only track time, but do so only when specific contextual information (e.g., object identity/location) is cued. These time context-sensitive neurons represent a novel way in which the brain unites disparate streams that comprise an episode and will aid in our understanding of how we store and retrieve episodic memories.
Impact of Antarctic mixed-phase clouds on climate
Authors: Lawson R. Paul , Gettelman Andrew
Published: December 2014

Significance

Polar regions are foci of climate change, because of more-than-expected warming, problematic remote-sensing retrievals, and large uncertainties about cloud effects on radiation budgets. Antarctica is the world’s most remote, coldest, and driest location. Until recently, researchers have assumed that low-level clouds over the frozen Antarctic Plateau consist mainly of ice crystals. Now, measurements with a unique tethered balloon system and a ground-based lidar show that nearly 50% of clouds in the austral summer contain supercooled water which has a significant impact on the radiative properties of Antarctic clouds. Modifying a global climate model to relax the freezing below −20 °C results in a strong simulated radiative (cooling) effect, affecting the entire Antarctic Continent and extending out into the Southern Ocean.
Microbial biosynthesis of medium-chain 1-alkenes by a nonheme iron oxidase
Authors: Rui Zhe , Li Xin , Zhu Xuejun , Liu Joyce , Domigan Bonnie , Barr Ian , Cate Jamie H. D. , Zhang Wenjun
Published: December 2014

Significance

We have solved a long-standing mystery of the biosynthetic origin of 1-undecene, a ubiquitous hydrocarbon semivolatile metabolite of
Pseudomonas
. Our study revealed an unprecedented family of nonheme oxidases that specifically convert medium-chain fatty acids into the corresponding terminal olefins using an oxygen-activating, nonheme iron-dependent mechanism. Our findings unveil previously unidentified chemistry in the nonheme Fe(II) enzyme family, aid the functional study of this ubiquitous metabolite in
Pseudomonas
, expand the scarce enzyme inventory for the transformation of fatty acid precursors to hydrocarbons, and serve as the basis for engineering efforts to establish bioprocesses to produce medium-chain terminal olefins, useful as fuels and chemical building blocks, from renewable resources.
αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors
Authors: Devesa Isabel , Ferrándiz-Huertas Clotilde , Mathivanan Sakthikumar , Wolf Christoph , Luján Rafael , Changeux Jean-Pierre , Ferrer-Montiel Antonio
Published: December 2014

Significance

Pain is a societal burden with enormous economic and social costs. More than 50% of pain patients find current therapies unsatisfactory. A major reason for this pharmacological failure is our limited understanding of the cellular processes underlying pain. Algesic sensitization of nociceptors is a complex event in pain transduction that involves the potentiation of thermosensory channels. The molecular mechanisms remain controversial because of nociceptor heterogeneity that suggests the existence of cell-type–specific strategies. We show that algesic sensitization of transient receptor potential vanilloid 1 (TRPV1) involves the exocytotic recruitment of new receptors in peptidergic nociceptors and the modulation of channel gating in nonpeptidergic sensory neurons. Furthermore, algesic delivery of TRPV1 channels is concomitant with pro-inflammatory neuropeptide secretion, ensuring rapid modulation of pain transduction.
Overexpression of Q-rich prion-like proteins suppresses polyQ cytotoxicity and alters the polyQ interactome
Authors: Ripaud Leslie , Chumakova Victoria , Antonin Matthias , Hastie Alex R. , Pinkert Stefan , Körner Roman , Ruff Kiersten M. , Pappu Rohit V. , Hornburg Daniel , Mann Matthias , Hartl F. Ulrich , Hipp Mark S.
Published: December 2014

Significance

Expansion of a poly-glutamine (polyQ) repeat is the causal mutation of several inherited neurological disorders, including Huntington’s disease. In a yeast genetic screen, we identified several proteins with Q-rich, prion-like domains that reduce the toxicity of mutant polyQ proteins when overexpressed. One of these, glycine threonine serine repeat protein (Gts1p), was characterized in more detail. Association with Gts1p did not prevent aggregation but altered the physical properties and the interactome of the aggregates. Specifically, Gts1p expression reduced the sequestration of other prion-like proteins into the polyQ aggregates. These findings link polyQ toxicity in yeast with the coaggregation of prion proteins and show that short Q-rich peptides are able to shield toxic forms of polyQ proteins, directing them into nontoxic aggregates.
GATA2 facilitates steroid receptor coactivator recruitment to the androgen receptor complex
Authors: He Bin , Lanz Rainer B. , Fiskus Warren , Geng Chuandong , Yi Ping , Hartig Sean M. , Rajapakshe Kimal , Shou John , Wei Liping , Shah Shrijal S. , Foley Christopher , Chew Sue Anne , Eedunuri Vijay K. , Bedoya Diego J. , Feng Qin , Minami Takashi , Mitsiades Constantine S. , Frolov Anna , Weigel Nancy L. , Hilsenbeck Susan G. , Rosen Daniel G. , Palzkill Timothy , Ittmann Michael M. , Song Yongcheng , Coarfa Cristian , O’Malley Bert W. , Mitsiades Nicholas
Published: December 2014

Significance

Androgen receptor (AR) signaling is a key driver of prostate cancer (PC), even in the context of resistance to current therapies, creating an unmet need for novel approaches to inhibit AR. We demonstrate that the transcription factor GATA-binding protein 2 (GATA2) is critical for both AR expression and optimal transcriptional activity. GATA2 colocalizes with AR and Forkhead box protein A1 on chromatin to enhance recruitment of steroid receptor coactivators and formation of the transcriptional holocomplex. A GATA2 inhibitor suppressed the expression and transcriptional function of AR (including the constitutively active splice variants) and exerted potent anticancer activity against PC cells. We propose GATA2 inhibition as a previously unexplored approach to extinguish both ligand-dependent and ligand-independent AR transcriptional activity and to improve clinical outcomes for PC patients.
Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation
Authors: Qin Yong Jie , Chan Sun On , Chong Kelvin Kam Lung , Li Benjamin Fuk Loi , Ng Tsz Kin , Yip Yolanda Wong Ying , Chen Haoyu , Zhang Mingzhi , Block Norman L. , Cheung Herman S. , Schally Andrew V. , Pang Chi Pui
Published: December 2014

Significance

We have shown that the growth hormone-releasing hormone–growth hormone–insulin-like growth factor-1 (GHRH–GH–IGF1) axis is involved in experimentally induced acute inflammation in the iris and ciliary body, where its activation is associated with inflammatory responses. Blocking GHRH–GH–IGF1 axis activity by the GHRH receptor (GHRH-R) antagonist is effective in alleviating inflammatory responses. These findings demonstrate a novel activity of GHRH–GH–IGF1 axis signaling in ocular inflammation and suggest a potential therapeutic application of GHRH-R antagonist.
Nucleoporin MOS7/Nup88 is required for mitosis in gametogenesis and seed development in
Arabidopsis
Authors: Park Guen Tae , Frost Jennifer M. , Park Jin-Sup , Kim Tae Ho , Lee Jong Seob , Oh Sung Aeong , Twell David , Brooks Janie Sue , Fischer Robert L. , Choi Yeonhee
Published: December 2014

Significance

During plant reproduction, meiosis generates haploid spores that undergo mitoses, forming gametophytes, in male and female parts of the flower. Haploid cells within gametophytes differentiate into sperm and eggs, which form the next generation. We discovered that the
MOS7
(Modifier of Snc1,7) gene plays a critical role in microtubule organization and dynamics during mitosis in
Arabidopsis
sexual reproduction. MOS7 absence results in impaired gametogenesis, failure of ovule and pollen development, and seed abortion. Although mitoses during gamete formation are unique to plants, the regulation of mitosis itself is highly conserved between plants and vertebrates. Notably, we find that MOS7 protein primarily produced prior to meiosis is inherited by gametophytes, and, only if there is sufficient MOS7 protein, will mitosis correctly occur during gametogenesis.
Emergence of superconductivity in heavy-electron materials
Authors: Yang Yi-feng , Pines David
Published: December 2014

Significance

Although the pairing glue for the unconventional superconductivity found in heavy-electron materials has been identified as quantum critical spin fluctuations associated with their proximity to antiferromagnetic order, until now we have lacked a simple expression for their superconducting transition temperature,
T

c

, that explains why
T

c

changes with pressure, or varies from one material to another. The experiment-based expression proposed here parameterizes the effective frequency-dependent quasiparticle interactions in terms of their unusual normal-state properties; it provides a quantitative explanation of the measured pressure-induced variation in
T

c

in the “hydrogen atoms” of unconventional superconductivity, CeCoIn
5
and CeRhIn
5
, predicts a similar pressure variation for other heavy-electron quantum critical superconductors, and quantifies their variations in
T

c

with a single parameter.
The influence of playing surface on physiological and performance responses during and after soccer simulation
Authors: Stone Keeron J. , Hughes Michael G. , Stembridge Michael R. , Meyers Robert W. , Newcombe Daniel J. , Oliver Jon L.
Published: December 2014

The aim of this study was to investigate the effect of playing surface on physiological and performance responses during and in the 48 h after simulated soccer match play. Blood lactate, single‐sprint, repeated‐sprint and agility of eight amateur soccer players were assessed throughout a 90‐min soccer‐simulation protocol (SSP) completed on natural turf (NT) and artificial turf. Counter‐movement jump, multiple‐rebound jump, sprint (10 m, 60 m), L‐agility run (L‐AR), creatine kinase (CK) and perception of muscle soreness (PMS) were measured before, immediately after, 24 h and 48 h after exercise. Analyses revealed significant changes in blood lactate and single‐sprint performance (both P < 0.05) during the SSP but with no significant differences between surfaces. Conversely, repeated‐sprint performance demonstrated an interaction effect, with reductions in performance evident on NT only (P < 0.05). Whilst L‐AR and 10‐m sprint performance remained unchanged, 60‐m sprint and multiple‐rebound jump performance were impaired, and PMS and CK were elevated immediately following the SSP (all P < 0.05) but with no surface effects. Although performance, CK and PMS were negatively affected to some degree in the 48 h after the SSP, there was no surface effect. For the artificial and natural surfaces used in the present study, physiological and performance responses to simulated soccer match play appear to be similar. Whilst a potential for small differences in performance response exists during activity, surface type does not affect the pattern of recovery following simulated match play.
The development and validation of the Interpersonal Support in Physical Activity Consultations Observational Tool
Authors: Rouse Peter C. , Duda Joan L. , Ntoumanis Nikos , Jolly Kate , Williams Geoffrey C.
Published: December 2014

This study describes the development and psychometric characteristics of an observational instrument that examines four aspects of interpersonal support (or lack of) provided during physical activity (PA) promotion consultations (i.e., Autonomy Support, Involvement, Structure and Interpersonal Control), as identified by Self‐determination Theory (SDT). The reliability and validity of the Interpersonal Support in Physical Activity Consultations Observational Tool (ISPACOT) were examined within an exploratory randomised control trial. Recorded consultations (N = 42) conducted by qualified PA advisors (N = 14) at 13 leisure centres across the West Midlands (UK) were rated. Intra‐class correlation coefficients (ICC) indicated moderate to high inter‐rater reliability for overall interpersonal support (0.80), and the Autonomy Support (0.74), Involvement (0.73) and Structure (0.91) dimensions, but low reliability for Interpersonal Control (0.35). The advisors, who conducted PA promotion consultations that were rated as low in their interpersonally supportive features, were perceived by their clients as being less supportive (F(1,10) = 5.0, p <.05). Ratings on the ISPACOT differentiated advisors who were trained in SDT principles and those who were not. Overall, the findings provided preliminary evidence for the reliability and convergent validity of the ISPACOT.
Deformation of hyperbolic manifolds in 𝑃𝐺𝐿(𝑛,𝐂) and discreteness of the peripheral representations
Authors: Guilloux Antonin
Published: December 2014

Let

M
M

be a cusped hyperbolic

3
3

-manifold, e.g. a knot complement. Thurston showed that the space of deformations of its fundamental group in

P
G
L

(
2
,

C

)

\mathrm {PGL}(2,\mathbf {C})

(up to conjugation) is of complex dimension the number

ν
\nu

of cusps near the hyperbolic representation. It seems natural to ask whether some representations remain discrete after deformation. The answer is generically not. A simple reason for it lies inside the cusps: the degeneracy of the peripheral representation (i.e. representations of fundamental groups of the

ν
\nu

peripheral tori). They indeed generically become non-discrete, except for a countable set. This last set corresponds to hyperbolic Dehn surgeries on

M
M

, for which the peripheral representation is no more faithful.

We work here in the framework of

P
G
L

(
n
,

C

)

\mathrm {PGL}(n,\mathbf {C})

. The hyperbolic structure lifts, via the

n
n

-dimensional irreducible representation, to a representation

ρ

g
e
o
m

\rho _{\mathrm {geom}}

. We know from the work of Menal-Ferrer and Porti that the space of deformations of

ρ

geom

\rho _{\textrm {geom}}

has complex dimension

(
n
−
1
)
ν

(n-1)\nu

.

We prove here that, unlike the

P
G
L

(
2
)

\mathrm {PGL}(2)

-case, the generic behaviour becomes the discreteness (and faithfulness) of the peripheral representation: in a neighbourhood of the geometric representation, the non-discrete peripheral representations are contained in a real analytic subvariety of codimension

≥
1

\geq 1

.
Prokinetics Prescribing in Paediatrics
Authors: Mt‐Isa Shahrul , Tomlin Stephen , Sutcliffe Alastair , Underwood Martin , Williamson Paula , Croft Nicholas M. , Ashby Deborah
Published: December 2014

Objectives:

Domperidone and metoclopramide are prokinetics commonly prescribed off‐label to infants and younger children in an attempt to treat gastro‐oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children.

Methods:

We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case–control studies.

Results:

The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10‐fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified.

Conclusions:

These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good‐quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies.
Ancient mitochondrial DNA from the northern fringe of the Neolithic farming expansion in Europe sheds light on the dispersion process
Authors: Malmström Helena , Linderholm Anna , Skoglund Pontus , Storå Jan , Sjödin Per , Gilbert M. Thomas P. , Holmlund Gunilla , Willerslev Eske , Jakobsson Mattias , Lidén Kerstin , Götherström Anders
Published: December 2014

The European Neolithization process started around 12 000 years ago in the Near East. The introduction of agriculture spread north and west throughout Europe and a key question has been if this was brought about by migrating individuals, by an exchange of ideas or a by a mixture of these. The earliest farming evidence in Scandinavia is found within the Funnel Beaker Culture complex (Trichterbecherkultur, TRB) which represents the northernmost extension of Neolithic farmers in Europe. The TRB coexisted for almost a millennium with hunter–gatherers of the Pitted Ware Cultural complex (PWC). If migration was a substantial part of the Neolithization, even the northerly TRB community would display a closer genetic affinity to other farmer populations than to hunter–gatherer populations. We deep-sequenced the mitochondrial hypervariable region 1 from seven farmers (six TRB and one Battle Axe complex, BAC) and 13 hunter–gatherers (PWC) and authenticated the sequences using postmortem DNA damage patterns. A comparison with 124 previously published sequences from prehistoric Europe shows that the TRB individuals share a close affinity to Central European farmer populations, and that they are distinct from hunter–gatherer groups, including the geographically close and partially contemporary PWC that show a close affinity to the European Mesolithic hunter–gatherers.
Paging through history: parchment as a reservoir of ancient DNA for next generation sequencing
Authors: Teasdale M. D. , van Doorn N. L. , Fiddyment S. , Webb C. C. , O'Connor T. , Hofreiter M. , Collins M. J. , Bradley D. G.
Published: December 2014

Parchment represents an invaluable cultural reservoir. Retrieving an additional layer of information from these abundant, dated livestock-skins via the use of ancient DNA (aDNA) sequencing has been mooted by a number of researchers. However, prior PCR-based work has indicated that this may be challenged by cross-individual and cross-species contamination, perhaps from the bulk parchment preparation process. Here we apply next generation sequencing to two parchments of seventeenth and eighteenth century northern English provenance. Following alignment to the published sheep, goat, cow and human genomes, it is clear that the only genome displaying substantial unique homology is sheep and this species identification is confirmed by collagen peptide mass spectrometry. Only 4% of sequence reads align preferentially to a different species indicating low contamination across species. Moreover, mitochondrial DNA sequences suggest an upper bound of contamination at 5%. Over 45% of reads aligned to the sheep genome, and even this limited sequencing exercise yield 9 and 7% of each sampled sheep genome post filtering, allowing the mapping of genetic affinity to modern British sheep breeds. We conclude that parchment represents an excellent substrate for genomic analyses of historical livestock.
Ancient and modern environmental DNA
Authors: Pedersen Mikkel Winther , Overballe-Petersen Søren , Ermini Luca , Sarkissian Clio Der , Haile James , Hellstrom Micaela , Spens Johan , Thomsen Philip Francis , Bohmann Kristine , Cappellini Enrico , Schnell Ida Bærholm , Wales Nathan A. , Carøe Christian , Campos Paula F. , Schmidt Astrid M. Z. , Gilbert M. Thomas P. , Hansen Anders J. , Orlando Ludovic , Willerslev Eske
Published: December 2014

DNA obtained from environmental samples such as sediments, ice or water (environmental DNA, eDNA), represents an important source of information on past and present biodiversity. It has revealed an ancient forest in Greenland, extended by several thousand years the survival dates for mainland woolly mammoth in Alaska, and pushed back the dates for spruce survival in Scandinavian ice-free refugia during the last glaciation. More recently, eDNA was used to uncover the past 50 000 years of vegetation history in the Arctic, revealing massive vegetation turnover at the Pleistocene/Holocene transition, with implications for the extinction of megafauna. Furthermore, eDNA can reflect the biodiversity of extant flora and fauna, both qualitatively and quantitatively, allowing detection of rare species. As such, trace studies of plant and vertebrate DNA in the environment have revolutionized our knowledge of biogeography. However, the approach remains marred by biases related to DNA behaviour in environmental settings, incomplete reference databases and false positive results due to contamination. We provide a review of the field.
Ancient genomics
Authors: Der Sarkissian Clio , Allentoft Morten E. , Ávila-Arcos María C. , Barnett Ross , Campos Paula F. , Cappellini Enrico , Ermini Luca , Fernández Ruth , da Fonseca Rute , Ginolhac Aurélien , Hansen Anders J. , Jónsson Hákon , Korneliussen Thorfinn , Margaryan Ashot , Martin Michael D. , Moreno-Mayar J. Víctor , Raghavan Maanasa , Rasmussen Morten , Velasco Marcela Sandoval , Schroeder Hannes , Schubert Mikkel , Seguin-Orlando Andaine , Wales Nathan , Gilbert M. Thomas P. , Willerslev Eske , Orlando Ludovic
Published: December 2014

The past decade has witnessed a revolution in ancient DNA (aDNA) research. Although the field's focus was previously limited to mitochondrial DNA and a few nuclear markers, whole genome sequences from the deep past can now be retrieved. This breakthrough is tightly connected to the massive sequence throughput of next generation sequencing platforms and the ability to target short and degraded DNA molecules. Many ancient specimens previously unsuitable for DNA analyses because of extensive degradation can now successfully be used as source materials. Additionally, the analytical power obtained by increasing the number of sequence reads to billions effectively means that contamination issues that have haunted aDNA research for decades, particularly in human studies, can now be efficiently and confidently quantified. At present, whole genomes have been sequenced from ancient anatomically modern humans, archaic hominins, ancient pathogens and megafaunal species. Those have revealed important functional and phenotypic information, as well as unexpected adaptation, migration and admixture patterns. As such, the field of aDNA has entered the new era of genomics and has provided valuable information when testing specific hypotheses related to the past.
Evaluating intra- and inter-individual variation in the human placental transcriptome
Authors: Hughes David A , Kircher Martin , He Zhisong , Guo Song , Fairbrother Genevieve L , Moreno Carlos S , Khaitovich Philipp , Stoneking Mark
Published: December 2014

Background: Gene expression variation is a phenotypic trait of particular interest as it represents the initial link between genotype and other phenotypes. Analyzing how such variation apportions among and within groups allows for the evaluation of how genetic and environmental factors influence such traits. It also provides opportunities to identify genes and pathways that may have been influenced by non-neutral processes. Here we use a population genetics framework and next generation sequencing to evaluate how gene expression variation is apportioned among four human groups in a natural biological tissue, the placenta. Results: We estimate that on average, 33.2%, 58.9% and 7.8% of the placental transcriptome is explained by variation within individuals, among individuals and among human groups, respectively. Additionally, when technical and biological traits are included in models of gene expression they account for roughly 2% of total gene expression variation. Notably, the variation that is significantly different among groups is enriched in biological pathways associated with immune response, cell signaling and metabolism. Many biological traits demonstrated correlated changes in expression in numerous pathways of potential interest to clinicians and evolutionary biologists. Finally, we estimate that the majority of the human placental transcriptome (65% of expressed genes) exhibits expression profiles consistent with neutrality; the remainder are consistent with stabilizing selection (26%), directional selection (4.9%), or diversifying selection (4.8%). Conclusion: We apportion placental gene expression variation into individual, population and biological trait factors and identify how each influence the transcriptome. Additionally, we advance methods to associate expression profiles with different forms of selection.
A Wheat CCAAT Box-Binding Transcription Factor Increases the Grain Yield of Wheat with Less Fertilizer Input
Authors: Qu Baoyuan , He Xue , Wang Jing , Zhao Yanyan , Teng Wan , Shao An , Zhao Xueqiang , Ma Wenying , Wang Junyi , Li Bin , Li Zhensheng , Tong Yiping
Published: December 2014

Increasing fertilizer consumption has led to low fertilizer use efficiency and environmental problems. Identifying nutrient-efficient genes will facilitate the breeding of crops with improved fertilizer use efficiency. This research performed a genome-wide sequence analysis of the A (NFYA), B (NFYB), and C (NFYC) subunits of Nuclear Factor Y (NF-Y) in wheat (Triticum aestivum) and further investigated their responses to nitrogen and phosphorus availability in wheat seedlings. Sequence mining together with gene cloning identified 18 NFYAs, 34 NFYBs, and 28 NFYCs. The expression of most NFYAs positively responded to low nitrogen and phosphorus availability. In contrast, microRNA169 negatively responded to low nitrogen and phosphorus availability and degraded NFYAs. Overexpressing TaNFYA-B1, a low-nitrogen- and low-phosphorus-inducible NFYA transcript factor on chromosome 6B, significantly increased both nitrogen and phosphorus uptake and grain yield under differing nitrogen and phosphorus supply levels in a field experiment. The increased nitrogen and phosphorus uptake may have resulted from the fact that that overexpressing TaNFYA-B1 stimulated root development and up-regulated the expression of both nitrate and phosphate transporters in roots. Our results suggest that TaNFYA-B1 plays essential roles in root development and in nitrogen and phosphorus usage in wheat. Furthermore, our results provide new knowledge and valuable gene resources that should be useful in efforts to breed crops targeting high yield with less fertilizer input.
Direct nano-scale patterning of Ag films using hard X-ray induced oxidation
Authors: Kim Jae Myung , Lee Su Yong , Kang Hyon Chol , Noh Do Young
Published: December 2014

The morphological change of silver nano-particles (AgNPs) exposed to an intense synchrotron X-ray beam was investigated for the purpose of direct nano-scale patterning of metal thin films. AgNPs irradiated by hard X-rays in oxygen ambient were oxidized and migrated out of the illuminated region. The observed X-ray induced oxidation was utilized to fabricate nano-scale metal line patterns using sectioned WSi2/Si multilayers as masks. Lines with a width as small as 21 nm were successfully fabricated on Ag films on silicon nitride. Au/Ag nano-lines were also fabricated using the proposed method.
On substituted pyrazole derivatives. II. (E)-1-(4-{[1-(4-Fluorophenyl)-3,5-dimethyl-1H-pyrazol-4-yl]diazenyl}phenyl)ethanone and (E)-1-(4-chlorophenyl)-3,5-dimethyl-4-[2-(2-nitrophenyl)diazenyl]-1H-pyrazole
Authors: Bustos Carlos , Alvarez-Thon Luis , Oportus Tania , Mesías-Salazar Angela , Baggio Ricardo
Published: December 2014

The molecular structures of (E)-1-(4-{[1-(4-fluorophenyl)-3,5-dimethyl-1H-pyrazol-4-yl]diazenyl}phenyl)ethanone, C19H17FN4O, (III), and (E)-1-(4-chlorophenyl)-3,5-dimethyl-4-[2-(2-nitrophenyl)diazenyl]-1H-pyrazole, C17H14ClN5O2, (IV), prepared by reaction of the corresponding β-diketohydrazones with substituted arylhydrazines in acid media, are nonplanar, with the planes of the lateral phenyl rings forming dihedral angles with that of the central pyrazole ring varying from 2.71 (7) to 45.22 (7)°. The crystal structures are supported by C—H...O, C—H...π and π–π weak intermolecular interactions together with some unusual trifurcated C—Cl...Cl—C contacts, which are discussed in detail.
A new tetragonal structure type for Li2B2C
Authors: Pavlyuk Volodymyr , Milashys Viktoriya , Dmytriv Grygoriy , Ehrenberg Helmut
Published: December 2014

The ternary dilithium diboron carbide, Li2B2C (tetragonal, space groupP\overline{4}m2,tP10), crystallizes as a new structure type and consists of structural fragments which are typical for structures of elemental lithium and boron or binary borocarbide B13C2. The symmetries of the occupied sites are .m. and 2mm. for the B and C atoms, and \overline{4}m2 and 2mm. for the Li atoms. The coordination polyhedra around the Li atoms are cuboctahedra and 15-vertex distorted pseudo-Frank–Kasper polyhedra. The environment of the B atom is a ten-vertex polyhedron. The nearest neighbours of the C atom are two B atoms, and this group is surrounded by a deformed cuboctahedron with one centred lateral facet. Electronic structure calculations using the TB–LMTO–ASA method reveal strong B...C and B...B interactions.
Structure and magnetic properties of a mixed-ligand copper(II) complex
Authors: Lin Rong-Guang , Wang Yu-Lin , Liang Qian
Published: December 2014

The hydrothermal synthesis of the novel complex poly[[μ2-N1,N4-bis(pyridin-3-yl)naphthalene-1,4-dicarboxamide-κ2N3:N3′](μ4-phthalato-κ4O1:O1:O1′:O2′)copper(II)], [Cu(C8H4O4)(C22H16N4O2)]n, is described. With the phthalate ligand connecting neighbouring CuIIcations, an infinite one-dimensional chain is formed. Adjacent one-dimensional chains are connected by the dicarboxamide ligand, forming an intriguing two-dimensional framework. The magnetic properties and thermal stability of this complex are also described.
Crystallographic investigations of select cathinones: emerging illicit street drugs known as `bath salts'
Authors: Wood Matthew R. , Lalancette Roger A. , Bernal Ivan
Published: December 2014

The name `bath salts', for an emerging class of synthetic cathinones, is derived from an attempt to evade prosecution and law enforcement. These are truly illicit drugs that have psychoactive CNS (central nervous system) stimulant effects and they have seen a rise in abuse as recreational drugs in the last few years since first having been seen in Japan in 2006. The ease of synthesis and modification of specific functional groups of the parent cathinone make these drugs particularly difficult to regulate. MDPV (3,4-methylenedioxypyrovalerone) is commonly encountered as its hydrochloride salt (C16H21NO3·HCl), in either the hydrated or the anhydrous forms. This `bath salt' has various names in the US,e.g.`Super Coke', `Cloud Nine', and `Ivory Wave', to name just a few. We report here the structures of two forms of the HCl salt, one as a mixed bromide/chloride salt, C16H22NO3+·0.343Br−·0.657Cl−[systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide/chloride (0.343/0.657)], and the other with the H7O3+cation, as well as the HCl counter-ion [systematic name: hydroxonium 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one dichloride, H7O3+·C16H22NO3+·2Cl−]. This is one of a very few structures (11 to be exact) in which we have a new example of a precisely determined hydroxonium cation. During the course of researching the clandestine manufacture of MDPV, we were surprised by the fact that a common precursor of this illicit stimulant is known to be the fragrant species piperonal, which is present in the fragrances of orchids, most particularly in the case of the vanilla orchid. We found that MDPV can be made by a Grignard reaction of this heliotropin. This may also explain the unexpected appearance of the bromide counter-ion in some of the salts we encountered (C16H21NO3·HBr), one of which is presented here [systematic name: 1-(benzo[d][1,3]dioxol-5-yl)-2-(pyrrolidin-1-ium-1-yl)pentan-1-one bromide, C16H22NO3+·Br−]. Complexation of MDPV with a forensic crystallizing reagent, HAuCl4, yields the tetrachloridoaurate salt of this drug, (C16H22NO3)[AuCl4]. The heavy-metal complexing agent HAuCl4has been used for over a century to identify common quarternary nitrogen-containing drugsviamicroscopic identification. Another street drug, called ethylone (3,4-methylenedioxyethylcathinone), is regularly sold and abused as its hydrochloride salt (C12H15NO3·HCl), and its structure is herein described (systematic name:N-{1-[(benzo[d][1,3]dioxol-5-yl)carbonyl]ethyl}ethanaminium chloride, C12H16NO3+·Cl−). Marketed and sold as a `bath salt', `plant feeder', or `cleaning product', this drug is nothing more than a slight chemical modification of the banned drug methylone (3,4-methylenedioxymethcathinone). As with previously popular synthetic cathinones, the abuse of ethylone has seen a recent increase due to regulatory efforts on previous generations of cathinones that are now banned.
Two novel organic–inorganic hybrid materials from tetrachloridometallate(II) salts and 4-[(E)-2-(pyridin-1-ium-2-yl)ethenyl]pyridinium
Authors: Campos-Gaxiola José J. , Arredondo Rea Susana P. , Corral Higuera Ramón , Höpfl Herbert , Cruz Enríquez Adriana
Published: December 2014

Two organic–inorganic hybrid compounds have been prepared by the combination of the 4-[(E)-2-(pyridin-1-ium-2-yl)ethenyl]pyridinium cation with perhalometallate anions to give 4-[(E)-2-(pyridin-1-ium-2-yl)ethenyl]pyridinium tetrachloridocobaltate(II), (C12H12N2)[CoCl4], (I), and 4-[(E)-2-(pyridin-1-ium-2-yl)ethenyl]pyridinium tetrachloridozincate(II), (C12H12N2)[ZnCl4], (II). The compounds have been structurally characterized by single-crystal X-ray diffraction analysis, showing the formation of a three-dimensional network throughX—H...ClnM−(X= C, N+;n= 1, 2;M= CoII, ZnII) hydrogen-bonding interactions and π–π stacking interactions. The title compounds were also characterized by FT–IR spectroscopy and thermogravimetric analysis (TGA).
Crystal structure of 8-[7,8-bis(4-chlorobenzoyl)-7H-cyclopenta[a]acenaphthylen-9-yl]naphthalene-1-carboxylic acid
Authors: Jacob Jomon P. , Sithambaresan M. , Kunjachan Christy , Kurup M. R. Prathapachandra
Published: December 2014

The title compound, C40H22Cl2O4, was formed by a Michael–Aldol domino reaction sequence, which coupled acenaphthenequinone with 4-chloroacetophenone in the presence of KOH in methanol. The dihedral angles between the central cyclopenta[a]acenaphthylene fused-ring system (r.m.s. deviation = 0.066 Å) and the 4-chlorobenzoyl rings are 62.25 (10) and 70.19 (10)°. The dihedral angle between the central ring system and the naphthoic acid grouping is 62.46 (7)°. This twisting of the pendant rings facilitates the formation of an intramolecular aromatic π–π stacking interaction between the 4-chlorobenzoyl and naphthoic acid rings, with centroid–centroid distances of 3.4533 (16) and 3.5311 (16) Å, and a C—H...π interaction between one of the H atoms of the central moiety and the 4-chlorobenzoyl ring with an H...π distance of 2.57 Å. In the crystal, carboxylic acid inversion dimers generateR22(8) loops. The dimers are linked by weak C—H...O and C—H...Cl hydrogen bonds and C—H...π interactions, generating a three-dimensional architecture.
Crystal structure ofcis-bis(μ-β-alanine-κ2O:O′)bis[trichloridorhenium(III)](Re–Re) sesquihydrate
Authors: Golichenko Alexander A. , Domasevitch Konstantin V. , Kytova Dina E. , Shtemenko Alexander V.
Published: December 2014

The structure of the title compound, [Re2Cl6(C3H7NO2)2]·1.5H2O, comprises a dinuclear complex cation [Re—Re = 2.2494 (3) Å] involvingcis-oriented double carboxylate bridges, four equatorial chloride ions and two weakly bonded chloride ligands in the axial positions at the two rhenium(III) atoms. In the crystal, two complex molecules and two water molecules constitute hydrogen-bonded dimers, while an extensive hydrogen-bonding network involving the groups of the zwitterionic ligand is important for generation of the framework. An additional partially occupied water molecule is disordered over two sets of sites about a symmetry centre with a site-occupancy ratio of 0.3:0.2.
Antioxidant soybean tar Glyteer rescues T‐helper‐mediated downregulation of filaggrin expression via aryl hydrocarbon receptor
Authors: Takei Kenjiro , Mitoma Chikage , Hashimoto‐Hachiya Akiko , Uchi Hiroshi , Takahara Masakazu , Tsuji Gaku , Kido‐Nakahara Makiko , Nakahara Takeshi , Furue Masutaka
Published: December 2014

Soybean tar Glyteer (Gly) has been widely used for the treatment of various inflammatory skin diseases in Japan since 1924 as an alternative to coal tar remedy. Recently, coal tar has been shown to induce barrier repair in atopic dermatitis via aryl hydrocarbon receptor (AhR). In this study, we demonstrated that Gly activated AhR by inducing its cytoplasmic to nuclear translocation in keratinocytes. The AhR ligation by Gly was biologically active, with significant and dose‐dependent upregulation of CYP1A1 expression, which is a specific marker for AhR activation. Gly upregulated the expression of filaggrin in an AhR‐dependent manner because its enhancing effect was completely abrogated in AhR‐knockdown keratinocytes. T‐helper (Th)2 cytokines inhibited the expression of filaggrin; however, Gly completely restored the Th2‐mediated inhibition of filaggrin expression. Furthermore, Gly coordinately upregulated a series of epidermal differentiation complex genes, including involucrin, loricrin and hornerin. In addition, Gly exhibited potent antioxidant activity through the activation of nuclear factor‐erythroid 2‐related factor‐2 (Nrf2) and downstream antioxidant enzymes such as NAD(P)H:quinone oxidoreductase 1 (Nqo1), which actually inhibited the generation of reactive oxygen species in keratinocytes treated with tumor necrosis factor‐α or benzo[α]pyrene. In conclusion, antioxidant Gly rescues the downregulated expression of filaggrin (and plausibly other barrier proteins) in a Th2‐skewed milieu via AhR activation, which may partly explain its empirical anti‐inflammatory therapeutic effects.