bluuebunny/crossref_metadata_2025 huggingface dataset:
Growth control of Saccharomyces cerevisiae through dose of oxygen atoms
Authors: Hashizume Hiroshi , Ohta Takayuki , Hori Masaru , Ito Masafumi
Published: September 2015

To investigate the dose-dependent effects of neutral oxygen radicals on the proliferation as well as the inactivation of microorganisms, we treated suspensions of budding yeast cells with oxygen radicals using an atmospheric-pressure oxygen radical source, varying the fluxes of O(3Pj) from 1.3 × 1016 to 2.3 × 1017 cm−2 s−1. Proliferation was promoted at doses of O(3Pj) ranging from 6 × 1016 to 2 × 1017 cm−3, and suppressed at doses ranging from 3 × 1017 to 1 × 1018 cm−3; cells were inactivated by O(3Pj) doses exceeding 1 × 1018 cm−3, even when the flux was varied over the above flux range. These results showed that the growth of cells was regulated primarily in response to the total dose of O(3Pj).
Fine structure of modal focusing effect in a three dimensional plasma-sheath-lens formed by disk electrodes
Authors: Stamate Eugen , Yamaguchi Masahito
Published: September 2015

Modal and discrete focusing effects associated with three-dimensional plasma-sheath-lenses show promising potential for applications in ion beam extraction, mass spectrometry, plasma diagnostics and for basic studies of plasma sheath. The ion focusing properties can be adjusted by controlling the geometrical structure of the plasma-sheath-lens and plasma parameters. The positive and negative ion kinetics within the plasma-sheath-lens are investigated both experimentally and theoretically and a modal focusing ring is identified on the surface of disk electrodes. The focusing ring is very sensitive to the sheath thickness and can be used to monitor very small changes in plasma parameters. Three dimensional simulations are found to be in very good agreement with experiments.
Long-term stability assessment of AlGaN/GaN field effect transistors modified with peptides: Device characteristics vs. surface properties
Authors: Rohrbaugh Nathaniel , Bryan Isaac , Bryan Zachary , Collazo Ramon , Ivanisevic Albena
Published: September 2015

AlGaN/GaN Field Effect Transistors (FETs) are promising biosensing devices. Functionalization of these devices is explored in this study using an in situ approach with phosphoric acid etchant and a phosphonic acid derivative. Devices are terminated on peptides and soaked in water for up to 168 hrs to examine FETs for both device responses and surface chemistry changes. Measurements demonstrated threshold voltage shifting after the functionalization and soaking processes, but demonstrated stable FET behavior throughout. X-ray photoelectron spectroscopy and atomic force microscopy confirmed peptides attachment to device surfaces before and after water soaking. Results of this work point to the stability of peptide coated functionalized AlGaN/GaN devices in solution and support further research of these devices as disposable, long term, in situ biosensors.
Powerful lasers mimic intergalactic plasmas in the lab
Authors: Miller Johanna L.
Published: September 2015

A scaled-down experiment provides a platform to study how magnetic fields evolve as galaxy clusters merge.
How many asteroids are out there, exactly?
Authors: Kramer David
Published: September 2015

The effort to find objects that might threaten Earth is far from complete, and NASA admits it won’t meet a 2020 congressional deadline to find the bigger ones.
Mechanical metamaterials roll off the 3D printing press
Authors: Matthews Jermey N. A.
Published: September 2015

Researchers are exploring applications that extend beyond optical invisibility cloaks.
Information: From Maxwell’s demon to Landauer’s eraser
Authors: Lutz Eric , Ciliberto Sergio
Published: September 2015

Thought experiments that long puzzled the thermodynamics community are now being performed in the lab—and they’re forging a deeper understanding of the second law.
New Red-Emitting Phosphor La2Zr3(MoO4)9:Eu3+ and the Influence of Host Absorption on its Luminescence Efficiency
Authors: Baur Florian , Jüstel Thomas
Published: September 2015

This work investigates the optical properties of Eu3+-activated La2Zr3(MoO4)9. A series of solid solutions with Eu3+ concentrations in the range of 0–100 % were prepared by conventional high temperature solid-state synthesis. An unusual change in the lattice parameters was observed. The phosphor exhibits a broad absorption band in the UV spectral region, and measurements on the non-doped material at 100 K were conducted to elucidate the nature of the absorption band. As demonstrated, Mo6+ charge transfer absorption negatively influences the luminescence efficiency of the phosphor. The temperature-dependent emission spectra revealed that the emission intensity exhibits a bi-sigmoidal temperature dependence. This behaviour results from competing absorption via Mo6+ charge transfer processes, which strongly decrease the efficiency of the phosphor. For application purposes, it is therefore advisable to choose materials that do not exhibit host absorption in the spectral range where excitation is expected.
Occurrence, relative abundance and spatial distribution of microplastics and zooplankton NW of Sardinia in the Pelagos Sanctuary Protected Area, Mediterranean Sea
Authors: Panti Cristina , Giannetti Matteo , Baini Matteo , Rubegni Fabrizio , Minutoli Roberta , Fossi Maria Cristina
Published: September 2015

Environmental context
Plastic materials are accumulating in the marine environment where they can now be found in the remotest areas of the world's oceans. Microplastics (plastic particles ≤5mm), abundant in marine surface waters, are also found in neritic and pelagic waters of Mediterranean marine protected areas. Microplastics can accumulate along marine food chains, having noxious effects on marine organisms at different trophic levels and creating a serious threat to marine ecosystems.

Abstract
Floating plastic debris tends to fragment into smaller pieces, termed microplastics, which may increase the likelihood of ingestion of plastics by marine organisms entering the food web. This study analyses the amount and spatial distribution of microplastics and zooplankton in an area near Asinara National Park (NW Sardinia) and overlapping the Pelagos Sanctuary (Mediterranean Sea). Analysis showed microplastics in 81% of the 27 samples analysed, with a mean value of 0.17±0.32 items m–3. From geographic information system processing of the data, microplastics appeared more abundant (by a factor of four) in the pelagic than in the neritic environment, and showed a size range of the same order as major zooplanktonic taxa determined in the area. These findings suggest a potential risk of mesozooplankton and species preying on plankton mistaking microplastics for food. Further functional and toxicological studies are therefore necessary to assess the hazard associated with microplastics in the marine food web.
Exceptional accumulation and retention of dimethylsulfoniopropionate by molluscs
Authors: Hill Richard W. , Dacey John W. H.
Published: September 2015

Environmental context
Animals that eat marine algae strongly affect the rate at which a compound that algae synthesise, dimethylsulfoniopropionate (DMSP), is converted to the important atmospheric climate gas dimethylsulfide (DMS). In studying the processing of DMSP by algae-eating molluscs, we have discovered that some molluscs accumulate and retain DMSP exceptionally well, but this can be very variable. With this knowledge, investigators will be able to design improved experiments to understand the effects of molluscs on DMS production in local ecosystems.

Abstract
Molluscs often play major roles in processing phytoplankton-synthesised dimethylsulfoniopropionate (DMSP) in local ecosystems. We find that some mollusc species retain tissue DMSP exceptionally tightly and exhibit unusually great and statistically non-normal interindividual variation in DMSP accumulation and retention. Individual mussels (Mytilus, Geukensia) living within a single clump, for example, range 6- to 11-fold in tissue [DMSP] and are often non-normal in statistical distribution. These properties cannot be explained by the elevation of the substrate on which the mussels are living or by mussel position in a clump. When mussels (Mytilus edulis) are deprived of DMSP for up to 5 weeks in depuration experiments, some individuals retain high tissue [DMSP], whereas others exhibit reduced [DMSP]. Such interindividual divergence helps explain non-normal distributions of tissue [DMSP] after depuration. We re-analyse published data from which the half-time for tissue DMSP loss during depuration can be calculated. In the only mollusc studied in this way (Haliotis), the half-time is 13–25 times longer than in similar size fish. Besides posing a challenge for DMSP mass balance studies, retention and interindividual variation may point to as yet unknown properties of molluscs: tight retention suggests functional roles for DMSP, and non-normal statistical distributions suggest discontinuities among individuals in DMSP metabolism.
Tasman Sea biological response to dust storm events during the austral spring of 2009
Authors: Gabric A. J. , Cropp R. , McTainsh G. , Butler H. , Johnston B. M. , O'Loingsigh T. , Van Tran Dien
Published: September 2015

During the austral spring of 2009 several significant dust storms occurred in south-east Australia including the so-called ‘Red Dawn’ event in late September. Estimates of 2.5 Mt total suspended particulate sediment lost off the Australian coast in the 3000km long dust plume make it the largest off-continent loss of soil ever reported. Much of this material was transported over the coastline of New South Wales and into the adjacent Tasman Sea. Long-term model simulations of dust deposition over the south-west Tasman Sea suggest the amount deposited during the spring of 2009 was approximately three times the long-term monthly average. Previous satellite-based analyses of the biological response of Tasman Sea waters to dust-derived nutrients are equivocal or have observed no response. Satellite-derived surface chlorophyll concentrations in the southern Tasman during the spring of 2009 are well above the climatological mean, with positive anomalies as high as 0.5mgm–3. Dust transport simulations indicate strong deposition to the ocean surface, which during both the ‘Red Dawn’ event and mid-October 2009 dust storm events was enhanced by heavy precipitation. Cloud processing of the dust aerosol may have enhanced iron bioavailability for phytoplankton uptake.
Discovery of phosphonic acid natural products by mining the genomes of 10,000 actinomycetes
Authors: Ju Kou-San , Gao Jiangtao , Doroghazi James R. , Wang Kwo-Kwang A. , Thibodeaux Christopher J. , Li Steven , Metzger Emily , Fudala John , Su Joleen , Zhang Jun Kai , Lee Jaeheon , Cioni Joel P. , Evans Bradley S. , Hirota Ryuichi , Labeda David P. , van der Donk Wilfred A. , Metcalf William W.
Published: September 2015

Significance

The discovery of natural products, an important source of human medicines, is critical for the development of new therapeutics against health threats, including cancer and multidrug-resistant pathogens. Yet, in recent years, industrial development of pharmaceuticals from natural products has been stymied due to a variety of reasons, including the repeated discovery of previously known compounds. Here, we demonstrate large-scale genomics as one potential solution to this problem by mining a collection of 10,000 actinomycetes for novel phosphonic acids, an important class of natural products with antimicrobial, antiviral, antimalarial, and herbicidal activities. The framework described here provides a foundation for rapid, large-scale discovery of other classes of natural products and their use as lead compounds in the pharmaceutical industry.
Discovery of a novel amino acid racemase through exploration of natural variation in
Arabidopsis thaliana
Authors: Strauch Renee C. , Svedin Elisabeth , Dilkes Brian , Chapple Clint , Li Xu
Published: September 2015

Significance

We describe how untargeted metabolic profiling and genome-wide association analysis was used in
Arabidopsis thaliana
to link natural products (secondary metabolites) with genes controlling their production. This powerful approach exposed metabolite–enzyme connections even without prior knowledge of the metabolite identity or the biochemical function of the associated enzyme. Further chemical and genetic analysis synergistically led to the discovery and characterization of a
d
-amino acid derivative,
N
-malonyl-
d
-allo-isoleucine, and a novel amino acid racemase responsible for its biosynthesis. Little is known about
d
-amino acid metabolism and its natural variation in plants. Additionally, this is the first functional characterization of a eukaryotic member of a large family of phenazine biosynthesis protein phzF-like proteins conserved across all the kingdoms.
NDRG1
links p53 with proliferation-mediated centrosome homeostasis and genome stability
Authors: Croessmann Sarah , Wong Hong Yuen , Zabransky Daniel J. , Chu David , Mendonca Janet , Sharma Anup , Mohseni Morassa , Rosen D. Marc , Scharpf Robert B. , Cidado Justin , Cochran Rory L. , Parsons Heather A. , Dalton W. Brian , Erlanger Bracha , Button Berry , Cravero Karen , Kyker-Snowman Kelly , Beaver Julia A. , Kachhap Sushant , Hurley Paula J. , Lauring Josh , Park Ben Ho
Published: September 2015

Significance

The mechanism of how loss of the tumor suppressor p53 can lead to genomic instability is not fully understood. This study demonstrates that under physiologic low levels of proliferation, homozygous loss of tumor protein 53 (
TP53
) via genome editing, but not common p53 missense mutations, results in an inability to increase expression of
N-Myc down-regulated gene 1
(
NDRG1
)
.
In turn, failure to upregulate NDRG1 protein under low proliferative states leads to supernumerary centrosome formation, a known mechanism of aneuploidy. These results provide a mechanistic link between loss of
TP53
, proliferation,
NDRG1
, and genomic instability and help explain how cells with a low proliferative index and p53 loss can acquire additional genetic alterations that lead to cancer.
Epigenetic silencing of tumor suppressor genes during in vitro Epstein–Barr virus infection
Authors: Saha Abhik , Jha Hem C. , Upadhyay Santosh K. , Robertson Erle S.
Published: September 2015

Significance

Aberrant promoter methylation of tumor suppressor genes (TSGs) has been found in a large number of human cancers, including Epstein–Barr virus (EBV)-associated cancers. However, how epigenetic modification controls TSG expression in primary B lymphocytes in response to EBV infection has not been fully investigated. In vitro EBV readily transforms quiescent B-cells into lymphoblastoid cell lines, providing a working model for understanding the underlying molecular mechanisms of B-cell lymphoma development. To our knowledge, our work represents the first report to demonstrate that EBV-infection of naïve B lymphocytes resulted in global transcriptional repression of TSGs through recruitment of hypermethylation activities at CpG islands. These results can be further used as potential prognostic-markers and for current therapeutic enhancements against acute-infection and EBV-associated B-cell lymphomas.
Dynamics of an experimental microbial invasion
Authors: Acosta Francisco , Zamor Richard M. , Najar Fares Z. , Roe Bruce A. , Hambright K. David
Published: September 2015

Significance

Current models for biological invasions are predominantly based on macroorganisms. Few invasion model assumptions have been validated for microbial systems. Further research on microbial invasion dynamics is required to determine whether macrobial models are appropriate for microbes, as well as to understand present and future distributions of invasive microorganisms, particularly in the face of contemporary environmental changes. We studied the establishment of an invasive protist in natural microbial assemblages in replicate experimental microcosms and found that, under adequate environmental conditions, invasion success was determined by the number of invading propagules rather than resource availability and the diversity of the invaded communities. This study is among the first to test invasibility hypotheses using an actual invasive microbial species in natural communities.
Differential control of Yorkie activity by LKB1/AMPK and the Hippo/Warts cascade in the central nervous system
Authors: Gailite Ieva , Aerne Birgit L. , Tapon Nicolas
Published: September 2015

Significance

The correct regulation of tissue growth in developing organisms is essential for functional organ formation. The evolutionarily conserved transcriptional coactivator Yorkie (Yki)/Yes-activated protein (YAP) responds to a variety of upstream inputs to promote tissue growth. Yki/YAP is known to regulate stem cell proliferation, thus affecting final organ size. The Hippo (Hpo)/Warts kinase cascade is a key inhibitor of Yki activity in many epithelial tissues. Here, we show that Yki is inhibited by the nutrient-sensing liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK) cascade independent of Hpo/Warts in a population of neural progenitors in the developing
Drosophila
larval brain. Our results suggest a tissue-specific nutrient-dependent mode of Yki activity regulation. Furthermore, a tissue-specific differential wiring of Hpo signaling could represent an adjustment to the proliferation requirements of different tissue types.
Roles of helix H69 of 23S rRNA in translation initiation
Authors: Liu Qi , Fredrick Kurt
Published: September 2015

Significance

In this work, we dissect the interplay between helix H69 of the large subunit ribosomal RNA, initiation factor IF3, and initiator tRNA, interactions upon which the speed and accuracy of translation initiation rely. Our data clarify the molecular mechanisms that control the initiation process and explain the essentiality of H69 in the cell.
Marine and terrestrial herbivores display convergent chemical ecology despite 400 million years of independent evolution
Authors: Rasher Douglas B. , Stout E. Paige , Engel Sebastian , Shearer Tonya L. , Kubanek Julia , Hay Mark E.
Published: September 2015

Significance

We report, for the first time to our knowledge, compounds that specialist marine herbivores use to find their prey. The seaweedHalimeda incrassataproduces metabolites that deter feeding by generalist herbivores. However, a specialist sea slug,Elysia tuca, follows these defensive compounds and not only attacks the seaweed but does so preferentially while the seaweed is reproducing.ElysiasequesterHalimeda’schemical defenses (to deter predators) and chloroplasts (becoming photosynthetic).Elysiafeeding reducesHalimedagrowth by ∼50%, but the alga drops branches occupied byElysia, possibly to avoid fungal infection associated with herbivory and to rid itself ofElysia. These interactions parallel many involving terrestrial insects and plants, even though marine and terrestrial herbivores have evolved independently for 400 million years.
Cysteine as a ligand platform in the biosynthesis of the FeFe hydrogenase H cluster
Authors: Suess Daniel L. M. , Bürstel Ingmar , De La Paz Liliana , Kuchenreuther Jon M. , Pham Cindy C. , Cramer Stephen P. , Swartz James R. , Britt R. David
Published: September 2015

Significance

Hydrogen production is central to a solar fuel paradigm, and a variety of metabolic processes use H
2
as an electron donor or protons as an electron acceptor. Hydrogenases mediate the biological redox interconversion of protons and H
2
, with FeFe hydrogenases among the most active. This reactivity occurs at the “H cluster,” which features an organometallic subcluster that is synthesized and inserted in a complex series of steps. The accessory protein HydG generates an [Fe(CO)
2
(CN)] intermediate en route to the H cluster, and the mechanism of this process is under intensive investigation. We now report that free
l
-cysteine serves as the ligand platform on which the [Fe(CO)
2
(CN)] synthon is built and plays a role in both Fe
2+
binding and synthon release.
Arabidopsis
ALIX is required for the endosomal localization of the deubiquitinating enzyme AMSH3
Authors: Kalinowska Kamila , Nagel Marie-Kristin , Goodman Kaija , Cuyas Laura , Anzenberger Franziska , Alkofer Angela , Paz-Ares Javier , Braun Pascal , Rubio Vicente , Otegui Marisa S. , Isono Erika
Published: September 2015

Significance

The regulation of protein abundance of receptors and transporters at the plasma membrane is important for proper signaling in many biological pathways. The removal of plasma membrane proteins can occur via the endocytic protein degradation pathway, in which posttranslational modification by ubiquitin plays a key role. The activity of ubiquitinating and deubiquitinating enzymes can determine the ubiquitination status of a given target protein, and it has been shown that both classes of enzymes have important physiological roles. However, how these enzymes themselves are regulated at the molecular level has not yet been completely understood. In this study, we report a possible mechanism by which the deubiquitinating enzyme AMSH3 is regulated by its interacting protein, apoptosis-linked gene-2 interacting protein X (ALIX), in
Arabidopsis
.
Assembly, translocation, and activation of XerCD-
dif
recombination by FtsK translocase analyzed in real-time by FRET and two-color tethered fluorophore motion
Authors: May Peter F. J. , Zawadzki Pawel , Sherratt David J. , Kapanidis Achillefs N. , Arciszewska Lidia K.
Published: September 2015

Significance

This study develops and exploits an expanded single-molecule fluorescence technique to understand the molecular mechanism of assembly, translocation, and disassembly of a hexameric DNA motor, FtsK, which functions ubiquitously in bacterial chromosome segregation. Assembly of single hexamers on DNA and their subsequent rapid translocation were directly assayed. FtsK hexamers dissociated soon after encountering and activating XerCD-
dif
recombination complexes. This work contrasts with previously published reports, which suggested that FtsK can reverse spontaneously during translocation, or upon encountering XerCD-
dif
. Furthermore, in some previous assays, the readout was DNA looping; here, we show that looping does not occur with single hexamer translocation. The technique used provides a blueprint for mechanistic real-time studies of individual protein–nucleic acid complexes.
Low clouds suppress Arctic air formation and amplify high-latitude continental winter warming
Authors: Cronin Timothy W. , Tziperman Eli
Published: September 2015

Significance

Future-greenhouse simulations, and evidence of frost-intolerant species in high-latitude continental interiors during past equable climates, show significantly amplified warming at high latitudes over land in winter, with physical mechanisms that are still not understood. We show that the process of Arctic air formation, in which a high-latitude maritime air mass is advected over a continent, cooled at the surface, and transformed into a much colder continental polar air mass, may change dramatically and even be suppressed in warmer climates due to an increase in the duration of optically thick low clouds. This leads to two-degree warming over the continent in response to each degree of warming over the nearby ocean, possibly explaining both past and future continental warming.
Chronophin coordinates cell leading edge dynamics by controlling active cofilin levels
Authors: Delorme-Walker Violaine , Seo Ji-Yeon , Gohla Antje , Fowler Bruce , Bohl Ben , DerMardirossian Céline
Published: September 2015

Significance

Cell motility plays important roles in normal physiology and numerous disease states, including cancers. Cofilin, a key player in cell locomotion, controls the direction and the force of cell protrusion. Our study establishes the cofilin phosphatase chronophin (CIN) as a major component of a PI3-kinase–mediated, Rac1-dependent signaling mechanism that activates cofilin downstream of EGF receptor in mammary carcinoma cells. During EGF stimulation, CIN redistributes to the cell edge, where it regulates cofilin-dependent actin turnover and coordinates cell protrusion and retraction dynamics. Our data uncover previously unidentified molecular mechanisms regulating cofilin in time and space in tumor cells and expand our understanding of cancer cell movement, a critical step in the process of metastasis.
Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis
Authors: Chen Alan C. , Donovan Adriana , Ned-Sykes Renee , Andrews Nancy C.
Published: September 2015

Significance

Transferrin receptor 1 (Tfr1) facilitates cellular iron acquisition by binding to and internalizing iron-loaded transferrin. Although this function is essential for red blood cell precursors, the role of Tfr1 in nonhematopoietic tissues has not been thoroughly studied. In this study, we investigated the role of Tfr1 in the intestine by developing mutant mice in which Tfr1 is inactivated specifically in the intestinal epithelium. We discovered that inactivation of Tfr1 has pleiotropic consequences leading to the loss of intestinal epithelial proliferation and homeostasis and induction of genes involved in epithelial–mesenchymal transition. These effects are not related to the iron uptake, revealing a surprising role for this ubiquitous membrane protein.
The genome of
Aiptasia
, a sea anemone model for coral symbiosis
Authors: Baumgarten Sebastian , Simakov Oleg , Esherick Lisl Y. , Liew Yi Jin , Lehnert Erik M. , Michell Craig T. , Li Yong , Hambleton Elizabeth A. , Guse Annika , Oates Matt E. , Gough Julian , Weis Virginia M. , Aranda Manuel , Pringle John R. , Voolstra Christian R.
Published: September 2015

Significance

Coral reefs form marine-biodiversity hotspots of enormous ecological, economic, and aesthetic importance that rely energetically on a functional symbiosis between the coral animal and a photosynthetic alga. The ongoing decline of corals worldwide due to anthropogenic influences, including global warming, ocean acidification, and pollution, heightens the need for an experimentally tractable model system to elucidate the molecular and cellular biology underlying the symbiosis and its susceptibility or resilience to stress. The small sea anemone
Aiptasia
is such a system, and our analysis of its genome provides a foundation for research in this area and has revealed numerous features of interest in relation to the evolution and function of the symbiotic relationship.
Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism
Authors: Prusiner Stanley B. , Woerman Amanda L. , Mordes Daniel A. , Watts Joel C. , Rampersaud Ryan , Berry David B. , Patel Smita , Oehler Abby , Lowe Jennifer K. , Kravitz Stephanie N. , Geschwind Daniel H. , Glidden David V. , Halliday Glenda M. , Middleton Lefkos T. , Gentleman Steve M. , Grinberg Lea T. , Giles Kurt
Published: September 2015

Prions are proteins that adopt alternative conformations that become self-propagating; the PrP
Sc
prion causes the rare human disorder Creutzfeldt–Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA is a slowly evolving disorder characterized by progressive loss of autonomic nervous system function and often signs of parkinsonism; the neuropathological hallmark of MSA is glial cytoplasmic inclusions consisting of filaments of α-synuclein. To determine whether human α-synuclein forms prions, we examined 14 human brain homogenates for transmission to cultured human embryonic kidney (HEK) cells expressing full-length, mutant human α-synuclein fused to yellow fluorescent protein (α-syn140*A53T–YFP) and TgM83
+/−
mice expressing α-synuclein (A53T). The TgM83
+/−
mice that were hemizygous for the mutant transgene did not develop spontaneous illness; in contrast, the TgM83
+/+
mice that were homozygous developed neurological dysfunction. Brain extracts from 14 MSA cases all transmitted neurodegeneration to TgM83
+/−
mice after incubation periods of ∼120 d, which was accompanied by deposition of α-synuclein within neuronal cell bodies and axons. All of the MSA extracts also induced aggregation of α-syn*A53T–YFP in cultured cells, whereas none of six Parkinson’s disease (PD) extracts or a control sample did so. Our findings argue that MSA is caused by a unique strain of α-synuclein prions, which is different from the putative prions causing PD and from those causing spontaneous neurodegeneration in TgM83
+/+
mice. Remarkably, α-synuclein is the first new human prion to be identified, to our knowledge, since the discovery a half century ago that CJD was transmissible.
Postcranial morphology of the middle Pleistocene humans from Sima de los Huesos, Spain
Authors: Arsuaga Juan Luis , Carretero José-Miguel , Lorenzo Carlos , Gómez-Olivencia Asier , Pablos Adrián , Rodríguez Laura , García-González Rebeca , Bonmatí Alejandro , Quam Rolf M. , Pantoja-Pérez Ana , Martínez Ignacio , Aranburu Arantza , Gracia-Téllez Ana , Poza-Rey Eva , Sala Nohemi , García Nuria , Alcázar de Velasco Almudena , Cuenca-Bescós Gloria , Bermúdez de Castro José María , Carbonell Eudald
Published: September 2015

Significance

The middle Pleistocene Sima de los Huesos (SH) fossil collection provides the rare opportunity to thoroughly characterize the postcranial skeleton in a fossil population, comparable only to that obtained in the study of the Neandertal hypodigm and recent (and fossil) modern humans. The SH paleodeme can be characterized as relatively tall, wide, and muscular individuals, who are less encephalized than both Neandertals and modern humans. Some (but not all) Neandertal derived traits are present, which phylogenetically links this population with Neandertals. Thus, the full suite of Neandertal features did not arise all at once, and the evolution of the postcranial skeleton could be characterized as following a mosaic pattern.
Identification of the
VERNALIZATION 4
gene reveals the origin of spring growth habit in ancient wheats from South Asia
Authors: Kippes Nestor , Debernardi Juan M. , Vasquez-Gross Hans A. , Akpinar Bala A. , Budak Hikment , Kato Kenji , Chao Shiaoman , Akhunov Eduard , Dubcovsky Jorge
Published: September 2015

Significance

A precise regulation of flowering time is critical for plant reproductive success and for cereal crops to maximize grain production. In wheat, barley, and other temperate cereals, vernalization genes play an important role in the acceleration of reproductive development after long periods of low temperatures during the winter (vernalization). In this study, we identified
VERNALIZATION 4
(
VRN-D4
), a vernalization gene that was critical for the development of spring growth habit in the ancient wheats from South Asia. We show that mutations in regulatory regions of
VRN-D4
are shared with other
VRN-A1
alleles and can be used to modulate the vernalization response. These previously unknown alleles provide breeders new tools to engineer wheat varieties better adapted to different or changing environments.
Structure of
Drosophila
Oskar reveals a novel RNA binding protein
Authors: Yang Na , Yu Zhenyu , Hu Menglong , Wang Mingzhu , Lehmann Ruth , Xu Rui-Ming
Published: September 2015

Oskar (Osk) protein plays critical roles during
Drosophila
germ cell development, yet its functions in germ-line formation and body patterning remain poorly understood. This situation contrasts sharply with the vast knowledge about the function and mechanism of
osk
mRNA localization. Osk is predicted to have an N-terminal LOTUS domain (Osk-N), which has been suggested to bind RNA, and a C-terminal hydrolase-like domain (Osk-C) of unknown function. Here, we report the crystal structures of Osk-N and Osk-C. Osk-N shows a homodimer of winged-helix–fold modules, but without detectable RNA-binding activity. Osk-C has a lipase-fold structure but lacks critical catalytic residues at the putative active site. Surprisingly, we found that Osk-C binds the 3′UTRs of
osk
and
nanos
mRNA in vitro. Mutational studies identified a region of Osk-C important for mRNA binding. These results suggest possible functions of Osk in the regulation of stability, regulation of translation, and localization of relevant mRNAs through direct interaction with their 3′UTRs, and provide structural insights into a novel protein–RNA interaction motif involving a hydrolase-related domain.
Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle
Authors: Suhara Tomohiro , Hishiki Takako , Kasahara Masataka , Hayakawa Noriyo , Oyaizu Tomoko , Nakanishi Tsuyoshi , Kubo Akiko , Morisaki Hiroshi , Kaelin William G. , Suematsu Makoto , Minamishima Yoji Andrew
Published: September 2015

Significance

When oxygen availability becomes limited, organs and cells activate the hypoxic response to generate energy. This response releases a large amount of lactate into the circulation as a result of anaerobic glycolysis. However, we found that activating the hypoxic response in the liver by inhibiting the oxygen sensor prolyl hydroxylase domain-containing protein 2 (PHD2) enhances the uptake of lactate for gluconeogenesis, also known as the Cori cycle, and ameliorates lactic acidosis. Our findings suggest that PHD2 serves as a viable drug target for the treatment of life-threatening lactic acidosis, which is frequent complication of severe infectious and ischemic diseases, as well as of biguanide treatment in patients with diabetes with renal failure.
spenito
is required for sex determination in
Drosophila melanogaster
Authors: Yan Dong , Perrimon Norbert
Published: September 2015

Significance

Sex determination is a fundamental biological problem faced by all metazoans. To understand the sex determination pathway, it is important to identify all the genes involved in this process. In this study, we have identified a novel gene,
spenito
(
nito
), which is required for sex determination in
Drosophila melanogaster
. Loss of
nito
function in the soma transforms female tissues to male, and loss of
nito
function in female germ-line stem cells changes their sexual identity and prevents them from proper differentiation. We show that
nito
is a cofactor for
Sex-lethal
(
Sxl
) auto regulation, a process that remains an important textbook model for regulated alternative splicing.
Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells
Authors: Vomund Anthony N. , Zinselmeyer Bernd H. , Hughes Jing , Calderon Boris , Valderrama Carolina , Ferris Stephen T. , Wan Xiaoxiao , Kanekura Kohsuke , Carrero Javier A. , Urano Fumihiko , Unanue Emil R.
Published: September 2015

Significance

This report documents that beta cells from islets of Langerhans normally transfer some of their secretory granules to resident phagocytes. The transfer involves a close contact interaction between live beta cells and phagocytes, increases upon glucose stimulation, and requires mobilization of intracellular Ca
++
. In autoimmune diabetes, the CD4 T cells to various peptides of the insulin B chain recognize the transferred antigens in the phagocytes represented in islets by macrophages and a subset of dendritic cells. We have identified a process whereby antigens become available for recognition by autoreactive T cells in type 1 diabetes.
Subunit composition of a DEG/ENaC mechanosensory channel of
Caenorhabditis elegans
Authors: Chen Yushu , Bharill Shashank , Isacoff Ehud Y. , Chalfie Martin
Published: September 2015

Significance

The molecular organization of eukaryotic mechanosensory channels is largely uncharacterized. This characterization, having the correct parts list, is a necessary beginning step toward understanding how the channel transduces mechanical signals. Here we investigate the organization of the degenerin/epithelial sodium channel (DEG/ENaC) mechanosensory transduction channel in the six touch receptor neurons of
Caenorhabditis elegan
s. Previous work has suggested that four membrane proteins formed a channel complex: the DEG/ENaC proteins MEC-4 and MEC-10 form the channel pore and the stomatin-like protein MEC-2 and paraoxonase-like protein MEC-6 act as auxiliary proteins. Using single molecule imaging, we find that the transduction complex is simpler, being a MEC-4:MEC-4:MEC-10 trimer. In contrast to the previous suggestion, this trimer does not appear to associate substantially with MEC-2 or MEC-6.
Vba4p, a vacuolar membrane protein, is involved in the drug resistance and vacuolar morphology of Saccharomyces cerevisiae
Authors: Kawano-Kawada Miyuki , Pongcharoen Pongsanat , Kawahara Rieko , Yasuda Mayu , Yamasaki Takashi , Akiyama Koichi , Sekito Takayuki , Kakinuma Yoshimi
Published: September 2015

In the vacuolar basic amino acid (VBA) transporter family of Saccharomyces cerevisiae, VBA4 encodes a vacuolar membrane protein with 14 putative transmembrane helices. Transport experiments with isolated vacuolar membrane vesicles and estimation of the amino acid contents in vacuoles showed that Vba4p is not likely involved in the transport of amino acids. We found that the vba4Δ cells, as well as vba1Δ and vba2Δ cells, showed increased susceptibility to several drugs, particularly to azoles. Although disruption of the VBA4 gene did not affect the salt tolerance of the cells, vacuolar fragmentation observed under high salt conditions was less prominent in vba4Δ cells than in wild type, vba1Δ, and vba2Δ cells. Vba4p differs from Vba1p and Vba2p as a vacuolar transporter but is important for the drug resistance and vacuolar morphology of S. cerevisiae.
Mechanisms underlying reductions in stroke volume at rest and during exercise at high altitude
Authors: Stembridge Mike , Ainslie Philip N. , Shave Rob
Published: September 2015

High‐altitude exposure challenges the cardiovascular system to maintain oxygen delivery to the mitochondria under conditions of hypoxic stress. Following acclimatisation (3–5 days), stroke volume (SV) falls to below sea‐level values but heart rate remains elevated, such that cardiac output is maintained compared to sea level. The decrease in SV has been a topic of research for over 40 years, but the underlying mechanisms are incompletely understood. Impaired systolic contractile function secondary to reduced coronary arterial oxygen tension has been investigated as a potential cause for the decrease in SV. However, despite in vitro evidence of impaired cardiac contractile force in severe hypoxia, the majority of studies to date have reported enhanced in vivo ventricular systolic function at rest and during exercise in humans up to and above 5000 m. However, the elevated function observed at rest has recently been suggested to reduce the functional reserve available during exercise. While in vivo systolic function appears enhanced at high altitude, a decrease in left ventricular end‐diastolic volume (EDV) and altered filling patterns of both ventricles has been observed. The reduction in ventricular filling will undoubtedly affect SV, and four potential mechanisms have been proposed to explain the reduction in left ventricular filling. In this article, both historical and recent reports of systolic function at high altitude will be reviewed, and evidence supporting and refuting each of the four mechanisms underpinning reduced left ventricular filling will be discussed.
Cognitive costs of encoding novel natural activities: Can “learning by doing” be distracting and deceptive?
Authors: von Stülpnagel Rul , Schult Janette C. , Richter Claudia , Steffens Melanie C.
Published: September 2015

Findings from action memory research suggest that the enactment of simple actions and naturalistic activities results in similar memory performance to that from their observation. However, little is known about potential differences between the conditions during the encoding of the to-be-studied actions and activities. We analysed the cognitive costs of encoding two novel naturalistic activities studied via enactment or via observation in four experiments. In addition to memory performance, we measured objective cognitive costs with a secondary task and subjective cognitive costs with repeated ratings of mental effort and estimates of general activity difficulty. Memory performance was comparable across study conditions throughout all experiments. The enactment of activities repeatedly resulted in slower reaction times in the secondary task than did observation, suggesting higher objective costs. In contrast, subjective costs were rated lower after enactment than after observation. Findings from a pantomimic enactment condition suggested that the low ratings of subjective costs after enactment represent a misinterpretation of task demands. Our findings imply that the widespread belief about “learning by doing” as an easy way of learning does not stem from an actual advantage in memory performance, but rather from continuous feedback about one's performance resulting from enactment.
Distinct germinal center selection at local sites shapes memory B cell response to viral escape
Authors: Adachi Yu , Onodera Taishi , Yamada Yuki , Daio Rina , Tsuiji Makoto , Inoue Takeshi , Kobayashi Kazuo , Kurosaki Tomohiro , Ato Manabu , Takahashi Yoshimasa
Published: September 2015

Respiratory influenza virus infection induces cross-reactive memory B cells targeting invariant regions of viral escape mutants. However, cellular events dictating the cross-reactive memory B cell responses remain to be fully defined. Here, we demonstrated that lung-resident memory compartments at the site of infection, rather than those in secondary lymphoid organs, harbor elevated frequencies of cross-reactive B cells that mediate neutralizing antibody responses to viral escape. The elevated cross-reactivity in the lung memory compartments was correlated with high numbers of VH mutations and was dependent on a developmental pathway involving persistent germinal center (GC) responses. The persistent GC responses were focused in the infected lungs in association with prolonged persistence of the viral antigens. Moreover, the persistent lung GCs supported the exaggerated B cell proliferation and clonal selection for cross-reactive repertoires, which served as the predominant sites for the generation of cross-reactive memory progenitors. Thus, we identified the distinct GC selection at local sites as a key cellular event for cross-reactive memory B cell response to viral escape, a finding with important implications for developing broadly protective influenza vaccines.
BigBWA: approaching the Burrows–Wheeler aligner to Big Data technologies
Authors: Abuín José M. , Pichel Juan C. , Pena Tomás F. , Amigo Jorge
Published: September 2015

Summary: BigBWA is a new tool that uses the Big Data technology Hadoop to boost the performance of the Burrows–Wheeler aligner (BWA). Important reductions in the execution times were observed when using this tool. In addition, BigBWA is fault tolerant and it does not require any modification of the original BWA source code.

Availability and implementation: BigBWA is available at the project GitHub repository: https://github.com/citiususc/BigBWA

Contact:  josemanuel.abuin@usc.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Insights Into Triticum aestivum Seedling Root Rot Caused by Fusarium graminearum
Authors: Wang Qing , Vera Buxa Stefanie , Furch Alexandra , Friedt Wolfgang , Gottwald Sven
Published: September 2015

Fusarium graminearum is one of the most common and potent fungal pathogens of wheat (Triticum aestivum), known for causing devastating spike infections and grain yield damage. F. graminearum is a typical soil-borne pathogen that builds up during consecutive cereal cropping. Speculation on systemic colonization of cereals by F. graminearum root infection have long existed but have not been proven. We have assessed the Fusarium root rot disease macroscopically in a diverse set of 12 wheat genotypes and microscopically in a comparative study of two genotypes with diverging responses. Here, we show a ‘new’ aspect of the F. graminearum life cycle, i.e., the head blight fungus uses a unique root-infection strategy with an initial stage typical for root pathogens and a later stage typical for spike infection. Root colonization negatively affects seedling development and leads to systemic plant invasion by tissue-adapted fungal strategies. Another major outcome is the identification of partial resistance to root rot. Disease severity assessments and histological examinations both demonstrated three distinct disease phases that, however, proceeded differently in resistant and susceptible genotypes. Soil-borne inoculum and root infection are considered significant components of the F. graminearum life cycle with important implications for the development of new strategies of resistance breeding and disease control.
Outcomes of ORIF >7 Days After Injury in Displaced Pediatric Lateral Condyle Fractures
Authors: Silva Mauricio , Paredes Alejandro , Sadlik Gal
Published: September 2015

Background:

The purpose of the present study was to evaluate the effects of surgical timing on the outcome of pediatric lateral condyle fractures (LCF). We hypothesize that performing open reduction and internal fixation (ORIF) for a displaced LCF between 7 and 14 days after the occurrence of injury does not result in significant changes in outcome, as compared with those treated within the first 7 days.

Methods:

A total of 181 pediatric LCFs treated with ORIF, with a mean follow-up of 38 weeks and a mean age of 5 years, were included. All information related to the patient’s elbow injury was prospectively collected. We identified 2 specific groups: 133 LCFs that were treated within the first 7 days after injury (group 1), and 48 that were treated between 7 and 14 days after injury (group 2). A satisfactory outcome was one in which there was evidence of healing of the fracture, a range of motion of at least 85% of the normal, contralateral side at the latest follow-up, and no evidence of complications, loss of fixation, infection, or avascular necrosis of the lateral condyle.

Results:

Overall, the mean time from injury to surgery was 5 days (range, 0 to 14 d). Initial fracture displacement was slightly larger in group 1 versus group 2, by a mean of 2.6 mm (P=0.004). There were no iatrogenic nerve injuries or vascular complications in either group. There was no difference in the mean surgical time between groups (P=0.004). At the latest follow-up appointment, elbows in both groups had similar range of motion (P=0.5), a low and similar rate of complications, and comparable rates of satisfactory outcomes (88.0% vs. 87.5%; P=0.6).

Conclusion:

Our study suggests that performing an ORIF for a displaced pediatric LCF up to 14 days after the original injury does not adversely affect the outcome of the procedure.

Level of Evidence:

Level II—comparative study.