bluuebunny/crossref_metadata_2025 huggingface dataset:
Tunable quantum order in bilayer Bi2Te3: Stacking dependent quantum spin Hall states
Authors: Kou Liangzhi , Niu Chengwang , Fu Huixia , Ma Yandong , Yan Binghai , Chen Changfeng
Published: June 2018

Recent years have seen the rising importance of interface stacking in determining the electronic properties of multilayer materials stemming from the interlayer coupling; however, the stacking effects on exotic topological quantum orders largely remain to be explored. Here, we show by first-principles studies that bilayer Bi2Te3 host stacking is dependent on quantum spin Hall effects, with a topological phase transition induced by a change in the interlayer stacking pattern. The spin-filtered helical edge states are concomitantly switched on/off along with the changing interlayer stacking pattern. Since few-layer Bi2Te3 has already been experimentally synthesized, the present finding opens an avenue for exploring the fundamental mechanisms and the practical implications of the quantum phenomena associated with band topology in this versatile and intriguing 2D material.
Allometric scaling of estuarine ecosystem metabolism
Authors: Nidzieko Nicholas J.
Published: June 2018

Significance

Coastal margins host some of the most productive habitats on the planet, yet there is still significant uncertainty about the magnitude of carbon fluxes across the land/ocean interface. Scaling up in situ measurements into whole-ecosystem estimates of how these habitats contribute to global biogeochemical cycling has been hindered by their apparent heterogeneity, complex circulation, and sizes that range from tens of meters to hundreds of kilometers. Here, I show that estuarine ecosystem metabolism varies predictably with ecosystem size. The significance of this study is not simply that larger estuaries have lower specific ecosystem metabolism than smaller estuaries, but that this size scaling arises because the residence time of limiting nutrients does not scale isometrically with estuary size.
Multiple generations of grain aggregation in different environments preceded solar system body formation
Authors: Ishii Hope A. , Bradley John P. , Bechtel Hans A. , Brownlee Donald E. , Bustillo Karen C. , Ciston James , Cuzzi Jeffrey N. , Floss Christine , Joswiak David J.
Published: June 2018

Significance

The initial solids from which the solar system formed consisted almost entirely of amorphous silicate, carbon, and ices. This dust was mostly destroyed and reworked by processes that led to the formation of planets. Surviving samples of presolar dust are most likely to be preserved in comets, small cold bodies that formed in the outer solar nebula. In interplanetary dust particles originating from comets, we observe organic carbon mantles on subgrains within amorphous-silicate−dominated grains called GEMS (glass with embedded metal and sulfides). Our observations constrain GEMS grain formation to cold and radiation-rich environments, making a compelling case that these exotic grains, unique to a relatively obscure class of extraterrestrial material, are surviving dust from (variable) interstellar environments and thus the original building materials of planetary systems.
Electron−hole separation in ferroelectric oxides for efficient photovoltaic responses
Authors: Kim Donghoon , Han Hyeon , Lee June Ho , Choi Jin Woo , Grossman Jeffrey C. , Jang Hyun Myung , Kim Donghun
Published: June 2018

Significance

Photovoltaics (PVs) benefitting from ferroelectric polarizations can overcome critical limitations of conventional type PVs. In this class, Bi
2
FeCrO
6
is known to be the best-performing material; however, a fundamental understanding of the origin is lacking, which has limited further performance improvements. Here, we carried out a theoretical investigation of the electronic structure of this material. As a result, electron−hole (
e-h
) pairs are observed to separate upon photoexcitation, which can be a dominant underlying mechanism for the exceptional PV responses. Based on this understanding, we further suggest five novel materials that can offer a combination of strong
e-h
separations and visible-light absorptions. We expect the community of ferroelectric PVs to immediately benefit from the features of the new suggested materials.
SMS texts on corruption help Ugandan voters hold elected councillors accountable at the polls
Authors: Buntaine Mark T. , Jablonski Ryan , Nielson Daniel L. , Pickering Paula M.
Published: June 2018

Significance

Text messages providing salient, nonpartisan, official information on budget corruption prompted Ugandan voters to take the performance of some politicians into account when voting. Holding politicians accountable via elections is a fundamental precursor to effective governance, economic development, and high-quality public services. The results indicate that communication technologies can combine with data on budget management to help voters make better informed choices at the polls and thus have the potential to enhance local electoral accountability by providing information that is difficult for politicians to control and manipulate.
Effect of environmental changes on vegetable and legume yields and nutritional quality
Authors: Scheelbeek Pauline F. D. , Bird Frances A. , Tuomisto Hanna L. , Green Rosemary , Harris Francesca B. , Joy Edward J. M. , Chalabi Zaid , Allen Elizabeth , Haines Andy , Dangour Alan D.
Published: June 2018

Significance

Environmental changes, including climate change, air pollution, and water scarcity and salinization, threaten global agricultural production, food security, and health. There is evidence that environmental change will reduce the yields of starchy staple crops, but impacts on (nonstaple) vegetables and legumes—important constituents of healthy diets—remain largely unknown. We systematically reviewed the available published evidence from experimental studies on the impact of environmental changes on yields and nutritional quality of (nonstaple) vegetables and legumes and found that environmental change would have a negative impact on yields without suitable responses from the agricultural sector. An enhanced understanding of the scale of environmental impacts on agricultural production is essential for the development of effective strategies to protect global population health.
Hypoxic tumor microenvironment activates GLI2 via HIF-1α and TGF-β2 to promote chemoresistance in colorectal cancer
Authors: Tang Yen-An , Chen Yu-feng , Bao Yi , Mahara Sylvia , Yatim Siti Maryam J. M. , Oguz Gokce , Lee Puay Leng , Feng Min , Cai Yu , Tan Ern Yu , Fong Sau Shung , Yang Zi-huan , Lan Ping , Wu Xiao-jian , Yu Qiang
Published: June 2018

Significance

Colorectal cancer patients often relapse due to resistance to chemotherapy. The tumor microenvironment is known to contribute to tumor aggressiveness and chemoresistance, but the underlying mechanisms remain elusive. In the current study, we have shown that cancer-associated fibroblasts (CAFs) which are often present in the tumor can greatly promote resistance of colorectal cancer cells to chemotherapy. In the low-oxygen condition (hypoxia), CAFs-secreted growth factor TGF-β2 can induce strong expression of
GLI2
, a gene that can induce resistance to therapy. As such, therapeutic targeting of TGF-β and GLI2 can be developed into a useful adjuvant to enhance the effect of chemotherapies.
Thallium isotopes reveal protracted anoxia during the Toarcian (Early Jurassic) associated with volcanism, carbon burial, and mass extinction
Authors: Them Theodore R. , Gill Benjamin C. , Caruthers Andrew H. , Gerhardt Angela M. , Gröcke Darren R. , Lyons Timothy W. , Marroquín Selva M. , Nielsen Sune G. , Trabucho Alexandre João P. , Owens Jeremy D.
Published: June 2018

Significance

Declining oxygen contents in today’s oceans highlight the need to better understand ancient, natural marine deoxygenation and associated extinctions. In the Early Jurassic, the Toarcian Oceanic Anoxic Event (T-OAE; ∼183 Ma) is associated with significant perturbations to the Earth system, historically defined by carbon isotopes. We reconstructed global oceanic (de)oxygenation using thallium isotopes from two ocean basins that suggest a stepwise decline of oxygen that initiated before and extended well after the classically defined T-OAE interval. This initial deoxygenation occurs with the start of massive volcanism and marine extinctions, while a later shift corresponds to the traditional T-OAE. This emphasizes the need for more nuanced records of ancient environmental and biogeochemical feedbacks that lead to and maintain widespread marine anoxia.
Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy
Authors: Slavi Nefeli , Toychiev Abduqodir H. , Kosmidis Stylianos , Ackert Jessica , Bloomfield Stewart A. , Wulff Heike , Viswanathan Suresh , Lampe Paul D. , Srinivas Miduturu
Published: June 2018

Significance

Vascular regeneration during retinal ischemia is critical for curtailing hypoxia-driven aberrant neovascularization and neuronal damage. Apoptotic cell death of astrocytes is a key initiating factor for improper vascular growth. Here we report that astrocytic connexin (Cx43) gap junction (GJ) channels are major contributors to astrocyte degeneration and vascular remodeling that follow tissue ischemia. Astrocyte apoptosis is due to phosphorylation of Cx43 by casein kinase 1δ (CK1δ), which in turn leads to an increase in GJ coupling and amplification of injury. Deletion of Cx43 or inhibition of its phosphorylation by CK1δ rescues astrocytes and leads to restoration of a functional vasculature in the retina, while reducing neovascularization and improving neuroretinal function, thereby providing viable options for the treatment of ischemic retinopathies.
Roles of Gag-RNA interactions in HIV-1 virus assembly deciphered by single-molecule localization microscopy
Authors: Yang Yantao , Qu Na , Tan Jie , Rushdi Muaz N. , Krueger Christopher J. , Chen Antony K.
Published: June 2018

Significance

Single-molecule localization microscopy (SMLM) is useful for deciphering dynamic organizations of structures densely labeled by specific proteins in the cellular context with nanoscopic resolution not attainable by conventional imaging tools. Here we employed SMLM to investigate the mechanism by which the HIV-1 viral RNA (vRNA) mediates the assembly of thousands of Gag proteins into a virus particle at the plasma membrane. In contrast to the general notion that vRNA only triggers Gag assembly and is dispensable for subsequent assembly, we found that vRNA is indispensable throughout assembly, scaffolding the formation of assembly intermediates and maintaining their architectures via balancing of external forces acting on the assembly environment. These previously unidentified features may facilitate understanding of HIV-1 and, potentially, other retroviruses.
Random critical point separates brittle and ductile yielding transitions in amorphous materials
Authors: Ozawa Misaki , Berthier Ludovic , Biroli Giulio , Rosso Alberto , Tarjus Gilles
Published: June 2018

Significance

Understanding how amorphous solids yield in response to external deformations is crucial both for practical applications and for theoretical reasons. Here we show that despite large differences in the materials’ microscopic interactions, a degree of universality emerges as there are only two ways in which amorphous solids respond to a deformation: One, typical of well-annealed materials, is characterized by an abrupt failure with a macroscopic stress drop and the sudden emergence of sharp shear bands; the other, typical of poorly annealed materials, shows merely a smooth crossover. By varying the preparation protocol, one can change the response of a given material from one to the other, and this change is controlled by a random critical point.
Differentiated human airway organoids to assess infectivity of emerging influenza virus
Authors: Zhou Jie , Li Cun , Sachs Norman , Chiu Man Chun , Wong Bosco Ho-Yin , Chu Hin , Poon Vincent Kwok-Man , Wang Dong , Zhao Xiaoyu , Wen Lei , Song Wenjun , Yuan Shuofeng , Wong Kenneth Kak-Yuen , Chan Jasper Fuk-Woo , To Kelvin Kai-Wang , Chen Honglin , Clevers Hans , Yuen Kwok-Yung
Published: June 2018

Significance

Influenza virus infection represents a major threat to public health worldwide. There is no biologically relevant, reproducible, and readily available in vitro model for predicting the infectivity of influenza viruses in humans. Based on the long-term expanding 3D human airway organoids, we developed proximal differentiation and further established a 2D monolayer culture of airway organoids. The resultant 3D and 2D proximal differentiated airway organoids can morphologically and functionally simulate human airway epithelium and as a proof of concept can discriminate human-infective influenza viruses from poorly human-infective viruses. Thus, the proximal differentiated airway organoids can be utilized to predict the infectivity of influenza viruses and, more broadly, provide a universal platform for studying the biology and pathology of the human airway.
An archaeal primase functions as a nanoscale caliper to define primer length
Authors: Yan Jiangyu , Holzer Sandro , Pellegrini Luca , Bell Stephen D.
Published: June 2018

Significance

The first phosphodiester linkage made during DNA replication is in the context of a short RNA primer synthesized by the dedicated RNA polymerase, primase. Primase, after synthesizing a defined short oligoribonucleotide, then transfers this primer to a DNA polymerase for extension. The mechanisms by which primer length is constrained remain elusive. Here, we dissect the basis of “counting” by an archaeal primase and propose a caliper-like mechanism to account for length determination.
LOW PHOTOSYNTHETIC EFFICIENCY 1 is required for light-regulated photosystem II biogenesis in
Arabidopsis
Authors: Jin Honglei , Fu Mei , Duan Zhikun , Duan Sujuan , Li Mengshu , Dong Xiaoxiao , Liu Bing , Feng Dongru , Wang Jinfa , Peng Lianwei , Wang Hong-Bin
Published: June 2018

Significance

Photosystem II (PSII) reaction center protein D1 is encoded by chloroplast gene
psbA
and is crucial to the biogenesis and functional maintenance of PSII. D1 proteins are highly dynamic under varying light conditions and thus require efficient synthesis, but the mechanism remains poorly understood. We reported that
Arabidopsis
LPE1 directly binds to the 5′ UTR of
psbA
mRNA in a light-dependent manner through a redox-based mechanism and facilitates the association of HCF173 with
psbA
mRNA to regulate D1 translation. These findings fill a major gap in our understanding of the mechanism of light-regulated D1 synthesis in higher plants and imply that higher plants and primitive photosynthetic organisms share conserved mechanisms but use distinct regulators to regulate biogenesis of PSII subunits.
(Middle-) Class analysis in Africa: does it work?
Authors: Southall Roger
Published: June 2018

Recent interest in the growth of middle classes in Africa (and elsewhere) has been characterised by immense theoretical diversity. While this diversity indicates the complexity (and limitations) of class analysis, it remains important for the latter to be guided by the classic concerns around power, wealth and inequality which characterise radical debate.
Comparing the Commercial Theaters of Early Modern London and Madrid
Authors: Amelang David J.
Published: June 2018

Comparative studies have revealed uncanny similarities between the theatrical cultures of Shakespearean England and Golden Age Spain, and in particular between the Elizabethan amphitheaters and the Spanishcorrales de comedia(courtyard playhouses). Contrary to conventional wisdom, however, Spain’s (and, in particular, Madrid’s) courtyard theaters may have resembled the English indoor public playhouses, especially London’s Blackfriars, more than the Globe-like amphitheaters with which they are so often matched. That thecorralescould simultaneously play the part of both Globe and Blackfriars also helps account for the absence of indoor public playhouses in Habsburg Spain.
Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells†
Authors: Richardson Lauren , Dixon Christopher Luke , Aguilera-Aguirre Leopoldo , Menon Ramkumar
Published: June 2018

Term and preterm parturition are associated with oxidative stress (OS)-induced p38 mitogen-activated protein kinase (p38MAPK)-mediated fetal tissue (amniochorion) senescence. p38MAPK activation is a complex cell- and stimulant-dependent process. Two independent pathways of OS-induced p38MAPK activation were investigated in amnion epithelial cells (AECs) in response to cigarette smoke extract (CSE: a validated OS inducer in fetal cells): (1) the OS-mediated oxidation of apoptosis signal-regulating kinase (ASK)-1 bound Thioredoxin (Trx[SH]2) dissociates this complex, creating free and activated ASK1-signalosome and (2) transforming growth factor-mediated activation of (TGF)-beta-activated kinase (TAK)1 and TGF-beta-activated kinase 1-binding protein (TAB)1. AECs isolated from normal term, not-in-labor fetal membranes increased p38MAPK in response to CSE and downregulated it in response to antioxidant N-acetylcysteine. In AECs, both Trx and ASK1 were localized; however, they remained dissociated and not complexed, regardless of conditions. Silencing either ASK1 or its downstream effectors (MKK3/6) did not affect OS-induced p38MAPK activation. Conversely, OS increased TGF-beta's release from AECs and increased phosphorylation of both p38MAPK and TAB1. Silencing of TAB1, but not TAK1, prevented p38MAPK activation, which is indicative of TAB1-mediated autophosphorylation of p38MAPK, an activation mechanism seldom seen. OS-induced p38MAPK activation in AECs is ASK1-Trx signalosome-independent and is mediated by the TGF-beta pathway. This knowledge will help to design strategies to reduce p38MAPK activation-associated pregnancy risks.
Theta Oscillations Index Frontal Decision-Making and Mediate Reciprocal Frontal–Parietal Interactions in Willed Attention
Authors: Rajan Abhijit , Siegel Scott N , Liu Yuelu , Bengson Jesse , Mangun George R , Ding Mingzhou
Published: June 2018

Attention can be attracted reflexively by sensory signals, biased by learning or reward, or focused voluntarily based on momentary goals. When voluntary attention is focused by purely internal decision processes (will), rather than instructions via external cues, we call this “willed attention.” In prior work, we reported ERP and fMRI correlates of willed spatial attention in trial-by-trial cuing tasks. Here we further investigated the oscillatory mechanisms of willed attention by contrasting the event-related EEG spectrogram between instructional and choice cues. Two experiments were conducted at 2 different sites using the same visuospatial attention paradigm. Consistent between the 2 experiments, we found increases in frontal theta power (starting at ~500 ms post cue) for willed attention relative to instructed attention. This frontal theta increase was accompanied by increased frontal–parietal theta-band coherence and bidirectional Granger causality. Additionally, the onset of attention-related posterior alpha power lateralization was delayed in willed attention relative to instructed attention, and the amount of delay was related to the timing of frontal theta increase. These results, replicated across 2 experiments, suggest that theta oscillations are the neuronal signals indexing decision-making in the frontal cortex, and mediating reciprocal communications between the frontal executive and parietal attentional control regions during willed attention.
A transform method for the biharmonic equation in multiply connected circular domains
Authors: Luca Elena , Crowdy Darren G
Published: June 2018

A new transform approach for solving mixed boundary value problems for the biharmonic equation in simply and multiply connected circular domains is presented. This work is a sequel to Crowdy (2015, IMA J. Appl. Math., 80, 1902–1931) where new transform techniques were developed for boundary value problems for Laplace’s equation in circular domains. A circular domain is defined to be a domain, which can be simply or multiply connected, having boundaries that are a union of circular arc segments. The method provides a flexible approach to finding quasi-analytical solutions to a wide range of problems in fluid dynamics and plane elasticity. Three example problems involving slow viscous flows are solved in detail to illustrate how to apply the method; these concern flow towards a semicircular ridge, a translating and rotating cylinder near a wall as well as in a channel geometry.
Management of inflammatory rheumatic conditions in the elderly
Authors: Lahaye Clément , Tatar Zuzana , Dubost Jean-Jacques , Tournadre Anne , Soubrier Martin
Published: June 2018

The number of elderly people with chronic inflammatory rheumatic diseases is increasing. This heterogeneous and comorbid population is at particular risk of cardiovascular, neoplastic, infectious and iatrogenic complications. The development of biotherapies has paved the way for innovative therapeutic strategies, which are associated with toxicities. In this review, we have focused on the scientific and therapeutic changes impacting the management of elderly patients affected by RA, SpA or PsA. A multidimensional health assessment resulting in an integrated therapeutic strategy was identified as a major research direction for improving the management of elderly patients.
Generalization of the minimum covariance determinant algorithm for categorical and mixed data types
Authors: Beaton Derek , Sunderland Kelly M. ,   ADNI, Levine Brian , Mandzia Jennifer , Masellis Mario , Swartz Richard H. , Troyer Angela K. ,   ONDRI, Binns Malcolm A. , Abdi Hervé , Strother Stephen C.
Published: June 2018

The minimum covariance determinant (MCD) algorithm is one of the most common techniques to detect anomalous or outlying observations. The MCD algorithm depends on two features of multivariate data: the determinant of a matrix (i.e., geometric mean of the eigenvalues) and Mahalanobis distances (MD). While the MCD algorithm is commonly used, and has many extensions, the MCD is limited to analyses of quantitative data and more specifically data assumed to be continuous. One reason why the MCD does not extend to other data types such as categorical or ordinal data is because there is not a well-defined MD for data types other than continuous data. To address the lack of MCD-like techniques for categorical or mixed data we present a generalization of the MCD. To do so, we rely on a multivariate technique called correspondence analysis (CA). Through CA we can define MD via singular vectors and also compute the determinant from CA’s eigenvalues. Here we define and illustrate a generalized MCD on categorical data and then show how our generalized MCD extends beyond categorical data to accommodate mixed data types (e.g., categorical, ordinal, and continuous). We illustrate this generalized MCD on data from two large scale projects: the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), with genetics (categorical), clinical instruments and surveys (categorical or ordinal), and neuroimaging (continuous) data. We also make R code and toy data available in order to illustrate our generalized MCD.
A cerebellar role in evidence-guided decision-making
Authors: Deverett Ben , Koay Sue Ann , Oostland Marlies , Wang Samuel S.-H.
Published: June 2018

To make successful evidence-based decisions, the brain must rapidly and accurately transform sensory inputs into specific goal-directed behaviors. Most experimental work on this subject has focused on forebrain mechanisms. Here we show that during perceptual decision-making over a period of seconds, decision-, sensory-, and error-related information converge on the lateral posterior cerebellum in crus I, a structure that communicates bidirectionally with numerous forebrain regions. We trained mice on a novel evidence-accumulation task and demonstrated that cerebellar inactivation reduces behavioral accuracy without impairing motor parameters of action. Using two-photon calcium imaging, we found that Purkinje cell somatic activity encoded choice- and evidence-related variables. Decision errors were represented by dendritic calcium spikes, which are known to drive plasticity. We propose that cerebellar circuitry may contribute to the set of distributed computations in the brain that support accurate perceptual decision-making.
Modeling large fluctuations of thousands of clones during hematopoiesis: the role of stem cell self-renewal and bursty progenitor dynamics in rhesus macaque
Authors: Xu Song , Kim Sanggu , Chen Irvin S. Y. , Chou Tom
Published: June 2018

In a recent clone-tracking experiment, millions of uniquely tagged hematopoietic stem cells (HSCs) were autologously transplanted into rhesus macaques and peripheral blood containing thousands of tags were sampled and sequenced over 14 years to quantify the abundance of hundreds to thousands of tags or “clones.” Two major puzzles of the data have been observed: consistent differences and massive temporal fluctuations of clone populations. The large sample-to-sample variability can lead clones to occasionally go “extinct” but “resurrect” themselves in subsequent samples. Although heterogeneity in HSC differentiation rates, potentially due to tagging, and random sampling of the animals’ blood and cellular demographic stochasticity might be invoked to explain these features, we show that random sampling cannot explain the magnitude of the temporal fluctuations. Moreover, we show through simplerneutralmechanistic and statistical models of hematopoiesis of tagged cells that a broad distribution in clone sizes can arise from stochastic HSC self-renewal instead of tag-induced heterogeneity. The very large clone population fluctuations that often lead to extinctions and resurrections can be naturally explained by a generation-limited proliferation constraint on the progenitor cells. This constraint leads to bursty cell population dynamics underlying the large temporal fluctuations. We analyzed experimental clone abundance data using a new statistic that counts clonal disappearances and provide least-squares estimates of two key model parameters in our model, the total HSC differentiation rate and the maximum number of progenitor-cell divisions.

Author summary

Hematopoiesis of virally tagged cells in rhesus macaques is analyzed in the context of a mechanistic and statistical model. We find that the clone size distribution and the temporal variability in the abundance of each clone (viral tag) in peripheral blood are consistent with (i) stochastic HSC self-renewal during bone marrow repair, (ii) clonal aging that restricts the number of generations of progenitor cells, and (iii) infrequent and small-size samples. By fitting data, we infer two key parameters that control the level of fluctuations of clone sizes in our model: the total HSC differentiation rate and the maximum proliferation capacity of progenitor cells. Our analysis provides insight into the mechanisms of hematopoiesis and a framework to guide future multiclone barcoding/lineage tracking measurements.
Synchrotron FTIR and Raman spectroscopy 1 ectroscopy provide unique spectral fingerprints for Arabidopsis floral stem vascular tissues
Authors: Dinant S , Wolff N , De Marco F , Vilaine F , Gissot L , Aubry E , Sandt C , Bellini C , Le Hir R
Published: June 2018

Cell walls are highly complex structures that are modified during plant growth and development. For example, the development of phloem and xylem vascular cells, which participate in the transport of sugars and water as well as support, can be influenced by cell-specific cell wall composition. Here, we used synchrotron radiation-based infrared (SR-FTIR) and Raman spectroscopy to analyze the cell wall composition of wild-type and double mutant sweet11-1sweet12-1, which impairs sugar transport, Arabidopsis floral stem vascular tissue. The SR-FTIR spectra showed that in addition to modified xylem cell wall composition, phloem cell walls in the double mutant line were characterized by modified hemicellulose composition. Moreover, combining Raman spectroscopy with a Classification and Regression Tree (CART) method identified combinations of Raman shifts that could distinguish xylem vessels and fibers. Additionally, the disruption of SWEET11 and SWEET12 genes impacts xylem cell wall composition in a cell-specific manner, with changes in hemicelluloses and cellulose observed at the xylem vessel interface. These results suggest that the facilitated transport of sugars by transporters that exist between vascular parenchyma cells and conducting cells is important to ensuring correct phloem and xylem cell wall composition.

Highlight

Combining vibrational spectroscopy techniques and multivariate analysis shows that the disruption of SWEET genes impacts phloem cell wall composition and that the effect on xylem cell wall composition is cell-specific.
Diffusible Signal Factor signaling regulates multiple functions in the opportunistic pathogen Stenotrophomonas maltophilia
Authors: An Shi-qi , Tang Ji-liang
Published: June 2018

Stenotrophomonas maltophilia is a Gram-negative bacterium commonly isolated from nosocomial infections. Analysis of the genome of the clinical Stenotrophomonas maltophilia isolate K279a indicates that it encodes a diffusible signal factor (DSF)-dependent cell-cell signaling mechanism that is highly similar to the system previously described in phytopathogens from the genera Xanthomonas and Xylella. Here we demonstrate that in S. maltophilia strain K279a, DSF signaling regulates factors contributing to virulence, biofilm formation and motility of this important opportunistic pathogen.
Culturing the ubiquitous freshwater actinobacterial acI lineage by supplying a biochemical ‘helper’ catalase
Authors: Kim Suhyun , Kang Ilnam , Seo Ji-Hui , Cho Jang-Cheon
Published: June 2018

Unlike the ocean from which abundant microorganisms with streamlined genomes such as Prochlorococcus, Pelagibacter, and Nitrosopumilus have been isolated, no stable axenic bacterial cultures are available for the ubiquitous freshwater actinobacterial acI lineage. The acI lineage is among the most successful limnic bacterioplankton found on all continents, often representing more than half of all microbial cells in the lacustrine environment and constituting multiple ecotypes. Dilution-to-extinction culturing followed by whole-genome amplification recently yielded 20 complete acI genomes from lakes in Asia and Europe. However, stably growing pure cultures have not been established despite various efforts at cultivation using growth factors predicted from genome information. Here, we report two pure cultures of the acI lineage successfully maintained by supplementing the growth media with catalase. Catalase was critical for stabilizing growth by degrading hydrogen peroxide, irrespective of the genomic presence of the catalase-peroxidase (katG) gene, making the acI strains the first example of the Black Queen hypothesis reported for freshwater bacteria. The two strains, representing two novel species, displayed differential phenotypes and distinct preferences for reduced sulfurs and carbohydrates, some of which were difficult to predict based on genomic information. Our results suggest that culture of previously uncultured freshwater bacteria can be facilitated by a simple catalase-supplement method and indicate that genome-based metabolic prediction can be complemented by physiological analyses.
Comparative sensitivity of the test with tuberculosis recombinant allergen, containing ESAT6-CFP10 protein, and Mantoux test with 2 TU PPD-L in newly diagnosed tuberculosis children and adolescents in Moscow
Authors: Slogotskaya Liudmila , Bogorodskaya Elena , Ivanova Diana , Sevostyanova Tatiana
Published: June 2018

Background. A group of Russian scientists has developed Diaskintest, which comprises Mycobacterium tuberculosis-specific recombinant proteins CFP10-ESAT6, for skin testing (0.2 µg/0.1 ml).

Study purpose: to evaluate the comparative sensitivity of TST with 2 TU PPD-L and a skin test with tuberculous recombinant allergen (Diaskintest) containing the ESAT6-CFP10 protein in children and adolescents with newly diagnosed respiratory tuberculosis during mass screening in the primary medical service in Moscow, 2013–2016.

Materials and methods. The trial was a comprehensive retrospective group study of children and adolescents diagnosed in Moscow with respiratory tuberculosis in 2013–2016, aged 0 to 17 years inclusive. From 441 patients selected for analysis 408 patients had both tests (TST with 2 TU PPD-L and Diaskintest) performed, in 193 patients both tests were given simultaneously, of them 162 patients were BCG-vaccinated.

Results. Comparative results of both tests in 408 patients with tuberculosis: at cut-off 5 mm, both tests has similar sensitivity: Diaskintest 98.3 % (95 % CI 97.0–99.6 %), TST 98.0 % (95 % CI 96.7–99.4 %), at cut-off 10 mm, the sensitivity decreases for both tests: Diaskintest 90.0 % (95 % CI 87.0–93.0 %), TST 88.7 % (95 % CI 85.6–91.9 %), but at cut-off 15 mm, the decrease in sensitivity is statistically significant: for Diaskintest 61.5 % (95 % CI 56.7–66.3 %), and for TST 46.3 % (95 % CI 41.4–51.3 %), p <0.0001.

The results of simultaneous setting of tests on different hands in 193 people (including 162 BCG-vaccinated), do not differ from the results for 408 people.

The correlation between the results of Diaskintest and TST was significant in all groups.

Conclusion. In children and adolescents with respiratory tuberculosis, Diaskintest of 0.2 µg/ml and the Mantoux test with 2 TU PPD-L have high sensitivity (98%) at a cut-off of 5 mm; however, at cut-off 15 mm sensitivity is significantly reduced, and the decrease is more pronounced in the Mantoux test. The advantage of Diaskintest is that, unlike the Mantoux test, it has high specificity under the conditions of mass BCG vaccination. The test is cost-effective, simple to carry out, and can be used in mass screening.
Secretion of an Argonaute protein by a parasitic nematode and the evolution of its siRNA guides
Authors: Chow FWN , Koutsovoulos G , Ovando-Vázquez C , Neophytou K , Bermúdez-Barrientos JR , Laetsch DR , Robertson E , Kumar S , Claycomb JM , Blaxter M , Abreu-Goodger C , Buck AH
Published: June 2018

Extracellular RNA has been proposed to mediate communication between cells and organisms however relatively little is understood regarding how specific sequences are selected for export. Here we describe a specific Argonaute protein (exWAGO) that is secreted in extracellular vesicles (EVs) released by the gastrointestinal nematodeHeligmosomoides bakeri, at multiple copies per EV. Phylogenetic and gene expression analyses demonstrate exWAGO orthologues are highly conserved and abundantly expressed in related parasites but highly diverged in free-living genusCaenorhabditis. We show that the most abundant small RNAs released from the nematode parasite are not microRNAs as previously thought, but rather secondary small interfering RNAs (siRNAs) that are produced by RNA-dependent RNA Polymerases. The siRNAs that are released in EVs have distinct evolutionary properties compared to those resident in free-living or parasitic nematodes. Immunoprecipitation of exWAGO demonstrates that it specifically associates with siRNAs from transposons and newly evolved repetitive elements that are packaged in EVs and released into the host environment. Together this work demonstrates molecular and evolutionary selectivity in the small RNA sequences that are released in EVs into the host environment and identifies a novel Argonaute protein as the mediator of this.
Systematic discovery of uncharacterized transcription factors inEscherichia coliK-12 MG1655
Authors: Gao Ye , Yurkovich James T. , Seo Sang Woo , Kabimoldayev Ilyas , Dräger Andreas , Chen Ke , Sastry Anand V. , Fang Xin , Mih Nathan , Yang Laurence , Eichner Johannes , Cho Byung-Kwan , Kim Donghyuk , Palsson Bernhard O.
Published: June 2018

Transcriptional regulation enables cells to respond to environmental changes. Yet, among the estimated 304 candidate transcription factors (TFs) inEscherichia coliK-12 MG1655, 185 have been experimentally identified and only a few tens of them have been fully characterized by ChIP methods. Understanding the remaining TFs is key to improving our knowledge of theE. colitranscriptional regulatory network (TRN). Here, we developed an integrated workflow for the computational prediction and comprehensive experimental validation of TFs using a suite of genome-wide experiments. We applied this workflow to: 1) identify 16 candidate TFs from over a hundred candidate uncharacterized genes; 2) capture a total of 255 DNA binding peaks for 10 candidate TFs resulting in six high-confidence binding motifs; 3) reconstruct the regulons of these 10 TFs by determining gene expression changes upon deletion of each TF; and 4) determine the regulatory roles of three TFs (YiaJ, YdcI, and YeiE) as regulators of L-ascorbate utilization, proton transfer and acetate metabolism, and iron homeostasis under iron limited condition, respectively. Together, these results demonstrate how this workflow can be used to discover, characterize, and elucidate regulatory functions of uncharacterized TFs in parallel.
Identification and characterization of genes encoding the nuclear envelope LINC complex in the monocot speciesZea mays
Authors: Gumber Hardeep K. , McKenna Joseph F. , Estrada Amado L. , Tolmie Andrea F. , Graumann Katja , Bass Hank W.
Published: June 2018

The LINC (Linker of Nucleoskeleton to Cytoskeleton) complex is an essential multi-protein structure spanning the nuclear envelope. It connects the cytoplasm to the nucleoplasm, functions to maintain nuclear shape and architecture, and regulates chromosome dynamics during cell division. Knowledge of LINC complex composition and function in the plant kingdom is primarily limited to Arabidopsis, but critically missing from the evolutionarily distant monocots which include grasses, the most important agronomic crops worldwide. To fill this knowledge gap, we identified and characterized 22 maize genes, including a new grass-specific KASH gene family. Using bioinformatic, biochemical, and cell biological approaches, we provide evidence that representative KASH candidates localize to the nuclear periphery and interact with ZmSUN2in vivo. FRAP experiments using domain-deletion constructs verified that this SUN-KASH interaction was dependent on the SUN but not the coiled-coil domain of ZmSUN2. A summary working model is proposed for the entire maize LINC complex encoded by conserved and divergent gene families. These findings expand our knowledge of the plant nuclear envelope in a model grass species, with implications for both basic and applied cellular research.

SUMMARY STATEMENT

Genes encoding maize candidates for the core LINC and associated complex proteins have been comprehensively identified with functional validation by one or more assays for several of the KASH genes.
BigStitcher: Reconstructing high-resolution image datasets of cleared and expanded samples
Authors: Hörl David , Rusak Fabio Rojas , Preusser Friedrich , Tillberg Paul , Randel Nadine , Chhetri Raghav K. , Cardona Albert , Keller Philipp J. , Harz Hartmann , Leonhardt Heinrich , Treier Mathias , Preibisch Stephan
Published: June 2018

New methods for clearing and expansion of biological objects create large, transparent samples that can be rapidly imaged using light-sheet microscopy. Resulting image acquisitions are terabytes in size and consist of many large, unaligned image tiles that suffer from optical distortions. We developed the BigStitcher software that efficiently handles and reconstructs large multi-tile, multi-view acquisitions compensating all major optical effects, thereby making single-cell resolved whole-organ datasets amenable to biological studies.
Optimizing sequential decisions in the drift-diffusion model
Authors: Nguyen Khanh P. , Josić Krešimir , Kilpatrick Zachary P.
Published: June 2018

To make decisions organisms often accumulate information across multiple timescales. However, most experimental and modeling studies of decision-making focus on sequences of independent trials. On the other hand, natural environments are characterized by long temporal correlations, and evidence used to make a present choice is often relevant to future decisions. To understand decision-making under these conditions we analyze how a model ideal observer accumulates evidence to freely make choices across a sequence of correlated trials. We use principles of probabilistic inference to show that an ideal observer incorporates information obtained on one trial as an initial bias on the next. This bias decreases the time, but not the accuracy of the next decision. Furthermore, in finite sequences of trials the rate of reward is maximized when the observer deliberates longer for early decisions, but responds more quickly towards the end of the sequence. Our model also explains experimentally observed patterns in decision times and choices, thus providing a mathematically principled foundation for evidence-accumulation models of sequential decisions.
Enterococcus faecalisV583 LuxS/AI-2 system is devoid of role in intra-species quorum-sensing but contributes to virulence in aDrosophilahost model
Authors: Gaspar Frederic , Teixeira Neuza , Montero Natalia , Aleksandrzak-Piekarczyk Tamara , Matos Renata , Gonzalez-Zorn Bruno , Jacinto António , Barreto Crespo Maria Teresa , Silva Lopes Maria de Fátima
Published: June 2018

The AI-2 i nterspecies quorum-sensing molecule is produced by the LuxS enzyme and has been ascribed a role in virulence in several bacteria. The nosocomial pathogenEnterococcus faecalisinhabits several different environments where multispecies communities are established. However, despite the presence of aluxSgene in this pathogen, its role inE. faecalispathogenesis has never been assessed. In the present work, we deleted theluxSgene from the vancomycin-resistant clinical isolateE. faecalisV583 and demonstrated the lack of AI-2 production by the mutant strain. Using microarrays and externally added (S)-4,5-dihydroxy-2,3-pentanedione we showed that AI-2 is not sensed byE. faecalisas a canonical quorum-sensing molecule and that theluxSmutation caused pleiotropic effects in gene expression, which could not be complemented by extracellularly added AI-2. These global differences in gene expression affected several gene functional roles, mainly those enrolled in metabolism and transport. Metabolic phenotypi ng of theluxSmutant, using Biolog plates, showed differences in utilization of galactose. AI-2 production by LuxS was shown to be irrelevant for some phenotypes related to the pathogenic potential ofE. faecalisnamely biofilm formation, adhesion to Caco-2 cells, resistance to oxidative stress and survival inside J-774 macrophages. However, theluxSmutant was attenuated when tested in theDrosophilaseptic injury model, as its deletion led to delayed fly death. Overall our findings show that differential gene expression related to theluxSmutation cannot be ascribed to quorum-sensing. Moreover, the role of LuxS appears to be limited to metabolism.
Microglial and Astrocyte priming in the APP/PS1 model of Alzheimer’s Disease: increased vulnerability to acute inflammation and cognitive deficits
Authors: Lopez-Rodriguez Ana Belen , Hennessy Edel , Murray Carol , Lewis Anouchka , Barra Niamh de , Fagan Steven , Rooney Michael , Nazmi Arshed , Cunningham Colm
Published: June 2018

Alzheimer’s disease (AD) causes devastating cognitive decline and has no disease-modifying therapies. Neuroinflammation is a significant contributor to disease progression but its precise contribution remains unclear. An emerging literature indicates that secondary inflammatory insults including acute trauma and infection alter the trajectory of chronic neurodegenerative diseases and the roles of microglia and astrocytes require elucidation. The current study, using the APP/PS1 mouse model of AD, demonstrates that microglia are primed by β-amyloid pathology to induce exaggerated IL-1β responses to acute stimulation with LPS or IL-1β. Despite disease-associated NLRP3 inflammasome activation, evidenced by ASC speck formation, APP/PS1 microglial cells show neither IL-1β induction nor NFκB p65 nuclear localisation. Upon secondary stimulation with LPS or IL-1β, NFκB-p65 nuclear localisation and exaggerated pro-IL-1 induction occur. Microglial priming was also unmasked by secondary stimulation with systemic LPS leading to significant cognitive impairment in APP/PS1 mice compared to WT LPS-treated mice. Astrocytes have also recently emerged as displaying significant phenotypic heterogeneity. Here, by-passing microglial priming, and acutely challenging mice with intra-hippocampal IL-1β we demonstrate that astrocytes proximal to Aβ-plaques are also primed to produce exaggerated CCL2, CXCL1 and CXCL10 responses. Many astrocytosis-associated genes in APP/PS1 mice share these exaggerated responses to IL-1β, while others are equally induced in both strains. Collectively the data show that the amyloid-laden brain shows multiple vulnerabilities to secondary inflammatory challenge: both microglia and astrocytes are primed to produce exaggerated secondary inflammation and systemic LPS is sufficient to cause cognitive impairments relevant to delirium, selectively in animals with prior amyloid pathology.
Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons
Authors: Deneault Eric , White Sean H. , Rodrigues Deivid C. , Ross P. Joel , Faheem Muhammad , Zaslavsky Kirill , Wang Zhuozhi , Alexandrova Roumiana , Pellecchia Giovanna , Wei Wei , Piekna Alina , Kaur Gaganjot , Howe Jennifer L. , Kwan Vickie , Thiruvahindrapuram Bhooma , Walker Susan , Pasceri Peter , Merico Daniele , Yuen Ryan K.C. , Singh Karun K. , Ellis James , Scherer Stephen W.
Published: June 2018

Autism Spectrum Disorder is phenotypically and genetically heterogeneous, but genomic analyses have identified candidate susceptibility genes. We present a CRISPR gene editing strategy to insert a protein tag and premature termination sites creating an induced pluripotent stem cell (iPSC) knockout resource for functional studies of 10 ASD-relevant genes (AFF2/FMR2, ANOS1, ASTN2, ATRX, CACNA1C, CHD8, DLGAP2, KCNQ2, SCN2A, TENM1). Neurogenin 2 (NEUROG2)-directed differentiation of iPSCs allowed production of cortical excitatory neurons, and mutant proteins were not detectable. RNAseq revealed convergence of several neuronal networks. Using both patch-clamp and multi-electrode array approaches, the electrophysiological deficits measured were distinct for different mutations. However, they culminated in a consistent reduction in synaptic activity, including reduced spontaneous excitatory post-synaptic current frequencies in AFF2/FMR2-, ASTN2-, ATRX-, KCNQ2- and SCN2A-null neurons. Despite ASD susceptibility genes belonging to different gene ontologies, isogenic stem cell resources can reveal common functional phenotypes, such as reduced functional connectivity.