bluuebunny/crossref_metadata_2025_split huggingface dataset:
OsHKT1;5 mediates Na+ exclusion in the vasculature to protect leaf blades and reproductive tissues from salt toxicity in rice
Authors: Kobayashi Natsuko I. , Yamaji Naoki , Yamamoto Hiroki , Okubo Kaoru , Ueno Hiroki , Costa Alex , Tanoi Keitaro , Matsumura Hideo , Fujii‐Kashino Miho , Horiuchi Tomoki , Nayef Mohammad Al , Shabala Sergey , An Gynheung , Ma Jian Feng , Horie Tomoaki 
Published: May 2017

SummarySalt tolerance quantitative trait loci analysis of rice has revealed that the SKC1 locus, which is involved in a higher K+/Na+ ratio in shoots, corresponds to the OsHKT1;5 gene encoding a Na+‐selective transporter. However, physiological roles of OsHKT1;5 in rice exposed to salt stress remain elusive, and no OsHKT1;5 gene disruption mutants have been characterized to date. In this study, we dissected two independent T‐DNA insertional OsHKT1;5 mutants. Measurements of ion contents in tissues and 22Na+ tracer imaging experiments showed that loss‐of‐function of OsHKT1;5 in salt‐stressed rice roots triggers massive Na+ accumulation in shoots. Salt stress‐induced increases in the OsHKT1;5 transcript were observed in roots and basal stems, including basal nodes. Immuno‐staining using an anti‐OsHKT1;5 peptide antibody indicated that OsHKT1;5 is localized in cells adjacent to the xylem in roots. Additionally, direct introduction of 22Na+ tracer to leaf sheaths also demonstrated the involvement of OsHKT1;5 in xylem Na+ unloading in leaf sheaths. Furthermore, OsHKT1;5 was indicated to be present in the plasma membrane and found to localize also in the phloem of diffuse vascular bundles in basal nodes. Together with the characteristic 22Na+ allocation in the blade of the developing immature leaf in the mutants, these results suggest a novel function of OsHKT1;5 in mediating Na+ exclusion in the phloem to prevent Na+ transfer to young leaf blades. Our findings further demonstrate that the function of OsHKT1;5 is crucial over growth stages of rice, including the protection of the next generation seeds as well as of vital leaf blades under salt stress.
ETHQV6.3 is involved in melon climacteric fruit ripening and is encoded by a NAC domain transcription factor
Authors: Ríos Pablo , Argyris Jason , Vegas Juan , Leida Carmen , Kenigswald Merav , Tzuri Galil , Troadec Christelle , Bendahmane Abdelhafid , Katzir Nurit , Picó Belén , Monforte Antonio J. , Garcia‐Mas Jordi 
Published: May 2017

SummaryFruit ripening is divided into climacteric and non‐climacteric types depending on the presence or absence of a transient rise in respiration rate and the production of autocatalytic ethylene. Melon is ideal for the study of fruit ripening, as both climacteric and non‐climacteric varieties exist. Two introgressions of the non‐climacteric accession PI 161375, encompassed in the QTLs ETHQB3.5 and ETHQV6.3, into the non‐climacteric ‘Piel de Sapo’ background are able to induce climacteric ripening independently. We report that the gene underlying ETHQV6.3 is MELO3C016540 (CmNAC‐NOR), encoding a NAC (NAM, ATAF1,2, CUC2) transcription factor that is closely related to the tomato NOR (non‐ripening) gene. CmNAC‐NOR was functionally validated through the identification of two TILLING lines carrying non‐synonymous mutations in the conserved NAC domain region. In an otherwise highly climacteric genetic background, both mutations provoked a significant delay in the onset of fruit ripening and in the biosynthesis of ethylene. The PI 161375 allele of ETHQV6.3 is similar to that of climacteric lines of the cantalupensis type and, when introgressed into the non‐climacteric ‘Piel de Sapo’, partially restores its climacteric ripening capacity. CmNAC‐NOR is expressed in fruit flesh of both climacteric and non‐climacteric lines, suggesting that the causal mutation may not be acting at the transcriptional level. The use of a comparative genetic approach in a species with both climacteric and non‐climacteric ripening is a powerful strategy to dissect the complex mechanisms regulating the onset of fruit ripening.
High‐throughput sequencing reveals bacterial community composition in the rhizosphere of the invasive plant Flaveria bidentis
Authors: Song Z , Zhang R H , Fu W D , Zhang T , Yan J , Zhang G L 
Published: May 2017

SummaryBacteria are important soil components as both decomposers and plant symbionts and play a major role in plant–microbe interaction processes. However, little is known about the diversity of bacterial communities in the rhizosphere of the invasive plant Flaveria bidentis. In this study, we used high‐throughput sequencing to investigate bacterial communities in the rhizosphere of F. bidentis, compared with those of native crop maize and control plant Setaria viridis. We obtained >70 000 analysis reads from the three samples and used bioinformatics and multivariate statistics to analyse the results. An analysis of indicators showed that F. bidentis samples had lower richness but higher diversity than maize and S. viridis samples. Operational taxonomic unit (OTU)‐based bioinformatics and statistical analysis also demonstrated that F. bidentis significantly altered the bacterial rhizosphere community. Higher abundance of Actinobacteria and lower abundance of Firmicutes were observed in F. bidentis rhizosphere than those of maize and S. viridis. Redundancy analysis (RDA) revealed the correlations between soil bacteria communities, soil nutrients and the abundance of bacterial groups. Our results provide a starting point for investigations of the effects of F. bidentis on soil bacterial diversity and a theoretical basis for the microecological mechanism of F. bidentis invasion.
Novel Sampling Method for Assessing Human-Pathogen Interactions in the Natural Environment Using Boot Socks and Citizen Scientists, with Application to Campylobacter Seasonality
Authors: Jones Natalia R. , Millman Caroline , van der Es Mike , Hukelova Miroslava , Forbes Ken J. , Glover Catherine , Haldenby Sam , Hunter Paul R. , Jackson Kathryn , O'Brien Sarah J. , Rigby Dan , Strachan Norval J. C. , Williams Nicola , Lake Iain R. ,   for the ENIGMA Consortium
Published: May 2017

ABSTRACT

This paper introduces a novel method for sampling pathogens in natural environments. It uses fabric boot socks worn over walkers' shoes to allow the collection of composite samples over large areas. Wide-area sampling is better suited to studies focusing on human exposure to pathogens (e.g., recreational walking). This sampling method is implemented using a citizen science approach: groups of three walkers wearing boot socks undertook one of six routes, 40 times over 16 months in the North West (NW) and East Anglian (EA) regions of England. To validate this methodology, we report the successful implementation of this citizen science approach, the observation that
Campylobacter
bacteria were detected on 47% of boot socks, and the observation that multiple boot socks from individual walks produced consistent results. The findings indicate higher
Campylobacter
levels in the livestock-dominated NW than in EA (55.8% versus 38.6%). Seasonal differences in the presence of
Campylobacter
bacteria were found between the regions, with indications of winter peaks in both regions but a spring peak in the NW. The presence of
Campylobacter
bacteria on boot socks was negatively associated with ambient temperature (
P
= 0.011) and positively associated with precipitation (
P
< 0.001), results consistent with our understanding of
Campylobacter
survival and the probability of material adhering to boot socks.
Campylobacter jejuni
was the predominant species found;
Campylobacter coli
was largely restricted to the livestock-dominated NW. Source attribution analysis indicated that the potential source of
C. jejuni
was predominantly sheep in the NW and wild birds in EA but did not differ between peak and nonpeak periods of human incidence.

IMPORTANCE
There is debate in the literature on the pathways through which pathogens are transferred from the environment to humans. We report on the success of a novel method for sampling human-pathogen interactions using boot socks and citizen science techniques, which enable us to sample human-pathogen interactions that may occur through visits to natural environments. This contrasts with traditional environmental sampling, which is based on spot sampling techniques and does not sample human-pathogen interactions. Our methods are of practical value to scientists trying to understand the transmission of pathogens from the environment to people. Our findings provide insight into the risk of
Campylobacter
exposure from recreational visits and an understanding of seasonal differences in risk and the factors behind these patterns. We highlight the
Campylobacter
species predominantly encountered and the potential sources of
C. jejuni
.
Digitally Barcoding
Mycobacterium tuberculosis
Reveals
In Vivo
Infection Dynamics in the Macaque Model of Tuberculosis
Authors: Martin Constance J. , Cadena Anthony M. , Leung Vivian W. , Lin Philana Ling , Maiello Pauline , Hicks Nathan , Chase Michael R. , Flynn JoAnne L. , Fortune Sarah M. 
Published: May 2017

ABSTRACT

Infection with
Mycobacterium tuberculosis
causes a spectrum of outcomes; the majority of individuals contain but do not eliminate the infection, while a small subset present with primary active tuberculosis (TB) disease. This variability in infection outcomes is recapitulated at the granuloma level within each host, such that some sites of infection can be fully cleared while others progress. Understanding the spectrum of TB outcomes requires new tools to deconstruct the mechanisms underlying differences in granuloma fate. Here, we use novel genome-encoded barcodes to uniquely tag individual
M. tuberculosis
bacilli, enabling us to quantitatively track the trajectory of each infecting bacterium in a macaque model of TB. We also introduce a robust bioinformatics pipeline capable of identifying and counting barcode sequences within complex mixtures and at various read depths. By coupling this tagging strategy with serial positron emission tomography coregistered with computed tomography (PET/CT) imaging of lung pathology in macaques, we define a lesional map of
M. tuberculosis
infection dynamics. We find that there is no significant infection bottleneck, but there are significant constraints on productive bacterial trafficking out of primary granulomas. Our findings validate our barcoding approach and demonstrate its utility in probing lesion-specific biology and dissemination. This novel technology has the potential to greatly enhance our understanding of local dynamics in tuberculosis.

IMPORTANCE
Classically,
M. tuberculosis
infection was thought to result in either latent infection or active disease. More recently, the field has recognized that there is a spectrum of
M. tuberculosis
infection clinical outcomes. Within a single host, this spectrum is recapitulated at the granuloma level, where there can simultaneously be lesional sterilization and poorly contained disease. To better understand the lesional biology of TB infection, we digitally barcoded
M. tuberculosis
to quantitatively track the fate of each infecting bacterium. By combining this technology with serial PET-CT imaging, we can dynamically track both bacterial populations and granuloma trajectories. We demonstrate that there is little constraint on the bacterial population at the time of infection. However, the granuloma imposes a strong bottleneck on dissemination, and the subset of granulomas at risk of dissemination can be distinguished by physical features.
Microbiota-Derived Short-Chain Fatty Acids Modulate Expression of
Campylobacter jejuni
Determinants Required for Commensalism and Virulence
Authors: Luethy Paul M. , Huynh Steven , Ribardo Deborah A. , Winter Sebastian E. , Parker Craig T. , Hendrixson David R. 
Published: May 2017

ABSTRACT

Campylobacter jejuni
promotes commensalism in the intestinal tracts of avian hosts and diarrheal disease in humans, yet components of intestinal environments recognized as spatial cues specific for different intestinal regions by the bacterium to initiate interactions in either host are mostly unknown. By analyzing a
C. jejuni
acetogenesis mutant defective in converting acetyl coenzyme A (Ac-CoA) to acetate and commensal colonization of young chicks, we discovered evidence for
in vivo
microbiota-derived short-chain fatty acids (SCFAs) and organic acids as cues recognized by
C. jejuni
that modulate expression of determinants required for commensalism. We identified a set of
C. jejuni
genes encoding catabolic enzymes and transport systems for amino acids required for
in vivo
growth whose expression was modulated by SCFAs. Transcription of these genes was reduced in the acetogenesis mutant but was restored upon supplementation with physiological concentrations of the SCFAs acetate and butyrate present in the lower intestinal tracts of avian and human hosts. Conversely, the organic acid lactate, which is abundant in the upper intestinal tract where
C. jejuni
colonizes less efficiently, reduced expression of these genes. We propose that microbiota-generated SCFAs and lactate are cues for
C. jejuni
to discriminate between different intestinal regions. Spatial gradients of these metabolites likely allow
C. jejuni
to locate preferred niches in the lower intestinal tract and induce expression of factors required for intestinal growth and commensal colonization. Our findings provide insights into the types of cues
C. jejuni
monitors in the avian host for commensalism and likely in humans to promote diarrheal disease.

IMPORTANCE
Campylobacter jejuni
is a commensal of the intestinal tracts of avian species and other animals and a leading cause of diarrheal disease in humans. The types of cues sensed by
C. jejuni
to influence responses to promote commensalism or infection are largely lacking. By analyzing a
C. jejuni
acetogenesis mutant, we discovered a set of genes whose expression is modulated by lactate and short-chain fatty acids produced by the microbiota in the intestinal tract. These genes include those encoding catabolic enzymes and transport systems for amino acids that are required by
C. jejuni
for
in vivo
growth and intestinal colonization. We propose that gradients of these microbiota-generated metabolites are cues for spatial discrimination between areas of the intestines so that the bacterium can locate niches in the lower intestinal tract for optimal growth for commensalism in avian species and possibly infection of human hosts leading to diarrheal disease.
Different Roles of Mitochondrial Calcium Uniporter Complex Subunits in Growth and Infectivity of
Trypanosoma cruzi
Authors: Chiurillo Miguel A. , Lander Noelia , Bertolini Mayara S. , Storey Melissa , Vercesi Anibal E. , Docampo Roberto 
Published: May 2017

ABSTRACT

Trypanosoma cruzi
is the agent of Chagas disease, and the finding that this parasite possesses a mitochondrial calcium uniporter (TcMCU) with characteristics similar to that of mammalian mitochondria was fundamental for the discovery of the molecular nature of MCU in eukaryotes. We report here that ablation of
TcMCU
, or its paralog
TcMCUb
, by clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 led to a marked decrease in mitochondrial Ca
2+
uptake without affecting the membrane potential of these cells, whereas overexpression of each gene caused a significant increase in the ability of mitochondria to accumulate Ca
2+
. While
TcMCU-
knockout (KO) epimastigotes were viable and able to differentiate into trypomastigotes, infect host cells, and replicate normally, ablation of
TcMCUb
resulted in epimastigotes having an important growth defect, lower rates of respiration and metacyclogenesis, more pronounced autophagy changes under starvation, and significantly reduced infectivity. Overexpression of
TcMCUb
, in contrast to what was proposed for its mammalian ortholog, did not result in a dominant negative effect on TcMCU.

IMPORTANCE
The finding of a mitochondrial calcium uniporter (MCU) in
Trypanosoma cruzi
was essential for the discovery of the molecular nature of this transporter in mammals. In this work, we used the CRISPR/Cas9 technique that we recently developed for
T. cruzi
to knock out two components of the uniporter: MCU, the pore subunit, and MCUb, which was proposed as a negative regulator of MCU in human cells. In contrast to what occurs in human cells, MCU is not essential, while MCUb is essential for growth, differentiation, and infectivity; has a bioenergetic role; and does not act as a dominant negative subunit of MCU.
Fault core process and clay content derived from XRF analysis: Salina Creek Fault, Utah
Authors: Brown Alton A. , Davies Russell K. , Treverton Anne Covault 
Published: May 2017

Abstract
The distribution of fault rocks interpreted across a modelled fault in oil or gas reservoirs is most often described by its clay content derived from standard industry algorithms such as shale gouge ratio and clay smear factor. These distributions are below the mapping resolution in seismic data, and the actual processes and mechanisms for the fault-rock development are not well understood. A well-exposed and well-preserved low-throw fault in an old railroad tunnel near Salina, Utah provides the access and scale to interpret fault-rock distributions, measure their clay contents and describe the fault-rock development. A significant number of fault-rock elemental compositions were measured quickly on the outcrop surface using a hand-held X-ray fluorescence (XRF) elemental analyser with a novel surface preparation and analysis strategy. The elemental data were converted to clay contents using a small set of samples where elemental composition was calibrated to X-ray diffraction mineralogy. The mineralogy data provide a basis for evaluating the degree of mixing of protolith beds during fault-rock development in the fault core. The fault core is not randomly mixed fragments derived from the protolith (gouge or breccia), but rather discrete, thin layers parallel to the fault surface, many of which can be traced back to a source sandstone or mudstone bed. The mineralogical composition of some fault-rock layers are unchanged from their protolith source bed, but other layers are mechanical mixtures of several source beds. The shale gouge ratio algorithm under-represents the average measured fault-rock clay content. The clay smear algorithm more accurately describes the clay content distribution, but underestimates the clay content heterogeneity along the smear length. A key uncertainty for predicting fault sealing remains prediction of the lengths and continuity of smears.
Immune-Related Gene Expression Profiling After PD-1 Blockade in Non–Small Cell Lung Carcinoma, Head and Neck Squamous Cell Carcinoma, and Melanoma
Authors: Prat Aleix , Navarro Alejandro , Paré Laia , Reguart Noemí , Galván Patricia , Pascual Tomás , Martínez Alex , Nuciforo Paolo , Comerma Laura , Alos Llucia , Pardo Nuria , Cedrés Susana , Fan Cheng , Parker Joel S. , Gaba Lydia , Victoria Iván , Viñolas Nuria , Vivancos Ana , Arance Ana , Felip Enriqueta 
Published: May 2017

Abstract
Antibody targeting of the immune checkpoint receptor PD1 produces therapeutic activity in a variety of solid tumors, but most patients exhibit partial or complete resistance to treatment for reasons that are unclear. In this study, we evaluated tumor specimens from 65 patients with melanoma, lung nonsquamous, squamous cell lung or head and neck cancers who were treated with the approved PD1-targeting antibodies pembrolizumab or nivolumab. Tumor RNA before anti-PD1 therapy was analyzed on the nCounter system using the PanCancer 730-Immune Panel, and we identified 23 immune-related genes or signatures linked to response and progression-free survival (PFS). In addition, we evaluated intra- and interbiopsy variability of PD1, PD-L1, CD8A, and CD4 mRNAs and their relationship with tumor-infiltrating lymphocytes (TIL) and PD-L1 IHC expression. Among the biomarkers examined, PD1 gene expression along with 12 signatures tracking CD8 and CD4 T-cell activation, natural killer cells, and IFN activation associated significantly with nonprogressive disease and PFS. These associations were independent of sample timing, drug used, or cancer type. TIL correlated moderately (∼0.50) with PD1 and CD8A mRNA levels and weakly (∼0.35) with CD4 and PD-L1. IHC expression of PD-L1 correlated strongly with PD-L1 (0.90), moderately with CD4 and CD8A, and weakly with PD1. Reproducibility of gene expression in intra- and interbiopsy specimens was very high (total SD &lt;3%). Overall, our results support the hypothesis that identification of a preexisting and stable adaptive immune response as defined by mRNA expression pattern is reproducible and sufficient to predict clinical outcome, regardless of the type of cancer or the PD1 therapeutic antibody administered to patients. Cancer Res; 77(13); 3540–50. ©2017 AACR.
Noninvasive Interrogation of DLL3 Expression in Metastatic Small Cell Lung Cancer
Authors: Sharma Sai Kiran , Pourat Jacob , Abdel-Atti Dalya , Carlin Sean D. , Piersigilli Alessandra , Bankovich Alexander J. , Gardner Eric E. , Hamdy Omar , Isse Kumiko , Bheddah Sheila , Sandoval Joseph , Cunanan Kristen M. , Johansen Eric B. , Allaj Viola , Sisodiya Vikram , Liu David , Zeglis Brian M. , Rudin Charles M. , Dylla Scott J. , Poirier John T. , Lewis Jason S. 
Published: May 2017

Abstract
The Notch ligand DLL3 has emerged as a novel therapeutic target expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine carcinomas. Rovalpituzumab teserine (Rova-T; SC16LD6.5) is a first-in-class DLL3-targeted antibody–drug conjugate with encouraging initial safety and efficacy profiles in SCLC in the clinic. Here we demonstrate that tumor expression of DLL3, although orders of magnitude lower in surface protein expression than typical oncology targets of immunoPET, can serve as an imaging biomarker for SCLC. We developed 89Zr-labeled SC16 antibody as a companion diagnostic agent to facilitate selection of patients for treatment with Rova-T based on a noninvasive interrogation of the in vivo status of DLL3 expression using PET imaging. Despite low cell-surface abundance of DLL3, immunoPET imaging with 89Zr-labeled SC16 antibody enabled delineation of subcutaneous and orthotopic SCLC tumor xenografts as well as distant organ metastases with high sensitivity. Uptake of the radiotracer in tumors was concordant with levels of DLL3 expression and, most notably, DLL3 immunoPET yielded rank-order correlation for response to SC16LD6.5 therapy in SCLC patient–derived xenograft models. Cancer Res; 77(14); 3931–41. ©2017 AACR.