bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure of AdoMet radical enzyme 7‐carboxy‐7‐deazaguanine synthase from Escherichia coli suggests how modifications near [4Fe–4S] cluster engender flavodoxin specificity
Authors: Grell Tsehai A.J. , Bell Benjamin N. , Nguyen Chi , Dowling Daniel P. , Bruender Nathan A. , Bandarian Vahe , Drennan Catherine L.
Published: October 2018

7‐Carboxy‐7‐deazaguanine synthase, QueE, catalyzes the radical mediated ring contraction of 6‐carboxy‐5,6,7,8‐tetrahydropterin, forming the characteristic pyrrolopyrimidine core of all 7‐deazaguanine natural products. QueE is a member of the S‐adenosyl‐L‐methionine (AdoMet) radical enzyme superfamily, which harnesses the reactivity of radical intermediates to perform challenging chemical reactions. Members of the AdoMet radical enzyme superfamily utilize a canonical binding motif, a CX3CXϕC motif, to bind a [4Fe‐4S] cluster, and a partial (β/α)6 TIM barrel fold for the arrangement of AdoMet and substrates for catalysis. Although variations to both the cluster‐binding motif and the core fold have been observed, visualization of drastic variations in the structure of QueE from Burkholderia multivorans called into question whether a re‐haul of the defining characteristics of this superfamily was in order. Surprisingly, the structure of QueE from Bacillus subtilis revealed an architecture more reminiscent of the classical AdoMet radical enzyme. With these two QueE structures revealing varying degrees of alterations to the classical AdoMet fold, a new question arises: what is the purpose of these alterations? Here, we present the structure of a third QueE enzyme from Escherichia coli, which establishes the middle range of the spectrum of variation observed in these homologs. With these three homologs, we compare and contrast the structural architecture and make hypotheses about the role of these structural variations in binding and recognizing the biological reductant, flavodoxin.

Broader impact statement: We know more about how enzymes are tailored for catalytic activity than about how enzymes are tailored to react with a physiological reductant. Here, we consider structural differences between three 7‐carboxy‐7‐deazaguanine synthases and how these differences may be related to the interaction between these enzymes and their biological reductant, flavodoxin.
Methods to identify the substrates of thiol‐disulfide oxidoreductases
Authors: Fujimoto Takushi , Inaba Kenji , Kadokura Hiroshi
Published: October 2018

The formation of a disulfide bond is a critical step in the folding of numerous secretory and membrane proteins and catalyzed in vivo. A variety of mechanisms and protein structures have evolved to catalyze oxidative protein folding. Those enzymes that directly interact with a folding protein to accelerate its oxidative folding are mostly thiol‐disulfide oxidoreductases that belong to the thioredoxin superfamily. The enzymes of this class often use a CXXC active‐site motif embedded in their thioredoxin‐like fold to promote formation, isomerization, and reduction of a disulfide bond in their target proteins. Over the past decade or so, an increasing number of substrates of the thiol‐disulfide oxidoreductases that are present in the ER of mammalian cells have been discovered, revealing that the enzymes play unexpectedly diverse physiological functions. However, functions of some of these enzymes still remain unclear due to the lack of information on their substrates. Here, we review the methods used by researchers to identify the substrates of these enzymes and provide data that show the importance of using trichloroacetic acid in sample preparation for the substrate identification, hoping to aid future studies. We particularly focus on successful studies that have uncovered physiological substrates and functions of the enzymes in the periplasm of Gram‐negative bacteria and the endoplasmic reticulum of mammalian cells. Similar approaches should be applicable to enzymes in other cellular compartments or in other organisms.
MicroRNAs as prognostic markers in prostate cancer
Authors: Suer Ilknur , Guzel Esra , Karatas Omer F. , Creighton Chad J. , Ittmann Michael , Ozen Mustafa
Published: October 2018

Background

Prostate cancer (PCa) is the most commonly diagnosed malignancy in men who are especially over the age of 50 years in the western countries. Currently used therapeutic modalities mostly fail to give positive clinical outcomes and nearly 30% of the PCa patients eventually develop clinical recurrence. Therefore, understanding the underlying mechanisms of PCa progression is of paramount importance to help determining the course of disease. In this study, we aimed at profiling the differentially expressed microRNAs in recurrent PCa samples.

Methods

We profiled the microRNA expression of 20 recurrent and 20 non‐recurrent PCa patients with microRNA microarray, and validated the differential expression of significantly deregulated microRNAs in 40 recurrent and 39 non‐recurrent PCa specimens using quantitative reverse‐transcription PCR (qRT‐PCR). Data were statistically analyzed using two‐sided Student's t‐test, Pearson Correlation test, Receiver operating characteristic (ROC) analysis.

Results

Our results demonstrated that a total of 682 probes were significantly deregulated in recurrent versus non‐recurrent PCa specimen comparison. Among those, we confirmed the significant downregulation of miR‐424 and upregulation of miR‐572 with further qRT‐PCR analysis in a larger sample set. Further ROC analysis showed that these microRNAs have enough power to distinguish recurrent specimens from non‐recurrent ones on their own.

Conclusions

Here, we report that differential expression of miR‐424 and miR‐572 in recurrent PCa specimens can serve as novel biomarkers for prediction of PCa progression.
An explorative study towards the chemical synthesis of the immunoglobulin G1 Fc CH3 domain
Authors: Grassi Luigi , Roschger Cornelia , Stanojlović Vesna , Cabrele Chiara
Published: October 2018

Monoclonal antibodies, fusion proteins including the immunoglobulin fragment c (Ig Fc) CH2‐CH3 domains, and engineered antibodies are prominent representatives of an important class of drugs and drug candidates, which are referred to as biotherapeutics or biopharmaceuticals. These recombinant proteins are highly heterogeneous due to their glycosylation pattern. In addition, enzyme‐independent reactions, like deamidation, dehydration, and oxidation of sensitive side chains, may contribute to their heterogeneity in a minor amount. To investigate the biological impact of a spontaneous chemical modification, especially if found to be recurrent in a biotherapeutic, it would be necessary to reproduce it in a homogeneous manner. Herein, we undertook an explorative study towards the chemical synthesis of the IgG1 Fc CH3 domain, which has been shown to undergo spontaneous changes like succinimide formation and methionine oxidation. We used Fmoc‐solid‐phase peptide synthesis (SPPS) and native chemical ligation (NCL) to test the accessibility of large fragments of the IgG1 Fc CH3 domain. In general, the incorporation of pseudoproline dipeptides improved the quality of the crude peptide precursors; however, sequences larger than 44 residues could not be achieved by standard stepwise elongation with Fmoc‐SPPS. In contrast, the application of NCL with cysteine residues, which were either native or introduced ad hoc, allowed the assembly of the C‐terminal IgG1 Fc CH3 sequence 371 to 450. The syntheses reported here show advantages and limitations of the chemical approaches chosen for the preparation of the synthetic IgG1 Fc CH3 domain and will guide future plans towards the synthesis of both the native and selectively modified full‐length domain.
The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging
Authors: Bi Si‐Xing , Li Xiao‐Hu , Wei Chuan‐Sheng , Xiang Hui‐Hui , Shen Yu‐Xian , Yu Yong‐Qiang
Published: October 2018

To investigate the suppressive effects of xanthatin on glioma growth in a nude mouse xenograft model and rat orthotopic implantation model using magnetic resonance imaging (MRI) to dynamically monitor the antitumour growth and antiangiogenesis effects of xanthatin. The nude mouse xenograft tumour model and rat orthotopic implantation model were established to observe the antitumour effects of xanthatin in vivo. In the rat orthotopic implanted tumour model, MRI scanning was used to dynamically monitor the antitumour growth effect and evaluate the antiangiogenesis effect of xanthatin. We found that xanthatin at a dose of 0.4 mg/10 g dramatically decreased the growth of xenograft tumours in nude mice. The antiangiogenesis effect of xanthatin C6 glioma was evaluated by dynamic contrast‐enhanced (DCE) MRI via comparison of the volume transfer constant (Ktrans) value, a parameter that reflects vessel permeability. We found that xanthatin at the doses of 8 and 16 mg/kg significantly decreased the Ktrans value, which suggests that xanthatin has antiangiogenesis effects. These data demonstrate the suppressive effects of xanthatin on C6 glioma occur via antiangiogenesis. Meanwhile, this study also provides evidence for the application of quantitative parameters of DCE‐MRI for dynamically evaluating the growth and angiogenesis of intracranial tumours and for experimental and clinical research.
Phytochemical information and pharmacological activities of Okra (Abelmoschus esculentus): A literature‐based review
Authors: Islam Muhammad Torequl
Published: October 2018

This review aimed at summarizing phytochemical reports and biological activities of Abelmoschus esculentus L. from the database sources. For this, an up‐to‐date search was made in the PubMed, Science Direct, MedLine, Scopus, and Google Scholar. The findings suggest that A. esculentus contains various nutrients and important phytochemicals. It possesses a number of important biological activities, including antioxidant, anti‐inflammatory and immunomodulatory, antibacterial, anticancer, antidiabetic, organ protective, and neuropharmacological activities. Moreover, the plant also has lipid‐lowering, trypsin inhibitory, hemagglutinating, antiadhesive, and antifatigue activities. The fruit and seeds are well tolerated in humans and other animals. In conclusion, A. esculentus may be one of the best sources of pharmacologically active lead compounds. More research is necessary on its toxicogenetic effects in animals.
Monitoring the ratio of two normal variables using variable sampling interval exponentially weighted moving average control charts
Authors: Nguyen Huu Du , Tran Kim Phuc , Heuchenne Cédric
Published: October 2018

We investigate in this paper a new type of control chart called VSI EWMA‐RZ by integrating the variable sampling interval feature (VSI) with the exponentially weighted moving average (EWMA) scheme to monitor the ratio of two normal random variables. Because the distribution of the ratio is skewed, we suggest designing two separated one‐sided charts instead of one two‐sided chart. A new coefficient is introduced allowing us to be free to choose a sampling interval provided that it optimizes the performance of the control chart. We also make a direct comparison between the VSI EWMA‐RZ charts and standard EWMA‐RZ control charts. The numerical simulations show that the proposed charts outperform the standard EWMA charts in detecting process shifts. An application is illustrated for the implementation of the VSI EWMA‐RZ control charts in the food industry.
Finite‐horizon fault estimation under imperfect measurements and stochastic communication protocol: Dealing with finite‐time boundedness
Authors: Dong Hongli , Hou Nan , Wang Zidong , Liu Hongjian
Published: October 2018

In this paper, we analyze the finite‐horizon fault estimation issue for a kind of time‐varying nonlinear systems with imperfect measurement signals under the stochastic communication protocol (SCP). The imperfect measurements result from randomly occurring sensor nonlinearities obeying sensor‐wise Bernoulli distributions. The Markov‐chain‐driven SCP is introduced to regulate the signal transmission to alleviate the communication congestion. The aim of the considered issue is to propose the design algorithm of a group of time‐varying fault estimators such that the estimation error dynamics satisfies both the H∞ and the finite‐time boundedness (FTB) performance requirements. First, sufficient conditions are set up to guarantee the existence of the satisfactory H∞ FTB fault estimators through intensive stochastic analyses and matrix operations. Then, the gains of such fault estimators are explicitly parameterized by resorting to the solution to recursive linear matrix inequalities. Finally, the correctness of the devised fault estimation approach is demonstrated by a numerical example.
Estimating causal effects of treatment in RCTs with provider and subject noncompliance
Authors: Sheng Elisa , Li Wei , Zhou Xiao‐Hua
Published: October 2018

Subject noncompliance is a common problem in the analysis of randomized clinical trials (RCTs). With cognitive behavioral interventions, the addition of provider noncompliance further complicates making causal inference. As a motivating example, we consider an RCT of a motivational interviewing (MI)‐based behavioral intervention for treating problem drug use. Treatment receipt depends on compliance of both a therapist (provider) and a patient (subject), where MI isreceivedwhen the therapist adheres to the MI protocol and the patient actively participates in the intervention. However, therapists cannot be forced to follow protocol and patients cannot be forced to cooperate in an intervention. In this article, we (1) define a causal estimand of interest based on a principal stratification framework,the average causal effect of treatment among provider‐subject pairs that comply with assignmentorACE(cc); (2) explore possible assumptions that identifyACE(cc); (3) develop novel estimators ofACE(cc); (4) evaluate estimators' statistical properties via simulation; and (5) apply our proposed methods for estimatingACE(cc) to data from our motivating example.
More Than Just Word of the Day: Vocabulary Apps for English Learners
Authors: Northrop Laura , Andrei Elena
Published: October 2018

The authors present a tool that teachers can use to evaluate the rigor of vocabulary apps for their English learners. The tool asks about effective instructional practices, types of instructional activities, and technology features. The authors used the evaluation tool to examine 53 vocabulary apps for English learners and found overall app quality to be poor. Although most apps included narration (58%), additional features that would benefit students learning English, such as automatic translation to another language or visuals, were largely absent. Finally, the authors present ways that, despite their limitations, vocabulary apps can be used to support English learners’ vocabulary development.
On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis
Authors: Bykerk Vivian P. , Burmester Gerd R. , Combe Bernard G. , Furst Daniel E. , Huizinga Tom W. J. , Ahmad Harris A. , Emery Paul
Published: October 2018

Clinical outcomes in patients with early rheumatoid arthritis (RA) were assessed by baseline symptom duration in the Assessing Very Early Rheumatoid arthritis Treatment trial (ClinicalTrials.gov; NCT01142726). Patients with early, active RA were randomized to subcutaneous (SC) abatacept 125 mg/week plus methotrexate (MTX), SC abatacept alone, or MTX monotherapy for 12 months. All RA treatments were withdrawn after 12 months in patients with Disease Activity Score in 28 joints (C-reactive protein; DAS28-CRP) < 3.2. In this post hoc analysis, the proportion of patients achieving protocol-defined remission (DAS28-CRP < 2.6) or improvement in physical function at 12 and at both 12 and 18 months was assessed according to symptom duration (≤ 3 months, > 3 to ≤ 6 months, or > 6 months) and treatment group. No clinically significant differences were seen in baseline demographics or characteristics across symptom duration groups. Irrespective of baseline symptom duration, a numerically higher proportion of abatacept plus MTX-treated patients achieved DAS-defined remission at month 12 and sustained remission at month 18 compared with MTX monotherapy. A numerically higher proportion of abatacept plus MTX-treated patients with symptom duration ≤ 3 months maintained DAS-defined remission after complete treatment withdrawal from 12 to 18 months compared with longer symptom duration groups. This subgroup also had the fastest onset of clinical response (DAS28-CRP < 2.6) after initiation of treatment. Health Assessment Questionnaire–Disability Index response was similar regardless of baseline symptom duration. Overall, symptom duration of ≤ 3 months was associated with a faster onset of clinical response and higher rates of drug-free remission following treatment with abatacept plus MTX.
Simulation and application of cooperative driving sense systems using prescan software
Authors: Wang Chia-Sui , Liu Ding-Yu , Hsu Kuei-Shu
Published: October 2018

The PreScan was used to construct and test environmental simulation sections for a vehicle sensor. It was employed to build simulation road sections or import real road sections and build virtual infrastructures, streets, and scenes, where vehicles, unexpected road incidents, traffic signals, human factors, light sources, and simulated weather changes were considered, which served as the basis for testing the vehicle sensor value using PreScan. The built-in PreScan vehicle modules were imported to the built virtual road sections and scenes, and cameras were installed at appropriate positions to measure the perspective of a moving vehicle. Furthermore, Simulink was used to model the vehicle sensors to be tested. Globally, tens of thousands of people have died in traffic accidents wherein more than half of the deaths were caused by drivers’ negligence. Therefore, traffic safety-related Advanced Driver Assistance Systems or autopilot systems have received increasing attention from vehicle manufacturers, with vehicle sensor performance being the key to safety. Previously, physical vehicles were mostly employed to test the vehicle sensors, which entailed high costs and risks. However, by employing PreScan in the tests, highly reliable real physical data can be obtained and high costs and risks associated with the use of physical vehicles could be avoided.
Multisite study of the relationships between antemortem [11C]PIB‐PET Centiloid values and postmortem measures of Alzheimer's disease neuropathology
Authors: La Joie Renaud , Ayakta Nagehan , Seeley William W. , Borys Ewa , Boxer Adam L. , DeCarli Charles , Doré Vincent , Grinberg Lea T. , Huang Eric , Hwang Ji‐Hye , Ikonomovic Milos D. , Jack Clifford , Jagust William J. , Jin Lee‐Way , Klunk William E. , Kofler Julia , Lesman‐Segev Orit H. , Lockhart Samuel N. , Lowe Val J. , Masters Colin L. , Mathis Chester A. , McLean Catriona L. , Miller Bruce L. , Mungas Daniel , O'Neil James P. , Olichney John M. , Parisi Joseph E. , Petersen Ronald C. , Rosen Howard J. , Rowe Christopher C. , Spina Salvatore , Vemuri Prashanthi , Villemagne Victor L. , Murray Melissa E. , Rabinovici Gil D.
Published: October 2018

Introduction

We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [11C]PIB–positron emission tomography ([11C]PIB‐PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ‐PET quantification.

Methods

Four centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings.

Results

CL values increased with each CERAD neuritic plaque score increment (median −3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. PET‐pathology associations were comparable across sites and unchanged when restricting the analyses to the 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate‐to‐frequent neuritic plaques (area under the curve = 0.910, sensitivity = 89.2%, specificity = 86.4%), whereas 24.4 CL identified intermediate‐to‐high AD neuropathological changes (area under the curve = 0.894, sensitivity = 84.1%, specificity = 87.9%).

Discussion

Our study demonstrated the robustness of a multisite Centiloid [11C]PIB‐PET study and established a range of pathology‐based CL thresholds.
Posterior Vertebral Endplate Fractures: A Retrospective Study on a Rare Etiology of Back Pain in Youth and Young Adults
Authors: Conlee Erin M. , Driscoll Sherilyn W. , Coleman Wood Krista A. , McIntosh Amy L. , Dekutoski Mark L. , Brandenburg Joline E.
Published: October 2018

Background

Posterior lumbar vertebral endplate fracture occurs with avulsion of the ring apophysis from the posterior vertebral body. Although this has been described in adolescents and young adults, proper diagnosis is often delayed or missed entirely. Surgery may be curative.

Objective

To determine the common clinical features and treatment outcomes in youth and young adults with posterior lumbar vertebral endplate fractures.

Design

Retrospective case series.

Setting

Academic medical institution.

Patients

Patients 10 to 25 years old from 2000 through 2012 with posterior vertebral endplate fracture diagnosis.

Main Outcome Measurements

Demographic characteristics, diagnostic studies, interventions, and change in symptoms postoperatively.

Results

A total of 16 patients had posterior vertebral endplate fractures (8 male patients; mean age, 15.2 years)—8.3% of 192 patients with inclusion age range undergoing spinal surgery for causes unrelated to trauma, scoliosis, or malignancy. The most common signs and symptoms were low back and radiating leg pain, positive straight leg raise, hamstring contracture, and abnormal gait. Cause was sports related for 12 patients (75%). Mean (range) time to diagnosis was 13.0 (3.0‐63.0) months. Diagnosis was most commonly made with lumbar magnetic resonance imaging (n = 6). Most fractures occurred at L5 (n = 8, 50%) and L4 (n = 5, 31.3%). Conservative measures were trialed before surgery. Nine patients had “complete relief” following surgery and seven “improved.”

Conclusions

Posterior vertebral endplate fracture should be considered in differential diagnosis of a youth or young adult with back pain, radiating leg pain, and limited knee extension, regardless of symptom onset. For patients in whom conservative management fails, consultation with an experienced physician whose practice specializes in spine medicine is recommended.

Level of Evidence

IV
Two Faces of Foreign Affairs Federalism and What They Mean for Climate Change Mitigation
Authors: Galbraith Jean
Published: October 2018

President Trump has done the impossible: he has made the international community enthusiastic about U.S. federalism. Even as they express dismay at Trump's plan to abandon the Paris Agreement, foreign leaders and internationalists have praised the efforts of  U.S. states and cities to combat climate change mitigation in accordance with the Agreement's goals. These leaders are responding to what I will call the outer face of foreign affairs federalism—the direct international engagement undertaken by U.S. states and cities. This outer face has gained visibility in recent years, spurred on not only by the exigencies of climate but also by developments in legal practice. Less noticed internationally but of great practical importance is the inner face of foreign affairs federalism—the ways in which U.S. states and cities interact with the federal government. In this contribution, I first describe these two faces of foreign affairs federalism as they relate to climate and then suggest some ways in which foreign leaders and internationalists could expand the outer face and respond to the inner face.
On Localism and the Persistent Power of the State
Authors: Carlarne Cinnamon P.
Published: October 2018

On June 1, 2017, President Trump declared that the United States would “cease all implementation of the non-binding Paris Accord and the draconian financial and economic burdens the agreement imposes on our country.” The United States’ de facto withdrawal from the Paris Agreement represented an important inflection point for conceptualizing the role of nonstate actors in addressing climate change. President Trump's announcement was met with an outpouring of resistance and widespread and concerted efforts to mobilize substate, nonprofit, and private actors to step into the void created by his announcement and to help keep the United States on track to pursue domestic and international commitments to address climate change despite federal recalcitrance. Within the leadership void created by the Trump Administration and amidst the increasingly extensive body of sub- and nonstate climate efforts, it is tempting to decenter the role of the state or to underestimate the persistent power of the state to shape the approach and effectiveness of nonstate actions. Failing to recognize that the state retains significant power in this field undermines efforts to understand the realities within which nonstate actors operate. This creates a set of heightened expectations for these actors that defies the reality of the political, economic, and social resources available to them and masks the challenges inherent in relying upon a fragmented, shifting, and differently accountable set of actors to effect pervasive change.
A Conservative Party? Pots and People in the Hebridean Neolithic
Authors: Copper Mike , Armit Ian
Published: October 2018

Recent analysis of the ceramic assemblage from the Neolithic loch islet settlement of Eilean Dòmhnuill, North Uist, in the Western Isles of Scotland has highlighted the intense conservatism of the potting traditions over a period of more than 800 years. Hebridean Neolithic pottery exhibits clear relationships with pottery from Argyll, Arran, and Bute, as well as Orkney and the north-east mainland of Scotland. It appears to have developed a distinctive, often decoratively elaborate regional form very soon after its initial appearance, which subsequently appears to have undergone little or no significant change until the introduction of Grooved Ware in the early 3rd millenniumbc. An association exists between large assemblages of elaborately decorated Hebridean pottery and a number of artificial islets in freshwater lochs, some very small and producing little or no evidence for domestic activities. This might be explained by the importance of commensality in mediating relations between small communities in the Western Isle at such sites following the introduction of agriculture in the 2nd quarter of the 4th millenniumbc. The conservatism and stasis evident at Eilean Dòmhnuill, in the face of environmental decline, raises wider issues around the adaptive capabilities of the first farming communities prior to significant social changes in the earlier 3rd millenniumbc.
Editorial note
Authors: MITKOV RUSLAN
Published: October 2018

Our passion to continually improve the journal and, as a result, our contribution to the community drives our quest for highly diversified and up-to-date content. We are launching a new category of papers, i.e., ‘keynote’ or ‘invited’ papers, which will be penned by leading lights in the field.
Substantial Increase in Heat Wave Risks in China in a Future Warmer World
Authors: Sun Ying , Hu Ting , Zhang Xuebin
Published: October 2018

Increases in the frequency and intensity of heat waves have serious impacts on human health, agriculture, energy and infrastructure. Here we use three simple metrics including the number of heat wave days, the length of heat wave season, and the annual hottest day temperature to characterize future changes in heat wave severity in China, based on large ensemble simulations conducted with the Canadian Earth System Model Version 2 (CanESM2) in the context of emergency preparedness. A heat wave day is defined as a day with daily maximum temperature reaching heat alert level (35 °C). We find that global warming is associated with more severe heat waves including more heat wave days, longer heat wave season and higher hottest day temperature, and expansion of regions impacted by heat waves. While the increase in the magnitude of extremes in heat wave metrics with global warming level is close to linear, the increase in the frequency of extremes is much faster. For example, the historically hottest summer in 2013 in Eastern China, which occurs about one in 5 years in the 2013 climate, is projected to become more frequent than one in 2 years under 1.5 °C global warming and almost every year would be worse than 2013 under 2 °C warming. Additionally, the increase in the frequency of the extreme events is larger for rarer extremes. The frequencies for once‐in‐5‐year, once‐in‐10‐year, and once‐in‐50‐year events increase by 2.5, 3.5, and 5.5 times under 1.5 °C global warming, respectively.
Tracking Water‐Rock Interaction at the Atlantis Massif (MAR, 30°N) Using Sulfur Geochemistry
Authors: Liebmann J. , Schwarzenbach E. M. , Früh‐Green G. L. , Boschi C. , Rouméjon S. , Strauss H. , Wiechert U. , John T.
Published: October 2018

Hydrothermal alteration and serpentinization of ultramafic rocks at oceanic core complexes involve extensive element exchange between fluid and rock and a wide range of biogeochemical processes. These processes influence the global sulfur cycle due to both biogenic and abiogenic removal of seawater sulfate. Hence, ocean floor serpentinization connects the hydrosphere, biosphere, and lithosphere. This work presents a study of the sulfur geochemistry of highly altered mafic and ultramafic samples from the Atlantis Massif located at 30°N along the Mid‐Atlantic Ridge. The analyzed samples were drilled during International Ocean Discovery Program Expedition 357 and collected during Alvin dives in 2000, 2003, and 2005. Multiple sulfur isotope analyses of sulfide and sulfate phases indicate that several processes took place during progressive hydrothermal alteration: (1) incorporation of seawater sulfate, (2) thermochemical sulfate reduction during interaction with high‐temperature (high‐T; 350–400 °C), low‐pH fluids and input of H2S derived from leaching gabbroic intrusions, (3) microbial sulfate reduction, and (4) oxidation of sulfides at high water‐rock ratios. Petrological examinations show that high‐T fluids mostly postdated the bulk serpentinization and that these fluid pulses were relatively localized (<1 dm scale) resulting in a highly heterogeneous mineralogy. Locally, high‐T fluid influx took place subsequent to microbial sulfate reduction and oxidation as indicated by geochemical modeling. Overall, this study documents the complex interplay of magmatic processes, fluid‐rock interaction, and microbial activity that take place during the formation of oceanic core complexes and where mantle rocks are exposed to seawater.
An Observationally Based Evaluation of Subgrid Scale Ice Thickness Distributions Simulated in a Large‐Scale Sea Ice‐Ocean Model of the Arctic Ocean
Authors: Ungermann Mischa , Losch Martin
Published: October 2018

A key parameterization in sea ice models describes the subgrid scale ice thickness distribution. Based on only a few observations, the ice thickness distribution model was shown to be consistent with field data and to improve the simulation's large‐scale properties. The available submarine and airborne observations enable to evaluate in greater detail the ability of a pan‐Arctic sea ice‐ocean model with an ice thickness distribution parameterization to reproduce observed thickness distributions in different regions and seasons. Many observations are reproduced accurately. Some cases of poorly simulated modes and tails of the distributions are tentatively attributed to simplified thermodynamics and inaccurate deformation fields. Variability on decadal timescales, however, is generally underestimated. Thickness distributions in individual grid cells of the model show similar differences between regions and seasons as observed regional mean distributions, but the modeled grid‐scale variability is lower than observed. Simulated modal thicknesses of first‐year ice are only insufficiently different from those of multiyear ice. The modal thickness proves to be a useful metric for quantifying model biases in both dynamics and thermodynamics. In addition to improving basin‐wide mean variables, the ice thickness distribution parameterization provides reliable and valuable additional subgrid scale data. At the same time the low climate sensitivity of the parameterization may affect longer simulations with strong climate change aspects.
Modulation of the ENSO on Winter Aerosol Pollution in the Eastern Region of China
Authors: Sun Jiaren , Li Haiyan , Zhang Wenjun , Li Tairu , Zhao Wei , Zuo Zhiyan , Guo Shu , Wu Dui , Fan Shaojia
Published: October 2018

The modulation of the El Niño/Southern Oscillation (ENSO) on winter aerosol pollution (WAP) in the eastern region of China (ERC) was investigated from a climatological perspective. The results show that the weakened East Asian winter monsoon during El Niño events has an important influence on increased WAP in ERC, especially over northern China. The enhancement of the East Asian winter monsoon related to La Niña events reduces WAP in northeast, east, and south China but increases it in central and western China. Compared to northern China, anomalies in dynamic and thermodynamic conditions related to ENSO lead to more uncertainties in its effect on aerosol pollution over southern China. El Niño (La Niña) events tend to cause southwesterly (northeasterly) wind anomalies in winter southern China, along with the blocking effect of Nanling Mountains on southward (northward) air pollution, which is not (is) beneficial for the transport outside or dilution in local aerosols over southern China. Meanwhile, positive (negative) water vapor convergence and rainfall anomalies caused by El Niño (La Niña) are (are not) beneficial for the local removal of aerosols. The dominance of both factors determines the ENSO modulation on aerosols over southern China. An atmospheric global climate model largely reproduces the observed findings. Consistent with the observation, El Niño events exacerbate WAP in most of ERC, whereas La Niña ones reduce it except for western China.
Decoupling of Two Closely Located Dipole Antennas by a Split‐Loop Resonator
Authors: Sharifian Mazraeh Mollaei M. , Hurshkainen A. , Kurdjumov S. , Glybovski S. , Simovski Constantin
Published: October 2018

In this paper, we theoretically and experimentally prove the possibility of the passive electromagnetic decoupling for two parallel resonant dipoles by a split‐loop resonator having the resonance band overlapping with that of the active dipoles. We show that the replacement of the decoupling dipole suggested in the literature as a tool for decoupling of two closely located dipole antennas by our split‐loop resonator results in the twofold enlargement of the operation band.
Hydrologic Observation, Model, and Theory Congruence on Evapotranspiration Variance: Diagnosis of Multiple Observations and Land Surface Models
Authors: Zeng Ruijie , Cai Ximing
Published: October 2018

This paper reconciles the state‐of‐the‐art observations and simulations of evapotranspiration (ET) temporal variability through a diagnostic framework composed of an observation‐model‐theory triplet. Specifically, a confirmed theoretical tool, Evapotranspiration Temporal VARiance Decomposition (EVARD), is used as a benchmark to estimate ET monthly variance (
) across the contiguous United States (CONUS) with inputs including hydroclimatic observations, Gravity Recovery and Climate Experiment‐based terrestrial water storage, four observation‐based products (ETRSUW by the University of Washington, ETRSMOD16 from MOD16 Global Terrestrial ET Data Set, ETFLUXNET upscaled from of fluxtower observations, and ETGLEAM from Global Land Evaporation Amsterdam Model), and four operational land surface models (LSMs: MOSAIC, NOAH, NOAH‐MP, and VIC). Five experiments are systematically designed to evaluate and diagnose possible errors and uncertainties in ET temporal variance estimated by the four observation‐based ET products and the four LSM simulations. Based on the results of these experiments, the following diagnostic hypotheses regarding the uncertainty of the observation‐based ET products are illustrated: ETRSUW captures the high
signals in the Midwest with negligible bias and moderate uncertainty over the contiguous United States; ETFLUXNET systematically underestimates
over CONUS but with the lowest level of uncertainty; ETRSMOD16 has medium bias with the highest level of uncertainty, and the spatial distribution of high
signal from ETRSMOD16 is different from other estimates; ETGLEAM has slight negative bias and medium uncertainty, and
in the West Coast is smaller than that from ETVARD. Regarding the LSMs, it is found that any of the four LSMs can be the best depending on a certain set of reference observations. The study reveals that LSMs have shown a reasonably worthy, though not perfect, capability in estimating ET and its variability in regions/aquifers with limited human interference. However, RS‐based observations and theoretical estimates suggest that all the four LSMs examined in this study are not able to accurately predict the ET variability in regions/aquifers heavily influenced by human activities like Central Valley and High Plains aquifers; they all underestimate ET variability along the West Coast due to seasonal vegetation responses to Mediterranean climate and human water use. In addition, LSMs underestimate intraannual ET variance in California and the High Plains with underestimated terrestrial storage change components in ET variance, due to the inappropriate representation of groundwater pumping and its impact on ET and other hydrologic processes. This paper urges advancing hydrologic knowledge by finding congruence among models, data, and theories.
RETRACTED ARTICLE: Periostin secreted by cancer-associated fibroblasts promotes cancer stemness in head and neck cancer by activating protein tyrosine kinase 7
Authors: Yu Binbin , Wu Kailiu , Wang Xu , Zhang Jianjun , Wang Lizhen , Jiang Yingying , Zhu Xueqin , Chen Wantao , Yan Ming
Published: October 2018

Protein tyrosine kinase 7 (PTK7) and cancer-associated fibroblasts (CAFs) play important roles in cancer stemness, respectively. However, little is known about interaction between CAFs and PTK7 in cancers. In this study, we showed that PTK7 was significantly correlated with the Wnt/β-Catenin pathway and aggressive clinicopathologic features in human head and neck squamous cell carcinoma (HNSCC). Meanwhile, animal experiments showed that PTK7 enhanced chemoresistance and lung metastasis of HNSCC in vivo. In addition, co-immunoprecipitation (co-IP) assay demonstrated that POSTN secreted by CAFs was a potential upstream ligand of PTK7 which might act as a receptor. Further analysis revealed that POSTN promoted the cancer stem cell (CSC)-like phenotype via PTK7–Wnt/β-Catenin signaling, including the proliferation and invasion of HNSCC cells in vitro, as well as tumor initiation and progression in vivo. Collectively, our study proved that CAF-derived POSTN might promote cancer stemness via interacting with PTK7 in HNSCC, suggesting that the combination of POSTN and PTK7 might be a potential prognostic and diagnostic indicator and a  promising therapeutic target.
Enhanced mRNA FISH with compact quantum dots
Authors: Liu Yang , Le Phuong , Lim Sung Jun , Ma Liang , Sarkar Suresh , Han Zhiyuan , Murphy Stephen J. , Kosari Farhad , Vasmatzis George , Cheville John C. , Smith Andrew M.
Published: October 2018

Fluorescence in situ hybridization (FISH) is the primary technology used to image and count mRNA in single cells, but applications of the technique are limited by photophysical shortcomings of organic dyes. Inorganic quantum dots (QDs) can overcome these problems but years of development have not yielded viable QD-FISH probes. Here we report that macromolecular size thresholds limit mRNA labeling in cells, and that a new generation of compact QDs produces accurate mRNA counts. Compared with dyes, compact QD probes provide exceptional photostability and more robust transcript quantification due to enhanced brightness. New spectrally engineered QDs also allow quantification of multiple distinct mRNA transcripts at the single-molecule level in individual cells. We expect that QD-FISH will particularly benefit high-resolution gene expression studies in three dimensional biological specimens for which quantification and multiplexing are major challenges.
Identifying long-term stable refugia for relict plant species in East Asia
Authors: Tang Cindy Q. , Matsui Tetsuya , Ohashi Haruka , Dong Yi-Fei , Momohara Arata , Herrando-Moraira Sonia , Qian Shenhua , Yang Yongchuan , Ohsawa Masahiko , Luu Hong Truong , Grote Paul J. , Krestov Pavel V. , Ben LePage  , Werger Marinus , Robertson Kevin , Hobohm Carsten , Wang Chong-Yun , Peng Ming-Chun , Chen Xi , Wang Huan-Chong , Su Wen-Hua , Zhou Rui , Li Shuaifeng , He Long-Yuan , Yan Kai , Zhu Ming-Yuan , Hu Jun , Yang Ruo-Han , Li Wang-Jun , Tomita Mizuki , Wu Zhao-Lu , Yan Hai-Zhong , Zhang Guang-Fei , He Hai , Yi Si-Rong , Gong Hede , Song Kun , Song Ding , Li Xiao-Shuang , Zhang Zhi-Ying , Han Peng-Bin , Shen Li-Qin , Huang Diao-Shun , Luo Kang , López-Pujol Jordi
Published: October 2018

Today East Asia harbors many “relict” plant species whose ranges were much larger during the Paleogene-Neogene and earlier. The ecological and climatic conditions suitable for these relict species have not been identified. Here, we map the abundance and distribution patterns of relict species, showing high abundance in the humid subtropical/warm-temperate forest regions. We further use Ecological Niche Modeling to show that these patterns align with maps of climate refugia, and we predict species’ chances of persistence given the future climatic changes expected for East Asia. By 2070, potentially suitable areas with high richness of relict species will decrease, although the areas as a whole will probably expand. We identify areas in southwestern China and northern Vietnam as long-term climatically stable refugia likely to preserve ancient lineages, highlighting areas that could be prioritized for conservation of such species.
Collagen prolyl 4-hydroxylase 1 is essential for HIF-1α stabilization and TNBC chemoresistance
Authors: Xiong Gaofeng , Stewart Rachel L. , Chen Jie , Gao Tianyan , Scott Timothy L. , Samayoa Luis M. , O’Connor Kathleen , Lane Andrew N. , Xu Ren
Published: October 2018

Collagen prolyl 4-hydroxylase (P4H) expression and collagen hydroxylation in cancer cells are necessary for breast cancer progression. Here, we show that P4H alpha 1 subunit (P4HA1) protein expression is induced in triple-negative breast cancer (TNBC) and HER2 positive breast cancer. By modulating alpha ketoglutarate (α-KG) and succinate levels P4HA1 expression reduces proline hydroxylation on hypoxia-inducible factor (HIF) 1α, enhancing its stability in cancer cells. Activation of the P4HA/HIF-1 axis enhances cancer cell stemness, accompanied by decreased oxidative phosphorylation and reactive oxygen species (ROS) levels. Inhibition of P4HA1 sensitizes TNBC to the chemotherapeutic agent docetaxel and doxorubicin in xenografts and patient-derived models. We also show that increased P4HA1 expression correlates with short relapse-free survival in TNBC patients who received chemotherapy. These results suggest that P4HA1 promotes chemoresistance by modulating HIF-1-dependent cancer cell stemness. Targeting collagen P4H is a promising strategy to inhibit tumor progression and sensitize TNBC to chemotherapeutic agents.
Oriented electron transmission in polyoxometalate-metalloporphyrin organic framework for highly selective electroreduction of CO2
Authors: Wang Yi-Rong , Huang Qing , He Chun-Ting , Chen Yifa , Liu Jiang , Shen Feng-Cui , Lan Ya-Qian
Published: October 2018

The design of highly stable, selective and efficient electrocatalysts for CO2 reduction reaction is desirable while largely unmet. In this work, a series of precisely designed polyoxometalate-metalloporphyrin organic frameworks are developed. Noted that the integration of {ε-PMo8VMo4VIO40Zn4} cluster and metalloporphyrin endows these polyoxometalate-metalloporphyrin organic frameworks greatly advantages in terms of electron collecting and donating, electron migration and electrocatalytic active component in the CO2 reduction reaction. Thus-obtained catalysts finally present excellent performances and the mechanisms of catalysis processes are discussed and revealed by density functional theory calculations. Most importantly, Co-PMOF exhibits remarkable faradaic efficiency ( > 94%) over a wide potential range (−0.8 to −1.0 V). Its best faradaic efficiency can reach up to 99% (highest in reported metal-organic frameworks) and it exhibits a high turnover frequency of 1656 h−1 and excellent catalysis stability ( > 36 h).
Determinants of promoter and enhancer transcription directionality in metazoans
Authors: Ibrahim Mahmoud M. , Karabacak Aslihan , Glahs Alexander , Kolundzic Ena , Hirsekorn Antje , Carda Alexa , Tursun Baris , Zinzen Robert P. , Lacadie Scott A. , Ohler Uwe
Published: October 2018

Divergent transcription from promoters and enhancers is pervasive in many species, but it remains unclear if it is a general feature of all eukaryotic cis regulatory elements. To address this, here we define cis regulatory elements in C. elegans, D. melanogaster and H. sapiens and investigate the determinants of their transcription directionality. In all three species, we find that divergent transcription is initiated from two separate core promoter sequences and promoter regions display competition between histone modifications on the + 1 and −1 nucleosomes. In contrast, promoter directionality, sequence composition surrounding promoters, and positional enrichment of chromatin states, are different across species. Integrative models of H3K4me3 levels and core promoter sequence are highly predictive of promoter and enhancer directionality and support two directional classes, skewed and balanced. The relative importance of features to these models are clearly distinct for promoters and enhancers. Differences in regulatory architecture within and between metazoans are therefore abundant, arguing against a unified eukaryotic model.
Mycoplasma genitalium adhesin P110 binds sialic-acid human receptors
Authors: Aparicio David , Torres-Puig Sergi , Ratera Mercè , Querol Enrique , Piñol Jaume , Pich Oscar Q. , Fita Ignacio
Published: October 2018

Adhesion of pathogenic bacteria to target cells is a prerequisite for colonization and further infection. The main adhesins of the emerging sexually transmitted pathogen Mycoplasma genitalium, P140 and P110, interact to form a Nap complex anchored to the cell membrane. Herein, we present the crystal structures of the extracellular region of the virulence factor P110 (916 residues) unliganded and in complex with sialic acid oligosaccharides. P110 interacts only with the neuraminic acid moiety of the oligosaccharides and experiments with human cells demonstrate that these interactions are essential for mycoplasma cytadherence. Additionally, structural information provides a deep insight of the P110 antigenic regions undergoing programmed variation to evade the host immune response. These results enlighten the interplay of M. genitalium with human target cells, offering new strategies to control mycoplasma infections.