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The salivary glands are closely associated with stress conditions and the neuroendocrine system. The concentrations of these salivary biomarkers fluctuate with a person’s disease status. Until now, salivary diagnostics have been promising; however, the analytical tools for detecting salivary biomarkers have remained burdensome due to the lack of user-friendly and cost-effective equipment. In this study, we used a microfluidic starch-coated paper-based chip to isolate ɑ-amylase from human saliva. The concentration of ɑ-amylase on the head and tail sections of the paper-based chip was compared in the presence or absence of starch. We found that ɑ-amylase was highly concentrated only in the head section of the starch-coated paper-based chip through Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). We expect our designed paper-based chip will aid in α-amylase detection technologies using saliva and small amounts of other biofluids including blood, tears, pancreatic juice, and urine.

The Centers for Medicare & Medicaid Services’ Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1’s potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1’s complex “time zero” definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA’s core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics.

To understand the degradation behaviour of rolled hanging scrolls for future conservation treatments, we evaluated the degradation–position profiles of naturally aged hanging scrolls and their mode...

Significance Populations living in remote rural communities would benefit from rapid, highly sensitive molecular, DNA-based diagnostics to inform the correct and timely treatment of infectious diseases. Such information is also becoming increasingly relevant in global efforts for disease elimination, where the testing of asymptomatic patients is now seen as being important for the identification of disease reservoirs. However, healthcare workers face practical and logistical problems in the implementation of such tests, which often involve complex instrumentation and centralized laboratories. Here we describe innovations in paper microfluidics that enable low-cost, multiplexed DNA-based diagnostics for malaria, delivered, in a first-in-human study, in schools in rural Uganda., Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in

Transparency in reporting benefits scientific communication on many levels. While specific needs and expectations vary across fields, the effective interpretation and use of research findings relies on the availability of core information about research materials, study design, data, and experimental and analytical methods. For preclinical research, transparency in reporting is a key focus in response to concerns of replication failure. The inconsistent reporting of key elements of experimental and analytical design, alongside ambiguous description of reagents and lack of access to underlying data and code, has been shown to impair replication (1) and raise doubt about the robustness of results (2, 3). In response to early concerns about replication of published results, funders, publishers, and other stakeholders have called for improvements in reporting transparency (4⇓⇓–7). Several initiatives ensued, including journal policies and joint efforts by journals, funders, and other stakeholders (8⇓–10). One of these initiatives, the Transparency and Openness Promotion (TOP) guidelines (11), outlines a policy framework at the journal level that over 1,000 journals and publishers have adopted. The National Academies have focused on reproducibility and replicability* challenges through several recent initiatives leading to consensus reports, including Reproducibility and Replicability in Science (12), Open Science by Design: Realizing a Vision for 21st Century Research (13), and Fostering Integrity in Research (14). Each of these reports concludes that lack of reporting transparency is one factor which contributes to these systemic problems. Building on these findings, the National Academies convened a public workshop in September 2019 titled “Enhancing Scientific Reproducibility in Biomedical Research Through Transparent Reporting.” The workshop was designed to discuss the current state of transparency in reporting biomedical research and to explore the possibility of improving the harmonization of guidelines across journals and funding agencies. During this workshop, we provided … [↵][1]1To whom correspondence may be addressed: Email: Malcolm.Macleod{at}ed.ac.uk (correspondence regarding the development and evaluation of the guideline) or mellor.david{at}gmail.com (for further information about implementation and stewardship). [1]: #xref-corresp-1-1

Xylanases are useful in several industrial segments, including pulp and paper bleaching, animal feed, and bread-making processes. However, the industrial use of these enzymes is closely related to its production cost and its catalytic properties. The process of solid state fermentation enables the use of agro-industrial residues as substrates for microbial cultivation and enzymes production, reducing costs. In the present study, different cultivation parameters were evaluated for the xylanase production by the thermophilic fungus Thermoascus aurantiacus , by solid state fermentation, using agro-industrial residues as substrates. High production of xylanase (1701.9 U g -1 of dry substrate) was obtained using wheat bran containing 65% of initial moisture, at 120 h of cultivation, and 45°C. The xylanase showed optimal activity at pH 5.0 and 75°C; its stability was maintained at pH 3.0–11.0. The enzyme retained its catalytic potential after 1 h, at 75°C. The enzymatic extract produced under optimized conditions showed reduced activities of endoglucanase and FPase. Our results, including the xylanase production by T. aurantiacus in low-cost cultivation medium, high structural stability of the enzyme, and reduced cellulolytic activity, encourage the application of this enzymatic extract in pulp and paper bleaching processes.

Significance Much progress has been made in developing bioinspired sensors and actuators based on engineered synthetic materials, although there remains a critical need to incorporate cost-effective and eco-friendly materials. Here naturally abundant pollen grains are used as a material template to produce paper that sensitively and reversibly responds as an actuator to variations in environmental humidity. The actuating properties of the all-natural paper are readily tuned by material characteristics, such as sheet thickness and surface roughness. We demonstrate self-actuation of the pollen-based paper by mimicking flower blooming. The results presented here point to pathways for the creation of self-propelled robots, flexible electronics, and multifunctional devices. They also offer the potential for digital printing and fabrication of complex and programmable natural actuators., Here we describe the development of a humidity-responsive sheet of paper that is derived solely from natural pollen. Adaptive soft material components of the paper exhibit diverse and well-integrated responses to humidity that promote shape reconfiguration, actuation, and locomotion. This mechanically versatile and nonallergenic paper can generate a cyclically high contractile stress upon water absorption and desorption, and the rapid exchange of water drives locomotion due to hydrodynamic effects. Such dynamic behavior can be finely tuned by adjusting the structure and properties of the paper, including thickness, surface roughness, and processing conditions, analogous to those of classical soapmaking. We demonstrate that humidity-responsive paper-like actuators can mimic the blooming of the Michelia flower and perform self-propelled motion. Harnessing the material properties of bioinspired systems such as pollen paper opens the door to a wide range of sustainable, eco-friendly, and biocompatible material innovation platforms for applications in sensing, actuation, and locomotion.

In this paper, chitosan and magnolol and their compound were used as antibacterial agents, and the antibacterial wrapping paper was prepared by coating these on paper surface to compare the antibacterial effects of chitosan and magnolol, The preservation effect of antibacterial wrapping paper on strawberry is studied too. The results showed that when the compound ratio of magnolol and chitosan was 2:1, the antibacterial wrapping paper functions the best preservation effect on strawberry.

Large material usage and high production cost restrict the widespread use of solar cells in our society as a clean energy source. A feasible way toward inexpensive solar cells is root in our ability to fabricate solar cells on cheap substrates as the substrate represents 25%–60% of total material costs in current solar cells. Recent efforts to develop solar cells on low cost, flexible, renewable, biodegradable, and versatile paper have rendered encouraging and intriguing results. Paper can not only be taken as a promising substrate to support various solar cells, but also can act as functional elements such as light management layer to improve the power conversion efficiency (PCE) of solar cells. The following sections summarize up-to-date progress on the solar cells fabricated on both common and emerging paper substrates and identify the major challenges for paper solar cells that need to be overcome before they can move from the laboratory to industry. Among these reports, a highest 6.7% PCE to date for solar cells on common paper is reported. Paper solar cells demonstrated their potential application in low-cost and disposable paper electronics as a power source. Possible applications include gadgets, product tracking, smart parcels, security identification, and copy protect.

Few recent developments in the biological sciences have been as profound or impactful as the budding field of microbiome research. To provide a platform for this new discipline, we invite all our colleagues working on microbiota-pathogen interaction or microbiota-host interaction to contribute a

In this study, we present a method for assembling biofunctionalized paper into a multiform structured scaffold system for reliable tissue regeneration using an origami-based approach. The surface of a paper was conformally modified with a poly(styrene-co-maleic anhydride) layer via initiated chemical vapor deposition followed by the immobilization of poly-l-lysine (PLL) and deposition of Ca(2+). This procedure ensures the formation of alginate hydrogel on the paper due to Ca(2+) diffusion. Furthermore, strong adhesion of the alginate hydrogel on the paper onto the paper substrate was achieved due to an electrostatic interaction between the alginate and PLL. The developed scaffold system was versatile and allowed area-selective cell seeding. Also, the hydrogel-laden paper could be folded freely into 3D tissue-like structures using a simple origami-based method. The cylindrically constructed paper scaffold system with chondrocytes was applied into a three-ring defect trachea in rabbits. The transplanted engineered tissues replaced the native trachea without stenosis after 4 wks. As for the custom-built scaffold system, the hydrogel-laden paper system will provide a robust and facile method for the formation of tissues mimicking native tissue constructs.

Exploring the differences between the academic and social impacts of journal cover and non-cover papers is crucial for evaluating scientific research. We compared the differences in citations and Altmetric scores between cover and non-cover papers published in Nature. Six dimensions were considered: coverage, annual geometric mean and median, interval distribution, correlation coefficient, impact significance, and subject terms. We analysed the citations of 1,266 cover and 10,241 non-cover papers from 2006 to 2015 and the characteristics of the Altmetric scores and interdisciplinary subjects of 503 cover and 5,361 non-cover papers from 2011 to 2015. The results of our empirical study demonstrate that the citations and Altmetric scores of cover papers are significantly higher than those of non-cover papers, though a smaller difference was observed in more recent years. The Spearman correlation coefficients of the citations with Altmetric scores and several subdivision indices of cover papers were higher than those of non-cover papers in more recent years. Furthermore, the degree of influence of cover papers on citations and Altmetric scores was higher than that of non-cover papers. In biological sciences, physical sciences, and other interdisciplinary subjects, the degree of interdisciplinarity between highly cited and high-Altmetric-score cover papers was relatively high.

Motivation Flow cytometry (FCM) and transcription profiling are the two widely used assays in translational immunology research. However, there is no data integration pipeline for analyzing these two types of assays together with experiment variables for biomarker inference. Current FCM data analysis mainly relies on subjective manual gating analysis, which is difficult to be directly integrated with other automated computational methods. Existing deconvolutional analysis of bulk transcriptomics relies on predefined marker genes in the transcriptomics data, which are unavailable for novel cell types and does not utilize the FCM data that provide canonical phenotypic definitions of the cell types. Results We developed a novel analytics pipeline—FastMix—for computational immunology, which integrates flow cytometry, bulk transcriptomics and clinical covariates for identifying cell type-specific gene expression signatures and biomarker genes. FastMix addresses the ‘large p, small n’ problem in the gene expression and flow cytometry integration analysis via a linear mixed effects model (LMER) for both cross-sectional and longitudinal studies. Its novel moment-based estimator not only reduces bias in parameter estimation but also is more efficient than iterative optimization. The FastMix pipeline also includes a cutting-edge flow cytometry data analysis method—DAFi—for identifying cell populations of interest and their characteristics. Simulation studies showed that FastMix produced smaller type I/II errors than competing methods. Validation using real data of two vaccine studies showed that FastMix identified a consistent set of signature genes as in independent single-cell RNA-seq analysis, producing additional interesting findings. Availability and implementation Source code of FastMix is publicly available at https://github.com/terrysun0302/FastMix. Supplementary information Supplementary data are available at Bioinformatics online.

Our system of research self-regulation, designed to provide internal checks and balances for those who participate in research involving human subjects, is under considerable stress. Much of this crisis has been caused by what we call mission creep, in which the workload of IRBs has expanded beyond their ability to handle effectively. Mission creep is caused by rewarding wrong behaviors, such as focusing more on procedures and documentation than difficult ethical questions; unclear definitions, which lead to unclear responsibilities; efforts to comply with unwieldy federal requirements even when research is not federally funded; exaggerated precautions to protect against program shutdowns; and efforts to protect against lawsuits. We recommend collecting data. We also call for refinements to our regulatory system that will provide a set of regulations designed for non-biomedical research. This will enable IRBs to direct attention to the areas of greatest risk while intentionally scaling back oversight in areas of lesser risk. We recommend removing some kinds of activity from IRB review altogether. Our system, if not broken, is seriously straining at the seams. It is imperative that we have a respected and effective system in place to protect human research subjects, so that much-needed research into the causes and prevention of disease and other research expanding the boundaries of knowledge can proceed. We hope that this White Paper will further the discussion about what reasonable procedures can be instituted to help get IRBs back on track and do what they were originally meant to do—protect the rights and welfare of human subjects while allowing the research enterprise to progress and its benefits to society to accrue.

Background: DBS samples collected from a fingerprick typically vary in volume and homogeneity and hence make an accurate quantitative analysis of DBS samples difficult. Results: We report a prototype which first defines a precise liquid volume and subsequently stores it to a conventional DBS matrix. Liquid volumes of 2.2 µl ± 7.1% (n = 21) for deionized water and 6.1 µl ± 8.8% (n = 15) for whole blood have been successfully metered and stored in DBS paper. Conclusion: The new method of collecting a defined volume of blood by DBS sampling has the potential to reduce assay bias for the quantitative evaluation of DBS samples while maintaining the simplicity of conventional DBS sampling.

Emlen funnels are small funnel-shaped orientation cagesused to record the spontaneously directed migratory rest-lessness (Zugunruhe) of night-migratory songbirds (Emlenand Emlen 1966). Today, almost every group studying thecompass orientation capabilities of migratory songbirdsuses the Emlen funnel method (e.g., Sandberg et al. 2002;Wiltschko and Wiltschko 2003; Ritz et al. 2004; Muheimet al. 2006; Chernetsov et al. 2008). This method providesthe most reliable and cost effective tool to analyze thespontaneous directional preference of many migratorysongbirds during the migratory season. Results from Emlenfunnel experiments also play a key role in the current rushtowards understanding how the magnetic compass sense inmigratory songbirds works (e.g., Ritz et al. 2004; Mouritsenand Ritz 2005).When Emlen first invented the method (Emlen andEmlen 1966), he used an inkpad at the bottom of the cageand lined the walls of the funnel with blotting paper toscore the ink marks as a measure of the bird’s directionalchoice. Later, Rabol (1979) got the idea to use typewritercorrection paper on the walls instead of ink and blottingpaper to record the birds’ directional preferences. This wasa significant improvement for the birds, since ‘‘Rotkehl-chen’’ (Robin Erithacus rubecula) would no longer become‘‘Blaukehlchen’’ (Bluethroat Luscinia svecica) after severalnights hopping on the inkpad. The refined typewriter cor-rection paper version of the Emlen funnel was adopted byvirtually every study using Emlen funnels after 1980 (e.g.,Mouritsen and Larsen 1998; Sandberg et al. 2002;Wiltschko and Wiltschko 2003; Ritz et al. 2004; Muheimet al. 2006). However, over the last 10 years, researchersusing the Emlen funnel method have been challengedby the disappearance of typewriters, which has made itexceedingly difficult to find a reliable supplier of appro-priately sized rolls of typewriter correction paper needed todo Emlen funnel experiments.The Wiltschko-lab in Frankfurt (e.g., Wiltschko andWiltschko 2003; Ritz et al. 2004) were instrumental inconvincing one of the producers of typewriter correctionpaper to make a final production run, which helped manycolleagues stock up on paper for several years. Unfortu-nately, the chalk-like coating on typewriter correctionpaper tends to harden with time, which means that itbecomes more and more difficult to accurately scorescratches on the paper. In addition to this problem, ourstock ran out several years ago, which made us initiate asearch for an alternative solution, as going back to the inkmethod would not be acceptable for animal welfarereasons.First, we visited the local crime unit to see if fingerprintdetection dust could help us. It did not work because itsfunction is based on the fat on the fingers which the duststicks to. But the claws of birds are normally fat free andthus claw marks cannot be visualized with fingerprintdetection dust. Second, we got the idea that maybe thepaper used in trucks to record their speed (tachopgraphcharts, ‘‘Fahrtenschreiberpapier’’ in German) could also beused to record the scratches left in Emlen funnels bymigratory birds. As a result, we tested various such papersfrom several different producers with variable success untilwe received a sample of ‘‘Thermal paper’’ product number‘‘SC55’’ from the company ‘‘Blumberg Systempapiere’’,Kalkumerstrasse 46, 40885 Ratingen-Lintorf, Germany

The role of mutation, which is an error process in gene evolution, in systems of cyclically competing species has been studied from various perspectives, and it is regarded as one of the key factors for promoting coexistence of all species. In addition to naturally occurring mutations, many experiments in genetic engineering have involved targeted mutation techniques such as recombination between DNA and somatic cell sequences and have studied genetic modifications through loss or augmentation of cell functions. In this paper, we investigate nonlinear dynamics with targeted mutation in cyclically competing species. In different ways to classic approaches of mutation in cyclic games, we assume that mutation may occur in targeted individuals who have been removed from intraspecific competition. By investigating each scenario depending on the number of objects for targeted mutation analytically and numerically, we found that targeted mutation can lead to persistent coexistence of all species. In addition, under the specific condition of targeted mutation, we found that targeted mutation can lead to emergences of bistable states for species survival. Through the linear stability analysis of rate equations, we found that those phenomena are accompanied by Hopf bifurcation which is supercritical. Our findings may provide more global perspectives on understanding underlying mechanisms to control biodiversity in ecological/biological sciences, and evidences with mathematical foundations to resolve social dilemmas such as a turnover of group members by resigning with intragroup conflicts in social sciences.

Despite progress in antimicrobial drug development, a critical need persists for new, feasible pathways to develop antibacterial agents to treat people infected with drug-resistant bacteria. Infections due to resistant gram-negative bacilli continue to cause unacceptable morbidity and mortality rates. Antibacterial agents have been historically studied in noninferiority clinical trials that focus on a single site of infection (eg, complicated urinary tract infections, intra-abdominal infections), yet these designs may not be optimal, and often are not feasible, for study of infections caused by drug-resistant bacteria. Over the past several years, multiple stakeholders have worked to develop consensus regarding paths forward with a goal of facilitating timely conduct of antimicrobial development. Here we advocate for a novel and pragmatic approach and, toward this end, present feasible trial designs for antibacterial agents that could enable conduct of narrow-spectrum, organism-specific clinical trials and ultimately approval of critically needed new antibacterial agents.

Singlet oxygen was shown to be involved in the mechanism of fading on a clay surface of a series of the triphenylmethane (TPM) dyes used in commercial carbonless copying paper. The dyes adsorbed on clays were found to be singlet oxygen sensitisers and the singlet oxygen produced reacted with the dyes themselves. The rate of fading of a particular dye depended upon the structure of the dyes, fluorans degrading faster than phthalides.

Pulp and paper mill sludges (PMS) are a significant by-product of the paper making industry worldwide, and composting with mineral nutrients in Tasmania is viewed as the most environmentally acceptable technology to convert this material into a useful horticultural or agricultural product, thereby eliminating the need for landfilling. The objective of this study was to determine the feasibility of composting PMS in large-scale periodically turned windrows based on optimal conditions previously determined in laboratory-scale reactors. Performance of the composting process and quality of the composted PMS is reported. PMS was composted with mineral nutrients at an initial C:N:P:K ratio of 35:1:0.6:0.1 in three windrows of 25 m in length, 3 m in width and 2 m in height with weekly turning for 21 weeks, following which the trial was terminated. Temperature at the pile center remained above 50°C for the duration of the trial, with pile pH peaking at 7.46 after 11 weeks. At termination, phytotoxicity was absent...

Dye- and quantum-dot-sensitized solar cells have attracted tremendous attention as one of the potential low-cost alternatives for p–n junction silicon solar cells. However, the conversion efficiencies of sensitized solar cells are still lower than those of silicon-based solar cells. Numerous research efforts have been made to enhance the sensitized solar cell efficiency over the past decades. Among the various attempts to improve the photovoltaic properties, the control of interface for reducing the charge recombination and the smart management of the light harvesting have proven to be most effective. Moreover, the p–n junction structure can offer higher open-circuit voltage than the conventional n-type sensitized solar cell. In this review paper, recent developments in sensitized solar cells and the underlying mechanisms will be briefly introduced.

High-pressure single-crystal X-ray and neutron diffraction data for copper(II) sulfate pentahydrate have been collected under precisely the same conditions, using the same sample mounted in a miniature diamond-anvil cell. The data were combined in a joint ‘XN’ structure refinement., Single-crystal X-ray and neutron diffraction data are usually collected using separate samples. This is a disadvantage when the sample is studied at high pressure because it is very difficult to achieve exactly the same pressure in two separate experiments, especially if the neutron data are collected using Laue methods where precise absolute values of the unit-cell dimensions cannot be measured to check how close the pressures are. In this study, diffraction data have been collected under the same conditions on the same sample of copper(II) sulfate pentahydrate, using a conventional laboratory diffractometer and source for the X-ray measurements and the Koala single-crystal Laue diffractometer at the ANSTO facility for the neutron measurements. The sample, of dimensions 0.40 × 0.22 × 0.20 mm3 and held at a pressure of 0.71 GPa, was contained in a miniature Merrill–Bassett diamond-anvil cell. The highly penetrating diffracted neutron beams passing through the metal body of the miniature cell as well as through the diamonds yielded data suitable for structure refinement, and compensated for the low completeness of the X-ray measurements, which was only 24% on account of the triclinic symmetry of the sample and the shading of reciprocal space by the cell. The two data-sets were combined in a single ‘XN’ structure refinement in which all atoms, including H atoms, were refined with anisotropic displacement parameters. The precision of the structural parameters was improved by a factor of up to 50% in the XN refinement compared with refinements using the X-ray or neutron data separately.

AlphaFold has recently become an important tool in providing models for experimental structure determination by X-ray crystallography and cryo-EM. Large parts of the predicted models typically approach the accuracy of experimentally determined structures, although there are frequently local errors and errors in the relative orientations of domains. Importantly, residues in the model of a protein predicted by AlphaFold are tagged with a predicted local distance difference test score, informing users about which regions of the structure are predicted with less confidence. AlphaFold also produces a predicted aligned error matrix indicating its confidence in the relative positions of each pair of residues in the predicted model. The phenix.process_predicted_model tool downweights or removes low-confidence residues and can break a model into confidently predicted domains in preparation for molecular replacement or cryo-EM docking. These confidence metrics are further used in ISOLDE to weight torsion and atom-atom distance restraints, allowing the complete AlphaFold model to be interactively rearranged to match the docked fragments and reducing the need for the rebuilding of connecting regions.

Deep-water access is arguably the most effective, but under-studied, mechanism that plants employ to survive during drought. Vulnerability to embolism and hydraulic safety margins can predict mortality risk at given levels of dehydration, but deep-water access may delay plant dehydration. Here, we tested the role of deep-water access in enabling survival within a diverse tropical forest community in Panama using a novel data-model approach. We inversely estimated the effective rooting depth (ERD, as the average depth of water extraction), for 29 canopy species by linking diameter growth dynamics (1990-2015) to vapor pressure deficit, water potentials in the whole-soil column, and leaf hydraulic vulnerability curves. We validated ERD estimates against existing isotopic data of potential water-access depths. Across species, deeper ERD was associated with higher maximum stem hydraulic conductivity, greater vulnerability to xylem embolism, narrower safety margins, and lower mortality rates during extreme droughts over 35years (1981-2015) among evergreen species. Species exposure to water stress declined with deeper ERD indicating that trees compensate for water stress-related mortality risk through deep-water access. The role of deep-water access in mitigating mortality of hydraulically-vulnerable trees has important implications for our predictive understanding of forest dynamics under current and future climates.

GroEL is a chaperone thought of as essential for bacterial life. However, some species of Mollicutes are missing GroEL. We use phylogenetic analysis to show that the presence of GroEL is polyphyletic among the Mollicutes, and that there is evidence for lateral gene transfer of GroEL to Mycoplasma penetrans from the Proteobacteria. Furthermore, we propose that the presence of GroEL in Mycoplasma may be required for invasion of host tissue, suggesting that GroEL may act as an adhesin–invasin.

Independent cryo electron microscopy (cryo-EM) studies of the closely related protein disaggregases ClpB and Hsp104 have resulted in two different models of subunit arrangement in the active hexamer. We compare the EM maps and resulting atomic structure fits, discuss their differences, and relate them to published experimental information in an attempt to discriminate between models. In addition, we present some general assessment criteria for low-resolution cryo-EM maps to offer non-structural biologists tools to evaluate these structures.

We compared species mean data on the size of functionally distinct brain regions to test the relative rates at which investment in higher-order cognitive processing (mushroom body calyces) versus peripheral sensory processing (optic and antennal lobes) increased with increasing brain size. Subjects were eusocial paper wasps from queen and worker castes of 10 species from different genera. Relative investment in central processing tissue increased with brain size at a higher rate than peripheral structure investment, demonstrating that tissue devoted to higher-order cognitive processing is more constrained by brain size. This pattern held for raw data and for phylogenetically independent contrasts. These findings suggest that there is a minimum necessary investment in peripheral sensory processing brain tissue, with little to gain from additional investment. In contrast, increased brain size provides opportunities to invest in additional higher-order cognitive processing tissue. Reproductive castes differed within species in brain tissue investment, with higher central-to-peripheral brain tissue ratios in queens than in workers. Coupled with previous findings that paper wasp queen, but not worker, brain architecture corresponds to ecological and social variation, queen brain evolution appears to be most strongly shaped by cognitive demands, such as social interactions. These evolutionary patterns of neural investment echo findings in other animal lineages and have important implications, given that a greater investment in higher-order processing has been shown to increase the prevalence of complex and flexible behaviors across the animal kingdom.

Human periodontal ligament fibroblast (HPDLF) is a major component of the resident cells in the periodontal microenvironment, and plays important roles in periodontitis through multiple mechanisms. Although lipopolysaccharide (LPS) has been shown to cause endoplasmic reticulum (ER) stress and activate the unfolded protein response (UPR) in HPDLF, the mechanisms governing HPDLF function in periodontitis are unclear. In this study, we tested the ability of unfolded protein response (UPR) to regulate HPDLF in vitro and examined the underlying mechanisms. We found LPS-pretreated HPDLF induced macrophage polarization toward M1 phenotype. UPR activation reduced the inflammatory cytokine production and downregulated the expression of TLR4 in HPDLF. The phosphorylation of NF-κB p65 and I-κB was also inhibited by UPR activation. Our findings demonstrate that the connection of LPS, UPR, and HPDLF may represent a new concrete theory of innate immunity regulation in periodontal diseases, and suggest that targeting of UPR in HPDLF may be developed as a potent therapy for periodontitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12192-021-01234-0.

The peopling of Remote Oceanic islands by Austronesian speakers is a fascinating and yet contentious part of human prehistory. Linguistic, archaeological, and genetic studies have shown the complex nature of the process in which different components that helped to shape Lapita culture in Near Oceania each have their own unique history. Important evidence points to Taiwan as an Austronesian ancestral homeland with a more distant origin in South China, whereas alternative models favor South China to North Vietnam or a Southeast Asian origin. We test these propositions by studying phylogeography of paper mulberry, a common East Asian tree species introduced and clonally propagated since prehistoric times across the Pacific for making barkcloth, a practical and symbolic component of Austronesian cultures. Using the hypervariable chloroplast ndhF-rpl32 sequences of 604 samples collected from East Asia, Southeast Asia, and Oceanic islands (including 19 historical herbarium specimens from Near and Remote Oceania), 48 haplotypes are detected and haplotype cp-17 is predominant in both Near and Remote Oceania. Because cp-17 has an unambiguous Taiwanese origin and cp-17-carrying Oceanic paper mulberries are clonally propagated, our data concur with expectations of Taiwan as the Austronesian homeland, providing circumstantial support for the "out of Taiwan" hypothesis. Our data also provide insights into the dispersal of paper mulberry from South China "into North Taiwan," the "out of South China-Indochina" expansion to New Guinea, and the geographic origins of post-European introductions of paper mulberry into Oceania.

Motivation CpG sites within the same genomic region often share similar methylation patterns and tend to be co-regulated by multiple genetic variants that may interact with one another. Results We propose a multi-trait methylation random field (multi-MRF) method to evaluate the joint association between a set of CpG sites and a set of genetic variants. The proposed method has several advantages. First, it is a multi-trait method that allows flexible correlation structures between neighboring CpG sites (e.g. distance-based correlation). Second, it is also a multi-locus method that integrates the effect of multiple common and rare genetic variants. Third, it models the methylation traits with a beta distribution to characterize their bimodal and interval properties. Through simulations, we demonstrated that the proposed method had improved power over some existing methods under various disease scenarios. We further illustrated the proposed method via an application to a study of congenital heart defects (CHDs) with 83 cardiac tissue samples. Our results suggested that gene BACE2, a methylation quantitative trait locus (QTL) candidate, colocalized with expression QTLs in artery tibial and harbored genetic variants with nominal significant associations in two genome-wide association studies of CHD. Availability and implementation https://github.com/chenlyu2656/Multi-MRF. Supplementary information Supplementary data are available at Bioinformatics online.

Fundamental investigations of human biology, and the development of therapeutics, commonly rely on 2D cell-culture systems that do not accurately recapitulate the structure, function, or physiology of living tissues. Systems for 3D cultures exist but do not replicate the spatial distributions of oxygen, metabolites, and signaling molecules found in tissues. Microfabrication can create architecturally complex scaffolds for 3D cell cultures that circumvent some of these limitations; unfortunately, these approaches require instrumentation not commonly available in biology laboratories. Here we report that stacking and destacking layers of paper impregnated with suspensions of cells in extracellular matrix hydrogel makes it possible to control oxygen and nutrient gradients in 3D and to analyze molecular and genetic responses. Stacking assembles the “tissue”, whereas destacking disassembles it, and allows its analysis. Breast cancer cells cultured within stacks of layered paper recapitulate behaviors observed both in 3D tumor spheroids in vitro and in tumors in vivo: Proliferating cells in the stacks localize in an outer layer a few hundreds of microns thick, and growth-arrested, apoptotic, and necrotic cells concentrate in the hypoxic core where hypoxia-sensitive genes are overexpressed. Altering gas permeability at the ends of stacks controlled the gradient in the concentration of the O 2 and was sufficient by itself to determine the distribution of viable cells in 3D. Cell cultures in stacked, paper-supported gels offer a uniquely flexible approach to study cell responses to 3D molecular gradients and to mimic tissue- and organ-level functions.

X-ray diffraction method was applied to quantifying pigments weight or composition of coatings. This method has some advantages over the method by electron probe microanalyzer (EPMA) which is conventionally used at present. One is that it is capable of distinguishing the different crystal forms of certain materials. It also permits analysis of samples deeply.The quantification principle follows Alexander's theory which states that the X-ray diffraction intensity ratio is proportional to the components weight ratio.Measurements were made for coated paper samples containing solely clay and calcium carbonate, which were prepared using a laboratory blade coater or by manual bar coating.First, the X-ray diffraction intensity ratio is approximately linear to coating weight under a limited range. But, the diffraction intensity ratio of clay peak to calcium carbonate peak for the samples with coatings of constant composition. This finding proved to derive from diffraction of calcium carbonate contained in base papers as fillers. To separate calcium carbonate diffraction stemmed from only coatings, the diffraction of internally loaded filler was calculated in the following ways. That is, the diffraction intensity of filler was calculated compared to cellulose (101), (101) peak after diffraction measurement of only base paper. Then its amount was subtracted from the total diffraction intensity of calcium carbonate contained in coated papers. The diffraction intensity ratio thus corrected resulted in almost constant value independent of coating weight. Besides, the diffraction intensity ratio of a series of coated paper samples proved to be proportional to coatings' formulation of coated paper samples.In conclusion, quantification of pigments contained in coatings by X-ray diffraction method was established. But some problems still remains to be solved. Firstly, the measurement of only base paper must be made to apply this method to commercial coated papers. Secondly, calendering or double coating process probably affect diffraction patterns.

In this November issue of Cell Research, we are proud to announce the winners of the 5th Sanofi-Cell Research Outstanding Paper Award, which were selected from papers published in the 2013 print issues of Cell Research. The 2013 Sanofi-Cell Research Outstanding Review Article Award goes to Dr George Daley, for his review paper entitled “A blueprint for engineering cell fate: current technologies to reprogram cell identify”1, which is co-authored with Dr Samantha A Morris. The winners of the 2013 Sanofi-Cell Research Outstanding Research Article Award are Dr Jiahuai Han, for his paper entitled “Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis”2; and Dr Rudolf Jaenisch, for his paper entitled “Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system”3. The award consists of a prize of € 3000 for the Outstanding Review Article Award and € 5000 for the Outstanding Research Article Award sponsored by Sanofi. The three award-winning papers are selected based on the voting by members of the Sanofi-Shanghai Institutes for Biological Sciences Steering Committee. The award-winning review by Drs Daley and Morris was published in the January issue of 2013. The review provides an expert analysis on the current strategies to manipulate cell identities and discuss challenges faced by the field in its marching towards the ultimate goal of harnessing the technology of cell fate conversion for the production of medically relevant cell populations. In the first award-winning research article, published in the August 2013 issue, Dr Jiahuai Han and his colleagues report the detailed characterization of Mlkl knockout mice, providing definitive in vivo genetic evidence for the critical role of Mlkl in mediating programmed necrosis, a form of cell death that is distinct from apoptosis. In the second award-winning research article, published in the October 2013 issue, Dr Rudolf Jaenisch and his colleagues utilized a modified version of the CRISPR/Cas9 system, a newly emerging genetic tool, to create RNA-guided transcriptional activators that could act to robustly activate endogenous target gene expression in vivo, thus providing a versatile system to specifically manipulate gene expression at both the cellular and organism levels. Please join us to congratulate Drs Daley, Morris, Han, and Jaenisch on their winning of the 2013 Sanofi-Cell Research Outstanding Paper Award. We have no doubt that this yearly award program, along with the rapidly rising status of the journal, will encourage more and more scientists to submit their best work to Cell Research.

The auditory biology of Monachinae seals is poorly understood. Limited audiometric data and certain anatomical features suggest that these seals may have reduced sensitivity to airborne sounds compared to related species. Here, we describe the in-air hearing abilities of a Hawaiian monk seal (Neomonachus schauinslandi) trained to participate in a psychophysical paradigm. We report absolute (unmasked) thresholds for narrowband signals measured in quiet conditions across the range of hearing and masked thresholds measured in the presence of octave-band noise at two frequencies. The behavioral audiogram indicates a functional hearing range from 0.1 to 33 kHz and poor sensitivity, with detection thresholds above 40 dB re 20 µPa. Critical ratio measurements are elevated compared to those of other seals. The apparently reduced terrestrial hearing ability of this individual—considered with available auditory data for a northern elephant seal (Mirounga angustirostris)—suggests that hearing in Monachinae seals differs from that of the highly sensitive Phocinae seals. Exploration of phylogenetic relationships and anatomical traits support this claim. This work advances understanding of the evolution of hearing in amphibious marine mammals and provides updated information that can be used for management and conservation of endangered Hawaiian monk seals. Supplementary Information The online version contains supplementary material available at 10.1007/s00359-021-01498-y.

International audience; Evergreen conifer forests are the most prevalent land cover type in North America. Seasonal changes in the color of evergreen forest canopies have been documented with near-surface remote sensing, but the physiological mechanisms underlying these changes, and the implications for photosynthetic uptake, have not been fully elucidated. Here, we integrate on-the-ground phenological observations, leaf-level physiological measurements, near surface hyperspectral remote sensing and digital camera imagery, towerbased CO 2 flux measurements, and a predictive model to simulate seasonal canopy color dynamics. We show that seasonal changes in canopy color occur independently of new leaf production, but track changes in chlorophyll fluorescence, the photochemical reflectance index, and leaf pigmentation. We demonstrate that at winter-dormant sites, seasonal changes in canopy color can be used to predict the onset of canopy-level photosynthesis in spring, and its cessation in autumn. Finally, we parameterize a simple temperature-based model to predict the seasonal cycle of canopy greenness, and we show that the model successfully simulates interannual variation in the timing of changes in canopy color. These results provide mechanistic insight into the factors driving seasonal changes in evergreen canopy color and provide opportunities to monitor and model seasonal variation in photosynthetic activity using color-based vegetation indices.

Evolutionary fitness of traits or behaviors is inclusive [1] of their ‘direct’ effects on the trait bearers’ reproduction and their ‘indirect’ effects on others’ reproduction (Figure 1). Inclusive fitness models lay bare that traits can be selectively advantageous even when they negatively impact direct fitness. A capstone of this approach is that Darwin's dilemma of sterile workers and nonreproductive helpers seems neatly solved by the simplicity of Hamilton's Rule (rb – c > 0). Workers work and helpers help to maximize their inclusive fitness.

This study assessed the potential of termite gut inhabiting bacteria towards bioconversion of cellulosic waste into biofuel. Total seven bacterial isolates from the gut of Heterotermes indicola were isolated. Among all the isolates, HI-1 produced the largest zone upon primary screening. Untreated paper had more cellulose content (73.03%) than acid (0.5%) treated paper that was used as a lignocellulosic substrate for saccharification. Among all the isolates tested, glucose yield (1.08mg/mL) was high for HI-1 isolate. Several factors were considered for optimizing augmented glucose yield (8.57mg/mL) and growth (8.07×108cfu/mL), such as temperature 37°C, pH 4.5, 5% (w/v) substrate concentration, 6 % bacterial inoculum size, agitation 150 rpm with PEG 0.25 % and Ca2+ ions 0.002 g/L. Overall 8-fold increase in glucose yield was achieved. Enzyme activity of HI-1 showed higher endoglucanase 0.29 ± 0.01 (U/mL/min) and exoglucanase 0.15±0.01 (U/mL/min) activity under optimum conditions, mentioned above. temperature 37°C, pH 4.5, substrate concentration 5%, inoculum size 6%, surfactants PEG 0.01%, ions Ca2+(0.002g/L) and agitation (120 rpm). Simultaneous saccharification and fermentation (SSF) of hydrolyzed office paper yielded 5.43mg/mL bioethanol. According to 16S rRNA sequence homology, the bacterial isolate H1 was identified as Alcaligenes faecalis. Bioethanol production from office paper untreated waste proved an effective strategy. Bacteria having natural tendency towards cellulosic waste consumption are promising for bioconversion of cellulosic waste to valuable products.

p53 is critical for tumor suppression but also elicits detrimental effects when aberrantly overexpressed. Thus, multiple regulators, including RNA-binding protein RBM38, are found to tightly control p53 expression. Interestingly, RBM38 is unique in that it can either suppress or enhance p53 mRNA translation via altered interaction with eIF4E potentially mediated by serine-195 (S195) in RBM38. Thus, multiple RBM38/eIF4E knock-in (KI) cell lines were generated to investigate the significance of eIF4E-RBM38 interaction in controlling p53 activity. We showed that KI of RBM38-S195D or -Y192C enhances, whereas KI of RBM38-S195K/R/L weakens, the binding of eIF4E to p53 mRNA and subsequently p53 expression. We also showed that KI of eIF4E-D202K weakens the interaction of eIF4E with RBM38 and thereby enhances p53 expression, suggesting that D202 in eIF4E interacts with S195 in RBM38. Moreover, we generated an Rbm38 S193D KI mouse model in which human-equivalent serine-193 is substituted with aspartic acid. We showed that S193D KI enhances p53-dependent cellular senescence and that S193D KI mice have a shortened life span and are prone to spontaneous tumors, chronic inflammation, and liver steatosis. Together, we provide in vivo evidence that the RBM38-eIF4E loop can be explored to fine-tune p53 expression for therapeutic development.

Metabolic rates are one of many measures that are used to explain species' response to environmental change. Static respirometry is used to calculate the standard metabolic rate (SMR) of fish, and when combined with exhaustive chase protocols it can be used to measure maximum metabolic rate (MMR) and aerobic scope (AS) as well. While these methods have been tested in comparison to swim tunnels and chambers with circular currents, they have not been tested in comparison with a no‐chase control. We used a repeated‐measures design to compare estimates of SMR, MMR and AS in European perch Perca fluviatilis following three protocols: (a) a no‐chase control; (b) a 3‐min exhaustive chase; and (c) a 3‐min exhaustive chase followed by 1‐min air exposure. We found that, contrary to expectations, exhaustive chase protocols underestimate MMR and AS at 18°C, compared to the no‐chase control. This suggests that metabolic rates of other species with similar locomotorty modes or lifestyles could be similarly underestimated using chase protocols. These underestimates have implications for studies examining metabolic performance and responses to climate change scenarios. To prevent underestimates, future experiments measuring metabolic rates should include a pilot with a no‐chase control or, when appropriate, an adjusted methodology in which trials end with the exhaustive chase instead of beginning with it.

Singlet oxygen is a reactive oxygen species undesired in living cells but a rare and valuable reagent in chemical synthesis. We present a fluorescence spectroscopic analysis of the singlet‐oxygen formation activity of commercial peroxidases and novel peroxygenases. Singlet‐oxygen sensor green (SOSG) is used as fluorogenic singlet oxygen trap. Establishing a kinetic model for the reaction cascade to the fluorescent SOSG endoperoxide permits a kinetic analysis of enzymatic singlet‐oxygen formation. All peroxidases and peroxygenases show singlet‐oxygen formation. No singlet oxygen activity could be found for any catalase under investigation. Substrate inhibition is observed for all reactive enzymes. The commercial dye‐decolorizing peroxidase industrially used for dairy bleaching shows the highest singlet‐oxygen activity and the lowest inhibition. This enzyme was immobilized on a textile carrier and successfully applied for a chemical synthesis. Here, ascaridole was synthesized via enzymatically produced singlet oxygen., H2O2 to 1 O2 to… The formation of singlet oxygen from hydrogen peroxide by heme peroxidases and peroxygenases, but not catalases, is shown by fluorescence spectroscopy. The most active peroxidase, based on kinetic analysis using the fluorescent trap singlet‐oxygen sensor green, was applied in a chemo‐enzymatic synthesis of ascaridole.

Small‐scale fisheries are an important livelihood and primary protein source for coastal communities in many of the poorest regions in the world, yet many are overfished and thus require effective and scalable management solutions. Positive ecological and socioeconomic responses to management typically lag behind immediate costs borne by fishers from fishing pressure reductions necessary for fisheries recovery. These short‐term costs challenge the long‐term success of these interventions. However, social marketing may increase perceptions of management benefits before ecological and socioeconomic benefits are fully realized, driving new social norms and ultimately long‐term sustainable behavior change. By conducting underwater visual surveys to quantify ecological conditions and by conducting household surveys with community members to quantify their perceptions of management support and socioeconomic conditions, we assessed the impact of a standardized small‐scale fisheries management intervention that was implemented across 41 sites in Brazil, Indonesia, and the Philippines. The intervention combines TURF reserves (community‐based territorial use rights for fishing coupled with no‐take marine reserves) with locally tailored social‐marketing behavior change campaigns. Leveraging data across 22 indicators and 4 survey types, along with data from 3 control sites, we found that ecological and socioeconomic impacts varied and that communities supported the intervention and were already changing their fishing practices. These results suggest that communities were developing new social norms and fishing more sustainably before long‐term ecological and socioeconomic benefits of fisheries management materialized., Article impact statement: Moving from overfishing to sustainability, behavior change campaigns can be used to transition fisheries from near‐term losses to long‐term gains.

SummaryCommercial tomato (Solanum lycopersicum) is one of the most widely grown vegetable crops worldwide. Heirloom tomatoes retain extensive genetic diversity and a considerable range of fruit quality and leaf morphological traits.Here the role of leaf morphology was investigated for its impact on fruit quality. Heirloom cultivars were grown in field conditions and BRIX by Yield (BY) and other traits measured over a fourteen-week period. The complex relationships among these morphological and physiological traits were evaluated using PLS-Path Modeling, and a consensus model developed.Photosynthesis contributed strongly to vegetative biomass and sugar content of fruits but had a negative impact on yield. Conversely leaf shape, specifically rounder leaves, had a strong positive impact on both fruit sugar content and yield. Cultivars such as Stupice and Glacier, with very round leaves, had the highest performance in both fruit sugar and yield. Our model accurately predicted BY for two commercial cultivars using leaf shape data as input.This study revealed the importance of leaf shape to fruit quality in tomato, with rounder leaves having significantly improved fruit quality. This correlation was maintained across a range of diverse genetic backgrounds and shows the importance of leaf morphology in tomato crop improvement.

The in vivo lifelong stability of an amphibole asbestos fibre extracted from a lung of a patient affected by malignant mesothelioma has been verified using synchrotron X-ray micro-diffraction., The six natural silicates known as asbestos may induce fatal lung diseases via inhalation, with a latency period of decades. The five amphibole asbestos species are assumed to be biopersistent in the lungs, and for this reason they are considered much more toxic than serpentine asbestos (chrysotile). Here, we refined the atomic structure of an amosite amphibole asbestos fibre that had remained in a human lung for ∼40 years, in order to verify the stability in vivo. The subject was originally exposed to a blend of chrysotile, amosite and crocidolite, which remained in his parietal pleura for ∼40 years. We found a few relicts of chrysotile fibres that were amorphous and magnesium depleted. Amphibole fibres that were recovered were undamaged and suitable for synchrotron X-ray micro-diffraction experiments. Our crystal structure refinement from a recovered amosite fibre demonstrates that the original atomic distribution in the crystal is intact and, consequently, that the atomic structure of amphibole asbestos fibres remains stable in the lungs for a lifetime; during which time they can cause chronic inflammation and other adverse effects that are responsible for carcinogenesis. The amosite fibres are not iron depleted proving that the iron pool for the formation of the asbestos bodies is biological (haemoglobin/plasma derived) and that it does not come from the asbestos fibres themselves.

The joint neutron/X-ray crystallographic structure of perdeuterated Aspergillus flavus urate oxidase in complex with the inhibitor 8-azaxanthine and a catalytic water bound in the peroxo hole is presented together with an integrated analysis using biomolecular simulations., Cofactor-independent urate oxidase (UOX) is an ∼137 kDa tetrameric enzyme essential for uric acid (UA) catabolism in many organisms. UA is first oxidized by O2 to de­hydro­isourate (DHU) via a peroxo intermediate. DHU then undergoes hydration to 5-hy­droxy­isourate (5HIU). At different stages of the reaction both catalytic O2 and water occupy the ‘peroxo hole’ above the organic substrate. Here, high-resolution neutron/X-ray crystallographic analysis at room temperature has been integrated with molecular dynamics simulations to investigate the hydration step of the reaction. The joint neutron/X-ray structure of perdeuterated Aspergillus flavus UOX in complex with its 8-azaxanthine (8AZA) inhibitor shows that the catalytic water molecule (W1) is present in the peroxo hole as neutral H2O, oriented at 45° with respect to the ligand. It is stabilized by Thr57 and Asn254 on different UOX protomers as well as by an O—H⋯π interaction with 8AZA. The active site Lys10–Thr57 dyad features a charged Lys10–NH3 + side chain engaged in a strong hydrogen bond with Thr57OG1, while the Thr57OG1–HG1 bond is rotationally dynamic and oriented toward the π system of the ligand, on average. Our analysis offers support for a mechanism in which W1 performs a nucleophilic attack on DHUC5 with Thr57HG1 central to a Lys10-assisted proton-relay system. Room-temperature crystallography and simulations also reveal conformational heterogeneity for Asn254 that modulates W1 stability in the peroxo hole. This is proposed to be an active mechanism to facilitate W1/O2 exchange during catalysis.

Two investigated DNA 18-mers indicate a dynamic equilibrium of conformations in solution and crystallize as duplexes with two consecutive T–T mismatches. Neither these mismatched nucleotides nor others found in the PDB exhibit unique structural features compared with Watson–Crick paired nucleotides., Solution and crystal data are reported for DNA 18-mers with sequences related to those of bacterial noncoding single-stranded DNA segments called repetitive extragenic palindromes (REPs). Solution CD and melting data showed that the CG-rich, near-palindromic REPs from various bacterial species exhibit dynamic temperature-dependent and concentration-dependent equilibria, including architectures compatible with not only hairpins, which are expected to be biologically relevant, but also antiparallel duplexes and bimolecular tetraplexes. Three 18-mer oligonucleotides named Hpar-18 (PDB entry 6rou), Chom-18 (PDB entry 6ros) and its brominated variant Chom-18Br (PDB entry 6ror) crystallized as isomorphic right-handed A-like duplexes. The low-resolution crystal structures were solved with the help of experimental phases for Chom-18Br. The center of the duplexes is formed by two successive T–T noncanonical base pairs (mismatches). They do not deform the double-helical geometry. The presence of T–T mismatches prompted an analysis of the geometries of these and other noncanonical pairs in other DNA crystals in terms of their fit to the experimental electron densities (RSCC) and their geometric fit to the NtC (dinucleotide conformational) classes (https://dnatco.datmos.org/). Throughout this work, knowledge of the NtC classes was used to refine and validate the crystal structures, and to analyze the mismatches.

Author(s): McCauley, DJ; Young, HS; Power, EA; Bird, DW; Durham, WH; McInturff, A; Dunbar, RB; Micheli, F; Young, HS

Conserved regions within the M1 family of metallo-aminopeptidases have been used to clone a zinc aminopeptidase from the industrially used fungus Aspergillus niger. The derived amino acid sequence of ApsA is highly similar to two yeast zinc aminopeptidases, LAPI and AAPI (53

Motivation Recent technological developments have facilitated an expansion of microbiome–metabolome studies, in which samples are assayed using both genomic and metabolomic technologies to characterize the abundances of microbial taxa and metabolites. A common goal of these studies is to identify microbial species or genes that contribute to differences in metabolite levels across samples. Previous work indicated that integrating these datasets with reference knowledge on microbial metabolic capacities may enable more precise and confident inference of microbe–metabolite links. Results We present MIMOSA2, an R package and web application for model-based integrative analysis of microbiome–metabolome datasets. MIMOSA2 uses genomic and metabolic reference databases to construct a community metabolic model based on microbiome data and uses this model to predict differences in metabolite levels across samples. These predictions are compared with metabolomics data to identify putative microbiome-governed metabolites and taxonomic contributors to metabolite variation. MIMOSA2 supports various input data types and customization with user-defined metabolic pathways. We establish MIMOSA2’s ability to identify ground truth microbial mechanisms in simulation datasets, compare its results with experimentally inferred mechanisms in honeybee microbiota, and demonstrate its application in two human studies of inflammatory bowel disease. Overall, MIMOSA2 combines reference databases, a validated statistical framework, and a user-friendly interface to facilitate modeling and evaluating relationships between members of the microbiota and their metabolic products. Availability and implementation MIMOSA2 is implemented in R under the GNU General Public License v3.0 and is freely available as a web server at http://elbo-spice.cs.tau.ac.il/shiny/MIMOSA2shiny/ and as an R package from http://www.borensteinlab.com/software_MIMOSA2.html. Supplementary information Supplementary data are available at Bioinformatics online.