bluuebunny/crossref_metadata_2025 huggingface dataset:
Supporting National Forest System Planning with Forest Inventory and Analysis Data
Authors: Wurtzebach Zachary , DeRose R Justin , Bush Renate R , Goeking Sara A , Healey Sean , Menlove Jim , Pelz Kristen A , Schultz Courtney , Shaw John D , Witt Chris
Published: December 2019

In 2012, the US Forest Service promulgated new regulations for land-management planning that emphasize the importance of scientifically credible assessment and monitoring strategies for adaptive forest planning and the maintenance or restoration of ecological integrity. However, in an era of declining budgets, the implementation of robust assessment and monitoring strategies represents a significant challenge for fulfilling the intent of the new planning rule. In this article, we explore opportunities for using data and products produced by the USDA Forest Service’s Forest Inventory and Analysis (FIA) Program to support the implementation of the 2012 Planning Rule. FIA maintains a nationally consistent statistical sample of field plots that covers most national forests with hundreds of plots. We suggest that leveraging FIA data and products can generate efficiencies for assessment, planning, and monitoring requirements detailed in the 2012 Planning Rule, and help fulfill the adaptive intent of the new planning rule. However, strong national leadership and investment in regional-level analytical capacity, FIA liaisons, and decision-support tools are essential for systematically realizing the benefits of FIA data for forest planning across the National Forest System.
Promoting Sustainability in Public Natural-Resource Agencies: Insights from the USDA Forest Service
Authors: Ma Zhao , Steele Diana , Cutler Aurora , Newcomb Katie
Published: December 2019

How employees think about and act upon sustainability is important for public natural-resource agencies. We analyzed survey data from 8,875 USDA Forest Service employees to assess their knowledge, attitudes, behaviors, and perceived opportunities and constraints for promoting broadly defined sustainability. Most survey respondents considered promoting sustainability important to Forest Service’s work, particularly to on-the-ground natural-resource management and planning. They recognized the interconnectedness between promoting sustainability and addressing climate change, and viewed it important to incorporate sustainability into what they were doing rather than developing new initiatives. These results highlight an opportunity for promoting sustainability as a unifying framework for Forest Service’s diverse work. To do so requires the cultivation of an agency-wide shared vision of the interconnectedness between sustainability, climate change, and the management and conservation of natural resources. This further requires efforts to enhance leadership commitment, sustainability-oriented social norms, and mechanisms for peer-to-peer exchange, learning, and support.
Efficacy evaluation of 2D, 3D U-Net semantic segmentation and atlas-based segmentation of normal lungs excluding the trachea and main bronchi
Authors: Nemoto Takafumi , Futakami Natsumi , Yagi Masamichi , Kumabe Atsuhiro , Takeda Atsuya , Kunieda Etsuo , Shigematsu Naoyuki
Published: December 2019

This study aimed to examine the efficacy of semantic segmentation implemented by deep learning and to confirm whether this method is more effective than a commercially dominant auto-segmentation tool with regards to delineating normal lung excluding the trachea and main bronchi. A total of 232 non-small-cell lung cancer cases were examined. The computed tomography (CT) images of these cases were converted from Digital Imaging and Communications in Medicine (DICOM) Radiation Therapy (RT) formats to arrays of 32 × 128 × 128 voxels and input into both 2D and 3D U-Net, which are deep learning networks for semantic segmentation. The number of training, validation and test sets were 160, 40 and 32, respectively. Dice similarity coefficients (DSCs) of the test set were evaluated employing Smart SegmentationⓇ Knowledge Based Contouring (Smart segmentation is an atlas-based segmentation tool), as well as the 2D and 3D U-Net. The mean DSCs of the test set were 0.964 [95% confidence interval (CI), 0.960–0.968], 0.990 (95% CI, 0.989–0.992) and 0.990 (95% CI, 0.989–0.991) with Smart segmentation, 2D and 3D U-Net, respectively. Compared with Smart segmentation, both U-Nets presented significantly higher DSCs by the Wilcoxon signed-rank test (P < 0.01). There was no difference in mean DSC between the 2D and 3D U-Net systems. The newly-devised 2D and 3D U-Net approaches were found to be more effective than a commercial auto-segmentation tool. Even the relatively shallow 2D U-Net which does not require high-performance computational resources was effective enough for the lung segmentation. Semantic segmentation using deep learning was useful in radiation treatment planning for lung cancers.
Is graphite lithiophobic or lithiophilic?
Authors: Duan Jian , Zheng Yuheng , Luo Wei , Wu Wangyan , Wang Tengrui , Xie Yong , Li Sa , Li Ju , Huang Yunhui
Published: December 2019

Graphite and lithium metal are two classic anode materials and their composite has shown promising performance for rechargeable batteries. However, it is generally accepted that Li metal wets graphite poorly, causing its spreading and infiltration difficult. Here we show that graphite can either appear superlithiophilic or lithiophobic, depending on the local redox potential. By comparing the wetting performance of highly ordered pyrolytic graphite, porous carbon paper (PCP), lithiated PCP and graphite powder, we demonstrate that the surface contaminants that pin the contact-line motion and cause contact-angle hysteresis have their own electrochemical-stability windows. The surface contaminants can be either removed or reinforced in a time-dependent manner, depending on whether the reducing agents (C6→LiC6) or the oxidizing agents (air, moisture) dominate in the ambient environment, leading to bifurcating dynamics of either superfast or superslow wetting. Our findings enable new fabrication technology for Li–graphite composite with a controllable Li-metal/graphite ratio and present great promise for the mass production of Li-based anodes for use in high-energy-density batteries.
An experimental workflow identifies nitrogenase proteins ready for expression in plant mitochondria
Authors: Okada S. , Gregg C. M. , Allen R. S. , Menon A. , Hussain D. , Gillespie V. , Johnston E. , Byrne K. , Colgrave M. , Wood C. C.
Published: December 2019

Industrial nitrogen fertilizer is intrinsic to modern agriculture yet expensive and environmentally harmful. We aim to reconstitute bacterial nitrogenase function within plant mitochondria to reduce nitrogen fertilizer usage. Many nitrogen fixation (Nif) proteins are required for biosynthesis and function of the mature nitrogenase enzyme, and these will need to be correctly processed and soluble within mitochondria as a pre-requisite for function. Here we present our workflow that assessed processing, solubility and relative abundance of 16Klebsiella oxytocaNif proteins targeted to the plant mitochondrial matrix using an Arabidopsis mitochondrial targeting peptide (MTP). The functional consequence of the N-terminal modifications required for mitochondrial targeting of Nif proteins was tested using bacterial nitrogenase assays. We found that despite the use of the same constitutive promoter and MTP, MTP::Nif processing and relative abundance in plant leaf varied considerably. Assessment of solubility for all MTP::Nif proteins found NifF, M, N, S, U, W, X, Y and Z were soluble, while NifB, E, H, J, K, Q and V were mostly insoluble. Although most Nif proteins tolerated the N-terminal extension as a consequence of mitochondrial processing, this extension in NifM reduced nitrogenase activity to 10% of controls. Using proteomics, we detected a ∼50-fold increase in the abundance of NifM when it contained the N-terminal MTP extension, which may account for this reduction seen in nitrogenase activity. Based on plant mitochondrial processing and solubility, and retention of function in a bacterial assay, our workflow has identified that NifF, N, S, U, W, Y and Z satisfied all these criteria. Future work can now focus on improving these parameters for the remaining Nif components to assemble a complete set of plant-ready Nif proteins for reconstituting nitrogen fixation in plant mitochondria.
Separation of Bioactive Small Molecules, Peptide from Natural Products and Proteins from Pathogenic Microbe by Rotofor-based Preparative Isoelectric Focusing (IEF) Method
Authors: Veerapandian Raja , Paudyal Anuja , Chang Adeline , Vediyappan Govindsamy
Published: December 2019

The primary purpose of purifying the bioactive small molecules is obtaining enough amount of specific molecules for their downstream applications. There are various methods available for serving this purpose. However, not all can afford for cost-effective purification methods, especially for complex biological samples. Here we demonstrate, the Rotofor based preparative IEF separation which shows the high possibility of separating and enriching desired molecules, including small molecules and peptides from the complex plant extract. This method is well-suited for use at any stage of a purification scheme and has been used for complex biological samples quantification and characterization. As a proof of concept, we fractionatedGymnema sylvestreplant extract and isolated a family of terpenoid saponin molecules at the acidic end and small peptide molecule near the basic end. To our knowledge, this is a first report that Rotofor can be used to fractionate bioactive small molecules from natural product sources. We also showed effective microbial protein separation usingCandida albicansfungus as a model system. The Rotofor based IEF has appealing features such as low cost, simplicity, high application potential and can be performed in any laboratory with the instrument setup.
Capture and visualization of liveMycobacterium tuberculosisbacilli from tuberculosis bioaerosols
Authors: Dinkele Ryan , Gessner Sophia , Koch Anastasia S. , Morrow Carl , Gqada Melitta , Kamariza Mireille , Bertozzi Carolyn R. , Smith Brian , McLoud Courtney , Kamholz Andrew , Bryden Wayne , Call Charles , Mizrahi Valerie , Wood Robin , Warner Digby F.
Published: December 2019

The tuberculosis (TB) pandemic demands urgent interventions such as those designed to interruptMycobacterium tuberculosis(Mtb) transmission, a challenge exacerbated by our poor understanding of the events enabling successful transfer of infectious bacilli between hosts. To address this problem, we developed the Respiratory Aerosol Sampling Chamber (RASC), a personal clean-room equipped with high-efficiency filtration and sampling technologies that allow biosafe capture and isolation of particulate matter – includingMtbbacilli – released by patients during natural breathing and (non-induced) cough. Here, we demonstrate the use of DMN-trehalose labelling to detect and quantify liveMtbbacilli among complex bioaerosol samples arrayed in a bespoke nanowell device following capture in the RASC. A pilot study identifiedMtbin more than 85 % of known TB patients, improving significantly on previous work which has relied on animal infection and cough sampling to estimate transmission events. Moreover, intra-patient comparisons of bioaerosol and sputum samples indicated thatMtbaerosols likely derive from a compartment other than sputum. These results support the utility of the RASC platform for research aimed at interruptingMtbtransmission, including the non-invasive detection ofMtb-infected individuals who are predicted to contribute to bacillary spread despite the absence of clinical symptoms.
A genome wide analysis ofEscherichia coliresponses to fosfomycin using TraDIS-Xpress reveals novel roles for phosphonate and phosphate transport systems
Authors: Yasir Muhammad , Turner Keith , Bastkowski Sarah , Charles Ian , Webber Mark A.
Published: December 2019

Fosfomycin is an antibiotic which has seen a revival in use due to its unique mechanism of action and resulting efficacy against isolates resistant to many other antibiotics. Mechanisms of resistance have been elucidated and loss of function mutations within the genes encoding the sugar importers, GlpT and UhpT are commonly selected for by fosfomycin exposure inE. coli. There has however not been a genome wide analysis of the basis for fosfomycin sensitivity reported to date. Here we used ‘TraDIS-Xpress’ a high-density transposon mutagenesis approach to assay the role of all genes inE. coliin fosfomycin sensitivity. The data confirmed known mechanisms of action and resistance as well as identifying a set of novel loci involved in fosfomycin sensitivity. The assay was able to identify sub domains within genes of importance and also revealed essential genes with roles in fosfomycin sensitivity based on expression changes. Novel genes identified included those involved in glucose metabolism, the phosphonate import and breakdown system,phnC-Mand the phosphate importer,pstSACB. The impact of these genes in fosfomycin sensitivity was validated by measuring the susceptibility of defined inactivation mutants. This work reveals a wider set of genes contribute to fosfomycin sensitivity including core sugar metabolism genes and two transport systems previously unrecognised as having a role in fosfomycin sensitivity. The work also suggests new routes by which drugs with a phosphonate moiety may be transported across the inner membrane of Gram-negative bacteria.

Importance

The emergence and spread of antibiotic resistant bacteria had resulted in increased use of alternative drugs which retain efficacy against isolates resistant to other classes of drugs. One example is fosfomycin; an old drug which has found greatly increased use in recent years. We studied the mechanisms of fosfomycin resistance by applying a genome wide screen based on comparing the fitness of a massive library of transposon mutants in the presence of fosfomycin. This approach identified the previously known mechanisms of resistance but also identified a number of new pathways which contribute to fosfomycin sensitivity including two importer systems. This information advances our knowledge about an increasingly important antibiotic and identifies new potential routes to resistance.
A method to determine the double bond position in unsaturated fatty acids by solvent plasmatization using liquid chromatography-mass spectrometry
Authors: Takashima Shigeo , Toyoshi Kayoko , Yamamoto Takuhei , Shimozawa Nobuyuki
Published: December 2019

Fatty acids (FAs) are the central components of life: they constitute biological membranes in the form of lipid, act as signaling molecules, and are used as energy sources. FAs are classified according to their chain lengths and the number and position of carbon-carbon double bond, and their physiological character is largely defined by these structural properties. Determination of the precise structural properties is crucial for characterizing FAs, but pinpointing the exact position of carbon-carbon double bond in FA molecules is challenging. Herein, a new analytical method is reported for determining the double bond position of mono- and poly-unsaturated FAs using liquid chromatography-mass spectrometry (LC-MS) coupled with solvent plasmatization. With the aid of plasma on ESI capirally, epoxidation or peroxidation of carbon-carbon double bond in FAs is facilitated. Subsequently, molecular fragmentation occurs at or beside the epoxidized or peroxidized double bond via collision-induced dissociation (CID), and the position of the double bond is elucidated. In this method, FAs are separated by LC, modified by plasma, fragmented via CID, and detected using a time-of-flight mass spectrometer in a seamless manner such that the FA composition in a mixture can be determined. Our method enables thorough characterization of FA species with distinguishing multiple isomers, and therefore can uncover the true diversity of FAs for their application in food, health, and medical sciences.
Redox-mediated regulation of a labile, evolutionarily conserved cross-β structure formed by the TDP43 low complexity domain
Authors: Lin Yi , Zhou Xiaoming , Kato Masato , Liu Daifei , Ghaemmaghami Sina , Tu Benjamin P. , McKnight Steven L.
Published: December 2019

An evolutionarily conserved low complexity (LC) domain is found within a 152 residue segment localized to the carboxyl-terminal region of the TDP43 RNA-binding protein. This TDP43 LC domain contains ten conserved methionine residues. Self-association of this domain leads to the formation of liquid-like droplets composed of labile, cross-β polymers. Exposure of polymers to low concentrations of H2O2leads to a phenomenon of droplet melting that can be reversed upon exposure of the oxidized protein to the MsrA and MsrB methionine sulfoxide reductase enzymes, thioredoxin, thioredoxin reductase and NADPH. Morphological features of the cross-β polymers were revealed by a method of H2O2-mediated footprinting. Similar TDP43 LC domain footprints were observed in highly polymerized, hydrogel samples, liquid-like droplet samples, and living cells. The ability of H2O2to impede cross-β polymerization was abrogated by a prominent ALS-causing mutation that changes methionine residue 337 to valine. These observations offer potentially useful insight into the biological role of TDP43 in facilitating synapse-localized translation, as well as aberrant aggregation of the protein in neurodegenerative disease.
Bridging theories for ecosystem stability through structural sensitivity analysis of ecological models in equilibrium
Authors: Kuiper Jan J. , Kooi Bob W. , Peterson Garry D. , Mooij Wolf M.
Published: December 2019

Ecologists are challenged by the need to bridge and synthesize different approaches and theories to obtain a coherent understanding of ecosystems in a changing world. Both food web theory and regime shift theory shine light on mechanisms that confer stability to ecosystems, but from a different angle. Empirical food web models are developed to analyze how equilibria in real multi-trophic ecosystems are shaped by species interactions, and often include linear functional response terms for simple estimation of interaction strengths from observations. Models of regime shifts focus on qualitative changes of equilibrium points in a slowly changing environment, and typically include non-linear functional response terms. Currently, it is unclear how the stability of an empirical food web model, expressed as the rate of system recovery after a small perturbation, relates to the vulnerability of the ecosystem to collapse. Here, we conduct structural sensitive analyses of classical consumer-resource models in equilibrium along an environmental gradient. Specifically, we change non-proportional interaction terms into linear ones, while maintaining the equilibrium biomass densities and flux of matter, to analyze how alternative model formulations shape the stability properties of the equilibria. The results reveal no consistent relationship between the stability of the original models and the linearized versions, even though they describe the same biomass values and material flows. We use these findings to discuss whether stability analysis of observed equilibria by empirical food web models can provide insight into regime shift dynamics, and highlight the challenge of bridging alternative modelling approaches in ecology and beyond.
Interactive mapping of language and memory with the GE2REC protocol
Authors: Banjac Sonja , Roger Elise , Cousin Emilie , Perrone-Bertolotti Marcela , Haldin Célise , Pichat Cédric , Lamalle Laurent , Minotti Lorella , Kahane Philippe , Baciu Monica
Published: December 2019

Previous studies have highlighted the importance of considering cognitive functions in a dynamic and interactive perspective and multiple evidence was brought for a language and memory interaction. In this study performed in healthy participants, we developed a new protocol entitled GE2REC that interactively accesses the neural representation of language-and-memory network. This protocol consists of three runs related to each other, providing a link between tasks, in order to assure an interactive measure of linguistic and episodic memory processes. GE2REC consists of a sentence generation (GE) in auditory modality and two recollecting (2REC) memory tasks, one recognition performed in visual modality, and another one recall performed in auditory modality. Its efficiency was evaluated in 20 healthy volunteers using a 3T MR imager. Our results corroborate the ability of GE2REC to robustly activate a fronto-temporo-parietal language network as well as temporal mesial, prefrontal and parietal cortices during encoding and recognition. GE2REC is useful because: (a) requires simultaneous and interactive language-and-memory processes and jointly maps their neural basis; (b) explores encoding and retrieval, managing to elicit activation of mesial temporal structures; (c) is short and easy to perform, hence being suitable for more restrictive settings, and (d) has an ecological dimension of tasks and stimuli. Overall, GE2REC can provide valuable information in terms of the practical foundation of exploration language and memory interconnection.
Disconnectome Associated with Progressive Ischemic Periventricular White Matter Lesions
Authors: Li Zhengjun , Dolui Sudipto , Habes Mohamad , Bassett Danielle S. , Wolk David , Detre John A.
Published: December 2019

Periventricular white matter (PVWM) hyperintensities on T2-weighted MRI are ubiquitous in older adults and associated with dementia. Efforts to determine how PVWM lesions impact structural connectivity to impinge on brain function remain challenging in part because white matter tractography algorithms for diffusion tensor imaging (DTI) may lose fidelity in the presence of lesions. We used a “virtual lesion” approach to characterize the “disconnectome” associated with periventricular white matter (PVWM) lesions. We simulated progressive ischemic PVWM lesions using sub-threshold cerebral blood flow (CBF) masks derived from a previously published group-averaged map acquired from N=436 middle aged subjects in which the lowest CBF values were seen in PVWM and morphologically recapitulated the spatial pattern of PVWM hyperintensities seen in typical aging. We mimicked the age-dependent evolution of PVWM lesion burden by varying the threshold applied to the CBF map. We found that the optic radiations, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, corpus callosum, temporopontine tract and fornix were affected in early simulated PVWM lesion burdens, and that the connectivity of subcortical, cerebellar, and visual regions were significantly disrupted with increasing simulated PVWM lesion burdens. We also validated the use of virtual lesions to simulate the disconnectome due to WM hyperintensities in a cognitively normal elderly cohort (N=46) by evaluating correlations between structural and functional connectomes. The virtual lesion approach provides new insights into the spatial-temporal changes of the brain structural connectome under progressive PVWM burdens during normal aging.

Significance Statement

We determined the disconnectomes caused by periventricular white matter (PVWM) lesions using the “virtual lesion” approach. We validated the approach using lesions, DTI and resting-state fMRI data from elderly subjects. We simulated disconnectome of progressive PVWM lesions using cerebral blood flow (CBF) masks in PVWM region with normative DTI data, which provides specificity for an ischemic mechanism and begins to address the possibility that connectivity may be affected by reduced CBF prior to the development of overt lesions on T2-weighted FLAIR MRI. The current study presented new insights into the spatial-temporal evolutions of the brain structural connectome under progressive PVWM burdens under normal aging.
G-domain prediction across the diversity of G protein families
Authors: Sanghavi Hiral M. , Rashmi Richa , Dasgupta Anirban , Majumdar Sharmistha
Published: December 2019

Guanine nucleotide binding proteins are characterized by a structurally and mechanistically conserved GTP-binding domain, indispensable for binding GTP. The G domain comprises of five adjacent consensus motifs called G boxes, which are separated by amino acid spacers of different lengths. Several G proteins, discovered over time, are characterized by diverse function and sequence. This sequence diversity is also observed in the G box motifs (specifically the G5 box) as well as the inter-G box spacer length. The Spacers and Mismatch Algorithm (SMA) introduced in this study, can predict G-domains in a given G protein sequence, based on user-specified constraints for approximate G-box patterns and inter-box gaps in each G protein family. The SMA parameters can be customized as more G proteins are discovered and characterized structurally. Family-specific G box motifs including the less characterized G5 motif as well as G domain boundaries were predicted with higher precision. Overall, our analysis suggests the possible classification of G protein families based on family-specific G box sequences and lengths of inter-G box spacers.

Significance Statement

It is difficult to define the boundaries of a G domain as well as predict G boxes and important GTP-binding residues of a G protein, if structural information is not available. Sequence alignment and phylogenetic methods are often unsuccessful, given the sequence diversity across G protein families. SMA is a unique method which uses approximate pattern matching as well as inter-motif separation constraints to predict the locations of G-boxes. It is able to predict all G boxes including the less characterized G5 motif which marks the carboxy-terminal boundary of a G domain. Thus, SMA can be used to predict G domain boundaries within a large multi-domain protein as long as the user-specified constraints are satisfied.

Classification

Biological Sciences/Biophysics and Computational Biology
Chloroplast SRP43 subunit Prevents Aggregation of Proteins
Authors: Furr Mercede , Okoto Patience , Moradi Mahmoud , Heyes Colin , Henry Ralph , Suresh Kumar Thallapuranam Krishnaswamy
Published: December 2019

Integration of light-harvesting chlorophyll binding proteins into the thylakoid membrane requires a specific chaperone, being the cpSRP43 subunit, of the signal recognition particle pathway in chloroplasts. cpSRP43, unique to the chloroplast, is responsible for transport of LHCPs through the stroma as well as assisting in the correct folding, assembly and disaggregation of these proteins for the acquisition of light energy. cpSRP43 is a highly flexible, multidomain protein capable of binding distinct partners in the cpSRP pathway. cpSRP43 is an irreplaceable component, necessary for the accurate and successful integration of LHCPs. It can act as a disaggregase without any input of external energy. Its action is based on the ability to associate with variable regions of different proteins owing to the domains and flexibility within its distinctive structure. Understanding the unique capabilities of cpSRP43 in the chloroplast begs the question of its usefulness outside of the plant cell, as well as its yet unknown roles still within the plant cell. Although the capabilities of cpSRP43 as a hub protein, adept to binding many unknown partners, has been alluded to in other works, it has yet to be thoroughly investigated. In this study we discover that cpSRP43 can act as a generic chaperone for proteins other than LHCP/not native to the chloroplast. The high thermal stability of cpSRP43 has been demonstrated in the previous chapter by its ability to retain its secondary structure as well as withstand aggregation upon heating and cooling cycles as confirmed by absorbance, intrinsic tryptophan fluorescence and far UV circular dichroism spectroscopy. This property gives cpSRP43 the basis to act as a generic chaperone and provide protection like that of typical heat shock proteins. Carbonic anhydrase, Concanavalin A and hFGF1 (acidic human fibroblast growth factor), were selected as candidates for chaperoning activity by cpSRP43. In all three cases, heat-induced aggregation of the candidate protein was either eliminated or significantly reduced in the presence of cpSRP43. In the case of hFGF1, the bioactivity was preserved after heat-treatment in the presence of cpSRP43. We have proposed a mechanism by which cpSRP43 is able to execute this action however further investigation is warranted to determine the exact mechanism(s) which may vary dependent on the target protein.
No title, no theme: The joined neural space between speakers and listeners during production and comprehension of multi-sentence discourse
Authors: Heidlmayr Karin , Weber Kirsten , Takashima Atsuko , Hagoort Peter
Published: December 2019

Speakers and listeners usually interact in larger discourses than single words or even single sentences. The goal of the present study was to identify the neural bases reflecting how the mental representation of the situation denoted in a multi-sentence discourse (situation model) is constructed and shared between speakers and listeners. An fMRI study using a variant of the ambiguous text paradigm was designed. Speakers produced ambiguous texts in the scanner and listeners subsequently listened to these texts in different states of ambiguity: preceded by a highly informative, intermediately informative or no title at all. Conventional BOLD activation analyses in listeners, as well as inter-subject correlation analyses between the speakers’ and the listeners’ hemodynamic time courses were performed. Critically, only the processing of disambiguated, coherent discourse with an intelligible situation model representation involved (shared) activation in bilateral lateral parietal and medial prefrontal regions. This shared spatiotemporal pattern of brain activation between the speaker and the listener suggests that the process of memory retrieval in medial prefrontal regions and the binding of retrieved information in the lateral parietal cortex constitutes a core mechanism underlying the communication of complex conceptual representations.
Supersized ribosomal RNA expansion segments in Asgard archaea
Authors: Penev Petar I. , Fakhretaha-Aval Sara , Patel Vaishnavi J. , Cannone Jamie J. , Gutell Robin R. , Petrov Anton S. , Williams Loren Dean , Glass Jennifer Blanchard
Published: December 2019

The ribosome's common core, comprised of ribosomal RNA (rRNA) and universal ribosomal proteins, connects all life back to a common ancestor and serves as a window to relationships among organisms. The rRNA of the common core is most similar to rRNA of extant bacteria. In eukaryotes, the rRNA of the common core is decorated by expansion segments (ESs) that vastly increase its size. Supersized ESs have not been observed previously in Archaea, and the origin of eukaryotic ESs remains enigmatic. We discovered that the large subunit (LSU) rRNA of two Asgard phyla, Lokiarchaeota and Heimdallarchaeota, considered to be the closest modern archaeal cell lineages to Eukarya, bridge the gap in size between prokaryotic and eukaryotic LSU rRNA. The elongated LSU rRNAs in Lokiarchaeota and Heimdallarchaeota stem from the presence of two supersized ESs, ES9 and ES39. We applied chemical footprinting experiments to study the structure of Lokiarchaeota ES39. Furthermore, we used covariation and sequence analysis to study the evolution of Asgard ES39s and ES9s. By defining the common eukaryotic ES39 signature fold, we found that Asgard ES39s have more and longer helices than eukaryotic ES39s. While Asgard ES39s have sequences and structures distinct from eukaryotic ES39s, we found overall conservation of a three-way junction across the Asgard species that matches eukaryotic ES39 topology, a result consistent with the accretion model of ribosomal evolution.
The Feasibility of Predicting Impending Malignant Ventricular Arrhythmias on the basis of Signal Complexity of Heartbeat Intervals
Authors: Chen Zheng , Kido Koshiro , Ono Naoaki , Altaf-Ul-Amin MD , Kanaya Shigehiko , Huang Ming
Published: December 2019

Malignant ventricular arrhythmias (MAs), such as ventricular tachycardia (VT) that presages cardiac arrest, present the highest hurdle for the healthcare community to overcome. Given that MAs occur unpredictably and lead to emergencies, convenient tracking devices, e.g. photoplethysmogram (PPG), that could predict MAs would be irreplaceably valuable. Since the use of heartbeat intervals (HbI) to predict the occurrence of arrhythmias is becoming more feasible, a further attempt to establish a new convenient approach for predicting impending MAs with HbI is worth trying. Assuming that intrinsic characteristics of MAs (VT and ventricular fibrillation: VF) can be revealed by a suitable approach on the basis of signal complexity, we propose an approach that first expresses the physiological status of the heart by HbI; then delineates the patterns of HbI by a new complexity metric (refined composite multi-scale entropy: RCMsEn); and finally trains a nonlinear machine learning model (random forest: RF) to learn the specific patterns of MAs so as to differentiate them from the normal sinus heart rhythm(N) and other prevalent arrhythmias (atrial fibrillation: AF, and premature ventricular contraction: V).

For calculating entropy values and predicting MAs as early as possible (which is the aim of this study), two specifications are of interest: the minimal length of HbI needed to delineate the MAs patterns sufficiently (lenmin), and the maximum time length at which our model can predict impending MAs (timemax). We compared the RF model with support vector machine (SVM) models based on linear and Gaussian kernels. Results show that the RF model performs the best, reaching a 99.24% recall and a 99.87% precision for a HbI of 500 heartbeats (thelenmin) 374 seconds (thetimemax) preceding the occurrence of MAs. The HbI samples in this study were extracted from an electrocardiograph (ECG). However, given the subtle difference (0.1 ms typically) between the R-R interval of ECG and the P-P interval of PPG, this approach could be extended to HbI acquired by the PPG sensor and thus should be of substantial theoretical and practical significance in cardiac arrest prevention.
Molecular Phylogenetic Analysis of16S rRNASequences Identified Two lineages ofH. pyloriStrains Detected from Different Regions in Sudan Suggestive of Differential Evolution
Authors: Idris Abeer Babiker , Hassan Hadeel Gassim , Salaheldin Ali Maryam Atif , Eltaher Sulafa Mohamed , Idris Leena Babiker , Altayb Hisham N. , Abass Amin Mohamed , Ahmed Ibrahim Mustafa Mohammed , Ibrahim El-Amin Mohamed , Hassan Mohamed A.
Published: December 2019

Background

H. pyloriis ubiquitous among humans, and one of the best studied examples of an intimate association between bacteria and humans. Under several diverse socio-demographic factors in Sudan, a continuous increase in the prevalence rate ofH. pyloriinfection has been noticed which represents a major public health challenge. In this study, we analyzed the molecular evolution ofH. pyloriStrains detected from different ethnic and regions of Sudan using16S rRNAgene and phylogenetic approach.

Materials and methods

A total of 75 gastric biopsies taken from patients who had been referred for endoscopy from different regions of Sudan. The DNA extraction was done by using the guanidine chloride method. Two sets of primers (universal and specific for H. pylori) were used to amplify the16S ribosomalgene. Sanger sequencing was performed; then Blast these sequences with those available in the NCBI nucleotide database. The evolutionary aspects were analyzed using a MEGA7 software.

Result

Molecular detection ofH. pylorihas shown that 28 (37.33%) of patients were positive forH. pylori. Bivariate analysis has found no significant differences exhibited across sociodemographic, endoscopy series andH. pyloriinfection. Nucleotide variations were found at five nucleotide positions (positions 219, 305, 578, 741 and 763-764) and one insertion mutation (750_InsC_751) was present in sixty-seven percent (7/12) of our strains. The phylogenetic tree diverged into two lineages.

Conclusion

The phylogenetic analysis of16S rRNAsequences identified two lineages ofH. pyloristrains detected from different regions in Sudan. Sex mutations were detected in regions of the16S rRNAnot closely associated with either tetracycline or tRNA binding sites. 66.67% of them were located in the central domain of16S rRNA. Studying the effect of these mutations on the functions of16S rRNAmolecules in protein synthesis and antibiotic resistance is of great importance.
Temporal interference stimulation targets deep brain regions by modulating neural oscillations
Authors: Esmaeilpour Zeinab , Kronberg Greg , Reato Davide , Parra Lucas C , Bikson Marom
Published: December 2019

Temporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range. A validated current-flow model of the human head estimates that amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. The electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05-2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1-2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms. Experiment and model confirm the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. This selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. The applied current required depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency of temporal interference stimulation.
ERK-mediated mechanochemical waves direct collective cell polarization
Authors: Hino Naoya , Rossetti Leone , Marín-Llauradó Ariadna , Aoki Kazuhiro , Trepat Xavier , Matsuda Michiyuki , Hirashima Tsuyoshi
Published: December 2019

During collective migration of epithelial cells, the migration direction is aligned over a large, tissue-scale expanse. Although the collective cell migration is known to be directed by mechanical forces transmitted via cell-cell junctions, it remains elusive how the intercellular force transmission is coordinated with intracellular biochemical signaling to achieve collective movements. Here we show that intercellular coupling of extracellular signal-regulated kinase (ERK)-mediated mechanochemical feedback in individual cells yields long-distance transmission of guidance cues. Mechanical stretch activates ERK through epidermal growth factor receptor (EGFR) activation, and the ERK activation triggers cell contraction. In addition, the contraction of the activated cell pulls neighboring cells via cell-cell junctions, evoking another round of ERK activation and contraction in the neighbors. Furthermore, anisotropic contraction based on front-rear cell polarization guarantees unidirectional propagation of ERK activation waves, and in turn, the ERK activation waves direct multicellular alignment of the polarity, leading to long-range ordered migration. Our findings reveal that mechanical forces mediate intercellular signaling underlying sustained transmission of guidance cues for collective cell migration.
LegoBody: facile generation of bispecific and multi-specific antibodies
Authors: Lang Shanshan , Yang Su , Bidlingmaier Scott , Lee Nam-Kyung , Liu Bin
Published: December 2019

Bispecific and multi-specific antibodies are capable of recognizing multiple ligands simultaneously or synergistically, creating complex biological interactions not achievable by monoclonal antibodies, thus expanding opportunities for novel therapy development. With the large number of monoclonal antibodies either approved or under clinical development, there are numerous opportunities to combine their specificities to further improve therapeutic potential. Although simple in concept, clinical development of bi- and multi-specific antibodies face several challenges, chief of which is how to efficiently and reliably produce bispecific and multi-specific antibodies with expected specificity and desired biophysical properties. In this study, we developed a modular approach that uses temporary linkers to enforce proper chain pairing and proteases such as thrombin to remove those linkers from the final product. Combined with the ‘knob-into-hole’ design, we can generate IgG-like, bi- or multi-specific antibodies from any pre-existing monoclonal antibodies. The approach is highly versatile and applicable to any monoclonal antibody pair or panel, expediting evaluation and therapeutic development of bi- and multi-specific antibodies.
Mechanisms governing irritant-evoked activation and calcium modulation of TRPA1
Authors: Zhao Jianhua , Lin King John V. , Paulsen Candice E. , Cheng Yifan , Julius David
Published: December 2019

The TRPA1 ion channel is a chemosensory receptor that is critical for detecting noxious chemical agents that elicit or exacerbate pain or itch. Here we use structural and electrophysiological methods to elucidate how a broad class of reactive electrophilic irritants activate TRPA1 through a two-step cysteine modification mechanism that promotes local conformational changes leading to widening of the selectivity filter to enhance calcium permeability and opening of a cytoplasmic gate. We also identify a calcium binding pocket that is remarkably conserved across TRP channel subtypes and accounts for all aspects of calcium-dependent TRPA1 regulation, including potentiation, desensitization, and activation by metabotropic receptors. These findings provide a structural basis for understanding how endogenous or exogenous chemical agents activate a broad-spectrum irritant receptor directly or indirectly through a cytoplasmic second messenger.
A metal artifact reduction method for small field of view CT imaging
Authors: Choi Seungwon , Moon Seunghyuk , Baek Jongduk
Published: December 2019

To reduce metal artifacts, several sinogram inpainting-based metal artifact reduction (MAR) methods have been proposed where projection data within the metal trace region of the sinogram are treated as missing and subsequently estimated. However, these methods generally assume data truncation does not occur and all metal objects reside inside the field-of-view (FOV). For small FOV imaging, these assumptions are violated, and thus existing inpainting-based MAR methods would not be effective. In this paper, we propose a new MAR method to reduce metal artifacts effectively in the presence of data truncation. The main idea behind the proposed method is the synthesis of a sinogram, which is treated as the originally measured sinogram. First, an initial reconstruction step is performed to remove truncation artifacts. The next step consists of a forward projection of the small FOV image, replacing the original sinogram with the synthesized sinogram. The final step is the application of sinogram inpainting based MAR methods using the synthesized sinogram. Verification of the proposed method was performed for three situations: extended cardiac-torso (XCAT) simulation, clinical data, and experimental data. The proposed method was applied with linear MAR (LMAR) and normalized MAR (NMAR), and the performance of the proposed method was compared with that of the previous method. For quantitative evaluation, normalized mean squared error (NMSE) and structure similarity (SSIM) were used. The results show the effectiveness of the proposed method to reduce residual metal artifacts, which are present in the results obtained with the previous method. The evaluation results using NMSE and SSIM also indicate that the proposed method is more effective than the previous method.
Improving Probabilistic Infectious Disease Forecasting Through Coherence
Authors: Gibson Graham Casey , Moran Kelly R. , Reich Nicholas G. , Osthus Dave
Published: December 2019

With an estimated $10.4 billion in medical costs and 31.4 million outpatient visits each year, influenza poses a serious burden of disease in the United States. To provide insights and advance warning into the spread of influenza, the U.S. Centers for Disease Control and Prevention (CDC) runs a challenge for forecasting weighted influenza-like illness (wILI) at the national and regional level. Many models produce independent forecasts for each geographical unit, ignoring the constraint that the national wILI is a weighted sum of regional wILI, where the weights correspond to the population size of the region. We propose a novel algorithm that transforms a set of independent forecast distributions to obey this constraint, which we refer to as probabilistically coherent. Enforcing probabilistic coherence led to an increase in forecast skill for 90% of the models we tested over multiple flu seasons, highlighting the importance of respecting the forecasting system’s geographical hierarchy.

Author Summary

Seasonal influenza causes a significant public health burden nationwide. Accurate influenza forecasting may help public health officials allocate resources and plan responses to emerging outbreaks. The U.S. Centers for Disease Control and Prevention (CDC) reports influenza data at multiple geographical units, including regionally and nationally, where the national data are by construction a weighted sum of the regional data. In an effort to improve influenza forecast accuracy across all models submitted to the CDC’s annual flu forecasting challenge, we examined the effect of imposing this geographical constraint on the set of independent forecasts, made publicly available by the CDC. We developed a novel method to transform forecast densities to obey the geographical constraint that respects the correlation structure between geographical units. This method showed consistent improvement across 90% of models and that held when stratified by targets and test seasons. Our method can be applied to other forecasting systems both within and outside an infectious disease context that have a geographical hierarchy.