bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA
Authors: Welkie David G. , Rubin Benjamin E. , Chang Yong-Gang , Diamond Spencer , Rifkin Scott A. , LiWang Andy , Golden Susan S.
Published: July 2018

Significance

Understanding how photosynthetic bacteria respond to and anticipate natural light–dark cycles is necessary for predictive modeling, bioengineering, and elucidating metabolic strategies for diurnal growth. Here, we identify the genetic components that are important specifically under light–dark cycling conditions and determine how a properly functioning circadian clock prepares metabolism for darkness, a starvation period for photoautotrophs. This study establishes that the core circadian clock protein KaiA is necessary to enable rhythmic derepression of a nighttime circadian program.
Solute movement in the t-tubule system of rabbit and mouse cardiomyocytes
Authors: Kong Cherrie H. T. , Rog-Zielinska Eva A. , Kohl Peter , Orchard Clive H. , Cannell Mark B.
Published: July 2018

Significance

Microscopic invaginations of the surface membrane, called t-tubules, carry electrical and chemical signals into cardiomyocytes. Previous studies have found slow rates of solute exchange inside t-tubules and have suggested that diffusion may be highly restricted. By combining fluorescent tracer measurements and detailed computational modeling, we show that small solutes (

≤

1 kDa) appear to move almost freely within t-tubules and most of the ∼5–16× slowing in exchange rate, compared with free diffusion, arises from t-tubule geometry effects. Larger solutes (>4 kDa) show restricted access into t-tubules, and species-dependent entry may also be impeded by differences in t-tubule mouth configuration. Our data and analyses provide a new pathway to understanding how disease-induced t-tubule derangement may contribute to altered cellular function.
Poisonous and venomous: marine alien species in the Mediterranean Sea and human health.
Authors: Galil B.
Published: July 2018

The Suez Canal is the main pathway of introduction of alien species into the Mediterranean Sea. Its successive enlargements left the entire sea prone to colonization by highly impacting invasive alien species, including poisonous and venomous ones. The temporal and spatial extent of occurrence in the Mediterranean Sea of nine species (fish, sea-urchin, jellyfish and stinging hydroid), the evidence of their impacts on human health in their native range, the frequency and severity of human health impacts in their introduced range are described, as well as management measures. This chapter aims to acquaint and forewarn the public, stake-holders and decision makers, and to urge the latter to take the necessary steps to control the pathways and vectors of introduction and prepare themselves for these new health hazards.
Invasive alien plant impacts on human health and well-being.
Authors: Lazzaro L. , Essl F. , Lugliè A. , Padedda B. M. , Pyšek P. , Brundu G.
Published: July 2018

In this chapter we review, based on information available in scientific literature and reports, the most common negative direct impacts of invasive alien plants and Cyanobacteria on human health and well-being. Poisonous or toxic plants, i.e. plants containing toxic compounds, may impact human health generally after the ingestion of part of the plant (see Nicotiana glauca) or of some product derived from toxic plants (see Senecio inaequidens poisoned products). Allergenic plants are among the most studied cases of impacts of alien plants, particularly concerning the role of allergenic pollen. Many invasive species are well-known allergenic species (e.g. Ambrosia artemisiifolia). Some species may cause contact dermatitis, due to chemical compounds capable of causing adverse cutaneous reactions (e.g. Heracleum mantegazzianum and Parthenium hysterophorus). A significant cause of impact is linked to plants armed with thorns, spines and prickles. Injuries caused by these plants, and their consequences, represent a common clinical issue, sometimes leading also to dermatitis, infection and chronic wounds. Finally we include a review of human impacts related to Cyanobacteria and toxic algal blooms, highlighting the impacts related to cyanotoxins, which seriously impede water uses and environment, causing hazards to human health and sanitary alarm, with acute and chronic effects.
Human health impact by alien spiders and scorpions.
Authors: Nentwig W.
Published: July 2018

Only a few alien spider species are of medical importance to humans because they are large and/or aggressive enough to inject venom and/or possess peculiar venom components. Spiders of serious medical concern include several Latrodectus (Theridiidae) and Loxosceles species (Sicariidae), numerously and globally introduced into many new areas. Loxosceles species are the only spiders that can cause severe local effects (necrosis) and both mentioned genera contain the only alien spider species that can provoke severe systemic effects. However, fatal issues are very rare. For all other spider species large enough to penetrate the human skin and introduced somewhere as alien species, 42 genera or species from 16 families are considered in detail. The venoms of these spiders cause only modest local (redness at the site of the bite, itching and swelling) and systemic (headache or nausea) effects and can be considered as harmless. In contrast to spiders, information on health issues of alien scorpions is rare and restricted to three species so far. One of them is potentially dangerous to humans, two species are not.
The invasive mosquitoes of medical importance.
Authors: Romi R. , Boccolini D. , Luca M. di , Medlock J. M. , Schaffner F. , Severini F. , Toma L.
Published: July 2018

Mosquitoes (Diptera: Culicidae) are the most important group of blood-sucking insects that are vectors of human diseases. This chapter focuses mainly on six species belonging to the Aedes, Culex and Anopheles genera, which, closely adapted to human habitats for thousands of years, have exploited human activities to spread and establish in areas far from their origin, becoming invasive. The mechanisms leading to the introduction and establishment of invasive mosquito species and the risk that they represent for human health in newly colonized areas are extensively described. In particular, this chapter focuses on the three powerful and widespread arbovirus disease vectors, Ae. aegypti, Ae. albopictus and Ae. japonicus, with shorter references to Ae. koreicus and other alien species recently recorded in Europe. The disease vectors belonging to the genus Culex are represented by the Cx. pipiens complex, whose history of travel between continents dates back centuries. The detailed story of the journey undertaken by species belonging to the Anopheles gambiae complex in the 19th century between Africa and Brazil represents the only significant example of invasion by Anophelinae mosquitoes. The last section of the chapter deals with the surveillance and control activities to be implemented in order to prevent the introduction and spread of invasive mosquito species.
Impact of alien mammals on human health.
Authors: Capizzi D. , Monaco A. , Genovesi P. , Scalera R. , Carnevali L.
Published: July 2018

We provide an overview of the impact of wild invasive alien mammals on human health, focusing specifically on species acting as zoonotic hosts or pathogens, along with the diseases and mechanisms of disease transmission associated with mammals in terrestrial, freshwater and marine environments. We checked for published data on the impact on human health for 129 alien invasive mammals, reported in 123 different countries. The highest number of invasive alien mammals causing impacts on human health is reported in Japan (31 species), followed by Australia (24) and Argentina, New Zealand and Cuba (19). However, Australia, Brazil, Mexico, the Bahamas and the Czech Republic are characterized by the highest proportions of alien mammals impacting human health of the total number of invasive mammals reported in the country (range from 93% to 96%). Carnivores are the taxonomic group with the highest numbers of alien species impacting on human health, followed by ungulates and rodents. Our review highlights the important role of alien mammals in threatening human health and welfare, particularly through the transmission of zoonoses. Alien mammals can act as vectors of both alien and native pathogens, and as hosts of either native or alien parasites (which in turn can act as vectors of either native or alien pathogens). In this way, alien mammals can introduce new pathogens, alter the epidemiology of local pathogens, become reservoir hosts and increase disease risk for humans, along with other species. The increasing movements of humans and other species because of climate change and other factors could result in the sudden emergence of disease outbreaks, including new diseases and in new locations. This shows the urgent need for a better understanding of the parasite-vector-host trio and the environmental, climatic and socio-economic factors involved, as well as the large potential for future zoonotic emergence.
Climate change and increase of impacts on human health by alien species.
Authors: Schindler S. , Rabitsch W. , Essl F.
Published: July 2018

There is mounting evidence that climate change will facilitate biological invasions. Regarding alien species relevant for human health, climate change can modify their impacts by altering the likelihood of their introduction, establishment, distribution and abundance, the scale of impacts and management. In this chapter, we summarize climate change impacts on health-relevant alien species with a focus on Europe. Climate change can support introductions of alien species impacting human health, but its role is moderate compared with the other aspects of globalization, such as increased trade and people's increased mobility. There is strong evidence that changing climate characteristics, notably temperature, are crucial for the establishment and spread of human health-relevant alien species. Resulting increases and shifts in distribution might cause increasing health impacts, particularly in cold regions such as temperate and polar regions or areas of higher elevation. In Europe, changes in health impacts caused by alien species are mainly related to arthropod vectors and plants with allergenic pollen. As numbers of alien species will probably increase, preventive management needs to be strengthened. Further, a better understanding of drivers and management options of alien diseases and vectors, as well as joint efforts in education and outreach to the public and decision-makers, is required. There is a need for action and research, particularly in the fields of pathway management, epidemiology, modelling and vector monitoring.
Jerry Edward Chipuk: A powerhouse for mitochondrial biology
Authors: O’Donnell Marie Anne , Infarinato Nicole
Published: July 2018

Chipuk studies the interaction between mitochondrial dynamics and cell death in cancer.
Liquid-chromatography retention order prediction for metabolite identification
Authors: Bach Eric , Szedmak Sandor , Brouard Céline , Böcker Sebastian , Rousu Juho
Published: July 2018

Motivation

Liquid Chromatography (LC) followed by tandem Mass Spectrometry (MS/MS) is one of the predominant methods for metabolite identification. In recent years, machine learning has started to transform the analysis of tandem mass spectra and the identification of small molecules. In contrast, LC data is rarely used to improve metabolite identification, despite numerous published methods for retention time prediction using machine learning.

Results

We present a machine learning method for predicting the retention order of molecules; that is, the order in which molecules elute from the LC column. Our method has important advantages over previous approaches: We show that retention order is much better conserved between instruments than retention time. To this end, our method can be trained using retention time measurements from different LC systems and configurations without tedious pre-processing, significantly increasing the amount of available training data. Our experiments demonstrate that retention order prediction is an effective way to learn retention behaviour of molecules from heterogeneous retention time data. Finally, we demonstrate how retention order prediction and MS/MS-based scores can be combined for more accurate metabolite identifications when analyzing a complete LC-MS/MS run.

Availability and implementation

Implementation of the method is available at https://version.aalto.fi/gitlab/bache1/retention_order_prediction.git.
A Curated Cancer Clinical Outcomes Database (C3OD) for accelerating patient recruitment in cancer clinical trials
Authors: Mudaranthakam Dinesh Pal , Thompson Jeffrey , Hu Jinxiang , Pei Dong , Chintala Shanthan Reddy , Park Michele , Fridley Brooke L , Gajewski Byron , Koestler Devin C , Mayo Matthew S
Published: July 2018

Data used to determine patient eligibility for cancer clinical trials often come from disparate sources that are typically maintained by different groups within an institution, use differing technologies, and are stored in different formats. Collecting data and resolving inconsistencies across sources increase the time it takes to screen eligible patients, potentially delaying study completion. To address these challenges, the Biostatistics and Informatics Shared Resource at The University of Kansas Cancer Center developed the Curated Cancer Clinical Outcomes Database (C3OD). C3OD merges data from the electronic medical record, tumor registry, bio-specimen and data registry, and allows querying through a single unified platform. By centralizing access and maintaining appropriate controls, C3OD allows researchers to more rapidly obtain detailed information about each patient in order to accelerate eligibility screening. This case report describes the design of this informatics platform as well as initial assessments of its reliability and usability.
Microbiology Comment Nudge Improves Pneumonia Prescribing
Authors: Musgrove Mary A , Kenney Rachel M , Kendall Ronald E , Peters Michael , Tibbetts Robert , Samuel Linoj , Davis Susan L
Published: July 2018

Background

Systematic and behavioral interventions are needed to improve antibiotic use for common conditions like pneumonia.

Methods

Single pretest, post-test quasi-experiment in a 4-hospital health system in metropolitan Detroit, Michigan. Hospitalized patients treated with anti-methicillin-resistant Staphylococcus aureus and antipseudomonal antibiotics for respiratory infections from August 1, 2015, through January 31, 2016, and August 1, 2016, through January 31, 2017, were eligible for inclusion. Beginning in May 2016, respiratory cultures with no dominant organism growth and no Pseudomonas sp. or Staphylococcus aureus were reported by the clinical microbiology laboratory as “commensal respiratory flora only: No S. aureus/MRSA [methicillin-resistant Staphylococcus aureus] or P. [Pseudomonas] aeruginosa.” Before intervention, these were reported as “commensal respiratory flora.” The primary end point was de-escalation or discontinuation of anti-methicillin-resistant Staphylococcus aureus or antipseudomonal therapy. Secondary clinical and safety outcomes included nephrotoxicity and in-hospital, all-cause mortality.

Results

Two hundred ten patients were included in the study. De-escalation/discontinuation was more commonly performed in the intervention group (39% vs 73%, P < .001). After adjusting for APACHE II and Charlson Comorbidity Index, the intervention comment was associated with a 5.5-fold increased odds of de-escalation (adjusted odds ratio, 5.5; 95% confidence interval, 2.8–10.7). Acute kidney injury was reduced in the intervention phase (31% vs 14%, P = .003). No difference in all-cause mortality was detected between the groups (30% vs 18%, P = .052).

Conclusion

A simple, behavioral nudge in microbiology reporting increased de-escalation and discontinuation of unnecessary broad-spectrum antibiotics. This highlights the importance of clear, persuasive communication of diagnostic testing in improving antibiotic prescribing behaviors.
Dissecting Symptomatology and Fumonisin Contamination Produced by Fusarium verticillioides in Maize Ears
Authors: Morales Laura , Marino Thiago P. , Wenndt Anthony J. , Fouts Julia Q. , Holland James B. , Nelson Rebecca J.
Published: July 2018

The fungus Fusarium verticillioides can infect maize ears, contaminating the grain with mycotoxins, including fumonisins. This global public health threat can be managed by breeding maize varieties that are resistant to colonization by F. verticillioides and by sorting grain after harvest to reduce fumonisin levels in food systems. Here, we employed two F. verticillioides inoculation techniques representing distinct infection pathways to dissect ear symptomatology and morphological resistance mechanisms in a diverse panel of maize inbred lines. The “point” method involved penetrating the ear with a spore-coated toothpick and the “inundative” method introduced a liquid spore suspension under the husk of the ear. We evaluated quantitative and qualitative indicators of external and internal symptom severity as low-cost proxies for fumonisin contamination, and found that kernel bulk density was predictive of fumonisin levels (78 to 84% sensitivity; 97 to 99% specificity). Inundative inoculation resulted in greater disease severity and fumonisin contamination than point inoculation. We also found that the two inoculation methods implicated different ear tissues in defense, with cob morphology being a more important component of resistance under point inoculation. Across both inoculation methods, traits related to cob size were positively associated with disease severity and fumonisin content. Our work demonstrates that (i) the use of diverse modes of inoculation is necessary for combining complementary mechanisms of genetic resistance, (ii) kernel bulk density can be used effectively as a proxy for fumonisin levels, and (iii) trade-offs may exist between yield potential and resistance to fumonisin contamination.
Evidence for Sexual Recombination inDidymella tanacetiPopulations, and Their Evolution Over Spring Production in Australian Pyrethrum Fields
Authors: Pearce Tamieka L. , Scott Jason B. , Pilkington Stacey J. , Pethybridge Sarah J. , Hay Frank S.
Published: July 2018

Tan spot, caused by Didymella tanaceti, is one of the most important foliar diseases affecting pyrethrum in Tasmania, Australia. Population dynamics, including mating-type ratios and genetic diversity of D. tanaceti, was characterized within four geographically separated fields in both late winter and spring 2012. A set of 10 microsatellite markers was developed and used to genotype 774 D. tanaceti isolates. Isolates were genotypically diverse, with 123 multilocus genotypes (MLG) identified across the four fields. Fifty-eight MLG contained single isolates and Psexanalysis estimated that, within many of the recurrent MLG, there were multiple clonal lineages derived from recombination. Isolates of both mating types were at a 1:1 ratio following clone correction in each field at each sampling period, which was suggestive of sexual recombination. No evidence of genetic divergence of isolates of each mating type was identified, indicating admixture within the population. Linkage equilibrium in two of the four field populations sampled in late winter could not be discounted following clone correction. Evaluation of temporal changes in gene and genotypic diversity identified that they were both similar for the two sampling periods despite an increased D. tanaceti isolation frequency in spring. Genetic differentiation was similar in populations sampled between the two sampling periods within fields or between fields. These results indicated that sexual reproduction may have contributed to tan spot epidemics within Australian pyrethrum fields and has contributed to a genetically diverse D. tanaceti population.
Polydatin suppresses VEGF‐induced angiogenesis through binding with VEGF and inhibiting its receptor signaling
Authors: Hu Wei-Hui , Wang Huai-You , Kong Xiang-Peng , Xiong Qing-Ping , Poon Karman Ka-Man , Xu Li , Duan Ran , Chan Gallant Kar-Lun , Dong Tina Ting-Xia , Tsim Karl Wah-Keung
Published: July 2018

Polydatin, also called piceid, is a stilbenoid glucoside of a resveratrol derivative. It derives mainly from the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. Although the role of P. cuspidatum root in angiogenesis has been reported, the active chemical or chemicals responsible for such function is not known. Here, polydatin was proposed to bind VEGF, which therefore altered the functions of VEGF in angiogenesis. Several lines of evidence supported the pharmaceutical effects of polydatin in VEGF‐induced angiogenesis. In human umbilical vein endothelial cells, polydatin inhibited VEGF‐stimulated cell proliferation, cell migration, and tube formation. Moreover, polydatin showed suppressive effects on the subintestinal vessel formation in zebrafish embryos. In signaling cascades, polydatin application attenuated VEGF‐induced phosphorylations of VEGF receptor 2 and JNK. Moreover, the VEGF‐induced phosphorylations of Akt, eNOS, and Erk were significantly decreased in the presence of polydatin. In parallel, the formation of reactive oxygen species, triggered by VEGF, was markedly decreased under polydatin application. Thus, our results supported the angiogenic roles of polydatin, as well as its signaling mechanism in blocking VEGF‐mediated responses. The current study provides support for the possible development of polydatin as a potential therapeutic agent for treatment and prevention of angiogenesis‐related diseases.—Hu, W.‐H., Wang, H.‐Y., Kong, X.‐P., Xiong, Q.‐P., Poon, K. K.‐M., Xu, L., Duan, R., Chan, G. K.‐L., Dong, T. T.‐X., Tsim, K. W.‐K. Polydatin suppresses VEGF‐induced angiogenesis through binding with VEGF and inhibiting its receptor signaling. FASEB J. 33, 532–544 (2019). www.fasebj.org
Cyberlindnera jadinii (teleomorph Candida utilis) candidaemia in a patient with aplastic anaemia: a case report
Authors: Treguier Pauline , David Marion , Gargala Gilles , Camus Vincent , Stamatoullas Aspasia , Menard Anne-Lise , Lenain Pascal , Contentin Nathalie , Lemasle Emilie , Lanic Helene , Tilly Hervé , Jardin Fabrice , Lepretre Stéphane
Published: July 2018

Introduction. We present what is believed to be the first report of candidaemia caused by Cyberlindnera (Pichia) jadinii (teleomorph of Candida utilis) in a patient with an aplastic anaemia.

Case presentation. The patient, a 21-year-old male, presented with hepatic cytolysis, cutaneous and pulmonary involvement, and septic shock. Cyberlindnera jadinii was identified by aerobic blood culture and MS. The patient initially received multiple and combined antifungal therapy, but continued to have persistent skin lesions and fever. He was successfully treated by emergency haploidentical haematopoietic stem cell transplantation, combined with triple antifungal therapy and supportive care.

Conclusion.
Cyberlindnera jadinii, teleomorph of Candida utilis, which is not usually invasive, can lead to an opportunistic invasive infection in unhealthy adult patients. For treatment of the invasive candida infection, it is necessary to combine antifungal therapy and supportive care.
Taking a Dive: Experiments in Deep Learning for Automatic Ontology-based Annotation of Scientific Literature
Authors: Manda Prashanti , Beasley Lucas , Mohanty Somya D.
Published: July 2018

I.

Text mining approaches for automated ontology-based curation of biological and biomedical literature have largely focused on syntactic and lexical analysis along with machine learning. Recent advances in deep learning have shown increased accuracy for textual data annotation. However, the application of deep learning for ontology-based curation is a relatively new area and prior work has focused on a limited set of models.

Here, we introduce a new deep learning model/architecture based on combining multiple Gated Recurrent Units (GRU) with a character+word based input. We use data from five ontologies in the CRAFT corpus as a Gold Standard to evaluate our model’s performance. We also compare our model to seven models from prior work. We use four metrics - Precision, Recall, F1 score, and a semantic similarity metric (Jaccard similarity) to compare our model’s output to the Gold Standard. Our model resulted in a 84% Precision, 84% Recall, 83% F1, and a 84% Jaccard similarity. Results show that our GRU-based model outperforms prior models across all five ontologies. We also observed that character+word inputs result in a higher performance across models as compared to word only inputs.

These findings indicate that deep learning algorithms are a promising avenue to be explored for automated ontology-based curation of data. This study also serves as a formal comparison and guideline for building and selecting deep learning models and architectures for ontology-based curation.
Computer Assisted Localization of a Heart Arrhythmia
Authors: Vogl Chris , Zheng Peng , Seslar Stephen P. , Aravkin Aleksandr Y.
Published: July 2018

We consider the problem of locating a point-source heart arrhythmia using data from a standard diagnostic procedure, where a reference catheter is placed in the heart, and arrival times from a second diagnostic catheter are recorded as the diagnostic catheter moves around within the heart.

We model this situation as a nonconvex feasibility problem, where given a set of arrival times, we look for a source location that is consistent with the available data. We develop a new optimization approach and fast algorithm to obtain online proposals for the next location to suggest to the operator as she collects data. We validate the procedure using a Monte Carlo simulation based on patients’ electrophysiological data. The proposed procedure robustly and quickly locates the source of arrhythmias without any prior knowledge of heart anatomy.
In Vitro Potentiation of Carbapenems with Tannic Acid Against Carbapenemase Producing Enterobacteriaceae: Exploring Natural Products as Potential Carbapenemase Inhibitors
Authors: Somboro Anou M. , Sekyere John Osei , Amoako Daniel G. , Kumalo Hezekiel M. , Khan René , Bester Linda A. , Essack Sabiha Y.
Published: July 2018

Resistance to antibiotics is increasing worldwide, necessitating urgent action to sustain the efficacy of existing antibiotics in clinical use. We show that tannic acid (TA) in combination with carbapenems can reduce and/or reverse the minimum inhibitory concentrations (MICs) of carbapenems to susceptible values in Enterobacteriaceae that express class A and B carbapenemases. MICs of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TA-carbapenemases inhibition assays and computational studies were undertaken to determine the effect of TA on carbapenem susceptibility in Enterobacteriaceae. TA had the greatest effect on metallo-β-lactamases (MBLs) followed by class A serine-β-lactamases (SBLs). Antibiotic susceptibility testing showed that TA reversed the MICs of MBLs to susceptible values whilst substantially reducing the MICs of SBLs (class A). Tolerable cytotoxicity effect was observed for the concentrations tested. TA inhibited enzymes with a marked difference between ≈50% inhibition (IC50) for NDM-1 and KPC-2. Computational studies including molecular docking, molecular dynamics simulations and binding free energy calculations showed that TA interact with both MBLs and SBLs hydrophobic sites. Moreover, TA had a stronger binding affinity for MBLs than SBLs as the MBLs, specifically VIM-1 and NDM-1, interact with a larger number of their catalytic active-site residues than that of OXA- 48 and KPC-2. These in vitro evaluations together with computational simulation explain the potentiating effect of TA toward carbapenems against carbapenem-resistance enterobacteriaceae. This study proposes TA as a promising adjuvant for MBLs and SBLs.
Asymmetric Diversification of Mating Pheromones in Fission Yeast
Authors: Seike Taisuke , Shimoda Chikashi , Niki Hironori
Published: July 2018

In fungi, mating between partners critically depends on the molecular recognition of two peptidyl mating pheromones by their respective receptors. The fission yeastSchizosaccharomyces pombehas two mating types, Plus (P) and Minus (M), which secrete two different mating pheromones: P-factor recognized by Mam2, and M-factor recognized by Map3, respectively. Our recent study demonstrated that a few mutations in both M-factor and Map3 can trigger reproductive isolation, a cause of speciation, inS. pombe. Here we explored the mechanism underlying reproductive isolation through genetic changes of pheromones and receptors. We investigated the diversity of genes encoding the pheromones and their receptor in 150S. pombewild strains. Whereas the amino acid sequences of M-factor and Map3 were completely conserved, those of P-factor and Mam2 were very diverse. In addition, the P-factor gene contained varying numbers of tandem repeats of P-factor (4–8 repeats). We also explored the recognition specificity of pheromones betweenS. pombe(Sp) and its close relativeSchizosaccharomyces octosporus(So). So-M-factor did not have an effect onS. pombeP-cells, but So-P-factor had a partial effect onS. pombeM-cells, allowing them to mate successfully. Thus, recognition of M-factor seems to be tight, whereas that of P-factor is relatively loose. Moreover, diversity of P-factor and Mam2 might be due to a P-factor-specific peptidase. Overall, the asymmetric system for pheromone recognition in yeasts seems to allow flexible adaptation to mutational changes in the combination of pheromone and receptor while maintaining tight recognition for mating partners.
Reconstitution of mammalian Cleavage Factor II involved in 3’ processing of mRNA precursors
Authors: Schäfer Peter , Tüting Christian , Schönemann Lars , Kühn Uwe , Treiber Thomas , Treiber Nora , Ihling Christian , Graber Anne , Keller Walter , Meister Gunter , Sinz Andrea , Wahle Elmar
Published: July 2018

Cleavage factor II (CF II) is a poorly characterized component of the multi-protein complex catalyzing 3’ cleavage and polyadenylation of mammalian mRNA precursors. We have reconstituted CF II as a heterodimer of hPcf11 and hClp1. The heterodimer is active in partially reconstituted cleavage reactions, whereas hClp1 by itself is not. Pcf11 moderately stimulates the RNA 5’ kinase activity of hClp1; the kinase activity is dispensable for RNA cleavage. CF II binds RNA with nanomolar affinity. Binding is mediated mostly by the two zinc fingers in the C-terminal region of hPcf11. RNA is bound without pronounced sequence-specificity, but extended G-rich sequences appear to be preferred. We discuss the possibility that CF II contributes to the recognition of cleavage/polyadenylation substrates through interaction with G-rich far-downstream sequence elements.
Multi-protein Bridging Factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting
Authors: Wang Jiyu , Zhou Jie , Yang Qidi , Grayhack Elizabeth J.
Published: July 2018

Stalled ribosomes in bacteria frameshift, but stalled ribosomes in eukaryotes do not frameshift and abort translation, suggesting that eukaryote-specific mechanisms might prevent frameshifting. We show that the conserved eukaryotic/archaeal protein Mbf1 acts with ribosomal proteins Rps3/uS3 and eukaryotic Asc1/RACK1 to prevent frameshifting at inhibitory CGA-CGA codon pairs inSaccharomyces cerevisiae. Mutations inRPS3that allow frameshifting implicate eukaryotic conserved residues near the mRNA entry site. Mbf1 and Rps3 cooperate to maintain the reading frame of stalled ribosomes, while Asc1 mediates distinct events that result in aborted translation. Frameshifting occurs through a +1 shift with a CGA codon in the P site and involves competition between codons entering the A site, implying that the wobble interaction of the P site codon destabilizes translation elongation. Thus, eukaryotes have evolved unique mechanisms involving both a universally conserved ribosome component and two eukaryotic-specific proteins to maintain the reading frame at ribosome stalls.
Yap/Taz-TEAD ACTIVITY LINKS MECHANICAL CUES TO CELL PROGENITOR BEHAVIOR DURING HINDBRAIN SEGMENTATION
Authors: Voltes Adrià , Hevia Covadonga F , Dingare Chaitanya , Calzolari Simone , Terriente Javier , Norden Caren , Lecaudey Virginie , Pujades Cristina
Published: July 2018

Cells perceive their microenvironment through chemical and physical cues. However, how mechanical signals are interpreted during embryonic tissue deformation resulting in specific cell behaviors is largely unexplored. The Yap/Taz family of transcriptional co-activators has emerged as an important regulator of tissue growth and regeneration, responding to physical cues from the extracellular matrix, cell shape and actomyosin cytoskeleton. In this work, we unveiled the role of Yap/Taz-TEAD activity as sensor of mechanical signals in the regulation of the progenitor behavior of boundary cells during hindbrain compartmentalization. Monitoringin vivoYap/Taz-activity during hindbrain segmentation we discovered that boundary cells respond to mechanical cues in a cell-autonomous manner through Yap/Taz-TEAD activity. Cell-lineage analysis revealed that Yap/Taz-TEAD boundary cells decrease their proliferative activity when Yap/Taz-TEAD ceased, preceding changes of cell fate: from proliferating progenitors to differentiated neurons. Functional experiments demonstrated the pivotal role of Yap/Taz-TEAD signaling in maintaining the progenitor features in the hindbrain boundary cell population.
Distinct and sequential re-replication barriers ensure precise genome duplication
Authors: Zhou Yizhuo , Pozo Pedro N. , Oh Seeun , Stone Haley M. , Cook Jeanette Gowen
Published: July 2018

Achieving complete and precise genome duplication requires that each genomic segment be replicated only once per cell division cycle. Protecting large eukaryotic genomes from re-replication requires an overlapping set of molecular mechanisms that prevent the first DNA replication step, the DNA loading of MCM helicase complexes to license replication origins. Previous reports have defined many such origin licensing inhibition mechanisms, but the temporal relationships among them are not clear, particularly with respect to preventing re-replication in G2 and M phases. Using a combination of mutagenesis, biochemistry, and single cell analyses in human cells, we define a new mechanism that prevents re-replication through hyperphosphorylation of the essential MCM loading protein, Cdt1. We demonstrate that Cyclin A/CDK1 hyperphosphorylates Cdt1 to inhibit MCM re-loading in G2 phase. The mechanism of inhibition is to block Cdt1 binding to MCM independently of other known Cdt1 inactivation mechanisms such as Cdt1 degradation during S phase or Geminin binding. Moreover, we provide evidence that protein phosphatase 1-dependent Cdt1 dephosphorylation at the mitosis-to-G1 phase transition re-activates Cdt1. We propose that multiple distinct, non-redundant licensing inhibition mechanisms act in a series of sequential relays through each cell cycle phase to ensure precise genome duplication.

Author Summary

The initial step of DNA replication is loading the DNA helicase, MCM, onto DNA during the first phase of the cell division cycle. If MCM loading occurs inappropriately onto DNA that has already been replicated, then cells risk DNA re-replication, a source of endogenous DNA damage and genome instability. How mammalian cells prevent any sections of their very large genomes from re-replicating is still not fully understood. We found that the Cdt1 protein, one of the critical MCM loading factors, is inhibited specifically in late cell cycle stages through a mechanism involving protein phosphorylation. This phosphorylation prevents Cdt1 from binding MCM; when Cdt1 can’t be phosphorylated MCM is inappropriately re-loaded onto DNA and cells are prone to re-replication. When cells divide and transition into G1 phase, Cdt1 is then dephosphorylated to re-activate it for MCM loading. Based on these findings we assert that the different mechanisms that cooperate to avoid re-replication are not redundant, but rather distinct mechanisms are dominant in different cell cycle phases. These findings have implications for understanding how genomes are duplicated precisely once per cell cycle and shed light on how that process is perturbed by changes in Cdt1 levels or phosphorylation activity.
mRNP architecture in translating and stress conditions reveals an ordered pathway of mRNP compaction
Authors: Khong Anthony , Parker Roy
Published: July 2018

Stress granules (SGs) are non-translating mRNP assemblies that form during stress. Herein, we use multiple smFISH probes for specific mRNAs to examine their SG recruitment and spatial organization. We observed that ribosome run-off is required for SG entry with long ORF mRNAs being delayed in SG accumulation, revealing SG transcriptome changes over time. Moreover, mRNAs are ~20X compacted from an expected linear length when translating and compact ~2 fold further in a stepwise manner beginning at the 5’ end during ribosome run-off. Surprisingly, the 5’ and 3’ ends of the examined mRNAs were separated in non-stress conditions, but in non-translating conditions, the ends of AHNAK and DYNC1H1 mRNAs become close, suggesting the closed-loop model of mRNPs preferentially forms on non-translating mRNAs. These results suggest translation inhibition triggers a mRNP reorganization that brings ends closer, which has implications for the regulation of mRNA stability and translation by 3’ UTR elements and the poly(A) tail.
Hidden in plain sight - highly abundant and diverse planktonic freshwater Chloroflexi
Authors: Mehrshad Maliheh , Salcher Michaela M. , Okazaki Yusuke , Nakano Shin-ichi , Šimek Karel , Andrei Adrian-Stefan , Ghai Rohit
Published: July 2018

Background

Representatives of the phylum Chloroflexi, though reportedly highly abundant (up to 30% of total prokaryotes) in the extensive deep water habitats of both marine (SAR202) and freshwater (CL500-11), remain uncultivated and uncharacterized. There are few metagenomic studies on marine Chloroflexi representatives, while the pelagic freshwater Chloroflexi community is largely unknown except for a single metagenome-assembled genome of CL500-11.

Results

Here we provide the first extensive examination of the community composition of this cosmopolitan phylum in a range of pelagic habitats (176 datasets) and highlight the impact of salinity and depth on their phylogenomic composition. Reconstructed genomes (53 in total) provide a perspective on the phylogeny, metabolism and distribution of three novel classes and two family-level taxa within the phylum Chloroflexi. We unraveled a remarkable genomic diversity of pelagic freshwater Chloroflexi representatives that thrive not only in the hypolimnion as previously suspected, but also in the epilimnion. Our results suggest that the lake hypolimnion provides a globally stable habitat reflected in lower species diversity among hypolimnion specific CL500-11 and TK10 clusters in distantly related lakes compared to a higher species diversity of the epilimnion specific SL56 cluster. Cell volume analyses show that the CL500-11 are amongst the largest prokaryotic cells in the water column of deep lakes and with a biomass:abundance ratio of two they significantly contribute to the deep lake carbon flow. Metabolic insights indicate participation of JG30-KF-CM66 representatives in the global cobalamin production via cobinamide to cobalamin salvage pathway.

Conclusions

Extending phylogenomic comparisons to brackish and marine habitats suggests salinity as the major influencer of the community composition of the deep-dwelling Chloroflexi in marine (SAR202) and freshwater (CL500-11) habitats as both counterparts thrive in intermediate brackish salinity however, freshwater habitats harbor the most phylogenetically diverse community of pelagic Chloroflexi representatives that reside both in epi- and hypolimnion.
Molecular Epidemiology and Mechanisms of Antibiotic Resistance in Gram-positive Bacteria in Africa: A Systematic Review and Meta-Analysis from a One Health Perspective
Authors: Sekyere John Osei , Mensah JEric
Published: July 2018

A systematic review and meta-analysis of antibiotic-resistant Gram-positive bacteria in Africa, showing the molecular epidemiology of resistant species from animal, human and environmental sources, is lacking. Thus, the current burden, type, and sources of Gram-positive bacterial resistance and their dissemination routes from farm to fork is absent. To fill this One Health information gap, we systematically searched PubMed, Web of Science and African Journals Online for English research articles reporting on the resistance mechanisms and clonality of resistant Gram-positive bacteria in Africa within 2007 to 2018. The review and all statistical analysis were undertaken with 130 included articles.

From our analyses, the same resistant Gram-positive bacterial clones, resistance genes, and mobile genetic elements (MGEs) are circulating in humans, animals and the environment. The resistance genes, mecA, erm(B), erm(C), tet(M), tet(K), tet(L), vanB, vanA, vanC, and tet(O), were found in isolates from humans, animals and the environment. Commonest clones and mobile genetic elements identified from all three sample sources included Staphylococcus aureus ST5 (n=208 isolates), ST 8 (n=116 isolates), ST 80 (n=123 isolates) and ST 88 (n=105 isolates), and IS16 (n=18 isolates), Tn916 (n=60 isolates) and SCCmec (n=202 isolates). Resistance to penicillin (n=4 224 isolates, 76.2%), erythromycin (n=3 552 isolates, 62.6%), ampicillin (n=1 507 isolates, 54.0%), sulfamethoxazole/trimethoprim (n=2 261 isolates, 46.0%), tetracycline (n=3 054 isolates, 42.1%), vancomycin (n=1 281 isolates, 41.2%), streptomycin (n=1 198 isolates, 37.0%), rifampicin (n=2 645 isolates, 33.1%), ciprofloxacin (n=1 394 isolates, 30.5%), clindamycin (n=1 256 isolates, 29.9%) and gentamicin (n=1 502 isolates, 27.3%) (p-value <0.0001) were commonest.

Mean resistance rates of 14.2% to 98.5% were recorded in 20 countries within the study period, which were mediated by clonal, polyclonal and horizontal transmission of resistance genes. A One Health approach to research, surveillance, molecular epidemiology, and antibiotic stewardship to contain ABR should be prioritized.
Redetermination of the solvent-free crystal structure of L-proline
Authors: Koenig Jonas J. , Neudörfl Jörg-M. , Hansen Anne , Breugst Martin
Published: July 2018

The title compound, (S)-pyrrolidine-2-carboxylic acid (C5H9NO2), commonly known as L-proline, crystallized without the inclusion of any solvent or water molecules through the slow diffusion of diethyl ether into a saturated solution of L-proline in ethanol. L-Proline crystallized in its zwitterionic form and the molecules are linked via N—H...O hydrogen bonds, resulting in a two-dimensional network. In comparison to the only other publication of a single-crystal structure of L-proline without inclusions [Kayushina & Vainshtein (1965). Kristallografiya, 10, 833–844], the R
1 value is significantly improved (0.039 versus 0.169) and thus, our data provides higher precision structural information.
The crystal structure of (E)-2-ethyl-N-(4-nitrobenzylidene)aniline: three-dimensional supramolecular assembly mediated by C—H...O hydrogen bonds and nitro...π(arene) interactions
Authors: Girisha Marisiddaiah , Sagar Belakavadi K. , Yathirajan Hemmige S. , Rathore Ravindranath S. , Glidewell Christopher
Published: July 2018

In the molecule of the title compound, C15H14N2O2, the 2-ethylphenyl group is disordered over two sets of atomic sites having occupancies of 0.515 (19) and 0.485 (19), and the dihedral angle between the two partial-occupancy aryl rings is 6(2)°. A combination of C—H...O hydrogen bonds and nitro...π(arene) interactions links the molecules into a continuous three-dimensional framework structure. Comparisons are made with the structures of some related compounds.
2-Methyl-3′-(4-methylphenyl)-4′-(2-nitrophenyl)-4′H-spiro[chroman-3,5′-isoxazol]-4-one
Authors: Mahfoud Asmae , Al Houari Ghali , El Yazidi Mohamed , Saadi Mohamed , El Ammari Lahcen
Published: July 2018

The title compound, C25H20N2O5, crystallizes with two molecules (A and B) in the asymmetric unit with similar conformations. The five-membered rings are both in envelope conformations with the spiro C atom as the flap. The six-membered heterocycles display half-chair conformations. The mean plane through the isoxazole ring is nearly perpendicular to those through the spiro-chroman system and the 4-nitrophenyl moieties, as indicated by the dihedral angles of 81.42 (9) and 87.58 (8)°, respectively, between them in molecule A. Equivalent data for molecule B are 75.58 (9) and 84.15 (8)°, respectively. The p-tolyl plane makes a dihedral angles of 24.10 (9) and 28.78 (8)° with the isoxazole ring in molecules A and B, respectively. In the crystal, molecules are linked by C—H...O and C—H...N hydrogen bonds and C—H...π interaction, forming a three-dimensional network.
Sustainable improvement in education
Authors: Myszewski Jan M.
Published: July 2018

Purpose

Education is a natural process of improvement. Education’s specific features and challenges include a large number of students, with different psychophysical characteristics, simultaneously taking part in a lesson. The purpose of this paper is to examine the factors that can help to meet the challenges of classroom teaching.

Design/methodology/approach

The principle of “equal opportunities in education” is adopted as the basic premise to improve education. The general sustainability model developed by the author is used as a reference model to analyze the sustainability of the education process.

Findings

The following elements of the process of sustainable development in education are defined: the improvement micro-projects, as the basic form of using and developing students’ knowledge, and the principles of sustainable development in the classroom as conditions necessary for the effectiveness of micro-projects, in the teaching process carried out in the classroom. They point to the key role of the teacher as the leader in the improvement process.

Originality/value

The principles of sustainable development define the conditions necessary to ensure the development of the reserve of the students’ knowledge capacity and the possibilities of using it in the classroom teaching process. The micro-project system enables personalization of the teaching process through the use of the capacity reserve contributed by students.
Key factors that improve knowledge-intensive business processes which lead to competitive advantage
Authors: Aureli Selena , Giampaoli Daniele , Ciambotti Massimo , Bontis Nick
Published: July 2018

Purpose

The purpose of this paper is to empirically test the knowledge-intensive process of creative problem-solving and its outcomes.

Design/methodology/approach

This study uses survey data from 113 leading Italian companies. To test the structural relations of the research model the authors used the partial least square (PLS) method.

Findings

Results show that work design and training have a positive direct impact on creative problem-solving process while organizational culture has a positive impact on both creative problem-solving process and its outcomes. Finally creative problem-solving process has a strong direct impact on its outcomes and this, in turn, on firms’ competitiveness.

Practical implications

This study suggests that managers must highlight the problem-solving process as it affects a firm’s capability to find creative solutions and therefore its competitiveness. Moreover, the present paper suggests managers should invest in specific knowledge management (KM) practices for enhancing knowledge-intensive business processes.

Originality/value

The present paper fills an important gap in the BPM literature by empirically testing the relationship among KM practices, multistage processes of creative problem-solving and their outcomes, and firms’ competitiveness.