bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimising tropical forest bird surveys using passive acoustic monitoring and repeated short-duration point counts
Authors: Metcalf Oliver C. , Barlow Jos , Marsden Stuart , de Moura Nárgila Gomes , Berenguer Erika , Ferreira Joice , Lees Alexander C.
Published: August 2020

Estimation of avian biodiversity is a cornerstone measure of ecosystem condition, with turnover in avian community composition underpinning many studies of land-use change in tropical forests. Surveys conducted using autonomous recorders have been frequently found to be more efficient than traditional point-count surveys. However, there has been limited research into optimal survey duration, despite autonomous recordings allowing for many more repeats of short-duration surveys with relative ease in comparison to traditional survey methods.

We use an acoustic dataset collected from a region of very high avian biodiversity - the eastern Brazilian Amazon - to test the effect of using short-duration surveys to increase temporal coverage without increasing total survey duration. We use this dataset to assess whether a survey protocol consisting of 240 15-second surveys at 29 locations, ‘short-duration surveys’, has an influence on resulting alpha and gamma diversity, and detection frequency, than ‘standard-duration surveys’ of four 15-minute surveys per location.

We find that repeated short-duration surveys outperform longer duration surveys in every metric considered herein, with short-duration surveys predicted to detect approximately 50% higher alpha diversity, and 10% higher gamma diversity. Short-duration surveys also detect species more often, at more survey locations. Conversely, standard-duration surveys are almost four times more likely to produce false negatives (i.e. to fail to detect species presence). Whilst there is no difference between the proportion of uncommon species detected by the two methods, when considering species detected multiple times at multiple locations, short-duration surveys detected three times more uncommon species than standard-duration surveys.

We conclude that short-duration recorded surveys should be considered the primary method for sampling the species richness of bird communities in tropical forests and is likely to be preferable to longer duration or traditional surveys in most environments.
Emerging Tumor Development by Simulating Single-cell Events
Authors: Rosenbauer Jakob , Berghoff Marco , Schug Alexander
Published: August 2020

Despite decades of substantial research, cancer remains a ubiquitous scourge in the industrialized world. Effective treatments require a thorough understanding of macroscopic cancerous tumor growth out of individual cells. Clinical imaging methods, however, only detect late-stage macroscopic tumors, while many quantitative experiments focus on small clusters of cancerous cells in microscopic detail but struggle to grow full tumorsin-vitro. Here, we introduce the critical scale-bridging link between both these scopes. We are able to simulate the growth of mm-sized tumors composed of 1.5 millionμm-resolved individual cells by employing highly parallelized code on a supercomputer. We observe the competition for resources and space, which can lead to hypoxic or necrotic tissue regions. Cellular mutations and tumor stem cells can lead to tissue heterogeneity and change tumor properties. We probe the effects of different chemotherapy and radiotherapy treatments and observe selective pressure. This improved theoretical understanding of cancer growth as emerging behavior from single-cells opens new avenues for various scientific fields, ranging from developing better early-stage cancer detection devices to testing treatment regimesin-silicofor personalized medicine.

Author summary

Experimental and microscopy techniques are rapidly advancing biology and the observability of tissue. The theoretical understanding of tissue either focuses on a few cells or continuous tissue. Here we introduce the scale-bridging theoretical link that is able to model single cells as well as tissue consisting of millions of those cells, harvesting the power of modern supercomputers. We close the gap between single-cells and tissue through access to the full time-resolved trajectories of each cell and the emerging behavior of the tissue. We apply our framework on a generalized model for tumor growth. Tumor heterogeneity, as well as tumor stem cells are introduced, and the changes of behavior in response to cancer treatments is observed and validated.
Fertility-LightGBM: A fertility-related protein prediction model by multi-information fusion and light gradient boosting machine
Authors: Yue Lingling , Wang Minghui , Yang Xinhua , Han Yu , Song Lili , Yu Bin
Published: August 2020

The identification of fertility-related proteins plays an essential part in understanding the embryogenesis of germ cell development. Since the traditional experimental methods are expensive and time-consuming to identify fertility-related proteins, the purposes of predicting protein functions from amino acid sequences appeared. In this paper, we propose a fertility-related protein prediction model. Firstly, the model combines protein physicochemical property information, evolutionary information and sequence information to construct the initial feature space ‘ALL’. Then, the least absolute shrinkage and selection operator (LASSO) is used to remove redundant features. Finally, light gradient boosting machine (LightGBM) is used as a classifier to predict. The 5-fold cross-validation accuracy of the training dataset is 88.5%, and the independent accuracy of the training dataset is 91.5%. The results show that our model is more competitive for the prediction of fertility-related proteins, which is helpful for the study of fertility diseases and related drug targets.
Local coupling between sleep spindles and slow oscillations supports the stabilization of motor memories
Authors: Solano Agustín , Riquelme Luis A. , Perez-Chada Daniel , Della-Maggiore Valeria
Published: August 2020

Recent studies from us and others suggest that traditionally declarative structures (e.g., hippocampus) mediate some aspects of the encoding and consolidation of procedural memories. This evidence points to the existence of converging physiological pathways across memory systems. Here, we examined whether the coupling between slow oscillations (SO) and spindles, a mechanism well established in the consolidation of declarative memories, is relevant for the stabilization of human motor memories. To this aim, we conducted an EEG study in which we quantified various parameters of these oscillations during a night of sleep that took place immediately after learning a visuomotor adaptation task. We hypothesized that if this coupling is instrumental to motor memory consolidation then spindles locked to the active phase of a slow oscillation would predict long-term memory. We found that visuomotor adaptation increased the overall density of fast (≥12 Hz) but not slow (<12Hz) spindles during NREM3. This modulation was manifested rather locally, over the hemisphere contralateral to the trained hand. Although motor learning did not affect the density of SOs, it substantially enhanced the number of fast spindles locked to the active phase of SOs. The fact that only coupled spindles of the left hemisphere predicted long-term memory overnight, points to the precise phase relationship between these oscillations as a fundamental signature of motor memory consolidation. Our work provides evidence in favor of a common mechanism at the basis of the stabilization of declarative and non-declarative memories.

Significance Statement

Ever since the discovery of memory systems, the study of the mechanisms supporting the consolidation of declarative and procedural memories has progressed somewhat in parallel. In the last few years, however, this framework is starting to change. We now know that structures originally thought of as purely declarative, such as the hippocampus, participate in the consolidation of procedural tasks. Here, we show that sleep modulates the stabilization of motor memories through a mechanism involved in the consolidation of declarative memories, based on the local synchrony between fast sleep spindles and slow oscillations. The fact that only coupled –but not uncoupled- spindles of the contralateral hemisphere predicted long-term memory supports a role of this association in the consolidation of motor memories.
Cdc42 activity is essential for the interplay between cAMP/PKA pathway and CatSper function
Authors: Luque Guillermina M. , Xu Xinran , Romarowski Ana , Gervasi María G. , Orta Gerardo , De la Vega-Beltrán José L. , Stival Cintia , Gilio Nicolás , Dalotto-Moreno Tomás , Krapf Dario , Visconti Pablo E. , Krapf Diego , Darszon Alberto , Buffone Mariano G.
Published: August 2020

Sperm acquire the ability to fertilize in a process called capacitation and undergo hyperactivation, a change in the motility pattern, which depends on Ca2+transport by CatSper channels. CatSper is essential for fertilization and it is subjected to a complex regulation that is not fully understood. Here, we report that similar to CatSper, Cdc42 distribution in the principal piece is confined to four linear domains and this localization is disrupted in CatSper1-null sperm. Cdc42 inhibition impaired CatSper activity and other Ca2+-dependent downstream events resulting in a severe compromise of the sperm fertilizing potential. We also demonstrate that Cdc42 is essential for CatSper function by modulating cAMP production by sAC, providing a new regulatory mechanism for the stimulation of CatSper by the cAMP/PKA-dependent pathway. These results reveal a broad mechanistic insight into the regulation of Ca2+in mammalian sperm, a matter of critical importance in male infertility as well as in contraception.
Gene families with stochastic exclusive gene choice underlie cell adhesion in mammalian cells
Authors: Iakovlev Mikhail , Faravelli Simone , Becskei Attila
Published: August 2020

Exclusive stochastic gene choice combines precision with diversity. This regulation enables most T-cells to express exactly one T-cell receptor isoform chosen from a large repertoire, and to react precisely against diverse antigens. Some cells express two receptor isoforms, revealing the stochastic nature of this process. A similar regulation of odorant receptors and protocadherins enable cells to recognize odors and confer individuality to cells in neuronal interaction networks, respectively. We explored whether genes in other families are expressed exclusively by analyzing single cell RNA-seq data with a simple metric. Chromosomal segments and families are more likely to express genes concurrently than exclusively, possibly due to the evolutionary and biophysical aspects of shared regulation. Nonetheless, gene families with exclusive gene choice were detected in multiple cell types, most of them are membrane proteins involved in ion transport and cell adhesion, suggesting the coordination of these two functions. Thus, stochastic exclusive expression extends beyond the prototypical families, permitting precision in gene choice to be combined with the diversity of intercellular interactions.
Stool methanogens in intestine mammal species
Authors: Guindo C.O. , Davoust B , Drancourt M , Grine G
Published: August 2020

Methanogens are being members of anaerobe microbiota of the digestive tract of both human and mammals. However, the sources, modes of acquisition and dynamics of digestive tract methanogens remain poorly investigated. In this study, we aimed to expand the spectrum of animals which could be sources of methanogens for human, by exploring methanogen carriage in animals in contact with the general population or with some restricted populations; comparing the repertoire of animal methanogens with the one of human methanogens in order to question methanogens as zoonotic microorganisms. We used RT-PCR, PCR-sequencing and multispacer sequence typing to investigate the presence of methanogens in 407 fecal specimens collected from nine different mammalian species. We detected by RT-PCR, the presence of methanogen DNA in all mammals here investigated and none of the negative controls. We obtained by sequencing, seven different species of methanogens, of which three (Methanobrevibacter smithii, Methanobrevibacter millerae and Methanomassiliicoccus luminyensis) are known to be part of the methanogens present in the human digestive tract. We obtained 24 M. smithii by PCR-sequencing including 12/24 (50%) in pigs, 6/24 (25%) in dogs, 4/24 (16.66%) in cats, and 1/24 (4.16%) in both sheep and horses. Genotyping these 24 M. smithii revealed five different genotypes, all know in humans. Our results are fairly representative of the methanogen community present in the digestive tract of certain animals domesticated by humans and other future studies must be done to try to cultivate methanogens here detected by molecular biology to better understand the dynamics of methanogens in animals and also the likely acquisition of methanogens in humans through direct contact with these animals or through consumption of the meat and/or milk of certain animals, in particular cows.
Knowledge and attitude regarding stem cell research and its application among medical students in Pakistan
Authors: Daud Mashal , Sajid Zaina , Ali Tooba
Published: August 2020

Background

The utilization of stem cells (SCs) has led the way into a new era of therapeutics known as regenerative medicine. Their renewal property offers exciting possibilities in reversing tissue damage caused by metabolic and degenerative changes. Research should be conducted increasingly to explore the possibilities of SC utilization in Pakistan.

Objectives

To assess the level of knowledge, perception, and attitude of medical students regarding stem cell research (SCR) and its application, to obtain a better insight into the future of stem cell therapy in Pakistan as it is a rapidly emerging field in medicine.

Materials and Methods

This cross-sectional study was carried out using a self-administered questionnaire filled by 206 medical students from different medical colleges in Pakistan. A convenience sampling method was used. Knowledge and attitude scores were calculated based on answers to 28 well-structured questions. Data was analyzed using SPSS.

Results

The mean values of the answers showed that 60.2% (n=124) of the students had a good knowledge and 39.8% (n=82) had poor knowledge of stem cells. Whereas, 56.8% (n=117) expressed a positive attitude and 43.2% (n=89) expressed a negative attitude towards SCR. Independent t-test applied on knowledge score and attitude showed that the mean knowledge score of people with a positive attitude is higher i.e. 21.25 as compared to the mean knowledge score of people with negative attitude i.e. 19.21. And the difference of the means is significant at p=0.007. Thus, the attitude of students was observed to be significantly dependent on their knowledge about SCR.

Conclusion

The results show that medical students have baseline knowledge about SC therapy and a positive attitude towards it. Seminars, workshops should be conducted and this topic should be added to their syllabus so that they obtain proper information about SCR and encourage further research.
Water requirement and growth indicators of forest tree species seedlings produced with automated irrigation management
Authors: Bueno Mateus Marques , dos Santos Leles Paulo Sérgio , Abreu João Felício Gonçalves , dos Santos Jaqueline Jesus Santana , de Carvalho Daniel Fonseca
Published: August 2020

The lack of information regarding the water requirement of tree species promotes water waste in the seedlings production in nurseries. Water requirement, the growth plant factors and water efficiencies for height and diameter were determined for Schizolobium parahyba (Vell.) Blake, Cytharexylum myrianthum Cham. and Ceiba speciosa Ravenna seedlings, under greenhouse conditions and automated irrigation management. We used sewage sludge biosolids as substrate in the seedling phase (280 cm-3 tube), and sandy soil material in the initial pot growth phase (18 dm-3 pot). In the seedlings phase, four water replacement levels were applied to the substrate, by drip irrigation, meaning average replacement ranging from 40 (V1) to 100% (V4) of species water requirement. Seedlings developed properly and 80 days after emergency, S. parahyba, C. myrianthum and C. speciosa seedlings received, respectively, 2.40, 1.08 and 0.85 L per plant, for V4. After growth phase (230 DAE), the total water volumes were, respectively, 70.0, 50.3 and 52.7 L per plant. Under adequate water supply, there were rapid recovery and growth of the species, even for the seedlings which showed different height and diameter in the tube phase. The growth plant factors values found were below 0.5 for all species indicating low sensibility to growth, both in height and in diameter, in response to water deficit. Water efficiency indicators point to distinct trends between the two phases, and C. speciosa present higher values of water efficiencies for height (80.7 and 17.0 cm L-1) and diameter (2.1 and 0.5 mm L-1) in both phases.
Repeated multi-domain, but not single-domain, cognitive training prevents cognitive decline and amyloid pathology found in the APPNL-G-Fmouse model of Alzheimer disease
Authors: Mehla Jogender , Deibel Scott H. , Karem Hadil , Hossain Shakhawat , Lacoursiere Sean G. , Sutherland Robert J. , McDonald Robert J. , Mohajerani Majid H.
Published: August 2020

Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may prevent/ or delay the progression of various neurodegenerative diseases including Alzheimer’s disease (AD). To investigate this protective effect, APPNL-G-F/NL-G-Fmice at 3 months of age were exposed to repeated, single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, 9 & 12 months of age. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for cognitive training groups and control group. After completion of behavioral testing, mice were sacrificed, and their brains were assessed for pathology. AppNL-G-Fmice given multi-domain cognitive training compared to APPNL-G-Fcontrol group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. There were mild reductions in microglosis in the brain of APPNL-G-Fmice with singledomain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.
Optimizing accuracy and depth of protein quantification in experiments using isobaric carriers
Authors: Specht Harrison , Slavov Nikolai
Published: August 2020

The isobaric carrier approach, which combines small isobarically-labeled samples with a larger isobarically-labeled carrier sample, is finding diverse applications in ultrasensitive mass-spectrometry analysis of very small samples, such as single cells. To enhance the growing use of isobaric carriers, we characterized the trade-offs of using isobaric carriers in controlled experiments with complex human proteomes. The data indicate that isobaric carriers directly enhances peptide sequence identification without simultaneously increasing the number of protein copies sampled from small samples. The results also indicate strategies for optimizing the amount of isobaric carrier and analytical parameters, such as ion accumulation time, for different priorities such as improved quantification or increased number of identified proteins. Balancing these trade-offs enables adapting isobaric carrier experiments to different applications, such as quantifying proteins from limited biopsies or organoids, building single-cell atlases, or modeling protein networks in single cells. In all cases, the reliability of protein quantification should be estimated and incorporated in all subsequent analysis. We expect that these guidelines will aid in explicit incorporation of the characterized trade-offs in experimental designs and transparent error propagation in data analysis.

Abstract Figure
Rice embryogenic trigger BABY BOOM1 promotes somatic embryogenesis by upregulation of auxin biosynthesis genes
Authors: Khanday Imtiyaz , Santos-Medellín Christian , Sundaresan Venkatesan
Published: August 2020

Somatic embryogenesis, a powerful tool for clonal propagation and for plant transformation, involves cellular reprogramming of differentiated somatic cells to acquire pluripotency. Somatic embryogenesis can be induced by treating explants with plant growth regulators. However, several plant species including agronomically important cereal crops remain recalcitrant to dedifferentiation and transformation except from embryonic tissues. Somatic embryogenesis can also be induced by ectopic expression of select embryonic factors, including in cereals byBABY BOOM (BBM)transcription factors. HowBBMgenes bypass the need for exogenous hormones is not well understood. Here, we investigated downstream targets during induction of somatic embryogenesis in rice byOsBBM1((Oryza sativa BABY BOOM1). Transient induction ofOsBBM1led to the upregulation of auxin biosynthesisOsYUCCAgenes. Continued induction ofOsBBM1resulted in somatic embryogenesis without the need for exogenous auxins. Genetic mutant analysis ofOsBBM1downstream targets,OsYUCCA6, OsYUCCA7andOsYUCCA9, show that they are required for normal rice development including root and shoot development. Somatic embryogenic potential ofOsYUCCAtriple mutants was highly compromised despite the presence of exogenous auxin. Additionally, we show that somatic embryogenesis induction by exogenous auxin in rice requires functionalBBMgenes. Thus,OsBBM1mediated cellular reprogramming and somatic embryogenesis likely involves increased localized auxin through direct upregulation ofOsYUCCAgenes. This study reveals mechanistic details of how somatic embryogenesis is established in differentiated tissues in rice, a monocot model and agronomically important cereal crop, with the potential utility to improve regeneration from tissue culture for recalcitrant plants in future.

One-sentence summary

Rice BABY BOOM1 induces somatic embryogenesis from differentiated tissues by promoting auxin biosynthesis through direct upregulation ofYUCCAgenes.
Lamellar cells in Pacinian and Meissner corpuscles are touch sensors
Authors: Nikolaev Yury A. , Feketa Viktor V. , Anderson Evan O. , Gracheva Elena O. , Bagriantsev Sviatoslav N.
Published: August 2020

The skin covering the human palm and other specialized tactile organs contains a high density of mechanosensory corpuscles tuned to detect transient pressure and vibration. These corpuscles comprise a sensory afferent neuron surrounded by lamellar cells1-3. The neuronal afferent is thought to be the mechanical sensor within the corpuscle, whereas the function of lamellar cells is unknown2,4,5. Here we show that lamellar cells within Meissner and Pacinian corpuscles detect tactile stimuli. We develop a preparation of bill skin from tactile-specialist ducks that permits electrophysiological recordings from lamellar cells and demonstrate that they contain mechanically-gated ion channels. We also show that lamellar cells from Meissner corpuscles generate mechanically-evoked action potentials using R-type voltage-gated calcium channels. These findings provide the first evidence for R-type channel-dependent action potentials in non-neuronal cells and demonstrate that lamellar cells are active detectors of touch. We propose that Meissner and Pacinian corpuscles use both neuronal and non-neuronal mechanoreception to detect mechanical signals.
Click evoked middle ear muscle reflex: Spectral and temporal aspectsa)
Authors: Boothalingam Sriram , Goodman Shawn S.
Published: August 2020

This study describes a time series-based method of middle ear muscle reflex (MEMR) detection using bilateral clicks. Although many methods can detect changes in the OAE evoking stimulus to monitor the MEMR, they do not discriminate between true MEMR-mediated vs. artifactual changes in the stimulus. We measured MEMR in 20 young clinically normal hearing individuals using 1-second-long click trains presented at six levels (65 to 95 dB peak-to-peak SPL in 6 dB steps). Changes in the stimulus levels over the 1 second period were well-approximated by two-term exponential functions. The magnitude of ear canal pressure changes due to MEMR increased monotonically as a function of click level but non-monotonically with frequency when separated into 1/3rd-octave wide bands between 1 and 3.2 kHz. MEMR thresholds estimated using this method were lower than that obtained from a clinical tympanometer in ∼94% of the participants. A time series-based method, along with statistical tests, may provide additional confidence in detecting the MEMR. MEMR effects were smallest at 2 kHz, between 1 and 3.2 kHz, which may provide avenues for minimizing the MEMR influence while measuring other responses (e.g., the medial olivocochlear reflex).
Enhancing c-MYC degradation via 20S proteasome activation inducesin vivoanti-tumor efficacy
Authors: Njomen Evert , Lansdell Theresa A. , Vanecek Allison , Benham Vanessa , Bernard Matt P. , Yang Ya-Ting , Schall Peter Z. , Isaac Daniel , Alkharabsheh Omar , Al-Janadi Anas , Giletto Matthew B. , Ellsworth Edmund , Taylor Catherine , Tang Terence , Lau Sarah , Bailie Marc , Bernard Jamie J. , Yuzbasiyan-Gurkan Vilma , Tepe Jetze J.
Published: August 2020

Enhancing proteasome activity is a potential new therapeutic strategy to prevent the accumulation of aberrant high levels of protein that drive the pathogenesis of many diseases. Herein, we examine the use of small molecules to activate the 20S proteasome to reduce aberrant signaling by the undruggable oncoprotein c-MYC, to treat c-MYC driven oncogenesis. Overexpression of c-MYC is found in more than 50% of all human cancer but remains undruggable because of its highly dynamic intrinsically disordered 3-D conformation, which renders traditional therapeutic strategies largely ineffective. We demonstrate herein that small molecule activation of the 20S proteasome targets dysregulated intrinsically disordered proteins (IDPs), including c-MYC, and reduces cancer growthin vitroandin vivomodels of multiple myeloma, and is even effective in bortezomib resistant cells and unresponsive patient samples. Genomic analysis of various cancer pathways showed that proteasome activation results in downregulation of many c-MYC target genes. Moreover, proteasome enhancement was well tolerated in mice and dogs. These data support the therapeutic potential of 20S proteasome activation in targeting IDP-driven proteotoxic disorders, including cancer, and demonstrate that this new therapeutic strategy is well toleratedin vivo.
Identification of an N-acetylneuraminic acid-presenting bacteria isolated from a healthy human microbiome
Authors: Han Zhen , Thuy-Boun Peter S. , Pfeiffer Wayne , Vartabedian Vincent F. , Torkamani Ali , Teijaro John R. , Wolan Dennis W.
Published: August 2020

N-acetylneuraminic acid is the most abundant sialic acid in humans and is generally expressed as the terminal sugar on intestinal mucus glycans. Several pathogenic bacterial species harvest sialic acid from the mucus, diet, as well as other intestinal sources and display this sugar on their own surface to evade sialic acid-binding immunoglobulin-type lectin (Siglec)-mediated host immune surveillance. While previous studies have identified bacterial enzymes associated with sialic acid catabolism, no reported methods permit the selective labeling, tracking, and quantitation of sialic acid-presenting microbes within complex multi-microbial systems. Here, we apply an interdisciplinary approach combining metabolic labeling, click chemistry, metagenomic, and whole-genome sequencing to selectively track and identify sialic acid-presenting microbes from a cultured healthy human fecal microbiome. We isolated and identified a new strain ofEscherichia colithat incorporates sialic acid onto its own surface. Analysis of the sequence data reveals that thisE. colistrain encodes for the NanT, NeuA, and NeuS genes necessary for harvesting environmental sialic acid and generating the capsular polysialic acid. We envision that this method is applicable to the detection and quantitation of sialic acid-presenting bacteria from human, animal, and environmental microbiomes, as well as investigating the importance of other carbohydrates to commensal and pathogenic bacteria.
Genomic diversity generated by a transposable element burst in a rice recombinant inbred population
Authors: Chen Jinfeng , Lu Lu , Robb Sofia M.C. , Collin Matthew , Okumoto Yutaka , Stajich Jason E. , Wessler Susan R.
Published: August 2020

Genomes of all characterized higher eukaryotes harbor examples of transposable element (TE) bursts - the rapid amplification of TE copies throughout a genome. Despite their prevalence, understanding how bursts diversify genomes requires the characterization of actively transposing TEs before insertion sites and structural rearrangements have been obscured by selection acting over evolutionary time. In this study rice recombinant inbred lines (RILs), generated by crossing a bursting accession and the reference Nipponbare accession were exploited to characterize the spread of the very activePing/mPingfamily through a small population and the resulting impact on genome diversity. Comparative sequence analysis of 272 individuals led to the identification of over 14,000 new insertions of themPingminiature inverted-repeat transposable element (MITE) with no evidence for silencing of the transposase-encodingPingelement. In addition to new insertions,Ping-encoded transposase was found to preferentially catalyze the excision ofmPingloci tightly linked to a secondmPinginsertion. Similarly, structural variations, including deletion of rice exons or regulatory regions, were enriched for those with breakpoints at one or both ends of linkedmPingelements. Taken together, these results indicate that structural variations are generated during a TE burst as transposase catalyzes both the high copy numbers needed to distribute linked elements throughout the genome and the DNA cuts at the TE ends known to dramatically increase the frequency of recombination.

Significance Statement

Transposable elements (TEs) represent the largest component of the genomes of higher eukaryotes. Among this component are some TEs that have attained very high copy numbers with hundreds, even thousands of elements. By documenting the spread ofmPingelements throughout the genomes of a rice population we demonstrate that such bursts of amplification generate functionally relevant genomic variations upon which selection can act. Specifically, continuedmPingamplification increases the number of tightly linked elements that, in turn, increases the frequency of structural variations that appear to be derived from aberrant transposition events. The significance of this finding is that it provides a TE-mediated mechanism that may generate much of the structural variation represented by pan-genomes in plants and other organisms.
Origin and evolutionary dynamics of multi-drug resistant and highly virulent community-associated methicillin-resistantStaphylococcus aureusST772-SCCmecV lineage
Authors: Bakthavatchalam Yamuna Devi , Vasudevan Karthick , Rao ShomaVinay , Varughese Santosh , Rupali Priscilla , Gina Maki , Zervos Marcus , Peter John Victor , Veeraraghavan Balaji
Published: August 2020

Background

Community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) are increasing in prevalence across the world. However, studies on the molecular epidemiology and the genomic investigation of MRSA are limited in India.

Objectives

To understand the molecular epidemiology of MRSA and to reconstruct the origin and evolution ofS. aureusbelonged to the sequence type (ST772).

Methods

A total of 233 non-repetitive MRSA isolates were screened for the presence staphylococcal cassette chromosome (SCCmec) types, multi-locus sequence types (MLST) and staphylococcal protein A (spa) types. Whole genome sequence data of ST772-SCCmecV (n=32) isolates were generated and analysed along with the publically available ST772-SCCmecV (n=273) genome.

Results

ST772 (27%), ST22 (19%) and ST239 (16%) were found as the predominant STs. Analysis of the core SNPs using Bayesian time scaled phylogenetic analysis showed ST772-SCCmecV was emerged on the Indian subcontinent in 1960s. The acquisition of integrated resistance plasmid (IRP) in the ST772-SCCmecV lineage during 1990s, fixation of SCCmecV (5C2) and the double serine mutations (S84L, S80Y) appears to have played a key role in the successful expansion. The IRP carries the loci for multiple antibiotic resistant genes: beta-lactam (blaZ), aminoglycosides (aphA3-sat-aadE), macrolide (mphC), macrolide-lincosamide-streptogramin B (msrA) and bacitracin (bacA,bacB).

Conclusion

The Panton Valentine Leukocidin (PVL) positive ST772 and ST22 MRSA lineages are observed in the hospital settings. ST772-SCCmecV has the multi-drug resistance trait of hospital-associated (HA) MRSA and the epidemiological characteristics of CA-MRSA. The antimicrobial use pattern may have driven the spread and survival of ST772 MRSA in hospitals.
Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting
Authors: Tantale Katiana , Garcia-Oliver Encarnation , L’Hostis Adèle , Yang Yueyuxio , Robert Marie-Cécile , Gostan Thierry , Basu Meenakshi , Kozulic-Pirher Alja , Andrau Jean-Christophe , Muller Florian , Basyuk Eugenia , Radulescu Ovidiu , Bertrand Edouard
Published: August 2020

Promoter-proximal polymerase pausing is a key process regulating gene expression. In latent HIV-1 cells, it prevents viral transcription and is essential for latency maintenance, while in acutely infected cells the viral factor Tat releases paused polymerase to induce viral expression. Pausing is fundamental for HIV-1, but how it contributes to bursting and stochastic viral reactivation is unclear. Here, we performed single molecule imaging of HIV-1 transcription, and we developed a quantitative analysis method that manages multiple time scales from seconds to days, and that rapidly fits many models of promoter dynamics. We found that RNA polymerases enter a long-lived pause at latent HIV-1 promoters (>20 minutes), thereby effectively limiting viral transcription. Surprisingly and in contrast to current models, pausing appears stochastic and not obligatory, with only a small fraction of the polymerases undergoing long-lived pausing in absence of Tat. One consequence of stochastic pausing is that HIV-1 transcription occurs in bursts in latent cells, thereby facilitating latency exit and providing a rationale for the stochasticity of viral rebounds.
Exogenous disturbances and endogenous self-organized processes are not mutually exclusive drivers of spatial patterns in macroalgal assemblages
Authors: He J. , Rindi L. , Mintrone C. , Benedetti-Cecchi L.
Published: August 2020

Complex spatial patterns are common in coastal marine systems, but mechanisms underlying their formation are disputed. Most empirical work has focused on exogeneous spatially structured disturbances as the leading cause of pattern formation in species assemblages. However, theoretical and observational studies suggest that complex spatial patterns, such as power laws in gap-size distribution, may result from endogenous self-organized processes involving local-scale interactions. The lack of studies simultaneously assessing the influence of spatially variable disturbances and local-scale interactions has fuelled the idea that exogenous and endogenous processes are mutually exclusive explanations of spatial patterns in marine ecosystems. To assess the relative contribution of endogenous and exogenous processes in the emergence of spatial patterns, an intertidal assemblage of algae and invertebrates was exposed for 2 years to various combinations of intensity and spatial patterns of disturbance. Localized disturbances impinging at the margins of previously disturbed clearings and homogenous disturbances without any spatial pattern generated heterogeneous distributions of disturbed gaps and macroalgal patches, characterized by a truncated or a pure power-law scaling. Spatially varying disturbances produced a spatial gradient in the distribution of algal patches and, to a lesser extent, also a power-scaling in both patch- and gap-size distributions. These results suggest that exogenous and endogenous processes are not mutually exclusive forces that can lead to the formation of similar spatial patterns in species assemblages.
No exploitation of temporal predictive context during visual search
Authors: Bouwkamp Floortje G. , de Lange Floris P. , Spaak Eelke
Published: August 2020

The human visual system can rapidly extract regularities from our visual environment, generating predictive context. It has been shown that spatial predictive context can be used during visual search. We set out to see whether observers can additionally exploit temporal predictive context, using an extended version of a contextual cueing paradigm. Though we replicated the contextual cueing effect, repeating search scenes in a structured order versus a random order yielded no additional behavioural benefit. This was true both for participants who were sensitive to spatial predictive context, and for those who were not. We argue that spatial predictive context during visual search is more readily learned and subsequently exploited than temporal predictive context, potentially rendering the latter redundant. In conclusion, unlike spatial context, temporal context is not automatically extracted and used during visual search.
Using Multilayer Heterogeneous Networks to Infer Functions of Phosphorylated Sites
Authors: Watson Joanne , Schwartz Jean-Marc , Francavilla Chiara
Published: August 2020

1

Mass spectrometry-based quantitative phosphoproteomics has become an essential approach in the study of cellular processes such as signaling. Commonly used methods to analyze phosphoproteomics datasets depend on generic, gene-centric annotations such as Gene Ontology terms which do not account for the function of a protein in a particular phosphorylation state. Analysis of phosphoproteomics data is hampered by a lack of phosphorylated site-specific annotations. We propose a method that combines shotgun phosphoproteomics data, protein-protein interactions, and functional annotations into a heterogeneous multilayer network. Phosphorylation sites are associated to potential functions using a random walk on heterogeneous network (RWHN) algorithm. We validated our approach against a model of the MAPK/ERK pathway and functional annotations from PhosphoSite Plus and were able to associate differentially regulated sites on the same proteins to their previously described specific functions. We further tested the algorithm on three previously published datasets and were able to reproduce their experimentally validated conclusions and to associate phosphorylation sites with known functions based on their regulatory patterns. Our approach provides a refinement of commonly used analysis methods and accurately predicts context-specific functions for sites with similar phosphorylation profiles.

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Crystal structure of dichlorido-1κCl,2κCl-(μ2-3,5-dimethyl-1H-pyrazolato-1κN
2:2κN
1)(3,5-dimethyl-1H-pyrazole-2κN
2){μ-2-[(2-hydroxyethyl)amino-1κ2
N,O]ethanolato-1:2κ2
O:O}dicopper(II)
Authors: Vynohradov Oleksandr S. , Pavlenko Vadim A. , Safyanova Inna S. , Znovjyak Kateryna , Shova Sergiu , Safarmamadov Safarmamad M.
Published: August 2020

The title compound, [Cu2(C5H7N2)(C4H10NO2)Cl2(C5H8N2)], is a pyrazolate aminoalcohol complex which contains two dimethylpyrazole molecules in monodentate and bidentate-bridged coordination modes and a monodeprotonated diethanolamine molecule. Both copper atoms are involved in the formation of non-planar five-membered chelate rings. One Cu atom is in a distorted tetrahedral environment formed by the pyridine nitrogen atom of the protonated dimethylpyrazole molecule, the N atom of the deprotonated bridged dimethylpyrazole, the Cl atom and the bridged O atom of the monodeprotonated diethanolamine. The second Cu atom has an intermediate environment between trigonal bipyramidal and square pyramidal, formed by the N atom of the deprotonated bridged dimethylpyrazole, the Cl atom and the N atom of the aminoalcohol, and two O atoms of the deprotonated and protonated OH groups. In the crystal, N—H...Cl hydrogen bonds link the molecules into antisymmetric chains running along the a-axis direction. Adjacent chains are connected by O—H...O hydrogen bonds involving the hydroxyl group as donor.
X-ray crystallographic structural studies of α-amylase I from Eisenia fetida
Authors: Hirano Yu , Tsukamoto Kana , Ariki Shingo , Naka Yuki , Ueda Mitsuhiro , Tamada Taro
Published: August 2020

The earthworm Eisenia fetida possesses several cold-active enzymes, including α-amylase, β-glucanase and β-mannanase. E. fetida possesses two isoforms of α-amylase (Ef-Amy I and II) to digest raw starch. Ef-Amy I retains its catalytic activity at temperatures below 10°C. To identify the molecular properties of Ef-Amy I, X-ray crystal structures were determined of the wild type and of the inactive E249Q mutant. Ef-Amy I has structural similarities to mammalian α-amylases, including the porcine pancreatic and human pancreatic α-amylases. Structural comparisons of the overall structures as well as of the Ca2+-binding sites of Ef-Amy I and the mammalian α-amylases indicate that Ef-Amy I has increased structural flexibility and more solvent-exposed acidic residues. These structural features of Ef-Amy I may contribute to its observed catalytic activity at low temperatures, as many cold-adapted enzymes have similar structural properties. The structure of the substrate complex of the inactive mutant of Ef-Amy I shows that a maltohexaose molecule is bound in the active site and a maltotetraose molecule is bound in the cleft between the N- and C-terminal domains. The recognition of substrate molecules by Ef-Amy I exhibits some differences from that observed in structures of human pancreatic α-amylase. This result provides insights into the structural modulation of the recognition of substrates and inhibitors.
Targeting the innate immune receptor TLR8 using small-molecule agents. Corrigendum
Authors: Sakaniwa Kentaro , Shimizu Toshiyuki
Published: August 2020

Three of the figures in the article by Sakaniwa & Shimizu [(2020), Acta Cryst. D76, 621–629] were incorrectly annotated. Corrected figures are published here.
Role of working capital management in profitability considering the connection between accounting and finance
Authors: Morshed Amer
Published: August 2020

Purpose

The study aims to explain the relationship between accounting and finance through measuring the effect of rational working capital management on profitability.

Design/methodology/approach

Employing the methodology of semi-structured interviews with sixteen financial managers.

Findings

The findings pointed out the relationship between accounting and finance is complementary, since it supports the accountant by the critical skills and information, like project evaluation, managing the company funding resources and working capital management. These skills put the accountant up to the financial manager stage. The working capital investment and financing policies have the most significant impact on profitability. These policies related to risk and return theory; since the conservative policy will reduce both the risk and return and the aggressive one will have the opposite impact.

Originality/value

It recommends accountants to be in professional stage and increase the profitability of the company to grab both accounting and finance information and skills.
Study on incentive and supervision mechanisms of technological innovation in megaprojects based on the principal-agent theory
Authors: Liu Jiawei , Ma Guanghong
Published: August 2020

Purpose

The high uncertainty of technological innovation in megaprojects brings great challenges to the R&D institution and also acts as a trigger for moral hazard. The incentive and supervision are effective means to improve the performance of innovation. The purpose of this paper is to propose appropriate incentive and supervision mechanisms to reduce information asymmetry and improve the efficiency of incentives. Suggestions on technological innovation are put forward to megaprojects management.

Design/methodology/approach

According to the principal-agent theory, the research develops incentive models under three states, i.e. information symmetry, information asymmetry and information asymmetry based on supervision mechanism. The Bayesian theory is employed to prove the effectiveness of the novel supervision method based on risk assessment.

Findings

The results indicate that under the information asymmetry, the incentive intensity is positively correlated with the social benefits coefficient, and negatively correlated with the patent benefits coefficient. The R&D effort and the owner's incentive intensity decline with the increase of information asymmetry. The supervision of risks can effectively reduce the degree of information asymmetry, and the higher the uncertainty of innovations, the more significant the effect of supervision is. As the supervision intensity increases, the incentive intensity, the R&D effort and the innovation output will increase. In addition, the R&D institutions with high innovation capability, low unit cost of R&D and low risk-aversion are more willing to make efforts to innovate.

Originality/value

This study fills the research gap on incentive and supervision of technological innovation in megaprojects. The externality of innovation benefits is considered in the model. The traditional incentive model is extended through the introduction of supervision. Furthermore, a novel supervision method based on risk assessment is proposed. The results validate the importance of risk management in technological innovation and provide a new insight for project management.
Triggerfish animation studios: the challenges of financing digital entertainment
Authors: Lowman Craig , Samuelsson Mikael , Bick Geoff
Published: August 2020

Learning outcomes

The learning outcomes of this paper are as follows: to critically assess and analyse public and private funding options and determine which private option is best suited to a company (finance – decision-making). To calculate the internal rate of return (IRR) of a project (finance – analytical). To critically assess the underlying structures of traditional and new industries (Strategy/BMI – analytical). To analyse the challenges and disruption potential of intermediated industries (Strategy/BMI – analytical).

Case overview/synopsis

The Triggerfish case looks at how films are funded in South Africa. The company is currently funding films mostly through government channels, but CEO Stuart Forrest would prefer to independently and privately fund their projects. The case looks at what returns can be expected by investors in film through the “recoupment waterfall” – the means whereby the producers and investors of a film recoup their investments and earn returns. The investment horizons of select private lenders (bank, mezzanine financiers, risk financers and venture capital firms) and public funders are explored. The case also explores the impact that video-on-demand platforms, such as Netflix and Disney+, is having on the traditional models of filmmaking.

Complexity academic level

This teaching case is aimed at postgraduate business students such as Master’s degrees in Business Administration degrees, postgraduate diplomas, executive education or specialist Master’s degrees.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 3: Entrepreneurship.