bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic Simulation to Visualize Gene Expression and Error Correction in Living Cells
Authors: Chen Kevin Y. , Zuckerman Daniel M. , Nelson Philip C. 
Published: September 2018

AbstractStochastic simulation can make the molecular processes of cellular control more vivid than the traditional differential-equation approach by generating typical system histories instead of just statistical measures such as the mean and variance of a population. Simple simulations are now easy for students to construct from scratch, that is, without recourse to black-box packages. In some cases, their results can also be compared directly to single-molecule experimental data. After introducing the stochastic simulation algorithm, this article gives two case studies, involving gene expression and error correction, respectively. Code samples and resulting animations showing results are given in the online supplement.
Active protein neddylation or ubiquitylation is dispensable for stress granule dynamics
Authors: Markmiller Sebastian , Fulzele Amit , Higgins Reneé , Yeo Gene W. , Bennett Eric J 
Published: September 2018

AbstractMany protein homeostasis stressors induce the formation of membraneless cytoplasmic stress granules (SGs) that contain large assemblies of repressed mRNAs and associated RNA binding proteins. Similar stressors have been shown to globally alter the function of the ubiquitin proteasome system (UPS) resulting in the accumulation of ubiquitylated proteins. Previous studies have demonstrated that ubiquitin and specific UPS components co-localize with SGs and that reducing the abundance or activity of ubiquitin pathway proteins can inhibit SG formation. These studies suggest that SG dynamics and composition may be regulated by ubiquitylation of SG resident proteins. Using ubiquitin-specific proteomic approaches, we demonstrate that many proteins, including some SG proteins are dynamically ubiquitylated upon SG-inducing sodium arsenite treatment. We utilized potent and selective inhibitors of the ubiquitin activating enzyme (UAE) or the NEDD8 activating enzyme (NAE) to directly test if active protein ubiquitylation or neddylation was required for SG dynamics. Using ubiquitin-site specific proteomics, we establish that UAE inhibition results in the rapid loss of nearly all protein ubiquitylation regardless of ubiquitin chain type. Addition of UAE or NAE inhibitors to cells did not alter arsenite-induced SG formation or dissolution. While we confirmed that ubiquitin co-localizes with both sodium arsenite and thapsigargin-induced SGs, antibodies that recognize all forms of ubiquitin more strongly co-localize with SGs compared to antibodies that preferentially recognize polyubiquitin or specific polyubiquitin-linkages. Interestingly, ubiquitin itself co-localizes with SGs in a UAE independent manner suggesting that the ubiquitin present within SGs is likely unconjugated ubiquitin. Our findings clearly demonstrate that active protein ubiquitylation or neddylation is not required for SG dynamics. These results suggest that ubiquitin-binding SG proteins may recruit free ubiquitin into SGs to modulate SG protein interactions.
Gut microbial compositions mirror caste-specific diets in a major lineage of eusocial insects
Authors: Otani Saria , Zhukova Mariya , Koné N’golo Abdoulaye , da Costa Rafael Rodrigues , Mikaelyan Aram , Sapountzis Panagiotis , Poulsen Michael 
Published: September 2018

AbstractEusocial insects owe their ecological success to the division of labour and processes within colonies often rely on the presence of specific microbial symbionts, but associations between microbial community compositions and castes with different tasks and diets within colonies remain largely unexplored. Fungus-growing termites evolved to use fungi to externally degrade plant material, complemented by specific and complex gut microbiotas. Here we explore to which extent division of labour and dietary differences within fungus-growing termite castes are linked to gut bacterial community structure. Using amplicon sequencing, we characterise community compositions in sterile (worker and soldier) and reproductive (queen and king) termites and combine this with gut enzyme, microscopy, andin situanalyses to further elucidate sterile caste-specific microbiota compositions. Gut bacterial communities are structured primarily according to termite caste and genus. In contrast to the observed rich and diverse sterile caste microbiotas, royal pair microbiotas are extremely skewed and dominated by few bacterial taxa, reflecting the specialised dietary intake and unique, reproduction-centred lifestyle of the queen and king.
Rat bone marrow derived mesenchymal stem cells differentiate to germ cell like cells
Authors: Kumar Kuldeep , Das Kinsuk , Madhusoodan AP , Kumar Ajay , Singh Purnima , Mondal Tanmay , Bag Sadhan 
Published: September 2018

Summary StatementThein vitrodifferentiation of rMSCs provides an excellent model for studying cell commitment and their potential in stem cell technology. We have demonstrated that rat bone marrow derived MSCs are able to differentiate into germ-line cellsin vitrowhich has an enormous scope in the advancement of fertility research. In future, this technique can be utilized in different domestic animal species for propagation of elite germ plasm.AbstractGerm cells undergo distinctive male or female pathways to produce spermatozoa or oocyte respectively essential for sexual reproduction. Mesenchymal stem cells (MSCs) have the capacity of trans-differentiation to form the multiple lineages of cells of mesoderm, endoderm, and ectoderm origin. Herein, MSCs were isolated from rat bone marrow and characterized by their morphological features, expression of surface markers by immunophenotyping and molecular biology tools as well as self renewal and differentiation capability. Thereafter, by inducing these cells with retinoic acid we could able to show that bone marrow derived MSCs are able to trans-differentiate into male germ cell-like cells which were further characterized by the expressions of germ cell specific markers. Thisin vitrostudy for the generation of germ-like cells suggests that bone marrow MSCs can be a potential source of germ cells that could be a sustainable source of sperm / oocyte production for potential therapeutic applications in future. Moreover, this technique can be applied in different domestic animal species for propagation of elite germ plasm.
Visualizing ATP-dependent substrate-processing dynamics of the human 26S proteasome at near-atomic resolution
Authors: Dong Yuanchen , Zhang Shuwen , Wu Zhaolong , Li Xuemei , Wang Wei Li , Zhu Yanan , Stoilova-McPhie Svetla , Lu Ying , Finley Daniel , Mao Youdong 
Published: September 2018

AbstractThe proteasome is an ATP-dependent 2.5-megadalton machine responsible for ubiquitylated protein degradation in all eukaryotic cells. Here we present cryo-EM structures of the substrate-engaged human 26S proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during polyubiquitylated protein degradation. These structures visualize a continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to processive substrate translocation, during which ATP hydrolysis sequentially navigate through all six ATPase subunits. Three principle modes of coordinated ATP hydrolysis are observed, featuring hydrolytic events in two oppositely positioned ATPases, in two consecutive ATPases, and in one ATPase at a time. They regulate deubiquitylation, translocation initiation and processive unfolding of substrates, respectively. A collective power stroke in the ATPase motor is generated by synchronized ATP binding and ADP release in the substrate-engaging and disengaging ATPases, respectively. It is amplified largely in the substrate-disengaging ATPase, and propagated unidirectionally by coordinated ATP hydrolysis in the third consecutive ATPase.
Neural responses to natural and model-matched stimuli reveal distinct computations in primary and non-primary auditory cortex
Authors: Norman-Haignere Sam V. , McDermott Josh H. 
Published: September 2018

AbstractA central goal of sensory neuroscience is to construct models that can explain neural responses to complex, natural stimuli. As a consequence, sensory models are often tested by comparing neural responses to natural stimuli with model responses to those stimuli. One challenge is that distinct model features are often correlated across natural stimuli, and thus model features can predict neural responses even if they do not in fact drive them. Here we propose a simple alternative for testing a sensory model: we synthesize stimuli that yield the same model response as a natural stimulus, and test whether the natural and “model-matched” stimulus elicit the same neural response. We used this approach to test whether a common model of auditory cortex – in which spectrogram-like peripheral input is processed by linear spectrotemporal filters – can explain fMRI responses in humans to natural sounds. Prior studies have that shown that this model has good predictive power throughout auditory cortex, but this finding could reflect stimulus-driven correlations. We observed that fMRI voxel responses to natural and model-matched stimuli were nearly equivalent in primary auditory cortex, but that non-primary regions showed highly divergent responses to the two sound sets, suggesting that neurons in non-primary regions extract higher-order properties not made explicit by traditional models. This dissociation between primary and non-primary regions was not clear from model predictions due to the influence of stimulus-driven response correlations. Our methodology enables stronger tests of sensory models and could be broadly applied in other domains.Author SummaryModeling neural responses to natural stimuli is a core goal of sensory neuroscience. Here we propose a new approach for testing sensory models: we synthesize a “model-matched” stimulus that yields the same model response as a natural stimulus, and test whether it produces the same neural response. We used model-matching to test whether a standard model of auditory cortex can explain human cortical responses measured with fMRI. Model-matched stimuli produced nearly equivalent voxel responses in primary auditory cortex, but highly divergent responses in non-primary regions. This dissociation was not evident using more standard approaches for model testing, and suggests that non-primary regions compute higher-order stimulus properties not captured by traditional models. The methodology could be broadly applied in other domains.
Synthetic genome defenses against selfish DNA elements stabilize engineered bacteria against evolutionary failure
Authors: Geng Peng , Leonard Sean P. , Mishler Dennis M. , Barrick Jeffrey E. 
Published: September 2018

AbstractMobile genetic elements drive evolution by disrupting genes and rearranging genomes. Eukaryotes have evolved epigenetic mechanisms, including DNA methylation and RNA interference, that silence mobile elements and thereby preserve the integrity of their genomes. We created an artificial reprogrammable epigenetic system based on CRISPR interference to give engineered bacteria a similar line of defense against transposons and other selfish elements in their genomes. We demonstrate that this CRISPR interference against mobile elements (CRISPRi-ME) approach can be used to simultaneously repress two different transposon families in Escherichia coli, thereby increasing the evolutionary stability of costly protein expression. We further show that silencing a transposon in Acinetobacter baylyi ADP1 reduces mutation rates by a factor of five, nearly as much as deleting all copies of this element from its genome. By deploying CRISPRi-ME on a broad-host-range vector we have created a generalizable platform for stabilizing the genomes of engineered bacterial cells for applications in metabolic engineering and synthetic biology.SignificanceEngineered cells often cease to function or lose productivity when mutations arise in their genomes. Mobile DNA elements, such as transposons, are major sources of these inactivating mutations. Eukaryotic genomes have evolved flexible epigenetic defenses against mobile DNA that help them to maintain genome integrity, but bacteria do not possess comparable silencing systems. We developed a synthetic control system based on CRISPR interference that can be used to give bacterial cells a reprogrammable line of defense against selfish DNA elements in their genomes. We show that this system effectively represses multicopy transposons and multiple families of transposons. Limiting selfish DNA proliferation within a genome in this way improves the reliability of genetically engineered functions in replicating bacterial cell populations.
Evolutionary analyses of base-pairing interactions in DNA and RNA secondary structures
Authors: Golden Michael , Murrell Ben , Pybus Oliver G. , Martin Darren , Hein Jotun 
Published: September 2018

AbstractPairs of nucleotides within functional nucleic acid secondary structures often display evidence of coevolution that is consistent with the maintenance of base-pairing. Here we introduce a sequence evolution model, MESSI, that infers coevolution associated with base-paired sites in DNA or RNA sequence alignments. MESSI can estimate coevolution whilst accounting for an unknown secondary structure. MESSI can also use GPU parallelism to increase computational speed. We used MESSI to infer coevolution associated with GC, AU (AT in DNA), GU (GT in DNA) pairs in non-coding RNA alignments, and in single-stranded RNA and DNA virus alignments. Estimates of GU pair coevolution were found to be higher at base-paired sites in single-stranded RNA viruses and non-coding RNAs than estimates of GT pair coevolution in single-stranded DNA viruses, suggesting that GT pairs do not stabilise DNA secondary structures to the same extent that GU pairs do in RNA. Additionally, MESSI estimates the degrees of coevolution at individual base-paired sites in an alignment. These estimates were computed for a SHAPE-MaP-determined HIV-1 NL4-3 RNA secondary structure and two corresponding alignments. We found that estimates of coevolution were more strongly correlated with experimentally-determined SHAPE-MaP pairing scores than three non-evolutionary measures of base-pairing covariation. To assist researchers in prioritising substructures with potential functionality, MESSI automatically ranks substructures by degrees of coevolution at base-paired sites within them. Such a ranking was created for an HIV-1 subtype B alignment, revealing an excess of top-ranking substructures that have been previously identified as having structure-related functional importance, amongst several uncharacterised top-ranking substructures.
Successful outcome of early ambulation after extensive skin grafting in extramammary Paget's disease
Authors: Maeda Takuya , Yoshino Koji , Nagai Kojiro , Oaku Satoe , Kato Megumi , Hata Hiroo 
Published: September 2018

AbstractExtramammary Paget's disease (EMPD) is a rare cutaneous malignancy that mainly affects the senior population. There is a relatively high risk of postoperative complications from surgery in the senior population, such as disuse syndrome, deep vein thrombosis and postoperative delirium. To prevent such postoperative complications, early ambulation is recommended. However, EMPD often requires extensive skin grafting because of the need for a large resection margin. To avoid skin graft failure, many institutions require that patients have several days of postoperative bedrest. For these reasons, there has been no consensus on standard postoperative rest for EMPD. In this study, we defined 20 patients who walked from the day after surgery as an “early ambulation group” and 23 patients with 5 days postoperative bedrest as a “control group”. We evaluated the skin graft survival, postoperative complications and the duration of hospitalization for both groups. Skin graft survival and complications related to the surgical wounds (infection and hemorrhage) in the early ambulation group were found to be comparable with those in the control group. Of note, the other complications (aspiration pneumonia, ileus, delirium, orthostatic hypotension and insomnia) were less frequent (P < 0.001) and the duration of postoperative hospitalization was shorter (P = 0.013) in the early ambulation group than in the control group. Our study suggests that early ambulation after surgery for EMPD does not impair skin graft survival but reduces postoperative complications and the duration of hospitalization.
Quantifying wildlife watchers’ preferences to investigate the overlap between recreational and conservation value of natural areas
Authors: Mancini Francesca , Coghill George M. , Lusseau David 
Published: September 2018

AbstractNature‐based recreation substantially benefits human wellbeing, for example, by improving physical and mental health. However, recreation can also have severe ecological impacts. The recreational value of landscapes and natural areas is often used to generate support for public spending in conservation. However, we still don't know whether nature‐based recreationists place greater recreational value on natural areas that have high conservation value compared to other green spaces.Here, we determine which attributes of nature‐based tourism provide recreational services. We used pictures of wildlife posted on Flickr to quantify wildlife watching activities in Scotland. We then determined the environmental variables key to attracting wildlife watchers to a destination, such as protected areas (PAs), the perceived naturalness, and the presence of different types of infrastructure.Infrastructure best predicts the intensity of wildlife watching activities in Scotland, while areas of high natural value are rarely used. PAs are weak attractors of wildlife watchers, with PAs designated to protect threatened habitats or species having low recreational value. In accessible and highly visited areas, higher biodiversity increases the intensity of wildlife watching activities.Synthesis and applications. Areas of high natural and conservation value and areas of high recreational value do not tend to overlap. Recreational ecosystem services are mainly provided by the wider countryside and highly transformed landscapes, as opposed to wild ecosystems and protected areas designated to protect environmental features of high conservation value. These results question the synergy between the goals of recreation and those of conservation and the use of recreation as a justification for economic investment in conservation. During wildlife watching activities most people experience an urbanised, highly transformed nature; it is important to determine how this human‐dominated nature can influence support for conservation of wild and remote areas.
Onmang Þæt – Incipient Grammaticalisation in Old and Middle English
Authors: Nykiel Jerzy 
Published: September 2018

AbstractThis paper examines the development and use of the temporal subordinatoronmang þæt. The development of the subordinator is seen as a special case of grammaticalisation, i.e. incipient grammaticalisation.Onmang þætarises through the incorporation of the prepositional phraseonmang+ demonstrative into the subordinator structure and in this respectonmang þætresembles the grammaticalisation of otherOEsubordinators. The grammaticalisation ofonmang þætis however arrested in earlyME, as the paper shows using a generative approach. I interpret this turn in the grammaticalisation of the subordinator as indicative of incipient grammaticalisation and I further use this observation as an avenue to identifying other features concomitant with incipient grammaticalisation. What I suggest is that incipient grammaticalisation should be associated with low frequency, minimal erosion, lack of fusion, and, finally, specialisation. I tentatively argue that options reduced via specialisation, as is the case withonmang þæt, may be the ones that qualify as cases of incipient grammaticalisation. Importantly, what follows is that incipient grammaticalisation as discussed in this study is not to be taken as referring to the early stages of grammaticalisation as such but to the grammaticalisation of infrequent structures available for a longer period of time.
Does social capital pay off? The case of small business resilience after Hurricane Katrina
Authors: Torres Ariana P. , Marshall Maria I. , Sydnor Sandra 
Published: September 2018

AbstractThis article uses objective and subjective measures of small business resilience and multiple categories of social capital pay‐offs to answer two main questions. Does social capital pay off after a natural disaster; and if it does, what type of social capital has the greatest impact on small business resilience? The pay‐off from bridging social capital—receiving support from the community—is what drives both objective and subjective resilience post‐Katrina. The results also show linking capital—support from institutions—can improve economic resilience. Our results provide evidence social capital is a key asset for long‐term resilience for small businesses. Business owners with links to the community and institutions—with more social capital—will be better off when facing a natural disaster.
Guidelines and considerations for designing field experiments simulating precipitation extremes in forest ecosystems
Authors: Asbjornsen Heidi , Campbell John L. , Jennings Katie A. , Vadeboncoeur Matthew A. , McIntire Cameron , Templer Pamela H. , Phillips Richard P. , Bauerle Taryn L. , Dietze Michael C. , Frey Serita D. , Groffman Peter M. , Guerrieri Rosella , Hanson Paul J. , Kelsey Eric P. , Knapp Alan K. , McDowell Nathan G. , Meir Patrick , Novick Kimberly A. , Ollinger Scott V. , Pockman Will T. , Schaberg Paul G. , Wullschleger Stan D. , Smith Melinda D. , Rustad Lindsey E. 
Published: September 2018

AbstractPrecipitation regimes are changing in response to climate change, yet understanding of how forest ecosystems respond to extreme droughts and pluvials remains incomplete. As future precipitation extremes will likely fall outside the range of historical variability, precipitation manipulation experiments (PMEs) are critical to advancing knowledge about potential ecosystem responses. However, fewPMEs have been conducted in forests compared to short‐statured ecosystems, and forestPMEs have unique design requirements and constraints. Moreover, past forestPMEs have lacked coordination, limiting cross‐site comparisons. Here, we review and synthesize approaches, challenges, and opportunities for conductingPMEs in forests, with the goal of guiding design decisions, while maximizing the potential for coordination.We reviewed 63 forestPMEs at 70 sites world‐wide. Workshops, meetings, and communications with experimentalists were used to generate and build consensus around approaches for addressing the key challenges and enhancing coordination.Past forestPMEs employed a variety of study designs related to treatment level, replication, plot and infrastructure characteristics, and measurement approaches. Important considerations for establishing new forestPMEs include: selecting appropriate treatment levels to reach ecological thresholds; balancing cost, logistical complexity, and effectiveness in infrastructure design; and preventing unintended water subsidies. Response variables in forestPMEs were organized into three broad tiers reflecting increasing complexity and resource intensiveness, with the first tier representing a recommended core set of common measurements.Differences in site conditions combined with unique research questions of experimentalists necessitate careful adaptation of guidelines for forestPMEs to balance local objectives with coordination among experiments. We advocate adoption of a common framework for coordinating forestPMEdesign to enhance cross‐site comparability and advance fundamental knowledge about the response and sensitivity of diverse forest ecosystems to precipitation extremes.