bluuebunny/crossref_metadata_2025_split huggingface dataset:
An orderly single-trial organization of population dynamics in premotor cortex predicts behavioral variability
Authors: Wei Ziqiang , Inagaki Hidehiko , Li Nuo , Svoboda Karel , Druckmann Shaul 
Published: July 2018

AbstractAnimals are not simple input-output machines. Their responses to even very similar stimuli are variable. A key, long-standing question in neuroscience is understanding the neural correlates of such behavioral variability. To reveal these correlates, behavior and neural population must be related to one another on single trials. Such analysis is challenging due to the dynamical nature of brain function (e.g. decision making), neuronal heterogeneity and signal to noise difficulties. By analyzing population recordings from mouse frontal cortex in perceptual decision-making tasks, we show that an analysis approach tailored to the coarse grain features of the dynamics was able to reveal previously unrecognized structure in the organization of population activity. This structure was similar on error and correct trials, suggesting what may be the underlying circuit mechanisms, was able to predict multiple aspects of behavioral variability and revealed long time-scale modulation of population activity.
Rethinking the efficacy of acellular pertussis vaccines for primary immunization
Authors: de Cellès M. Domenech , Rohani P. , King A. A. 
Published: July 2018

AbstractBackgroundThe US has experienced a nationwide resurgence of pertussis since the mid-1970s, despite high vaccine coverage. Short-lived immunity induced by Diphtheria-Tetanus-acellular Pertussis (DTaP) vaccines in young children is widely believed to be responsible for this growing burden. However, the duration of protection conferred by DTaP vaccines remains incompletely quantified.Methods and FindingsWe employed a rigorously validated, age-structured model of pertussis transmission to explore a range of hypotheses regarding the degree of waning DTaP-derived immunity. For every hypothesis, we calculated the vaccine effectiveness and the relative increase in the odds of acquiring pertussis (or odds ratio) in children aged 5 to 9 years. We then assessed the simulated DTaP vaccine traits that best reproduced the empirical values of odds ratios from recent US epidemiological studies. We found a marked association between the degree of waning immunity, the vaccine effectiveness, and the odds ratio. Unexpectedly, the odds ratio was positively associated with the vaccine effectiveness, as a consequence of non-linear, age-assortative dynamics. Based on the empirical odds ratios, we estimated that vaccine effectiveness exceeded 75% and that more than 65% of children remained immune to pertussis 5 years after the last DTaP dose.ConclusionsOur results show that temporal trends in the odds of acquiring pertussis are a seriously flawed measure of the durability of vaccine-induced protection. They further demonstrate that DTaP vaccines confer imperfect, but long-lived protection. We argue that control strategies should be based upon the best available estimates of vaccine properties and the age-structure of the transmission network.
Towards an autologous iPSC-derived patient-on-a-chip
Authors: Ramme Anja Patricia , Koenig Leopold , Hasenberg Tobias , Schwenk Christine , Magauer Corinna , Faust Daniel , Lorenz Alexandra K. , Krebs Anna , Drewell Christopher , Schirrmann Kerstin , Vladetic Alexandra , Lin Grace-Chiaen , Pabinger Stephan , Neuhaus Winfried , Bois Frederic , Lauster Roland , Marx Uwe , Dehne Eva-Maria 
Published: July 2018

AbstractMicrophysiological systems are fundamental for progressing towards a global paradigm shift in drug development through the generation of patient-on-a-chip models. An increasing number of single- and multi-organ systems have been adopted by the pharmaceutical and cosmetic industries for predictive substance testing. These models run on heterogeneous tissues and cell types from different donors. However, a patient is an individual. Therefore, patient-on-a-chip systems need to be built from tissues from one autologous source. Individual on-chip organ differentiation from a single induced pluripotent stem cell source could provide a solution to this challenge.We designed a four-organ chip based on human physiology. It enables the interconnection of miniaturized human intestine, liver, brain and kidney equivalents. All four organ models were predifferentiated from induced pluripotent stem cells from the same healthy donor and integrated into the microphysiological system. The cross talk led to further differentiation over a 14-day cultivation period under pulsatile blood flow conditions in one common medium deprived of growth factors. This model platform will pave the way for disease induction and subsequent drug testing.
How symbiosis and ecological context influence the variable expression of transgenerational wing induction upon fungal infection of aphids
Authors: Tan Wen-Hao , Reyes Miguel L. , Hoang Kim L. , Acevedo Tarik , Leon Fredrick , Barbosa Joshua D. , Gerardo Nicole M. 
Published: July 2018

AbstractAphids, like most animals, mount a diverse set of defenses against pathogens. For aphids, two of the best studied defenses are symbiont-conferred protection and transgenerational wing induction. Aphids can harbor bacterial symbionts that provide protection against pathogens, parasitoids and predators, as well as against other environmental stressors. In response to signals of danger, aphids also protect not themselves but their offspring by producing more winged than unwinged offspring as a way to ensure that their progeny may be able to escape deteriorating conditions. Such transgenerational wing induction has been studied most commonly as a response to overcrowding of host plants and presence of predators, but recent evidence suggests that pea aphids (Acyrthosiphon pisum) may also begin to produce a greater proportion of winged offspring when infected with fungal pathogens. Here, we explore this phenomenon further by asking how protective symbionts, pathogen dosage and environmental conditions influence this response. Overall, while we find some evidence that protective symbionts can modulate transgenerational wing induction in response to fungal pathogens, we observe that transgenerational wing induction in response to fungal infection is highly variable. That variability cannot be explained entirely by symbiont association, by pathogen load or by environmental stress, leaving the possibility that a complex interplay of genotypic and environmental factors may together influence this trait.
A comprehensive ensemble model for comparing the allosteric effect of ordered and disordered proteins
Authors: Zhang Luhao , Li Maodong , Liu Zhirong 
Published: July 2018

AbstractIntrinsically disordered proteins/regions (IDPs/IDRs) are prevalent in allosteric regulation. It was previously thought that intrinsic disorder is favorable for maximizing the allosteric coupling. Here, we propose a comprehensive ensemble model to compare the roles of both order-order transition and order-disorder transition in allosteric effect. It is revealed that the MWC pathway (order-order transition) has a higher probability than the EAM pathway (disorder-order transition) in allostery, suggesting a complicated role of IDPs/IDRs in regulatory proteins. In addition, an analytic formula for the maximal allosteric coupling response is obtained, which shows that too stable or too unstable state is unfavorable to endow allostery, and is thus helpful for rational design of allosteric drugs.Author SummaryAllosteric effect is an important regulation mechanism in biological processes, where the binding of a ligand at one site of a protein influences the function of a distinct site. Conventionally, allostery was thought to originate from structural transition. However, in recent years, intrinsically disordered proteins (IDPs) were found to be widely involved in allosteric regulation in despite of their lack of ordered structure under physiological condition. It is still a mystery why IDPs are prevalent in allosteric proteins and how they differ from ordered proteins in allostery. Here, we propose a comprehensive ensemble model which includes both ordered and disordered states of a two-domain protein, and investigate the role of various state combinations in allosteric effect. By sampling the parameter space, we conclude that disordered proteins are less competitive than ordered proteins in performing allostery from a thermodynamic point of view. The prevalence of IDPs in allosteric regulation is likely determined by all their advantage, but not only by their capacity in endowing allostery.
In situ protein micro-crystal fabrication by cryo-FIB for electron diffraction
Authors: Li Xinmei , Zhang Shuangbo , Sun Fei 
Published: July 2018

ABSTRACTMicroED (micro electron diffraction) is an emerging technique to use cryo-electron microscope to study the crystal structure of macromolecule from its micro/nano-crystals, which are not suitable for conventional X-ray crystallography. However, this technique has been prevented for its wide application by the limited availability of producing good micro-/nano-crystals and the inappropriate transfer of crystals. Here, we developed a complete workflow to prepare suitable crystals efficiently for MicroED experiment. This workflow includes in situ on-grid crystallization, single-side blotting, cryo-focus ion beam (cryo-FIB) fabrication, and cryo-electron diffraction of crystal cryo-lamella. This workflow enables us to apply MicroED to study many small macromolecular crystals with the size of 2 ~ 10 μm, which is too large for MicroED but quite small for conventional X-ray crystallography. We have applied this method to solve 2.5Å crystal structure of lysozyme from its micro-crystal within the size of 10×10×10 μm3. Our work will greatly expand the availability space of crystals suitable for MicroED and fill up the gap between MicroED and X-ray crystallography.
Gene expression patterns in synchronized islet populations
Authors: Mukhitov Nikita , Roper Michael G. 
Published: July 2018

AbstractIn vivo levels of insulin are oscillatory with a period of ~5-10 minutes, implying that the numerous islets of Langerhans within the pancreas are synchronized. While the synchronizing factors are still under investigation, one result of this behavior is expected to be coordinated intracellular [Ca2+] ([Ca2+]i) oscillations throughout the islet population. The role that coordinated [Ca2+]ioscillations have on controlling gene expression within pancreatic islets was examined by comparing gene expression levels in islets that were synchronized using a low amplitude glucose wave and an unsynchronized population. The [Ca2+]ioscillations in the synchronized population were homogeneous and had a significantly lower drift in their oscillation period as compared to unsynchronized islets. This reduced drift in the synchronized population was verified by comparing the drift ofin vivoandin vitroprofiles from published reports. Microarray profiling indicated a number of Ca2+-dependent genes were differentially regulated between the two islet populations. Gene set enrichment analysis revealed that the synchronized population had reduced expression of gene sets related to protein translation, protein turnover, energy expenditure, and insulin synthesis, while those that were related to maintenance of cell morphology were increased. It is speculated that these gene expression patterns in the synchronized islets results in a more efficient utilization of intra-cellular resources and response to environmental changes.
The USTC complex co-opts an ancient machinery to drive piRNA transcription inC. elegans
Authors: Weng Chenchun , Kosalka Asia , Berkyurek Ahmet C. , Stempor Przemyslaw , Feng Xuezhu , Mao Hui , Zeng Chenming , Li Wen-Jun , Yan Yong-Hong , Dong Meng-Qiu , Zuliani Cecilia , Barabas Orsolya , Ahringer Julie , Guang Shouhong , Miska Eric A. 
Published: July 2018

ABSTRACTPiwi-interacting RNAs (piRNAs) engage Piwi proteins to suppress transposons and non-self nucleic acids, maintain genome integrity, and are essential for fertility in a variety of organisms. InC. elegansmost piRNA precursors are transcribed from two genomic clusters that contain thousands of individual piRNA transcription units. While a few genes have been shown to be required for piRNA biogenesis the mechanism of piRNA transcription remains elusive. Here we used functional proteomics approaches to identify an upstream sequence transcription complex (USTC) that is essential for piRNA biogenesis. The USTC complex contains PRDE-1, TOFU-4, TOFU-5 and SNPC-4. The USTC complex form a unique piRNA foci in germline nuclei and coat the piRNA cluster genomic loci. USTC factors associate with the Ruby motif just upstream of type I piRNA genes. USTC factors are also mutually dependent for binding to the piRNA clusters and to form the piRNA foci. Interestingly, USTC components bind differentially to piRNAs in the clusters and other non-coding RNA genes. These results reveal USTC as a striking example of the repurposing of a general transcription factor complex to aid in genome defence against transposons.
Identifying the cognitive processes underpinning hippocampal-dependent tasks
Authors: Clark Ian A. , Hotchin Victoria , Monk Anna , Pizzamiglio Gloria , Liefgreen Alice , Maguire Eleanor A. 
Published: July 2018

AbstractAutobiographical memory, future thinking and spatial navigation are critical cognitive functions that are thought to be related, and are known to depend upon a brain structure called the hippocampus. Surprisingly, direct evidence for their interrelatedness is lacking, as is an understanding of why they might be related. There is debate about whether they are linked by an underlying memory-related process or, as has more recently been suggested, because they each require the endogenous construction of scene imagery. Here, using a large sample of participants and multiple cognitive tests with a wide spread of individual differences in performance, we found that these functions are indeed related. Mediation analyses further showed that scene construction, and not memory, mediated (explained) the relationships between the functions. These findings offer a fresh perspective on autobiographical memory, future thinking, navigation, and also on the hippocampus, where scene imagery appears to play an influential role.
TUBA1A mutations identified in lissencephaly patients dominantly disrupt neuronal migration and impair dynein activity
Authors: Aiken Jayne , Moore Jeffrey K. , Bates Emily A. 
Published: July 2018

SUMMARY‘Tubulinopathies’ are severe human brain malformations associated with mutations in tubulin genes. Despite the identification of many tubulin mutations in patients, we do not understand how these mutations impact the microtubule cytoskeleton, how the changes to microtubule function lead to brain malformations, or how different tubulin isotypes regulate microtubules to support normal neurodevelopment. TUBA1A α-tubulin is the most commonly affected tubulin isotype in tubulinopathy patients. Heterozygous mutations in TUBA1A have been identified in patients with diverse cortical malformations including microlissencephaly, lissencephaly, pachygyria, and polymicrogyria. Here we focus on mutations affecting the conserved arginine at position 402 (R402), which account for 30% of all reported TUBA1A mutations in patients. We demonstrate that exogenous expression of TUBA1A-R402C and TUBA1A-R402H patient alleles is sufficient to dominantly disrupt cortical neuron migration in the developing mouse brain, recapitulating the human lissencephaly phenotype. Intriguingly, ectopic expression of TUBA1A-R402C/H alleles does not alter morphology, axonal trafficking, or microtubule polymerization rates in cultured neurons, but does lead to subtle changes in axonal microtubule orientation. Further, we find that budding yeast α-tubulin with analogous R402C and R402H mutations assembles into microtubules but disrupts the activity of the microtubule motor dynein. The level of dynein impairment scales with abundance of R402 mutant α-tubulin in the cell. Together, our results support a model in which tubulinopathy mutations at R402 poison the microtubule network in young neurons by creating defective binding sites for dynein at the microtubule surface.
Bonding capability of Nigerian contracting firms
Authors: Oke Ayodeji Emmanuel 
Published: July 2018

Purpose
The ability of construction contractors to engage in construction bond agreement with guarantors depends on capital, experience, capacity and continuity. Using these criteria, the purpose of this paper is to provide insights into the bonding capacity of Nigerian contractors.

Design/methodology/approach
Factors required for bonding were examined based on a set of questions addressed to managers of contracting firms and personnel involved in issuing bonds and guarantees in commercial banks and insurance companies. The scorecard approach was employed to determine the bonding capability of the contractors.

Findings
Contractors’ financial strength and past performance on previous projects are the two important factors considered by guarantors in granting bond to contractors. However, the condition surrounding the bond, the legal capacity of the guarantor to issue bond and the identity of the guarantor are mostly considered by contractors in approaching a potential guarantor. Using the scorecard approach, about one-third of contractors have the necessary requirements to engage in construction bond agreement with guarantors. This ability of contractors is affected by years of experience of the firm but not by their location nor years of experience of their manager.

Practical implications
It is necessary for contracting firms to increase their capital base through merging, borrowing, etc., and also engage experienced professionals and workers in the execution of construction projects, as this will eventually improve their bonding ability.

Social implications
The study is limited to construction contractors registered with Ondo and Lagos State Governments and guarantors that are banks and insurance companies in Nigeria.

Originality/value
The paper specified various areas of concerns for Nigerian contracting firms in their bid to enhance their bonding ability. This will help them in overcoming various challenges and bottlenecks that may arise in securing bonds and guarantees from guarantors.
An investigation into public and private clients’ attitudes, commitment and impact on construction health and safety in Nigeria
Authors: Umeokafor Nnedinma 
Published: July 2018

Purpose
This purpose of this paper is to report the findings of a study that assessed the attitudes, commitment and impact of public and private sector clients’ involvement in construction health and safety (H&S) in Nigeria.

Design/methodology/approach
Structured questionnaires were designed based on literature review and a pilot study, and administered to public and private clients in Nigeria’s construction industry. Descriptive and inferential statistics were employed to analyse the data.

Findings
The result shows that while clients’ attitudes towards H&S are not encouraging, public clients commitment and attitudes are better than that of private clients. This is emphasised by the significant difference between the categories of clients and: accident investigation; clients auditing contractors H&S records at the preconstruction stage. The common client H&S practice includes conducting site visits and inspections and attending H&S meetings, while engaging in H&S awareness and H&S audit during construction are not common. However, when clients are involved in H&S, it has resulted in a reduction in accidents, compensation claims, rework and improved the relationship between clients and contractors.

Practical implications
The findings form a basis for improving client involvement in H&S (factoring in the differences in clients) which policymakers, the construction industry and academics will find beneficial.

Originality/value
The study contributes to understanding the attitudes and commitment of public and private clients in H&S, evidencing the implications of the differences in their needs, characteristics and behaviours. While the study is the first to investigate the area in Nigeria, it also extends the knowledge of the discourse comparatively in broader terms.
The evolution of stakeholder management practices in Australian mega construction projects
Authors: Yang Rebecca Jing , Jayasuriya Sajani , Gunarathna Chathuri , Arashpour Mehrdad , Xue Xiaolong , Zhang Guomin 
Published: July 2018

Purpose
The complicated nature of megaprojects requires appropriate analysis of multiple stakeholders to achieve project objectives and to accommodate stakeholder interests. During the last two decades, many stakeholder theories and empirical studies have sprouted. Although previous studies have contributed to the development of stakeholder theory, it seems that these theoretical advances have not been fully adopted and acknowledged in practices, especially in megaprojects. The purpose of this paper is to explore the evolution of stakeholder analysis and engagement practices adopted in the Australian megaprojects over the last two decades.

Design/methodology/approach
Four mega construction projects are described and analysed in this study. Secondary data were first assembled in order to get general knowledge of each case. Interviews were conducted with the project directors. Project documents were collected from the project teams and reviewed. Wherever the project information was unclear, e-mails were sent to the directors and the team members to confirm the details.

Findings
Project teams have started to apply snowball rolling and stakeholder attribute assessment methods to analyse stakeholders. However, there is still a way to adopt the “network” analysis perspective because the project teams are reluctant to use complicated tools which need specialists’ assistance. The stakeholder engagement practices have evolved to an extent where the project teams monitor the dynamics of stakeholders’ requirements. Projects teams have identified the importance of continuity to manage stakeholders in these massive projects. However, a structured method selection mechanism for stakeholder engagement has not been developed.

Originality/value
This study will help academics to understand the adoption progress and status of stakeholder management methods.