bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving the consistency of functional genomics screens using molecular features - a multi-omics, pan-cancer study
Authors: Wang Wenyu , Malyutina Alina , Pessia Alberto , Heckman Caroline A. , Tang Jing 
Published: May 2018

AbstractProbing the genetic dependencies of cancer cells helps understand the tumor biology and identify potential drug targets. RNAi-based shRNA and CRISPR/Cas9-based sgRNA have been commonly utilized in functional genetic screens to identify essential genes affecting growth rates in cancer cell lines. However, questions remain whether the gene essentiality profiles determined using these two technologies are comparable. In the present study, we collected 42 cell lines representing a variety of 10 tissue types, which had been screened both by shRNA and CRISPR techniques. We observed poor consistency of the essentiality scores between the two screens for the majority of the cell lines. The consistency did not improve after correcting the off-target effects in the shRNA screening, suggesting a minimal impact of off-target effects. We considered a linear regression model where the shRNA essentiality score is the predictor and the CRISPR essentiality score is the response variable. We showed that by including molecular features such as mutation, gene expression and copy number variation as covariates, the predictability of the regression model greatly improved, suggesting that molecular features may provide critical information in explaining the discrepancy between the shRNA and CRISPR-based essentiality scores. We provided a Combined Essentiality Score (CES) based on the model prediction and showed that the CES greatly improved the consensus of common essential genes. Furthermore, the CES also identified novel essential genes that are specific to individual cell types. Taken together, we provided a systematic approach to define a more accurate gene essentiality profile by integrating functional screen data and molecular profiles.
How will it look like? Human posterior parietal and dorsal premotor cortex encode the visual properties of an upcoming action
Authors: Pilacinski Artur , Wallscheid Melanie , Lindner Axel 
Published: May 2018

ABSTRACTBehavioral studies show that motor actions are planned by adapting motor programs to produce desired visual consequences. Does this mean that the brain plans these visual consequences independent of the motor actions required to obtain them? Here we addressed this question by investigating planning-related fMRI activity in human posterior parietal (PPC) and dorsal premotor (PMd) cortex. By manipulating visual movement of a virtual end-effector controlled via button presses we could dissociate motor actions from their sensory outcome. A clear representation of the visual consequences was visible in both PPC and PMd activity during early planning stages. Our findings suggest that in both PPC and PMd action plans are initially represented on the basis of the desired sensory outcomes while later activity shifts towards representing motor programs.
Molecular epidemiology and drug resistance patterns ofMycobacterium tuberculosiscomplex isolates from university students and the local community in Eastern Ethiopia
Authors: Mekonnen Abiyu , Merker Matthias , Collins Jeffrey M , Addise Desalegn , Aseffa Abraham , Petros Beyene , Ameni Gobena , Niemann Stefan 
Published: May 2018

AbstractBackgroundPrevious studies suggest the burden of pulmonary tuberculosis (PTB) in Ethiopia may be greater in university students relative to the overall population. However, little is known about the transmission dynamics of PTB among students and members of the communities surrounding university campuses in Eastern Ethiopia.MethodsA cross sectional study was conducted in Eastern Ethiopia among culture-confirmed PTB cases from university students (n=36) and community members diagnosed at one of four hospitals (n=152) serving the surrounding area. Drug susceptibility testing (DST) was performed on Mycobacterium Tuberculosis Complex (MTBC) isolates using BD Bactec MGIT 960 and molecular genotyping was performed using spoligotyping and 24-loci MIRU-VNTR. MTBC strains with Identical genotyping patterns were assigned to molecular clusters as surrogate marker for recent transmission and further contact tracing was initiated among clustered patients.ResultsAmong all study participants, four MTBC lineages and 11 sub-lineages were identified, with Ethiopia_3 being most common sub-lineage (29.4%) and associated with strain clustering (P= 0.016). We identified 13 (8.1%) strains phylogenetically related to the known Ethiopian sub-lineages with a distinct Spoligotyping patterns and designated as Ethiopia_4. The clustering rate of MTB strains was 52.9% for university students and 66.7% for community members with a Recent Transmission Index (RTI) of 17.6% and 48.4%, respectively. Female gender, urban residence, and new TB cases were significantly associated with strain clustering (p<0.05). Forty-eight (30%) of the study participants were resistant to one or more first line anti TB drugs, three patients were classified as multidrug resistant (MDR), defined by isoniazid and rifampicin resistance.ConclusionWe found evidence of significant PTB cases clustering and recent transmission among Ethiopian university students and the local community in eastern Ethiopia; with Ethiopia_3 being the predominant circulating sub-lineage. A country wide comprehensive molecular surveillance and drug resistance profiling of MTBC strains and Implementation of TB control programs within universities and the surrounding community should be considered to decrease TB transmission.
Regulation of Harvester Ant Foraging as a Closed-Loop Excitable System
Authors: Pagliara Renato , Gordon Deborah M. , Leonard Naomi Ehrich 
Published: May 2018

AbstractAnt colonies regulate activity in response to changing conditions without using centralized control. Harvester ant colonies forage in the desert for seeds, and their regulation of foraging manages a tradeoff between spending and obtaining water. Foragers lose water while outside in the dry air, but the colony obtains water by metabolizing the fats in the seeds they eat. Previous work shows that the rate at which an outgoing forager leaves the nest depends on its recent experience of brief antennal contact with returning foragers that carry a seed. We examine how this process can yield foraging rates that are robust to uncertainty and responsive to temperature and humidity across minutes to hour-long timescales. To explore possible mechanisms, we develop a low-dimensional analytical model with a small number of parameters that captures observed foraging behavior. The model uses excitability dynamics to represent response to interactions inside the nest and a random delay distribution to represent foraging time outside the nest. We show how feedback of outgoing foragers returning to the nest stabilizes the incoming and outgoing foraging rates to a common value determined by the “volatility” of available foragers. The model exhibits a critical volatility above which there is sustained foraging at a constant rate and below which there is cessation of foraging. To explain how the foraging rates of colonies adjust to temperature and humidity, we propose a mechanism that relies on foragers modifying their volatility after they leave the nest and get exposed to the environment. Our study highlights the importance of feedback in the regulation of foraging activity and points to modulation of volatility as a key to explaining differences in foraging activity in response to conditions and across colonies. Our results present opportunities for generalization to other contexts and systems with excitability and feedback across multiple timescales.Author SummaryWe investigate the collective behavior that allows colonies of desert harvester ants to regulate foraging activity in response to environmental conditions. We develop an analytical model connecting three processes: 1) the interactions between foragers returning to the nest and available foragers waiting inside the nest, 2) the effect of these interactions on the likelihood of available foragers to leave the nest to forage, and 3) the return of foragers to the nest after finding seeds. We propose a mechanism in which available foragers modify their response to interactions after their first exposure to the environment. We show how this leads to colony foraging rates that adjust to environmental conditions over time scales from minutes to hours. Our model may prove useful for studying resilience in other classes of systems with excitatory dynamics.
A proteome-wide screen reveals widespread roles for the phosphatase Cdc14 in theCandida albicanscell cycle
Authors: Kaneva Iliyana , Sudbery Ian , Dickman Mark J. , Sudbery Peter E. 
Published: May 2018

AbstractThe chromosome complement of the human fungal pathogenCandida albicansis unusually unstable, suggesting that process of nuclear division is error prone. The Cdc14 phosphatase plays a key role in organising the intricate choreography of mitosis and cell division. In order to understand the role of Cdc14 inC. albicanswe used quantitative proteomics to identify proteins that physically interact withCaCdc14. To distinguish genuine Cdc14-interactors from proteins that bound non-specifically bound to the affinity matrix we used an orthogonal approach of a substrate trapping mutant combined with mass spectrometry analysis using stable isotope labelling in cell culture (SILAC). The results identified 126 proteins that interact with Cdc14 of which 80% are novel. In this set, 53 proteins play known roles in the cell regulating the attachment of the mitotic spindle to kinetochores, mitotic exit, cytokinesis, licensing of DNA replication by re-activating pre-replication complexes, and DNA repair. Five Cdc14-interacting proteins with previously unknown functions localized to the Spindle Pole Bodies (SPBs). Intriguingly, 83 proteins that only interacted with Cdc14 in yeast were significantly enriched in components of the ergosterol biosynthesis pathway targeted by azole anti-fungal drugs. Thus we have greatly expanded the set of known substrates of this key cell cycle regulator inC. albicans.Author summaryCandida albicansis an important fungal pathogen causing life-threatening bloodstream infections in humans, as well as debilitating mucosal infections. Here we used Mass Spectroscopy to identify proteins that physically interacted with an enzyme called Cdc14. By removing phosphate groups from proteins, and thus regulating their function, this enzyme orchestrates the intricate molecular mechanisms of nuclear division to ensure that each daughter cell receives a full complement of chromosomes.C. albicansis unusual in the way that changes in chromosome number and composition are much more common than in other organisms. This suggests that the process of nuclear division may be more error prone inC. albicans. Our work identified 126 proteins that physically associate with Cdc14 and are thus potential substrates, including 53 proteins that we know are involved in many cell cycle processes that are necessary for nuclear and cell division. Thus, we have laid the ground work to study how changes in chromosomal composition may arise due to errors in nuclear division in this important pathogen. Unexpectedly, we found that Cdc14 may also act on proteins involved in the synthesis of ergosterol, a key lipid in the cell membrane. Azoles, a major class of antifungal drugs, inhibit the synthesis of ergosterol, so Cdc14 may also be involved in the action of azoles and thus one possible way in which drug resistance arises.
Par3 regulates Rac1 signaling and microtubule organization during planar polarization of auditory hair cells
Authors: Malt Andre Landin , Dailey Zachary , Holbrook-rasmussen Julia , Zheng Yuqiong , Du Quansheng , Lu Xiaowei 
Published: May 2018

AbstractIn the inner ear sensory epithelia, hair bundles atop sensory hair cells are mechanosensory apparati with planar polarized structure and orientation. This is established during development by the concerted action of tissue-level planar cell polarity (PCP) signaling and a hair cell-intrinsic, microtubule-mediated machinery. However, how various polarity signals are integrated during hair bundle morphogenesis is poorly understood. Here, we show that the conserved cell polarity protein Par3 plays a key role in planar polarization of hair cells. Par3 deletion in the inner ear resulted in defects in cochlear length, hair bundle orientation and kinocilium positioning. During PCP establishment, Par3 promotes localized Rac-Pak signaling through an interaction with Tiam1. Par3 regulates microtubule dynamics and organization, which is crucial for basal body positioning. Moreover, there is reciprocal regulation of Par3 and the core PCP molecule Vangl2. Thus, we conclude that Par3 is an effector and integrator of cell-intrinsic and tissue-level PCP signaling.One sentence summaryPar3 regulates planar polarity of auditory hair cells
Development and decline of the hippocampal long-axis specialization and differentiation during encoding and retrieval of episodic memories
Authors: Langnes Espen , Vidal-Piñeiro Didac , Sneve Markus H. , Amlien Inge K. , Walhovd Kristine B , Fjell Anders M 
Published: May 2018

AbstractChange in hippocampal function is a major factor in lifespan development and decline of episodic memory. Evidence indicates a long-axis specialization where anterior hippocampus is more engaged during encoding and posterior during retrieval. We tested the lifespan trajectory of hippocampal long-axis episodic memory-related activity and functional connectivity (FC). 496 participants (6.8-80.8 years) were scanned with functional MRI while encoding and retrieving associative memories. We found clear evidence for a long-axis encoding-retrieval specialization. These long-axis effects declined linearly during development and aging, eventually vanishing in the older adults. This was mainly driven by age effects on retrieval. Retrieval was associated with gradually lower activity from childhood to adulthood, followed by positive age-relationships until 70 years. Interestingly, this pattern characterized task engagement regardless of memory success or failure. Children engaged posterior hippocampus more than anterior, while anterior hippocampus was more activated relative to posterior already in teenagers. Intra-hippocampal connectivity increased during task, and this increase declined with age. In sum, the results suggest that hippocampal long-axis differentiation and communication during episodic memory tasks develop rapidly during childhood and adolescence, are markedly different in older compared to younger adults, and are related to task engagement, not the successful completion of the task.
Highly efficient homology-directed repair using Cas9 protein in Ceratitis capitata
Authors: Aumann Roswitha A. , Schetelig Marc F. , Häecker Irina 
Published: May 2018

AbstractBackgroundThe Mediterranean fruit fly Ceratitis capitata is a highly polyphagous and invasive insect pest, causing vast economical damage in horticultural systems. A currently used control strategy is the sterile insect technique (SIT) that reduces pest populations through infertile matings with mass-released, sterilized insects. Transgenic approaches hold great promise to improve key aspects of a successful SIT program. However, there is strict or even prohibitive legislation regarding the release of genetically modified organisms (GMO), while novel CRISPR-Cas technologies might allow to develop genetically enhanced strains for SIT programs classified as non-transgenic.ResultsHere we describe highly efficient homology-directed repair genome editing in C. capitata by injecting pre-assembled CRISPR-Cas9 ribonucleoprotein complexes using different guide RNAs and a short single-stranded oligodeoxynucleotide donor to convert an enhanced green fluorescent protein in C. capitata into a blue fluorescent protein. Six out of seven fertile and individually backcrossed G0 individuals generated 57-90% knock-in rate within their total offspring and 70-96% knock-in rate within their phenotypically mutant offspring.ConclusionConsidering the possibility that CRISPR-induced alterations in organisms could be classified as a non-GMO in the US and Europe, our approach to homology-directed repair genome editing can be used to genetically improve strains for pest control systems like SIT without the need to struggle with GMO directives. Furthermore, it can be used to recreate and use mutations, found in classical mutagenesis screens, for pest control systems.
Phenylhydrazones are active against non-replicatingMycobacterium tuberculosis
Authors: Bonnett Shilah A. , Dennison Devon , Bajpai Anumita , Files Megan , Parish Tanya 
Published: May 2018

AbstractThere is an urgent need for the development of shorter, simpler and more tolerable drugs to treat antibiotic tolerant populations ofMycobacterium tuberculosis. We previously identified a series of phenylhydrazones (PHY) active againstM. tuberculosis. We selected six representative compounds for further analysis. All compounds were active against non-replicatingM. tuberculosis, with two compounds demonstrating greater activity under hypoxic conditions than aerobic culture. Compounds had bactericidal activity with MBC/MIC of <4 and demonstrated an inoculum-dependent effect against aerobically replicating bacteria. Bacterial kill kinetics demonstrated a faster rate of kill against non-replicating bacilli generated by nutrient starvation. Compounds had limited activity against other bacterial species. In conclusion, we have demonstrated that the PHY compounds have some attractive properties in terms of their anti-tubercular activity.
CRISPR/Cas9 gene editing to make conditional mutants of the human malaria parasite Plasmodium falciparum
Authors: Kudyba Heather M. , Cobb David W. , Florentin Anat , Krakowiak Michelle , Muralidharan Vasant 
Published: May 2018

ABSTRACTMalaria is a significant cause of morbidity and mortality worldwide. This disease, which primarily affects those living in tropical and subtropical regions, is caused by infection with Plasmodium parasites. The development of better drugs to combat malaria can be accelerated by improving our understanding of the biology of this complex parasite. Genetic manipulation of these parasites is key to understanding their biology, but historically, the genome of P. falciparum has been difficult to manipulate. Recently, CRISPR/Cas9 genome editing has been utilized in malaria parasites, allowing for easier protein tagging, generation of conditional protein knockdowns, and deletion of genes. CRISPR/Cas9 genome editing has proven to be a powerful tool for advancing the field of malaria research. Here, we describe a CRISPR/Cas9 method for generating glmS-based conditional knockdown mutants in P. falciparum. The method is highly adaptable to other types of genetic manipulations, including protein tagging and gene knockouts.
Designing training programs for HRD, expectations of participants explored
Authors: Stoffers Jol , Schrijver Ilse , Kleefstra Anne 
Published: May 2018

Purpose
This paper aims to investigate the expectations of adult part-time participants enrolled in training programs. The purpose was to provide knowledge for the adequate design of those programs.

Design/methodology/approach
The design was a combination of complementary research methodologies. A literature review exploring the topic marked the start of the investigation. On the basis of this review, questions were formulated for group interviews, using the Delphi method, a qualitative research method.

Findings
The results revealed that participants in training programs have high expectations, in terms of facilities and organization, as well as in content, instructional formats, and trainers, albeit that these expectations differ per course.

Practical implications
Insights into participants’ expectations provide educational institutes with the opportunity to respond to the target group more appropriately, and to fulfill their obligation to facilitate lifelong learning for employees.This paper also supports human resource development professionals to select and design adequate training programs for their employees.

Originality/value
This is one of the few studies using the Delphi method, a qualitative research method, to investigate the expectations of adult part-time participants enrolled in training programs.
Overcoming data blindness; or do shrimp chew with their mouths open?
Authors: Hirsch Peter Buell 
Published: May 2018

Purpose
Alternative data is a term describing the data exhaust that organizations, especially asset managers, are using to develop insights about companies to give them a trading edge. As the use of this data becomes more prevalent, it is critical that business leaders understand how this kind of data can be used against their organizations. This viewpoint articulates some of the steps they will need to take to do this.

Design/methodology/approach
The methodology used in this viewpoint is a review of recent literature covering alternative data and its uses.

Findings
This paper describes the different ways in which alternative data is being used and cites surprising examples of how this can make companies vulnerable or threaten their reputation.

Research limitations/implications
As an overview of selected examples from secondary sources, this paper is not a comprehensive treatment of the subject.

Practical implications
By studying the issues raised in the paper, business leaders can arm themselves with insights into the use of alternative data and mitigate reputational fallout from its use against their companies.

Social implications
A better understanding of how alternative data is being used can help protect both individuals and social organizations from being treated inequitably and increase transparency in the use of large and hidden data sets.

Originality/value
To the best of the author’s knowledge, this is the first treatment of the use of alternative data from the perspective of corporate reputation.
Tensions within sustainability management: a socio-psychological framework
Authors: Kuntner Wilhelm , Weber Wolfgang G. 
Published: May 2018

PurposeThe purpose of this study is to contribute to the theoretical groundwork for socio-psychological investigations into the management of socially sustainable supply chains. It proposes an analytical framework for the study of the psychological conflict potential between the fulfillment of core labor standards and cost efficiency requirements.Design/methodology/approachTheoretical considerations are illustrated using an explorative qualitative-empirical case study.FindingsAn activity-theoretical approach makes it possible to combine the subjective experience of tensions between conflicting requirements on sustainability management and the practical imperatives of the capitalist-market economic system in a coherent socio-psychological analytical framework.Research limitations/implicationsThe proposed analytical framework serves as a starting point for theoretical considerations on socio-psychological determinants of the sustainability performance of the management of transnational supply chains.Originality/valueThis paper addresses the novel topic of how supply chain sustainability managers give sense to difficulties concerning the fulfillment of core labor standards while being constrained by cost efficiency requirements. To this end, in a hitherto unique way, concepts from activity theory, social cognitive theory of self-regulation and the theory of communicative action are combined into an analytical framework.