bluuebunny/crossref_metadata_2025_split huggingface dataset:
Object-based analyses in FIJI/ImageJ to measure local RNA translation sites in neurites in response to Aβ1-42 oligomers
Authors: Gamarra María , Blanco-Urrejola Maite , Batista Andreia F.R. , Imaz Josune , Baleriola Jimena 
Published: January 2020

AbstractSubcellular protein delivery is especially important in signal transduction and cell behavior, and is typically achieved by localization signals within the protein. However, protein delivery can also rely on localization of mRNAs that are translated at target sites. Although once considered heretical, RNA localization has proven to be highly conserved in eukaryotes.RNA localization and localized translation are especially relevant in polarized cells like neurons where neurites extend dozens to hundreds of centimeters away from the soma. Local translation confers dendrites and axons the capacity to respond to their environment in an acute manner without fully relying on somatic signals. The relevance of local protein synthesis in neuron development, maintenance and disease has not been fully acknowledged until recent years, partly due to the limited amount of locally produced proteins. For instance, in hippocampal neurons levels of newly-synthesized somatic proteins can be more than 20-30 times greater than translation levels of neuritic proteins. Thus local translation events can be easily overlooked under the microscope.Here we describe an object-based analysis used to visualize and quantify local RNA translation sites in neurites. Newly-synthesized proteins are tagged with puromycin and endogenous RNAs labelled with SYTO. After imaging, signals corresponding to neuritic RNAs and proteins are filtered with a Laplacian operator to enhance the edges. Resulting pixels are converted into objects and selected by automatic masking followed by signal smoothing. Objects corresponding to RNA or protein and colocalized objects (RNA and protein) are quantified along individual neurites. Colocalization between RNA and protein in neurites correspond to newly-synthesized proteins arising from localized RNAs and represent localized translation sites. To test the validity of our analyses we have compared control neurons to Aβ1-42-treated neurons. Aβ is involved in the pathology of Alzheimer’s disease and was previously reported to induce local translation in axons and dendrites which in turn contributes to the disease. We have observed that Aβ increases the synthesis of neuritic proteins as well as the fraction of translating RNAs in distal sites of the neurite, suggesting an induction of local protein synthesis. Our results thus confirm previous reports and validate our quantification method.
Acute oral toxicity and risks of exposure to the neonicotinoid thiamethoxam, and other classes of systemic insecticide, for the Common Eastern Bumblebee (Bombus impatiens)
Authors: Mundy-Heisz Kayla A. , Prosser Ryan S. , Raine Nigel E. 
Published: January 2020

AbstractThe Common Eastern Bumblebee (Bombus impatiens) is native to North America with an expanding range across Eastern Canada and the USA. This species is commercially produced primarily for greenhouse crop pollination and is a common and abundant component of the wild bumblebee fauna in agricultural, suburban and urban landscapes. However, there is a dearth of pesticide toxicity information about North American bumblebees. The present study determines the acute oral toxicity (48-hour LD50) of cyantraniliprole (>0.54 μg/bee), flupyradifurone (>1.7 μg/bee), sulfoxaflor (0.0194 μg/bee), and thiamethoxam (0.0012 μg/bee). Compared with published honey bee (Apis mellifera) LD50 values, the present study shows that thiamethoxam and sulfoxaflor are 4.2x and 7.5x more acutely toxic toB. impatiens, whereas flupyradifurone is more acutely toxic toA. mellifera. The current rule of thumb for toxicity extrapolation beyond the honey bee as a model species, termed 10x safety factor, may be sufficient for bumblebee acute oral toxicity. A comparison of three risk assessment equations suggested that the Standard Risk Approach (SRA) and Fixed Dose Risk Approach (FDRA) provide more nuanced levels of risk evaluation compared to the European Plant Protection Organization (EPPO) Hazard Quotient (HQ), primarily because SRA and FDRA take into account real world variability in pollen and nectar pesticide residues and the chances that bees are exposed to them.
Most commonly mutated genes in High Grade Serous Ovarian Carcinoma are nonessential for ovarian surface epithelial stem cell transformation
Authors: Yamulla Robert J. , Nalubola Shreya , Flesken-Nikitin Andrea , Nikitin Alexander Yu. , Schimenti John C. 
Published: January 2020

AbstractHigh grade serous ovarian carcinoma (HGSOC) is the most lethal gynecological cancer and the 5th leading cause of cancer-related deaths of women in the USA. Disease-associated mutations have been identified by the Cancer Genome Atlas Research Network. However, aside from mutations in TP53 or alterations in the RB1 pathway that are extremely common in HGSOC, the contributions of other mutation combinations have been difficult to assess experimentally or with genomic data alone. Previous research identified ALDH+ stem cells of the ovarian surface epithelium (OSE) as one of the putative cells of HGSOC origin. Here, we performed combinatorial CRISPR mutagenesis of 20 putative HGSOC driver genes to identify mutation combinations that transformed OSE stem cells (OSE-SC) and non-stem cells (OSE-NS). Overrepresented mutations and mutation combinations were identified in all transformants and were investigated directly in targeted assays. Our results support the OSE stem cell theory of HGSOC initiation and suggest that most commonly mutated genes in HGSOC have no effect on OSE-SC transformation initiation. We suggest a model in which combined disruption of RB1 and PTEN, in addition to TP53 deficiency, constitutes a core set of mutations required for efficient transformation in vitro. A few previously uncharacterized mutation combinations further enhanced transformation but may have done so via TP53-related mechanisms. Together, our results identify mutation combinations that are critical for OSE-SC transformation and may contribute to more accurate modeling of HGSOC development. Our cancer driver screening methodology may also serve as a model for high throughput functional assessment of commonly mutated genes uncovered in other cancers by large scale sequencing.
Layer and rhythm specificity for predictive routing
Authors: Bastos André M. , Lundqvist Mikael , Waite Ayan S. , Kopell Nancy , Miller Earl K. 
Published: January 2020

SummaryIn predictive coding, experience generates predictions that attenuate the feeding forward of predicted stimuli while passing forward unpredicted “errors”. Different models have different neural implementations of predictive coding. We recorded spikes and local field potentials from laminar electrodes in five cortical areas (V4, LIP, area 7A, FEF, and PFC) while monkeys performed a task that modulated visual stimulus predictability. Pre-stimulus predictions were associated with increased alpha/beta (8-30 Hz) power/coherence that fed back the cortical hierarchy primarily via deep-layer cortex. Unpredictable stimuli were associated with increases in spiking and in gamma-band (40-90 Hz) power/coherence that fed forward up the cortical hierarchy via superficial-layer cortex. Area 7A uniquely showed increases in high-beta (~22-28 Hz) power/coherence to unpredicted stimuli. These results suggest that predictive coding may be implemented via lower-frequency alpha/beta rhythms that “prepare” pathways processing predicted inputs by inhibiting feedforward gamma rhythms and associated spiking.
Sex dependent compensatory mechanisms to preserve blood pressure homeostasis in PGI2receptor deficient mice
Authors: Tang Soon Yew , Anderson Seán T. , Meng Hu , Sarantopoulou Dimitra , Ricciotti Emanuela , Hennessy Elizabeth J. , Grant Gregory R. , FitzGerald Garret A. 
Published: January 2020

AbstractInhibitors of microsomal prostaglandin E synthase-1 (mPges-1) are in the early phase of clinical development. Deletion of mPges-1 confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing prostaglandin (PG) E2, but increasing biosynthesis of prostacyclin (PGI2). In hyperlipidemic mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thrombogenesis, while suppression of PGE2accounts for its anti-atherogenic effect. However, the impact of mPges-1 depletion on blood pressure (BP) in this setting remains unknown.To address how differential effects on PGE2and PGI2might modulate salt-evoked BP responses in the absence of mPges-1, we generated mice lacking the I prostanoid (Ipr) receptor or mPges-1 on a hyperlipidemic background caused by deletion of the low density lipoprotein receptor (Ldlr KOs). Here, mPges-1 depletion significantly increased the BP response to salt loading in male Ldlr KO mice, whereas, despite the direct vasodilator properties of PGI2, Ipr deletion suppressed it. Furthermore, combined deletion of the Ipr abrogated the exaggerated BP response in male mPges-1 KO mice. Suppression of PGE2biosynthesis was enough to explain the exaggerated BP response to salt loading by either mPges-1/Ldlr depletion or by an MPGES-1 inhibitor in mice expressing human mPGES-1. However, the lack of a hypertensive response to salt in Ipr-deficient mice was attributable to reactive activation of the atrial natriuretic peptide pathway. Interestingly, these unexpected BP phenotypes were not observed in female mice fed a high salt diet. This is attributable to the protective effect of estrogen in Ldlr KO mice and in Ipr /Ldlr DKOs. Thus, estrogen compensates for a deficiency in PGI2to maintain BP homeostasis in response to high salt in hyperlipidemic female mice. In males, by contrast, augmented formation of ANP plays a similar compensatory role, restraining hypertension and oxidant stress in the setting of Ipr depletion. Hyperlipidemic males on a high salt diet might be at risk of a hypertensive response to mPGES-1 inhibitors.
Neural correlates of winning and losing fights in poison frog tadpoles
Authors: Fischer Eva K , Alvarez Harmony , Lagerstrom Katherine M , McKinney Jordan E , Petrillo Randi , Ellis Gwen , O’Connell Lauren A 
Published: January 2020

ABSTRACTAggressive competition for resources among juveniles is documented in many species, but the neural mechanisms regulating this behavior in young animals are poorly understood. In poison frogs, increased parental care is associated with decreased water volume of tadpole pools, resource limitation, and aggression. Indeed, the tadpoles of many poison frog species will attack, kill, and cannibalize other tadpoles. We examined the neural basis of conspecific aggression in Dyeing poison frog (Dendrobates tinctorius) tadpoles by comparing individuals that won aggressive encounters, lost aggressive encounters, or did not engage in a fight. We first compared patterns of generalized neural activity using immunohistochemical detection of phosphorylated ribosomes (pS6) as a proxy for neural activation associated with behavior. We found increased neural activity in the medial pallium and preoptic area of loser tadpoles, suggesting the amphibian homologs of the mammalian hippocampus and preoptic area may facilitate loser-associated behaviors. Nonapeptides (arginine vasotocin and mesotocin) and dopamine have been linked to aggression in other vertebrates and are located in the preoptic area. We next examined neural activity specifically in nonapeptide- and tyrosine-hydroxylase-positive cells using double-label immunohistochemistry. We found increased neural activity specifically in the preoptic area nonapeptide neurons of winners, whereas we found no differences in activity of dopaminergic cells among behavioral groups. Our findings suggest the neural correlates of aggression in poison frog tadpoles are similar to neural mechanisms mediating aggression in adults and juveniles of other vertebrate taxa.
The roles of aridification and sea level changes in the diversification and persistence of freshwater fish lineages
Authors: Buckley Sean J , Brauer Chris , Unmack Peter , Hammer Michael , Beheregaray Luciano B. 
Published: January 2020

ABSTRACTWhile the influence of Pleistocene climatic changes on divergence and speciation has been well-documented across the globe, complex spatial interactions between hydrology and eustatics over longer timeframes may also determine species evolutionary trajectories. Within the Australian continent, glacial cycles were not associated with changes in ice cover and instead largely resulted in fluctuations from moist to arid conditions across the landscape. Here, we investigate the role of hydrological and coastal topographic changes brought about by Plio-Pleistocene climatic changes on the biogeographic history of a small Australian freshwater fish, the southern pygmy perchNannoperca australis. Using 7,958 ddRAD-seq (double digest restriction-site associated DNA) loci and 45,104 filtered SNPs, we combined phylogenetic, coalescent and species distribution analyses to investigate the relative roles of aridification, sea level and tectonics and their associated biogeographic changes across southeast Australia. Sea-level changes since the Pliocene and reduction or disappearance of large waterbodies throughout the Pleistocene were determining factors in strong divergence across the clade, including the initial formation and maintenance of a cryptic species,N.‘flindersi’. Isolated climatic refugia and fragmentation due to lack of connected waterways maintained the identity and divergence of inter- and intraspecific lineages. Our historical findings suggest that predicted increases in aridification and sea level due to anthropogenic climate change might result in markedly different demographic impacts, both spatially and across different landscape types.
A cell atlas of human thymic development defines T cell repertoire formation
Authors: Park Jong-Eun , Botting Rachel A. , Conde Cecilia Domínguez , Popescu Dorin-Mirel , Lavaert Marieke , Kunz Daniel J. , Stephenson Emily , Ragazzini Roberta , Tuck Elizabeth , Wilbrey-Clark Anna , Ferdinand John R. , Webb Simone , Maunder Daniel , Vandamme Niels , Mahbubani Krishnaa , Polanski Krzysztof , Mamanova Lira , Fuller Andrew , Filby Andrew , Reynolds Gary , Dixon David , Saeb-Parsy Kourosh , Lisgo Steven , Henderson Deborah , Vento-Tormo Roser , Meyer Kerstin B. , Saeys Yvan , Bonfanti Paola , Behjati Sam , Clatworthy Menna R. , Taghon Tom , Haniffa Muzlifah , Teichmann Sarah A. 
Published: January 2020

AbstractThe thymus provides a nurturing environment for the differentiation and selection of T cells, a process orchestrated by their interaction with multiple thymic cell types. We utilised single-cell RNA-sequencing (scRNA-seq) to create a cell census of the human thymus and to reconstruct T-cell differentiation trajectories and T-cell receptor (TCR) recombination kinetics. Using this approach, we identified and locatedin situnovel CD8αα+T-cell populations, thymic fibroblast subtypes and activated dendritic cell (aDC) states. In addition, we reveal a bias in TCR recombination and selection, which is attributed to genomic position and suggests later commitment of the CD8+T-cell lineage. Taken together, our data provide a comprehensive atlas of the human thymus across the lifespan with new insights into human T-cell development.
Personality traits and intrapreneurial behaviour
Authors: Alam Muhammad Zubair , Kousar Shazia , Shabbir Aiza , Kaleem Muhammad Ali 
Published: January 2020

PurposeIntrapreneurship is rapidly concerning organizations to tailor their operations and strategies for competitive advantage. Research on intrapreneurial dimensions is in the developing stage, requiring more rigorous methods of investigation and application in various contexts. This study aims to focus on individual level intrapreneurship by examining the association of personality traits (PTs) on intrapreneurial behaviour (IB) moderated by knowledge sharing behaviour (KSB) and comparison of employees in engineering and functional departments.Design/methodology/approachA survey has been conducted for data collection using a structured questionnaire. Partial least squares structural equation modelling has been used for hypotheses testing, moderation and multi-group analysis on a sample of 534 respondents.FindingsResults reveal that PTs exerted a positive influence on IB. The impact of PTs on IB was more pronounced in the employees of functional departments. KSB moderates positively in the relationship between PTs and IB. Both groups significantly differ in dimensions of PTs.Practical implicationsOrganizations can do little to improve PTs of employees, which impacts on intrapreneurship in organizations. However, KSB in organizations can be improved by adopting various measures. KSB eventually promotes innovation in organizations resulting in an overall competitive advantage for firms.Originality/valueThis is the first study that contributes theoretically in intrapreneurship literature by providing insights on PTs impacting IB incorporating KSB and comparing the diverse group of employees.
Sustainable open innovation to address a grand challenge
Authors: Bogers Marcel , Chesbrough Henry , Strand Robert 
Published: January 2020

PurposeThis paper describes the case of how the Danish beer manufacturer, Carlsberg, developed the Green Fiber Bottle as part of its sustainability program through an open innovation approach in collaboration with complementary partners. It thereby illustrates how a grand challenge associated with sustainability can be effectively addressed through open innovation and reveals the opportunities and challenges that emerge in that context.Design/methodology/approachThe paper summarizes some key elements of the case and, in particular, discusses some of the lessons learned, which can be further explored in future research, practice, and policy.FindingsThe case suggests a number of key issues that are relevant when attempting to address grand challenges, in general, and sustainability in the food and beverage (F&B) industry, in particular, namely: leveraging open innovation in the face of sustainability as a grand challenge; sustainability beyond a solid business case; opportunities and challenges in the face of new business models; the importance of early wins for addressing societal challenges for signals and scaling; and the importance of the Nordic context and long-term vision.Originality/valueThe case describes a recent (and to some extent still ongoing) initiative of how a particular F&B company has explored new approaches to developing its sustainability program. Therefore, it highlights some of the unique characteristics of this case. This paper also lays the groundwork for the establishment of “Sustainable Open Innovation” as a domain in its own right.
Internationalization and family firm performance
Authors: Debicki Bart J. , Miao Chao , Qian Shanshan 
Published: January 2020

PurposeThe purpose of this paper is to evaluate the effect of internationalization on performance in family firms, as well as the potential impact of moderators on this relationship.Design/methodology/approachThis paper is a meta-analysis of the impact of internationalization on performance in family firms, as well as the role of several moderators shaping this relationship, based on 29 studies.FindingsThe findings indicate a significant positive effect of internationalization on family firm performance. This relationship was stronger in family firms with lower family ownership. Several methodological moderators were significant, such as the means of measuring performance and internationalization. The results also point to several cultural moderators, such as individualism, masculinity, low uncertainty avoidance and short-term orientation, which positively influence the main effect.Originality/valueThe authors provide discussions of the results, their practical and theoretical implications, as well as avenues for future research.
Power and area-efficient register designs involving EHO algorithm
Authors: Sabu Neethu Anna , K. Batri 
Published: January 2020

PurposeThis paper aims to design three low-power and area-efficient serial input parallel output (SIPO) register designs, namely, transistor count reduction technique shift register (TCRSR), series stacking in TCR shift register (S-TCRSR) and forced stacking of transistor in TCR shift register (FST in TCRSR). Shift registers (SR) are the basic building blocks of all types of digital applications. The performance of all the designs has been improved through one of the metaheuristic algorithms named elephant herding optimization (EHO) algorithm and hence suited for low-power very large scale integration (VLSI) applications. It is for the first time that the EHO algorithm is implemented in memory elements.Design/methodology/approachThe registers together with clock network consume 18-36 percentage of the total power consumption of a microprocessor. The proposed designs are implemented using low-power and high-performance double edge-triggered D flip-flops with least count of clocked transistors involving transmission gate. The second and third register designs are developed from the modified version of the first one employing series and forced stacking, thereby reducing static power because of sub-threshold leakage current. The performance parameters such as power-delay-product (PDP) and leakage power are further optimized using the EHO algorithm. A greater reduction in power is achieved in all the designs by utilizing the EHO algorithm.FindingsAll the designs are simulated at a supply voltage of 1 V/500 MHz when the input switching activity is 25 percentage in Cadence Virtuoso using 45 nm CMOS technology. Nine recently proposed SR designs are simulated in the same conditions, and the performance has been compared with the proposed ones. The simulated results prove the excellence of proposed designs in different performance parameters like leakage power, energy-delay-product (EDP), PDP, layout area compared with the recent designs. The PDPdq value has a reduction of 95.9per cent (TCRSR), 96.6per cent (S-TCRSR) and 97per cent (FST in TCRSR) with that of a conventional shift register (TGSR).Originality/valueThe performance of proposed low-power SR designs is enhanced using EHO algorithm. The optimized performance results have been compared with a few optimization algorithms. It is for the first time that EHO algorithm is implemented in memory elements.