bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatially Resolved In Silico Modeling of NKG2D Signaling Kinetics Reveals Key role of NKG2D and Vav1 Co-clustering in Generating Natural Killer cell Activation
Authors: Grewal Rajdeep Kaur , Das Jayajit 
Published: August 2021

AbstractNatural Killer (NK) cells provide key resistance against viral infections and tumors. A diverse set of activating and inhibitory NK cell receptors (NKRs) interact with cognate ligands presented by target host cells, where integration of dueling signals initiated by the ligand-NKR interactions determines NK cell activation or tolerance. Imaging experiments over decades have shown micron and sub-micron scale spatial clustering of activating and inhibitory NKRs. The mechanistic roles of these clusters in affecting downstream signaling and activation are often unclear. To this end, we developed a predictive in silico framework by combining spatially resolved mechanistic agent based modeling, published TIRF imaging data, and parameter estimation to determine mechanisms by which formation and spatial movements of activating NKG2D microclusters affect early time NKG2D signaling kinetics in a human cell line NKL. We show co-clustering of NKG2D and the guanosine nucleotide exchange factor Vav1 in NKG2D microclusters plays a dominant role over ligand (ULBP3) rebinding in increasing production of phospho-Vav1(pVav1), an activation marker of early NKG2D signaling. The in silico model successfully predicts several scenarios of inhibition of NKG2D signaling and time course of NKG2D spatial clustering over a short (∼3 min) interval. Modeling shows the presence of a spatial positive feedback relating formation and centripetal movements of NKG2D microclusters, and pVav1 production offers flexibility towards suppression of activating signals by inhibitory KIR ligands organized in inhomogeneous spatial patterns (e.g., a ring). Our in silico framework marks a major improvement in developing spatiotemporal signaling models with quantitatively estimated model parameters using imaging data.
Phosphorylated tau fluid biomarker sites recognize earlier neurofibrillary tangle maturity levels in the postmortem Alzheimer’s disease brain
Authors: Moloney Christina M. , Labuzan Sydney A. , Crook Julia E. , Siddiqui Habeeba , Castanedes-Casey Monica , Lachner Christian , Petersen Ronald C. , Duara Ranjan , Graff-Radford Neill R. , Dickson Dennis W. , Mielke Michelle M. , Murray Melissa E. 
Published: August 2021

AbstractAlzheimer’s disease (AD) biomarkers have become increasingly more reliable in predicting AD pathology. While phosphorylated tau fluid biomarkers have been studied for over 20 years, there is a lack of deep characterization of these sites in the postmortem brain. Neurofibrillary tangle-bearing neurons, one of the major neuropathologic hallmarks of AD, undergo morphologic changes that mature along a continuum as hyperphosphorylated tau aggregates. To facilitate interpretation of phosphorylated tau sites as an early fluid biomarker, our goal was to characterize which neurofibrillary tangle maturity levels (pretangle, intermediary 1, mature tangle, intermediary 2, and ghost tangle) they recognize. We queried the Florida Autopsied Multi-Ethnic (FLAME) cohort for cases from Braak stages I-VI. We excluded non-AD pathologies and tauopathies. A total of 24 cases, 2 males and 2 females for each Braak stage, were selected. We performed immunohistochemistry on the posterior hippocampus using antibodies directed towards phospho (p) threonine (T) 181, pT205, pT217, and pT231. Slides were digitized to enable quantification of tau burden. To examine differences in regional vulnerability between CA1 and subiculum, we developed a semi-quantitative system to rank the frequency of each neurofibrillary tangle maturity level. We identified all neurofibrillary tangle maturity levels at least once for each phosphorylated tau site. Primarily earlier neurofibrillary tangle maturity levels (pretangle, intermediary 1, mature tangle) were recognized for all phosphorylated tau sites. There was an increase in tau burden in the subiculum compared to CA1; however, this was attenuated compared to thioflavin-S positive tangle counts. On a global scale, tau burden generally increased with each Braak stage. These results provide neurobiologic evidence that these phosphorylated tau fluid biomarker sites are present during earlier neurofibrillary tangle maturity levels. This may help explain why these phosphorylated tau biomarker sites are observed before symptom onset in fluids.
pH-Triggered Assembly of Endomembrane Multicompartments in Synthetic Cells
Authors: Lussier Félix , Schröter Martin , Diercks Nicolas J. , Jahnke Kevin , Weber Cornelia , Frey Christoph , Platzman Ilia , Spatz Joachim P. 
Published: August 2021

AbstractBottom-up synthetic biology thrives to reconstruct basic cellular processes into a minimalist cellular replica to foster their investigation in greater details with a reduced number of variables. Among these cellular features, the endomembrane system is an important aspect of cells which is at the origin of many of their functions. Still, the reconstruction of these inner compartments within a lipid-based vesicle remains challenging and poorly controlled. Herein, we report the use of pH as external trigger to self-assemble compartmentalized giant unilamellar vesicles (GUVs) by either bulk, or droplet-based microfluidics. By co-encapsulating pH sensitive small unilamellar vesicles (SUVs), negatively charged SUVs and/or proteins, we show that acidification of the droplets efficiently produces GUVs while sequestrating the co-encapsulated material with flexibility and robustness. The method enables the simultaneous reconstruction of more than a single cellular phenotype from the bottom-up, corresponding to an important advancement in the current status quo of bottom-up synthetic biology.
Histopathological effects and micronucleus assay of glyphosate-based herbicides on cultured african catfish (Clarias Gariepinus, Burchell 1822)
Authors: Alarape S.A. , Adebiyi E.O. , Adeyemo O.K. 
Published: August 2021

AbstractGlyphosate, a brand of agricultural herbicides which intensive use has led to widespread contamination of different ecosystems. This study was designed to determine both organotoxicity and genotoxicity of glyphosate on African Catfish (Clarias gariepinus) exposed to different concentrations for 96 hours. Questionnaires were administered (physically and online) to determine the type of glyphosate-based herbicides mostly used by fish farmers. Seventy-five apparently healthy adult Clarias gariepinus (300g) were sourced from a local farmer, transported in a plastic keg to Fish and Wildlife Laboratory at the Department of Veterinary Public Health and Preventive medicine for two (2) weeks of acclimatization. After acclimatization, they were further divided into four (4) groups (T0 (Control), T1 (0.003ml/L), T2 (0.0045ml/L) and T3 (0.006ml/L)) by simple randomization and each group replicated into three (3) treatments. At the expiration of 96 hours of exposure, blood samples and organs (Gills, Kidney, and Liver) were collected for mononuclear assay and histopathological lesions respectively.Exposed groups showed erratic swimming, splashing, and restlessness. Mortalities rate was dose-dependent (two (2) mortalities at 0.0045ml/L concentration (T2) and five (5) mortalities 0.006ml/L concentration (T3)). Observed histopathological lesions occurred at higher dose treatment (0.0045ml/L (T2) and (0.006ml/L) T3)) concentrations. The gills showed diffuse stunted and eroded secondary lamellae and severe congestion of the blood channel at the core of the primary lamellae. Lesions in the Liver include severe diffuse vacuolation of the hepatocytes, moderate to severe portal congestion and mild diffuse vacuolation of hepatocytes and moderate diffuse vacuolation of hepatocytes, and severe portal congestion. In the kidney, there was mild to moderate congestion of the interstitium and focus of interstitial oedema within the parenchyma. There was presence of micronucleus in the fish nucleated red blood cells at higher dose concentrations.This study showed that Glyphosate-based herbicides are highly toxic to Clarias gariepinus, therefore their use near the fish farm or in areas close to the aquatic environment should be discouraged. The agricultural community should also be conscious of the potentially adverse effects of pesticides. This is to prevent the water body from the residue of herbicides that would have washed down to the water.
The Omega-3-fatty acid docosahexaenoic acid modulates intracellularmyo-inositol and its biosynthetic genes
Authors: Murray Marlene , Ok Taejun , Kang Haley , Lee Jee Yeon , Kim Bomi , Sung Hyukje , Tait Talisa , Colon Hidalgo Daniel , Guzman Yudy 
Published: August 2021

AbstractBipolar disorder is a debilitating mood disorder characterized by recurring episodes of mania and depression. It affects 2.6% of adults and has a lifetime prevalence among adults of 3.9%. Current mood stabilizers are not always effective and/or are not well tolerated by many patients; thus, there is a need to develop or identify more effective and less harmful treatments. Omega-3-fatty acids have been shown to be effective in the treatment of bipolar disorder; however, their mechanism of action is unknown.Myo-inositol depletion has been hypothesized as the mechanism by which mood stabilizers exert their therapeutic effect. Using an enzymatic assay, we determined intracellularmyo-inositol levels increased more than 2-fold when cells were grown in the presence of the omega-3 fatty acid docosahexaenoic acid (DHA). RT-qPCR was used to characterize the effects of DHA on genes in themyo-inositol biosynthetic pathway. We show DHA increases relative expression and has a concentration-dependent impact onINO1andINM1, which encodemyo-inositol-1-phosphate synthase andmyo-inositol monophosphate 1-phosphatase, respectively. We therefore conclude that the omega-3-fatty acid DHA exerts its therapeutic effect on bipolar disorder by increasing intracellularmyo-inositol, which may be accomplished by upregulating its biosynthetic genes.
Virtual Touch: Sensing and Feeling with Ultrasound
Authors: Moore Warren , Makdani Adarsh , Frier William , McGlone Francis 
Published: August 2021

AbstractThe sense of touch codes the detection and properties of physical objects on the body via mechanoreceptors within the skin. Technological advancements, such as ultrasonic haptic devices, are now able to ‘touch without touching’, claiming this is virtual touch. An initial aim of the study was to investigate subjective intensity and pleasantness ratings of ultrasound stimulation and the influence of top-down factors using the Touch Experience and Attitudes Questionnaire (TEAQ). Self-reported intensity and pleasantness ratings were measured in response to ultrasound stimuli. A second aim was to record from individual low threshold mechanoreceptors using the technique of microneurography in an attempt to determine which mechanoreceptors are activated by ultrasound stimulation of the skin. The major findings here were that microneurography found SAI and SAII units did not respond to ultrasound stimuli; intensity and pleasantness ratings were significantly different between age groups. Ultrasound can produce a variety of sensations with varying intensity and pleasantness ratings. A limitation of the study was the unexpected force difference generated between modulations. These findings have implications for mid-air haptics, somatosensory affective research, and virtual reality. Future research should focus on microneurography investigation of FA fibre responses to ultrasound.
Selective localization of Mfn2 near PINK1 enable its preferential ubiquitination by Parkin on mitochondria
Authors: Vranas Marta , Lu Yang , Rasool Shafqat , Croteau Nathalie , Krett Jonathan D. , Sauvé Véronique , Gehring Kalle , Fon Edward A. , Durcan Thomas M. , Trempe Jean-François 
Published: August 2021

AbstractMutations in Parkin and PINK1 cause an early-onset familial Parkinson’s disease. Parkin is a RING-In-Between-RING (RBR) E3 ligase that transfers ubiquitin from an E2 enzyme to a substrate in two steps: 1) thioester intermediate formation on Parkin, and 2) acyl transfer to a substrate lysine. The process is triggered by PINK1, which phosphorylates ubiquitin on damaged mitochondria, which in turn recruits and activates Parkin. This leads to the ubiquitination of outer mitochondrial membrane proteins and clearance of the organelle. While the targets of Parkin on mitochondria are known, the factors determining substrate selectivity remain unclear. To investigate this, we examined how Parkin catalyzes ubiquitin transfer to substrates. We found that His433 in the RING2 domain catalyzes acyl transfer. In cells, mutation of His433 impairs mitophagy. In vitro ubiquitination assays with isolated mitochondria show that Mfn2 is a kinetically preferred substrate. Using proximity-ligation assays, we show that Mfn2 specifically co-localizes with PINK1 and phospho-ubiquitin in U2OS cells upon mitochondrial depolarization. We propose a model whereby ubiquitination of Mfn2 is efficient by virtue of its localization near PINK1, which leads to the recruitment and activation of Parkin via phospho-ubiquitin at these sites.
Single-cell foundations of live social gaze interaction in the prefrontal cortex and amygdala
Authors: Monte Olga Dal , Fan Siqi , Fagan Nicholas A. , Chu Cheng-Chi J. , Zhou Michael B. , Putnam Philip T. , Nair Amrita R. , Chang Steve W. C. 
Published: August 2021

AbstractSocial gaze interaction powerfully shapes interpersonal communication in humans and other primates. However, little is known about the neural underpinnings of these social behavioral exchanges. Here, we studied neural responses associated with naturalistic, face-to-face, social gaze interactions between pairs of macaques. We examined spiking activity in a large number of neurons spanning four different brain regions involved in social behaviors – the amygdala, orbitofrontal cortex, anterior cingulate cortex, and dorsomedial prefrontal cortex. We observed widespread single-cell representations of social gaze interaction functionalities in these brain regions – social discriminability, social gaze monitoring, and mutual eye contact selectivity. Many of these neurons discriminated looking at social versus non-social stimuli with rich temporal heterogeneity, or parametrically tracked the gaze positions of oneself or the conspecific. Furthermore, many neurons displayed selectivity for mutual eye contact as a function of the initiator or follower of mutual gaze events. Crucially, a significant proportion of neurons coded for more than one of these three signatures of social gaze interaction, supporting the recruitment of partially overlapping neuronal ensembles. Our findings emphasize integrated contributions of the amygdala and prefrontal circuits within the social interaction networks in processing real-life social interactions.
Strong neutral sweeps occurring during a population contraction
Authors: Moinet Antoine , Peischl Stephan , Excoffier Laurent 
Published: August 2021

AbstractA strong reduction in diversity around a specific locus is often interpreted as a recent rapid fixation of a positively selected allele, a phenomenon called a selective sweep. Rapid fixation of neutral variants can however lead to similar reduction in local diversity, especially when the population experiences changes in population size, e.g., bottlenecks or range expansions. The fact that demographic processes can lead to signals of nucleotide diversity very similar to signals of selective sweeps is at the core of an ongoing discussion about the roles of demography and natural selection in shaping patterns of neutral variation. Here we quantitatively investigate the shape of such neutral valleys of diversity under a simple model of a single population size change, and we compare it to signals of a selective sweep. We analytically describe the expected shape of such “neutral sweeps” and show that selective sweep valleys of diversity are, for the same fixation time, wider than neutral valleys. On the other hand, it is always possible to parametrize our model to find a neutral valley that has the same width as a given selected valley. We apply our framework to the case of a putative selective sweep signal around the gene Quetzalcoatl inD. melanogasterand show that the valley of diversity in the vicinity of this gene is compatible with a short bottleneck scenario without selection. Our findings provide further insight in how simple demographic models can create valleys of genetic diversity that may falsely be attributed to positive selection.
Strategising management accounting: liberal origins and neoliberal trends
Authors: Alawattage Chandana , Wickramasinghe Danture 
Published: August 2021

PurposeThis paper draws on the concepts of biopolitics and neoliberal governmentality to provide a sociological analysis of the strategic turn in management accounting.Design/methodology/approachThis conceptual and review paper addresses four interrelated questions: How can the early history of management accounting be revisited from a biopolitical angle? How has strategising been linked to the neoliberal evolution of capitalism? How has this neoliberal connection transformed management accounting into its new form of strategising? What are the implications of this transformation for future research and pedagogical practices in management accounting?FindingsManagement accounting is strategised in four interrelated directions: by absorbing the jurisdictional and veridictional roles of the market into the calculative practices of management accounting; by transforming management accounting's centripetal hierarchical order of calculations to a centrifugal order the neoliberal governmentality demanded; by re-calculating the point of production as a site in which labour now takes the form of entrepreneurs of the self, performing not only material but also immaterial elements of managerial labour; and by rescoping management accounting to address issues the “fourth or the global age of security” brought, including the social and the environmental ones.Research limitations/implicationsThe research expands the existing frames of reference for exploring contemporary calculative practices in neoliberal governmentality.Social implicationsStrategic turn in management accounting implicates in issues of security, governance and ethics and offers “new opportunities” for expanding management accounting's relevance beyond economic enterprises to various civil society and political constituencies.Originality/valueThis paper makes a theoretical contribution to management accounting's contemporary developments by demonstrating how it moves into biopolitical circulation.
Impact of sustainable supply chain management and customer relationship management on organizational performance
Authors: Das Saikat , Hassan H.M. Kamrul 
Published: August 2021

PurposeThis paper aims to assess the effect of sustainable supply chain management (SSCM) , competitive advantage (CA) and customer relationship management (CRM) on organizational performance (OP).Design/methodology/approachA self-administered questionnaire was employed in the present study as a research tool, consisting of 20 items. Information was gathered from 93 executives employed in the supply chain management (SCM) division of the multiple organizations in Chattogram, the commercial hub of Bangladesh and the findings of the research were evaluated using SMART PLS 3.0.FindingsThe findings supported the hypotheses that were formulated. The analysis shows that SSCM and CRM are significantly related to OP. The results show, however, a positive but insignificant relationship between CA and OP. In developing countries, SSCM and CA are more likely to be employed by businesses in order to accomplish OP. However, the relation between CRM and OP has been given comparatively less importance. It has been suggested that CRM, together with SSCM, should be considered in order to achieve OP.Originality/valueEarlier study neglected to use the CRM in the measurement of OP along with CA and SSCM. This research seeks to emphasize the influence of CRM in the organization, together with SSCM. This lets companies understand the effect of SSCM and CRM in general since those companies must respond to consumer demands to product and industry developments and transfer appropriate resources to enhance manufacturing processes that combine technological and managerial efficiency.
Risk management factors contributing to transgressions in the procurement practices in South African SOEs
Authors: Myeza Lindani , Nkhi Naledi , Maroun Warren 
Published: August 2021

PurposeThe study aims to deepen the understanding of why risk management principles are circumvented, thereby contributing to transgressions in public procurement for South African state-owned enterprises (SOEs). A deeper understanding of why risk management principles are circumvented is especially important in South Africa, given the high social, economic and environmental risks to which national and major SOEs are exposed in the procurement process.Design/methodology/approachThe study uses a qualitative design, based on detailed semi-structured interviews with 19 participants comprising management advisors, forensic investigators and auditors to explore why risk management principles are circumvented by South Africa SOEs.FindingsThe results of the study indicate that the tone that is set at political and executive level plays an important role in determining compliance with risk management principles by lower-level staff. Intense levels of political influence at SOEs are the main reason behind risk management systems being undermined.Originality/valueThe current study is one of the first explorations of why transgressions in public procurement continue to be evident despite risk management reforms being adopted by South Africa public sector. The research responds to the call for more studies on why reforms in South Africa public sector are not reducing transgression in public procurement. The study provides primary evidence on the importance of political and executive leadership in influencing the effectiveness of risk management reforms in the public sector.