bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonistic interactions between odorants alter human odor perception
Authors: Fukutani Yosuke , Abe Masashi , Saito Haruka , Eguchi Ryo , Tazawa Toshiaki , de March Claire A. , Yohda Masafumi , Matsunami Hiroaki 
Published: August 2022

AbstractThe olfactory system detects a vast number of odorants using hundreds of olfactory receptors (ORs), the largest group of the G protein-coupled receptor (GPCR) superfamily. Each OR is activated by specific odorous ligands. Like other GPCRs, activation of ORs may be blocked through antagonism. Recent reports highlight widespread antagonisms in odor mixtures influencing olfactory neuron activities. However, it is unclear if and how these antagonisms influence perception of odor mixtures. Here we show that odorant antagonisms at the receptor level alter odor perception. Using a large-scale heterologous expression, we first identified a set of human ORs that are activated by methanethiol and hydrogen sulfide, two extremely potent volatile sulfur malodors. We then screened odorants that block activation of these ORs and identified a set of antagonists, including β-ionone. Finally, human sensory evaluation revealed that odor intensity and unpleasantness of methanethiol were decreased by β-ionone. Odor intensity of β-ionone itself is not correlated with the degree of suppression of malodor sensation. Suppression was also not observed when methanethiol and β-ionone were simultaneously introduced to different nostrils. Together, our data supports the model that odor sensation is altered through antagonistic interactions at the level of the ORs.
Single Cell Transcriptomics identifies a WNT7A-FZD5 Signaling Axis that maintains Fallopian Tube Stem Cells in Patient-derived Organoids
Authors: Alsaadi Abdulkhaliq , Artibani Mara , Hu Zhiyuan , Wietek Nina , Morotti Matteo , Gonzales Laura Santana , Alazzam Moiad , Jiang Jason , Abdul Beena , Soleymani majd Hooman , Blazer Levi L , Adams Jarret , Silvestri Francesca , Sidhu Sachdev S , Brugge Joan S. , Ahmed Ahmed Ashour 
Published: August 2022

Despite its significance to reproduction, fertility, sexually transmitted infections and various pathologies, the fallopian tube (FT) is relatively understudied. Strong evidence points to the FT as the tissue-of-origin of high grade serous ovarian cancer (HGSOC), the most fatal gynaecological malignancy. HGSOC precursor lesions arise specifically in the distal FT (fimbria) which is reported to be enriched in stem-like cells. Investigation of the role of FT stem cells in health and disease has been hampered by a lack of characterization of FT stem cells and lack of models that recapitulate stem cell renewal and differentiationin vitro. Using optimized organoid culture conditions to address these limitations, we found that FT stem cell renewal is highly dependent on WNT/β-catenin signaling and engineered endogenous WNT/β-catenin signaling reporter organoids to biomark, isolate and characterize putative FT stem cells. Using functional approaches as well as bulk and single cell transcriptomic analyses, we show that an endogenous hormonally-regulated WNT7A-FZD5 signaling axis is critical for self-renewal of human FT stem cells, and that WNT/β-catenin pathway-activated FT cells form a distinct transcriptomic cluster of cells enriched in ECM remodelling and integrin signaling pathways. In addition, we find that the WNT7A-FZD5 signaling axis is dispensable for mouse oviduct regeneration. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease.GRAPHICAL ABSTRACT
Primary Somatosensory Cortex Bidirectionally Modulates Sensory Gain and Nociceptive Behavior in a Layer-Specific Manner
Authors: Ziegler Katharina , Folkard Ross , Gonzalez Antonio J , Burghardt Jan , Antharvedi-Goda Sailaja , Martin-Cortecero Jesus , Isaías-Camacho Emilio , Kaushalya Sanjeev , Tan Linette Liqi , Kuner Thomas , Acuna Claudio , Kuner Rohini , Mease Rebecca , Groh Alexander 
Published: August 2022

AbstractThe primary somatosensory cortex (S1) is a hub for body sensation of both innocuous and noxious signals, yet its role in somatosensation versus pain is debated. Despite known contributions of S1 to sensory gain modulation, its causal involvement in subjective sensory experiences remains elusive. Here, in mouse S1, we reveal the involvement of cortical output neurons in layers 5 (L5) and 6 (L6) in the perception of innocuous and noxious somatosensory signals. We find that L6 activation can drive aversive hypersensitivity and spontaneous nocifensive behavior. Linking behavior to neuronal mechanisms, we find that L6 enhances thalamic somatosensory responses, and in parallel, strongly suppresses L5 neurons. Directly suppressing L5 reproduced the pronociceptive phenotype induced by L6 activation, suggesting an anti-nociceptive function for L5 output. Indeed, L5 activation reduced sensory sensitivity and reversed inflammatory allodynia. Together, these findings reveal a layer-specific and bidirectional role for S1 in modulating subjective sensory experiences.
Common neural choice signals can emerge artifactually amidst multiple distinct value signals
Authors: Frömer R. , Nassar M.R. , Ehinger B.V. , Shenhav A. 
Published: August 2022

AbstractPrevious work has identified characteristic neural signatures of value-based decision-making, including neural dynamics that closely resemble the ramping evidence accumulation process believed to underpin choice. Here, we test whether these signatures of the choice process can be temporally dissociated from additional, choice-independentvalue signals. Indeed, EEG activity during value-based choice revealed distinct spatiotemporal clusters, with a stimulus-locked cluster reflecting affective reactions to choice sets and a response-locked cluster reflecting choice difficulty. Surprisingly,neitherof these clusters met the criteria for an evidence accumulation signal. Instead, we found that stimulus-locked activity canmimican evidence accumulation process when aligned to the response. Re-analyzing four previous studies – including three perceptual decision-making studies – we show that response-locked signatures of evidence accumulation disappear when stimulus-locked and response-locked activity are modelled jointly. Collectively, our findings show that neural signatures of value can reflect choice-independent processes and look deceptively like evidence accumulation.Significance StatementTo choose, people must evaluate their options and select between them. Selection is well described by a process of accumulating evidence up to some threshold, with an electrophysiological signature in the centroparietal positivity (CPP). However, decision-making also gives rise to value signals reflecting affective reactions and other selection-unrelated processes. Measuring EEG while participants made value-based choices, we identified two spatiotemporally distinct value signals, neither reflecting evidence accumulation. Instead, we show that evidence accumulation signals found in the CPP can arise artifactually from overlapping stimulus- and response-related activity. These findings call for a significant reexamination of established links between neural and computational mechanisms of choice, while inviting deeper consideration of the array of cognitive and affective processes that occur in parallel.
GATA transcription factors drive initial Xist upregulation after fertilization through direct activation of a distal enhancer element
Authors: Lustig Liat Ravid , Kumar Abhishek Sampath , Schwämmle Till , Dunkel Ilona , Noviello Gemma , Weigert Raha , Pacini Guido , Buschow René , Ghauri Afrah , Stötzel Maximilian , Wittler Lars , Meissner Alexander , Schulz Edda G. 
Published: August 2022

AbstractTo ensure dosage compensation for X-linked genes between the sexes, one X chromosome is silenced during early embryonic development of female mammals. This process of X-chromosome inactivation (XCI) is initiated through upregulation of the RNA Xist from one X chromosome shortly after fertilization. Xist then mediates chromosome-wide gene silencing in cis and remains expressed in all cell types except the germ line and the pluripotent state, where XCI is reversed. The factors that drive Xist upregulation and thereby initiate XCI remain however unknown. We identify GATA transcription factors as potent Xist activators and demonstrate that they are essential for the activation of Xist in mice following fertilization. Through a pooled CRISPR activation screen we find that GATA1 can drive ectopic Xist expression in murine embryonic stem cells (mESCs). We demonstrate that all GATA factors can activate Xist directly via a GATA-responsive regulatory element (RE79) positioned 100 kb upstream of the Xist promoter. Additionally, GATA factors are essential for the induction of XCI in mouse preimplantation embryos, as simultaneous deletion of three members of the GATA family (GATA1/4/6) in mouse zygotes effectively prevents Xist upregulation. Thus, initiation of XCI and possibly its maintenance in distinct lineages of the preimplantation embryo is ensured by the combined activity of different GATA family members, and the absence of GATA factors in the pluripotent state likely contributes to X reactivation. We thus describe a form of regulation in which the combined action of numerous tissue-specific factors can achieve near-ubiquitous expression of a target gene.
Dynamic interplay between non-coding enhancer transcription and gene activity in development
Authors: Hamamoto Kota , Fukaya Takashi 
Published: August 2022

AbstractNon-coding transcription at the intergenic regulatory regions is a prevalent feature of metazoan genomes, but its biological function remains uncertain. Here, we devised a live-imaging system that permits simultaneous visualization of gene activity along with intergenic non-coding transcription at the single-cell resolution in Drosophila. Quantitative image analysis revealed that elongation of RNA polymerase II across the internal core region of enhancers leads to suppression of transcriptional bursting from linked genes. Super-resolution imaging and genome-editing analysis further demonstrated that enhancer transcription antagonizes molecular crowding of transcription factors, thereby interrupting the formation of transcription hub at the gene locus. We also show that a certain class of developmental enhancers are structurally optimized to co-activate gene transcription together with non-coding transcription effectively. We suggest that enhancer function is flexibly tunable through the modulation of hub formation via surrounding non-coding transcription during development.
Towards a framework for the scale-up of rehabilitation for patients with non-communicable disease in low-resource settings
Authors: Heine Martin , Derman Wayne , Hanekom Susan 
Published: August 2022

AbstractObjectiveTo explore and synthesize critical factors for the scale-up of comprehensive rehabilitation care for people with non-communicable disease in low-resourced settings.MethodsA core set of 81 articles were selected from two published scoping reviews. Using the principles of thematic analysis, the core set was analysed for factors that may directly or indirectly affect the feasibility or scale-up of rehabilitation. Categories and themes were formulated via an iterative team approach using the core set (n=81). Subsequently, we triangulated the thematic analysis against our findings from a feasibility study conducted in a low-resourced, urban, setting in South Africa. Next, a validation article set (n=63) was identified by updating the searches for the respective published reviews, and a purposeful sample of articles drawn from the validation set (n=13; 20%) was used to validate the factors identified in the primary analysis based on the principles of data saturation.FindingsA total of 40 different themes (i.e., critical factors) were derived from 169 categories. Subsequently the identified factors could be packaged into nine system elements principal for the scale-up of rehabilitation for people with NCDs in terms of increasing population coverage, increasing comprehensiveness, and integration within existing health structures.ConclusionA multitude of factors which affect the feasibility and scale-up of rehabilitation for NCDs in low resource settings were identified. These factors are multi-dimensional and multi-directional. Researchers and policy makers should consider these factors and their interconnectedness when planning to address the rehabilitation needs through implementation and scale-up initiatives.
Improving access to mental health services for those experiencing multiple disadvantage
Authors: Moreton Rachel , Welford Jo , Collinson Beth , Greason Laura , Milner Chris 
Published: August 2022

Purpose
This paper aims to explore the barriers to accessing mental health support for people experiencing multiple disadvantage along with some potential solutions for attempting to overcome these. It draws on evidence and learning from 12 voluntary sector-led partnerships in England funded by the National Lottery Community Fund’s Fulfilling Lives programme.

Design/methodology/approach
Qualitative research was undertaken with frontline staff, senior leaders, volunteers, beneficiaries and stakeholders from Fulfilling Lives partnerships. This comprised focus groups (21 participants) and individual face-to-face interviews (41 participants), both of which explored barriers and local solutions to accessing statutory mental health services. Following a thematic analysis of transcripts, research participants and stakeholders were invited to a face-to-face workshop to review and validate emerging findings (34 participants).

Findings
People experiencing multiple disadvantage face significant barriers in accessing support for their mental health. These include a complex system that is difficult to navigate, long waiting lists, high eligibility thresholds and models of support that lack flexibility. Fulfilling Lives partnerships have had the funding and the flexibility to trial different approaches. Promising solutions to barriers include the use of navigators, person-centred support and multi-agency networks and training. However, overcoming systemic barriers remains the most difficult challenge.

Originality/value
Fulfilling Lives was a rare example of substantial and long-term (eight years) funding to work with people experiencing multiple disadvantage. This provided a unique opportunity to try different approaches and gather learning. The programme evaluation provides insights into the experiences of people facing multiple disadvantage and those who support them and offers evidence-based suggestions for policy and practice.
Authentic assessment and work-based learning: the case of professional studies in a post-COVID Australia
Authors: Fergusson Lee , van der Laan Luke , Imran Sophia , Danaher Patrick Alan 
Published: August 2022

PurposeTo explore the conceptualisation and operationalisation of authentic assessment in work-based learning and research.Design/methodology/approachThe relationship between authentic assessment and work-based learning and research is examined using a postgraduate degree program at a regional university in Australia as a case example to identify unique pedagogical features of work-based learning as they are linked to assessment.FindingsA dynamic is created between formative and summative authentic assessment practices and the cross-current nature of learning in work and research, leading to a range of lifelong learning outcomes. A framework for such a dynamic is presented.Originality/valueThe pedagogy informing work-based learning emphasises developing higher-order thinking through reflective practice, developing competencies and capabilities associated with professional practice and developing academic writing and research skills to enhance professional identity at the postgraduate level for mid- to senior-career professionals. However, the relationship of authentic assessment to work-based learning and research has not been explicated in the literature and its application in post-COVID work environments has yet to be fully examined.
Climate change and its impact on rice acreage in high-latitude regions of China: an estimation by machine learning
Authors: Yu Yan , Tian Qingsong , Yan Fengxian 
Published: August 2022

PurposeFewer researchers have investigated the climatic and economic drivers of land-use change simultaneously and the interplay between drivers. This paper aims to investigate the nonlinear and interaction effects of price and climate variables on the rice acreage in high-latitude regions of China.Design/methodology/approachThis study applies a multivariate adaptive regression spline to characterize the effects of price and climate expectations on rice acreage in high-latitude regions of China from 1992 to 2017. Then, yield expectation is added into the model to investigate the mechanism of climate effects on rice area allocation.FindingsThe results of importance assessment suggest that rice price, climate and total agricultural area play an important role in rice area allocation, and the importance of temperature is always higher than that of precipitation, especially for minimum temperature. Based on the estimated hinge functions and coefficients, it is found that total agricultural area has strong nonlinear and interaction effects with climate and price as forms of third-order interaction. However, the order of interaction terms reduces to second order after absorbing the expected yield. Additionally, the marginal effects of driven factors are calculated at different quantiles. The total area shows a positive and increasing marginal effect with the increase of total area. But the positive impact of price on the rice area can only be observed when price reached 50% or higher quantiles. Climate variables also show strong nonlinear marginal effects, and most climatic effects would disappear or be weakened once absorbing the expected rice yield. Expected yield is an efficient mechanism to explain the correlation between crop area and climate variables, but the impact of minimum temperature cannot be completely modeled by the yield expectation.Originality/valueTo the best of the authors’ knowledge, this is the first study to examine the nonlinear response of land-use change to climate and economic in high-latitude regions of China using the machine learning method.
The three-phase expatriate cycle of developing global human resources in the banking industry in Taiwan
Authors: Hooi Lai Wan 
Published: August 2022

Purpose
The purpose of this paper is to explore the success factors needed for the development of global human resources from both the organisation’s and expatriates’ perspectives in emerging eastern economies. Specifically, this study focuses on pre-expatriation preparation, during-expatriation adjustment and post-expatriation repatriation.

Design/methodology/approach
In total, 23 Taiwanese personnel contributed to this case study. Data collected from the focus group discussion and open-ended asynchronous email interviews was analysed using the content analysis approach.

Findings
The results of this study revealed four main selection criteria for the selection process and five desired preparation methods from the organisation and the expatriates’ perspectives.

Originality/value
This study makes two main contributions to cross-cultural related global human resources research. Firstly, this study deepens understanding on the pathway to developing culturally intelligent global human resources for successful mission accomplishment from both the organisation and expatriates’ perspectives based on a three-phase expatriation process in emerging eastern economies. Secondly, this study provides an insight into the best practices that HR practitioners can use in developing global human resources for expatriation.
Philosophical understanding of the dynamics and control of occupational fraud in the public sector: contingency analysis
Authors: Maulidi Ach 
Published: August 2022

PurposeThis study aims to examine the roles of organisational control, structure, culture and technology in preventing occupational fraud. This study is essential in the current time. It brings a significant impact on both theory and practice. In the existing studies, there is a lack of clarity on a specific mechanism to prevent organisational fraud. The problem is that they tend to generalise the types of organisational fraud. Conceptually, organisational fraud may include corruption, double funding, asset misappropriation, bribery or falsification of documents. However, many scholars tend to neglect such diversities. Consequently, many occupational fraud cases become unstoppable, particularly corruption. To deal with this topical issue, the current study applies the term “occupational fraud” cited by the Association of Certified Fraud Examiners, consisting of corruption, asset misappropriation and fraudulent financial statement.Design/methodology/approachThis study surveyed three Indonesian Local Governments. This study focussed on management levels that have strong power for coordinating governmental activities. The author chose these local governments because their local leaders (the regents) were jailed due to corruption scandals. As expected, this study gives us different perceptions of how fraud mitigation should be designed in the organisation.FindingsThe results suggest that corruption is a little bit complex than other types of occupational fraud. It is improbable to be prevented through technological and administrative approaches. As such, organisations need to think of extra efforts that could perfectly tailor the organisational control and organisational culture, organisational structure and technological advancement. The benefit of this effort is related to diagnosing the fit or misfit of organisation designs in addressing the dynamic dimensions of corporate governance. Then, it can also strengthen the efficacy of preventive measures to deal with occupational fraud.Originality/valueThis study provides a provocative discussion regarding the public perception of occupational fraud, consisting of corruption, asset misappropriation and financial statement fraud. And this study also offers a new refined conceptual analysis of how to deal with such types of occupational fraud by incorporating contingency theory and the Committee of Sponsoring Organizations of the Treadway Commission (COSO’s) internal control components.