bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human cytomegalovirus vMIA inhibits MAVS oligomerization at peroxisomes in an MFF-dependent manner
Authors: Ferreira Ana Rita , Gouveia Ana , Magalhães Ana Cristina , Valença Isabel , Marques Mariana , Kagan Jonathan C. , Ribeiro Daniela 
Published: February 2022

AbstractUpon intracellular recognition of viral RNA, RIG-I-like proteins interact with MAVS at peroxisomes and mitochondria, inducing its oligomerization and the downstream production of direct antiviral effectors. The human cytomegalovirus (HCMV) is able to specifically evade this antiviral response, via its antiapoptotic protein vMIA. Besides suppressing the programmed cell death of infected cells, vMIA inhibits the antiviral signalling at mitochondria by inducing the organelle’s fragmentation, consequently hindering the interaction between MAVS and the endoplasmic reticulum protein STING. Here, we demonstrate that vMIA interferes with the peroxisomal antiviral signalling via a distinct mechanism that is independent of the organelle’s morphology and does not affect STING. vMIA interacts with MAVS at peroxisomes and inhibits its oligomerization, restraining downstream signalling, in an MFF-dependent manner. This study also demonstrates that vMIA is totally dependent on the organelle’s fission machinery to induce peroxisomal fragmentation, while this dependency is not observed at mitochondria. Furthermore, although we demonstrate that vMIA is also able to inhibit MAVS oligomerization at mitochondria, our results indicate that this process, such as the whole vMIA-mediated inhibition of the mitochondrial antiviral response, is independent of MFF. These observed differences in the mechanisms of action of vMIA towards both organelles, likely reflect their intrinsic differences and roles throughout the viral infection.This study uncovers specific molecular mechanisms that may be further explored as targets for antiviral therapy and highlights the relevance of peroxisomes as platforms for antiviral signalling against HCMV.
Stepwise remodelling and subcompartment formation in individual vesicles by three ESCRT-III proteins
Authors: Avalos-Padilla Yunuen , Georgiev Vasil N. , Ewins Eleanor , Robinson Tom , Orozco Esther , Lipowsky Reinhard , Dimova Rumiana 
Published: February 2022

AbstractThe endosomal sorting complex required for transport (ESCRT) is a multi-protein complex involved in several membrane remodelling processes. Different approaches have been used to dissect the mechanism by which ESCRT proteins produce scission in the membranes. However, the underlying mechanisms generating the membrane deformations remain poorly understood. In this study, giant unilamellar vesicles (GUVs), microfluidic technology and micropipette aspiration are combined to continuously follow the ESCRT-III-mediated membrane remodelling on the single-vesicle level for the first time. With this approach, we identify different mechanisms by which a minimal set of three ESCRT-III proteins from the phagocytic parasite Entamoeba histolytica reshape the membrane. These proteins modulate the membrane stiffness and spontaneous curvature to regulate the bud size and generate intraluminal vesicles in GUVs even in the absence of ATP. We show that the bud stability depends on the protein concentration and membrane tension. The approach introduced here should open the road to diverse applications in synthetic biology for establishing artificial cells with several membrane compartments.
An apical membrane complex controls rhoptry exocytosis and invasion in Toxoplasma
Authors: Sparvoli Daniela , Delabre Jason , Penarete-Vargas Diana Marcela , Mageswaran Shrawan Kumar , Tsypin Lev M. , Heckendorn Justine , Theveny Liam , Maynadier Marjorie , Cova Marta Mendonça , Berry-Sterkers Laurence , Guérin Amandine , Dubremetz Jean-François , Urbach Serge , Striepen Boris , Turkewitz Aaron P. , Chang Yi-Wei , Lebrun Maryse 
Published: February 2022

SUMMARYApicomplexan parasites possess secretory organelles called rhoptries that undergo regulated exocytosis upon contact with the host. This process is essential for the parasitic lifestyle of these pathogens and relies on an exocytic machinery sharing structural features and molecular components with free-living ciliates. Here, we performed a Tetrahymena-based transcriptomic screen to uncover novel exocytic factors in Ciliata and Apicomplexa. We identified membrane-bound proteins, named CRMPs, forming part of a large complex essential for rhoptry secretion and invasion in Toxoplasma. In contrast to previously described rhoptry exocytic factors, TgCRMPs are not required for the assembly of the rhoptry secretion machinery and only transiently associated with the exocytic site - prior to invasion. CRMPs and their partners contain putative host cell-binding domains, and CRMPa shares similarity to GPCR proteins. We propose that the CRMP complex acts as host-molecular sensor to ensure that rhoptry exocytosis occurs when the parasite contacts the host cell.
Mitochondrial structure and function adaptation in residual triple negative breast cancer cells surviving chemotherapy treatment
Authors: Baek Mokryun L. , Lee Junegoo , Pendleton Katherine E. , Berner Mariah J. , Goff Emily B. , Tan Lin , Martinez Sara A. , Wang Tao , Meyer Matthew D. , Lim Bora , Barrish James P. , Porter Weston , Lorenzi Philip L. , Echeverria Gloria V. 
Published: February 2022

ABSTRACTNeoadjuvant chemotherapy (NACT) used for triple negative breast cancer (TNBC) eradicates tumors in approximately 45% of patients. Unfortunately, TNBC patients with substantial residual cancer burden have poor metastasis free and overall survival rates. We previously demonstrated mitochondrial oxidative phosphorylation (OXPHOS) was elevated and was a unique therapeutic dependency of residual TNBC cells surviving NACT. We sought to investigate the mechanism underlying this enhanced reliance on mitochondrial metabolism. Mitochondria are morphologically plastic organelles that cycle between fission and fusion to maintain mitochondrial integrity and metabolic homeostasis. The functional impact of mitochondrial structure on metabolic output is highly context dependent and not understood in TNBC. Several chemotherapy agents are conventionally used for neoadjuvant treatment of TNBC patients. Upon comparing mitochondrial effects of commonly used chemotherapies, we found that DNA-damaging agents increased mitochondrial elongation, mitochondrial content, flux of glucose through the TCA cycle, and OXPHOS, whereas taxanes instead decreased mitochondrial elongation and OXPHOS. Additionally, short protein isoform levels of the mitochondrial inner membrane fusion protein optic atrophy 1 (OPA1) were associated with those observations. Further, we observed heightened OXPHOS, OPA1 protein levels, and mitochondrial elongation in a patient-derived xenograft (PDX) model of residual TNBC. Pharmacologic or genetic disruption of mitochondrial fusion and fission resulted in decreased or increased OXPHOS, respectively, revealing that longer mitochondria favor oxphos in TNBC cells. Using TNBC cell lines and an in vivo PDX model of residual TNBC, we found that sequential treatment with DNA-damaging chemotherapy, thus inducing mitochondrial fusion and OXPHOS, followed by MYLS22, a specific inhibitor of OPA1, was able to suppress mitochondrial fusion and OXPHOS and significantly inhibited residual tumor regrowth. Taken together, our findings suggest that TNBC mitochondria can optimize OXPHOS through modulation of mitochondrial structure. This may provide an opportunity to overcome mitochondrial adaptations of chemoresistant TNBC.
Multiscale mapping of in vivo 3D epidermal melanin distribution of human skin using a fast large-area multiphoton exoscope (FLAME)
Authors: Vicente Juvinch R. , Durkin Amanda , Shrestha Kristina , Balu Mihaela 
Published: March 2022

ABSTRACTMelanin plays a significant role in the regulation of epidermal homeostasis and photoprotection of human skin. The assessment of its epidermal distribution and overall content is of great interest due to its involvement in a wide range of physiological and pathological skin processes. Among several spectroscopic and optical imaging methods that have been reported for non-invasive quantification of melanin in human skin, the approach based on the detection of two-photon excited fluorescence lifetime distinguishes itself by enabling selective detection of melanin with sub-cellular resolution, thus facilitating its quantification while also resolving its depth-profile. A key limitation of prior studies on the melanin assessment based on this approach is their inability to account for the skin heterogeneity due to the reduced field of view of the images, which results in high dispersion of the measurement values. Pigmentation in both normal and pathological human skin is highly heterogeneous and its macroscopic quantification is critical for reliable measurements of the epidermal melanin distribution and for capturing melanin-related sensitive dynamic changes as a response to treatment. In this work, we employ a fast large-area multiphoton exoscope (FLAME), recently developed by our group for clinical skin imaging, that has the ability to evaluate the 3D distribution of epidermal melanin content in vivo macroscopically (millimeter scale) with microscopic resolution (sub-micron) and rapid acquisition rates (minutes). We demonstrate significant enhancement in the reliability of the melanin density and distribution measurements across Fitzpatrick skin types I to V by capturing the intra-subject pigmentation heterogeneity enabled by the large volumetric sampling. We also demonstrate the potential of this approach to provide consistent measurement results when imaging the same skin area at different times. These advances are critical for clinical and research applications related to monitoring pigment modulation as a response to therapies against pigmentary skin disorders, skin aging, as well as skin cancers.
Selective binding and transport of protocadherin 15 isoforms by stereocilia unconventional myosins in a heterologous expression system
Authors: Ballesteros Angela , Yadav Manoj , Cui Runjia , Kurima Kiyoto , Kachar Bechara 
Published: February 2022

AbstractDuring hair cell development, the mechanoelectrical transduction (MET) apparatus is assembled at the stereocilia tips, where it coexists with the stereocilia actin regulatory machinery. While the myosin-based tipward transport of actin regulatory proteins is well studied, isoform complexity and built-in redundancies in the MET apparatus have limited our understanding of how MET components are transported. We used a heterologous expression system to elucidate the myosin selective transport of isoforms of protocadherin 15 (PCDH15), the protein that mechanically gates the MET apparatus. We show that MYO7A selectively transports the CD3 isoform while MYO3A and MYO3B transports the CD2 isoform. Furthermore, MYO15A showed an insignificant role in the transport of PCDH15, and none of the myosins tested transport PCDH15-CD1. Our data suggest an important role for MYO3A, MYO3B, and MYO7A in the MET apparatus formation and highlight the intricate nature of MET and actin regulation during development and functional maturation of the stereocilia bundle.
Human neutrophils communicate remotely via glutamate-induced glutamate release
Authors: Kopach Olga , Sylantyev Sergyi , Bard Lucie , Michaluk Piotr , Gutierrez del Arroyo Ana , Ackland Gareth L. , Gourine Alexander V. , Rusakov Dmitri A. 
Published: February 2022

AbstractNeutrophils are white blood cells that are critical to the acute inflammatory and adaptive immune responses. Their swarming-pattern behaviour is controlled by multiple cellular cascades involving calcium-dependent release of various signalling molecules. Previous studies have reported that neutrophils express glutamate receptors and can release glutamate but evidence of direct neutrophil-neutrophil communication has been elusive. Here, we hold semi-suspended cultured human neutrophils in patch-clamp whole-cell mode to find that calcium mobilisation induced by stimulating one neutrophil can trigger an NMDA receptor-driven membrane current and calcium signal in neighbouring neutrophils. We employ an enzymatic-based imaging assay to image, in real time, glutamate release from neutrophils induced by glutamate released from their neighbours. These observations provide direct evidence for a positive-feedback inter-neutrophil communication that could contribute to mechanisms regulating communal neutrophil behaviour.
Nonlinear micro finite element models based on digital volume correlation measurements predict early microdamage in newly formed bone
Authors: Fernández Marta Peña , Sasso Sebastian J , McPhee Samuel , Black Cameron , Kanczler Janos , Tozzi Gianluca , Wolfram Uwe 
Published: March 2022

AbstractBone regeneration in critical-sized defects is a clinical challenge, with biomaterials under constant development aiming at enhancing the natural bone healing process. The delivery of bone morphogenetic proteins (BMPs) in appropriate carriers represents a promising strategy for bone defect treatment but optimisation of the spatial-temporal release is still needed for the regeneration of bone with biological, structural, and mechanical properties comparable to the native tissue. Nonlinear micro finite element (μFE) models can address some of these challenges by providing a tool able to predict the biomechanical strength and microdamage onset in newly formed bone when subjected to physiological or supraphysiological loads. Yet, these models need to be validated against experimental data. In this study, experimental local displacements in newly formed bone induced by osteoinductive biomaterials subjected to in situ X-ray computed tomography compression in the apparent elastic regime and measured using digital volume correlation (DVC) were used to validate μFE models. Displacement predictions from homogeneous linear μFE models were highly correlated to DVC-measured local displacements, while tissue heterogeneity capturing mineralisation differences showed negligible effects. Nonlinear μFE models improved the correlation and showed that tissue microdamage occurs at low apparent strains. Microdamage seemed to occur next to large cavities or in biomaterial-induced thin trabeculae, independent of the mineralisation. While localisation of plastic strain accumulation was similar, the amount of damage accumulated in these locations was slightly higher when including material heterogeneity. These results demonstrate the ability of the nonlinear μFE model to capture local microdamage in newly formed bone tissue and can be exploited to improve the current understanding of healing bone and mechanical competence. This will ultimately aid the development of BMPs delivery systems for bone defect treatment able to regenerate bone with optimal biological, mechanical, and structural properties.
Different efficacies of neutralizing antibodies and antiviral drugs on SARS-CoV-2 Omicron subvariants, BA.1 and BA.2
Authors: Ohashi Hirofumi , Hishiki Takayuki , Akazawa Daisuke , Kim Kwang Su , Woo Joohyeon , Shionoya Kaho , Tsuchimoto Kana , Iwanami Shoya , Moriyama Saya , Kinoshita Hitomi , Yamada Souichi , Kuroda Yudai , Yamamoto Tsukasa , Kishida Noriko , Watanabe Shinji , Hasegawa Hideki , Ebihara Hideki , Suzuki Tadaki , Maeda Ken , Fukushi Shuetsu , Takahashi Yoshimasa , Iwami Shingo , Watashi Koichi 
Published: March 2022

SummaryThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2 has spread in many countries, replacing the earlier Omicron subvariant BA.1 and other variants. Here, using a cell culture infection assay, we quantified the intrinsic sensitivity of BA.2 and BA.1 compared with other variants of concern, Alpha, Gamma, and Delta, to five approved-neutralizing antibodies and antiviral drugs. Our assay revealed the diverse sensitivities of these variants to antibodies, including the loss of response of both BA.1 and BA.2 to casirivimab and of BA.1 to imdevimab. In contrast, EIDD-1931 and nirmatrelvir showed a more conserved activities to these variants. The viral response profile combined with mathematical analysis estimated differences in antiviral effects among variants in the clinical concentrations. These analyses provide essential evidence that gives insight into variant emergence’s impact on choosing optimal drug treatment.
Aging queer in a pandemic: intersectionalities and perceptions
Authors: Faas A.J. , Jarrar Simon , Gonzalez Bautista Noémie 
Published: February 2022

PurposeThe purpose of this study is to highlight the experiences and issues of an overlooked demographic: older LGBTQ + adults in the US, in the context of the COVID-19 pandemic. This allows the authors to explore possible changes in policy and practice regarding the management of the pandemic with attention to elderly LGBTQ.Design/methodology/approachBuilding on the authors’ experience in disaster research and a study of older LGBTQ + adults in the San Francisco Bay Area, the authors analyze key trends in COVID-19 pandemic management while drawing lessons from the AIDS epidemic.FindingsThe authors have found that LGBTQ + people, especially older and transgender individuals, have unique experiences with hazards and public safety and healthcare professionals and organizations (e.g. heteronormative care, traumatic insensitivity, deprioritizing essential treatments as elective). Second, older LGBTQ + adults' perceptions of state responses to pandemics were heavily influenced by experiences with the HIV/AIDS pandemic. And third, experiences with the COVID-19 pandemic have important implications for preventing, responding to and recovering from future epidemics/pandemics.Originality/valueThe authors point to two parallel implications of this work. The first entails novel approaches to queering disaster prevention, response and recovery. And the second is to connect the management of the COVID-19 pandemic to the principles of harm reduction developed by grassroots organizations to suggest new ways to think about contagion and organize physical distancing, while still socializing to take care of people’s physical and mental health, especially the more marginalized like elderly LGBTQ + people.
Does gender balance in entrepreneurship education make a difference to prospective start-up behaviour?
Authors: Hägg Gustav , Politis Diamanto , Alsos Gry Agnete 
Published: February 2022

PurposeThis study aims to examine the role of gender balance in forming individuals’ understanding of entrepreneurship as manifested in the graduates’ occupational choices, asking: Does gender balance in entrepreneurship education influence start-up behaviour after graduation? Based on gender mainstreaming, this study builds on the assumption that gender balance influences classroom and student community discourses. This study presents two hypotheses suggesting a positive relationship between gender balance (student and mentor gender balance, respectively) and the likelihood of engaging in start-up behaviour after graduation.Design/methodology/approachThe context is an international one-year master's programme in entrepreneurship and innovation, which adopts an experienced-based pedagogical approach to support learning. This study applies binary logistic regression analysis to test the hypotheses on a sample of 107 graduates who responded to a web-based questionnaire on post-graduation career paths.FindingsThis study finds support for the first hypothesis indicating that student gender balance in the classroom has a significant positive impact on graduates' likelihood of engaging in start-up activity post-graduation. In the interpretation of these findings, this study emphasizes that a master's programme in entrepreneurship is an important arena where students' attitudes, values, aspirations and intentions towards entrepreneurship are shaped and their identity developed.Originality/valueWhile studies have demonstrated gender bias in the discourses on entrepreneurship education and content, there is little evidence of its consequences or how it is addressed. Findings of this study point directly to this gap by revealing that improved gender balance is not only beneficial to the underrepresented gender, but to the overall student group.
Discovering signals of platform failure risks from customer sentiment: the case of online P2P lending
Authors: Zhang Qiang , Zhu Xinyu , Zhao J. Leon , Liang Liang 
Published: February 2022

PurposeDigital platforms have grown significantly in recent years. Although high platform failure risks (PFR) have plagued the industry, the literature has only given this issue scant treatment. Customer sentiments are crucial for platforms and have a growing body of knowledge on its analysis. However, previous studies have overlooked rich contextual information emb`edded in user-generated content (UGC). Confronting the research gap of digital platform failure and drawbacks of customer sentiment analysis, we aim to detect signals of PFR based on our advanced customer sentiment analysis approach for UGC and to illustrate how customer sentiments could predict PFR.Design/methodology/approachWe develop a deep-learning based approach to improve the accuracy of customer sentiment analysis for further predicting PFR. We leverage a unique dataset of online P2P lending, i.e., a typical setting of transactional digital platforms, including 97,876 pieces of UGC for 2,467 platforms from 2011 to 2018.FindingsOur results show that the proposed approach can improve the accuracy of measuring customer sentiment by integrating word embedding technique and bidirectional long short-term memory (Bi-LSTM). On top of that, we show that customer sentiment can improve the accuracy for predicting PFR by 10.96%. Additionally, we do not only focus on a single type of customer sentiment in a static view. We discuss how the predictive power varies across positive, neutral, negative customer sentiments, and during different time periods.Originality/valueOur research results contribute to the literature stream on digital platform failure with online information processing and offer implications for digital platform risk management with advanced customer sentiment analysis.
The Role of Compensation As a Determinant of Performance and Employee Work Satisfaction: A Study at The PT Bank Rakyat Indonesia (Persero) Tbk
Authors: Rojikinnor Rojikinnor , Gani Abdul Juli Andi , Saleh Choirul , Amin Fadillah 
Published: February 2022

PurposeThe purpose of the study is to conduct an in-depth study of employee performance in connection with compensation, job satisfaction and the work environment of employees at the PT Bank Rakyat Indonesia (Persero) Tbk.Design/methodology/approachThis study was performed at the PT Bank Rakyat Indonesia (Persero) Tbk, which operates in Indonesia, and included all employees of the different branch offices in Sumatera, Jawa, Kalimantan, Sulawesi, Bali and Jayapura.FindingsCompensation does not directly affect employee performance but working environment does directly influence employee performance at the PT Bank Rakyat Indonesia (Persero) Tbk. There is the power of compensation and working environment on job satisfaction and employee performance at the PT Bank Rakyat Indonesia (Persero) Tbk.Originality/valueThe difference between this research and previous ones is the application of compensation influence testing on employee job satisfaction and performance within one bank in Indonesia.