bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Basal and Major Pilins in theCorynebacterium diphtheriaeSpaA Pilus Adopt Similar Structures that Competitively React with the Pilin Polymerase
Authors: Sue Christopher K. , Cheung Nicole A. , Mahoney Brendan J. , McConnell Scott A. , Scully Jack M. , Fu Janine Y. , Chang Chungyu , Ton-That Hung , Loo Joseph A. , Clubb Robert T. 
Published: February 2023

ABSTRACTMany species of pathogenic gram-positive bacteria display covalently crosslinked protein polymers (called pili or fimbriae) that mediate microbial adhesion to host tissues. These structures are assembled by pilus-specific sortase enzymes that join the pilin components together via lysine-isopeptide bonds. The archetypal SpaA pilus fromCorynebacterium diphtheriaeis built by theCdSrtA pilus-specific sortase, which crosslinks lysine residues within the SpaA and SpaB pilins to build the shaft and base of the pilus, respectively. Here, we show thatCdSrtA crosslinks SpaB to SpaA via a K139(SpaB)-T494(SpaA) lysine-isopeptide bond. Despite sharing only limited sequence homology, an NMR structure of SpaB reveals striking similarities with the N-terminal domain of SpaA (NSpaA) that is also crosslinked byCdSrtA. In particular, both pilins contain similarly positioned reactive lysine residues and adjacent disordered AB loops that are predicted to be involved in the recently proposed “latch” mechanism of isopeptide bond formation. Competition experiments using an inactive SpaB variant and additional NMR studies suggest that SpaB terminates SpaA polymerization by outcompetingNSpaA for access to a shared thioester enzyme-substrate reaction intermediate.
Tyrosine kinase inhibitors target B cells
Authors: Oksenych Valentyn 
Published: February 2023

AbstractAutoimmune disorders and some types of blood cancer originate when B lymphocytes malfunction. In particular, when B cells produce antibodies recognizing the body’s proteins, it leads to various autoimmune disorders. And when B cells of various developmental stages transform into cancer cells, it results in blood cancers, including multiple myeloma, lymphoma, and leukemia. Thus, new methods of targeting B cells are required for various patient groups. Here, we used protein kinase inhibitors alectinib, brigatinib, ceritinib, crizotinib, entrectinib, and lorlatinib previously approved as drugs treating anaplastic lymphoma kinase (ALK)-positive lung cancer cells. We hypothesized that the same inhibitors will efficiently target leukocyte tyrosine kinase (LTK)-positive, actively protein-secreting mature B lymphocytes, including plasma cells. We isolated CD19-positive human B cells from the blood of healthy donors and used two alternative methods to stimulate cell maturation toward plasma cells. Using cell proliferation and flow cytometry assays, we found that ceritinib and entrectinib eliminate plasma cells from B cell populations. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. More generally, we concluded that several drugs previously developed to treat ALK-positive malignant cells can be also used to treat LTK-positive B cells.
Chronic administration of XBD173 ameliorates cognitive deficits and neuropathology via 18 kDa translocator protein (TSPO) in a mouse model of Alzheimer’s disease
Authors: Pradhan Arpit Kumar , Neumüller Tatjana , Klug Claudia , Fuchs Severin , Schlegel Martin , Ballmann Markus , Tartler Katharina Johanna , Pianos Antoine , Garcia-Sanchez Maria , Liere Philippe , Schumacher Michael , Kreutzer Matthias , Rupprecht Rainer , Rammes Gerhard 
Published: February 2023

ABSTRACTAlzheimer’s disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ). There is increasing evidence that depression may precede AD and may be an early manifestation of dementia, suggesting common mechanisms underlying both diseases. Ligands targeting the mitochondrial translocator protein (18 kDa) (TSPO), promote neurosteroidogenesis and may be neuroprotective. Moreover, TSPO is upregulated in AD. To study whether the TSPO ligand XBD173 may exert early neuroprotective effects in AD pathology we investigated the impact of XBD173 on amyloid toxicity and neuroplasticity in mouse models. We show that XBD173 (emapunil), via neurosteroid-mediated signaling via delta subunit-containing GABAAreceptors, prevents the neurotoxic effect of Aβ on long-term potentiation (CA1-LTP) in the hippocampus and prevents the loss of spines. Chronic but not acute administration of XBD173 ameliorates spatial learning deficits in transgenic AD mice with arctic mutation (ArcAβ) mice. The heterozygous TSPO-knockout crossed with the transgenic arctic mutation model of AD mice (het TSPOKO X ArcAβ) treated with XBD173 does not show this improvement in spatial learning suggesting TSPO is needed for procognitive effects of XBD173. The neuroprotective profile of XBD173 in AD pathology is further supported by a reduction in plaques and soluble Aβ levels in the cortex, increased synthesis of neurosteroids, rescued spine density, reduction of complement protein C1q deposits, and reduced astrocytic phagocytosis of functional synapses both in the hippocampus and cortex. Our findings suggest that XBD173 may exert therapeutic effects via TSPO in a mouse model of AD.
Release of extracellular matrix components after human traumatic brain injury
Authors: Bambrick Michael , Johnson Mark , Esko Jeffrey D. , Choudhury Biswa , Toledo Alejandro Gomez , Staley Kevin , Duhaime Ann-Christine 
Published: February 2023

AbstractMost research on the evolution of damage after traumatic brain injury (TBI) focuses on cellular effects, but the analysis of human tissue slices and animal research have shown that TBI causes concomitant damage in the extracellular matrix, which can play a significant role in both short-term consequences such as edema, and late effects such as post-traumatic epilepsy (PTE). To test the hypothesis that traumatic brain injury (TBI) in human patients causes disruption of sulfated glycosaminoglycan (sGAG) in the extracellular matrix, we measured levels of these substances in the ventricular cerebrospinal fluid (CSF) in patients with severe TBI in the acute post-injury period, along with concomitant levels in blood and urine. We assessed whether levels corresponded to parenchymal injury load, distance of traumatic brain lesions from the ventricle, presence of polytrauma, or host demographic factors.MethodsSamples of CSF, blood, and urine were obtained within 72 hours of injury in patients who received external ventricular drains as part of their treatment of severe TBI, and levels of chondroitin and heparan sGAGs were measured, along with their disaccharide constituents. Basic demographic information, presence and severity of polytrauma, brain injury load based on imaging findings, and distance of radiologically visible parenchymal injury from the ventricle were analyzed for correlation with total subtype sGAG levels in each patient.ResultsLevels were measured in 14 patients ranging in age from 17-90 years. CSF sGAG levels were variable among patients, and sGAG levels were higher in plasma than in CSF and variable in urine. Patients with polytrauma had non-significantly higher blood sGAG compared to patients with isolated head injury. Subcategories of CSF sGAG levels correlated with distance from the ventricle of parenchymal injury but not with brain injury load, which may reflect rapid metabolism in the parenchyma, contamination by blood, or bulk directional CSF flow from the ventricle to the subarachnoid space.ConclusionThis study is the first to measure sGAG levels in ventricular CSF and also provides the first measurements in patients with TBI. Damage to the extracellular matrix may play a major role in acute and chronic injury sequelae, and these data demonstrate elevation locally of intracranial sGAGS after severe TBI and also suggest rapid local metabolism of these breakdown products. The consequences of extracellular matrix breakdown may provide unique therapeutic and preventive avenues to mitigate post-injury sequelae.
Repeated footshock stress induces an escalation of cocaine self-administration in male and female rats: Role of the cannabinoid receptor 1
Authors: Gaulden Andrew D. , Tepe Erin A. , Sia Eleni , Rollins Sierra S. , McReynolds Jayme R. 
Published: February 2023

AbstractStress is a significant contributor to the development and progression of substance use disorders (SUDs) and is problematic as it is unavoidable in daily life. Therefore, it is important to understand the neurobiological mechanisms that underlie the influence of stress on drug use. We have previously developed a model to examine the contribution of stress to drug-related behavior by administering a stressor, electric footshock stress, daily at the time of cocaine self-administration in rats resulting in an escalation of cocaine intake. This stress-induced escalation of cocaine intake involves neurobiological mediators of stress and reward such as cannabinoid signaling. However, all of this work has been conducted in male rats. Here we test the hypothesis that repeated daily stress can produce an escalation of cocaine in both male and female rats. We further hypothesize that cannabinoid receptor 1 (CB1R) signaling is recruited by repeated stress to influence cocaine intake in both male and female rats. Male and female Sprague-Dawley rats self-administered cocaine (0.5 mg/kg/inf, i.v.) during a modified short-access paradigm wherein the 2-hr access was separated into 4-30 min self-administration blocks separated by 4-5 min drug free period. Footshock stress produced a significant escalation of cocaine intake similarly in both male and female rats. Female stress-escalated rats did display greater time-out non-reinforced responding and greater “front-loading” behavior. In males, systemic administration of a CB1R inverse agonist/antagonist Rimonabant only attenuated cocaine intake in rats with a history of combined repeated stress and cocaine self-administration. However, in females, Rimonabant attenuated cocaine intake in the no stress control group but only at the highest dose of Rimonabant (3 mg/kg, i.p.) suggesting that females show a greater sensitivity to CB1R antagonism. However, female rats with a history of stress showed even greater sensitivity to CB1R antagonism as both doses of Rimonabant (1, 3 mg/kg) attenuated cocaine intake in stress-escalated rats similar to males. Altogether these data demonstrate that stress can produce significant changes in cocaine self-administration and suggests that repeated stress at the time of cocaine self-administration recruits CB1Rs to regulate cocaine-taking behavior across sexes.
Static and dynamic analysis of in-vivo imaging for early-detection of lymphedema via near-infrared fluorescence indocyanine green lymphangiography
Authors: Cheon Hwayeong , Lee Sang-Hun , Kim Sang Ah , Kim Bumchul , Suh Hyunsuk Peter , Jeon Jae Yong 
Published: February 2023

ABSTRACTBackgroundNear-infrared fluorescence indocyanine green (NIRF-ICG) lymphangiography, a primary modality for detecting lymphedema, which is a disease due to lymphatic obstruction, enables real-time observations of lymphatic flow and reveals not only the spatial distribution of drainage (static analysis), but also information on the lymphatic contraction (dynamic analysis).MethodsWe have produced lymphatic obstruction models in upper limbs through the dissection of proximal lymph nodes (LNs) and radiation (dissection limbs). After the model formation during 1 week, the static and dynamic analysis using NIRF-ICG lymphangiography were performed for six weeks. The drainage pattern and leakage of lymph fluid were observed and time-domain signals of lymphatic contraction were measured in the distal lymph vessels. The obtained signals were converted to the frequency-domain spectrums using the signal processing.ResultsThe results of both static and dynamic analyses proved to be effective in accurately identify the extent of lymphatic disruption in the dissection limbs. The static analysis showed abnormal drainage patterns and an increased leakage of lymph fluid to the periphery of the vessels compared to the control limbs. Meanwhile, the waveforms were changed and the frequency of the contractile signals was increased by 58% in the dynamic analysis. Specifically, our findings revealed that regular lymphatic contractions, observed at a frequency range of 0.08 ∼ 0.13 Hz in the control limbs, were absent in the dissection limbs. The contractile regularity was not fully restored until the end of the follow-up, indicating a persistent lymphatic disruption in the dissected limbs.ConclusionThe dynamic analysis was consistent with the static analysis, and it could detect the abnormalities of lymphatic circulation by observing the characteristics of signals without the need for a control group. As NIRF-ICG lymphangiography is currently used in clinical practice, our findings may be useful for the early detection of the lymphatic circulation problem.
LINE-associated cryptic splicing induces dsRNA-mediated interferon response and tumor immunity
Authors: Zheng Rong , Dunlap Mikayla , Lyu Jingyi , Gonzalez-Figueroa Carlos , Bobkov Georg , Harvey Samuel E. , Chan Tracey W. , Quinones-Valdez Giovanni , Choudhury Mudra , Vuong Amy , Flynn Ryan A. , Chang Howard Y. , Xiao Xinshu , Cheng Chonghui 
Published: February 2023

ABSTRACTRNA splicing plays a critical role in post-transcriptional gene regulation. Exponential expansion of intron length poses a challenge for accurate splicing. Little is known about how cells prevent inadvertent and often deleterious expression of intronic elements due to cryptic splicing. In this study, we identify hnRNPM as an essential RNA binding protein that suppresses cryptic splicing through binding to deep introns, preserving transcriptome integrity. Long interspersed nuclear elements (LINEs) harbor large amounts of pseudo splice sites in introns. hnRNPM preferentially binds at intronic LINEs and represses LINE-containing pseudo splice site usage for cryptic splicing. Remarkably, a subgroup of the cryptic exons can form long dsRNAs through base-pairing of inverted Alu transposable elements scattered in between LINEs and trigger interferon immune response, a well-known antiviral defense mechanism. Notably, these interferon-associated pathways are found to be upregulated in hnRNPM-deficient tumors, which also exhibit elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity. Targeting hnRNPM in tumors may be used to trigger an inflammatory immune response thereby boosting cancer surveillance.
The Care Burden and Influencing Factors of Family Caregivers of Older Adults with Dementia
Authors: Li Laiyou , Sun Ning , Wang Hongyin , Fan Chaoyan , Li Hongyu , Yang Shuang 
Published: February 2023

AbstractObjectiveTo analyze the current state of care burden of dementia caregivers and determine the influencing factors.MethodsUsing the questionnaire survey method, 600 family caregivers of older adults with dementia in five communities in Ningbo (China) were investigated from March to August 2022.ResultsThe average score of care burden of dementia was 52.36 ± 12.08. The total score of social support for older adults with dementia ranged from 19 to 56, with the average score being 34.79 ± 9.54. The total score of social support and the score of each dimension were negatively correlated with the total score of the care burden and the score of each dimension, with the correlation coefficient being between 0.490 and 0.689 (p <0.05). Six factors affecting the burden of care for family caregivers of older adults with dementia were total social support score, dementia level, monthly family income, years of care, educational level, and the duration of daily care for older adults with dementia (all p <0.001).ConclusionThe care burden of older adults with dementia is significant, with many influencing factors. Therefore, it is necessary to relieve the care burden of family caregivers through education support programs, self-efficacy training of caregivers, breathing care services, and psychological counseling to improve the quality of life, and relieve the pressure of social counseling and social support.
Investigating the impact of authenticity of social media influencers on followers' purchase behavior: mediating analysis of parasocial interaction on Instagram
Authors: Agnihotri Durgesh , Chaturvedi Pallavi , Kulshreshtha Kushagra , Tripathi Vikas 
Published: February 2023

PurposeThe current study has drawn attention to investigating the impact of social media influencers’ (SMIs) authenticity on followers buying behavior by using followers who have an ongoing relationship with an influencer and are knowledgeable about the influencer. The study further intends to reveal the mediating effect of parasocial interaction on the relationship between SMI's authenticity and followers' purchase behavior.Design/methodology/approachThe study has analyzed data from an online survey of 458 participants (Instagram followers) using structured equation modeling (CB-SEM) to investigate the relationship among authenticity attributes, parasocial interaction and followers' purchase behavior.FindingsCB-SEM results reveal that authenticity attributes positively influence followers' buying behavior. The findings from mediation analysis specify that parasocial interaction mediates the relationship between authenticity attributes (sincerity, truthful endorsement and visibility) and buying behavior excluding expertise, uniqueness attributes.Practical implicationsThe findings of the study reinforce the need to use authentic influencers by the marketers for the brand endorsements. Further, the findings of the study can benefit marketers in implementing strategic practice of social media influencer marketing.Originality/valueThe study overcomes the limitations of preceding studies by using Instagram followers who are well-informed about SMIs and have an ongoing relationship with them. This study has uniquely combined the behavioral data from real influencer campaigns with followers' assessment of an influencer's authenticity.
Assessing the effects of transformational leadership on innovative behavior: the role of affective commitment and psychological capital
Authors: Azinga Samuel Awuni , Obeng Anthony Frank , Ellis Florence Y.A. , Ansah Martin Owusu 
Published: February 2023

PurposeThis study examines the impact of transformational leadership on employees' innovative behavior via the mediating role of employee affective commitment and the moderating effect of psychological capital.Design/methodology/approachA sample of 555 employees from Ghana's textiles and dress-making industry through a three-wave self-administrated questionnaire participated in this study. The study's hypotheses were analyzed using Hierarchical Regression.FindingsResults revealed that the dimensions of transformational leadership positively influenced employee affective commitment and employees' innovative behavior. Furthermore, employee affective commitment positively influenced employees' innovative behavior. Moreover, employee affective commitment exercised mediation effects in the relationship between transformational leadership and employees' innovative behavior. Hope and Optimism moderated the employee affective commitment and employees' innovative behavior relationship. Self-efficacy negatively moderated the employee affective commitment and employees' innovative behavior relationship. Staggering, resilience had no moderation impact on the employee affective commitment and employees' innovative behavior relationship.Practical implicationsThe research provides guidlines to employers to prioritize training and development, institutionalize coaching and promote policies and investment that help to uphold employees’ positive emotions and positive psychological development.Originality/valueThis study tests the mediating role of employee affective commitment and moderating role of psychological capital in relation to transformational leadership and employees' innovative behavior. In addition, it assesses the interactive outcome of positive affect and positive psychological development of employees, which has attracted less theoretical and empirical deliberations.
Construction stakeholders' knowledge on zero carbon initiatives in New Zealand
Authors: Nidhin Bindhu Kumari Sreekandan Nair , Domingo Niluka , Bui Thao Thi Phuong , Wilkinson Suzanne 
Published: February 2023

PurposeIn light of climate change, the design and construction of buildings needs to shift from conventional to lower-carbon practices to maximise carbon reduction. Over the past few years, the zero carbon buildings (ZCBs) approach has been promoted worldwide as an effective way to reduce environmental impacts and mitigate climate change. Although zero-carbon policies, technologies, processes and products are widely available in the construction market, construction stakeholders play an important part in adopting relevant strategies to implement ZCBs successfully. This study investigates the knowledge of construction stakeholders involved in the design and construction of buildings regarding zero carbon initiatives in New Zealand.Design/methodology/approachThe research was conducted using a literature review and an online questionnaire survey with various New Zealand's construction stakeholders.FindingsThe findings indicate a low level of knowledge regarding the design and construction of ZCBs. To successfully deliver ZCBs, the study suggests that construction stakeholders must have their self-awareness increased, especially in improving knowledge of whole-of-life embodied carbon reduction. The governments and construction sectors should devote more effort to establishing training programmes and knowledge-sharing platforms to improve stakeholder knowledge in carbon literacy, building assessment methods, energy modelling and life cycle assessment.Originality/valueThe research implications may assist the real-world uptake of the ZCBs approach by offering academics and practitioners an insight into the ZCBs knowledge gaps.
Variations in strategic change cycle: Thailand's office board of investment, tri-county foundation and UN Women Egypt as case studies
Authors: Magued Shaimaa 
Published: February 2023

PurposeCombining two organizational change theories, life cycle and organizational development, this study examines how strategic change cycle has been adopted and implemented across three different organizations, a public organization, an NGO and an intergovernmental organization toward achieving their goals.Design/methodology/approachThis study triangulates three different qualitative research methods: open-ended semi-structured interviews conducted with UN Women Egypt's director, text analysis of the three organizations' websites and the discourse analysis of the Tri-County Foundation's leaders.FindingsStrategic change cycle has been differently formulated, adopted and implemented by the three organizations based on their goals, resources and contexts. While Office Board of Investment adopted a comprehensive reactive change, Tri-County Foundation followed a partial proactive transformation and UN Women Egypt developed a partial reactive strategy. Henceforth, public organizations and nonprofit organizations can develop different strategies of change in function of needs, resources, goals and context.Originality/valueThis study advances a theoretical framework on organizational change by integrating two theories, life cycle and organizational development, presenting four patterns of change: comprehensive reactive, comprehensive proactive, partial reactive and partial proactive.