bluuebunny/crossref_metadata_2025_split huggingface dataset:
Models of increased latent HIV reservoir turnover prior to cART initiation imply novel clearance strategies
Authors: Jagarapu Aditya , Mann Rajveer , Piovoso Michael J. , Zurakowski Ryan 
Published: June 2021

AbstractCD4+ T cells with a naive or memory phenotype carrying a replication-competent HIV provirus are recognized as the major component of the persistent HIV reservoir. These cells only minimally express viral protein, reducing viral cytotoxicity effects and making them difficult targets for immune responses as well as every available antiretroviral drug. In patients on suppressive antiretroviral therapy, the half-life of these cells is approximately 4-5 years, balanced by clonal expansion of the cells resulting in an overall reservoir half-life in excess of 40 years. A recent study has shown that prior to the initiation of antiretroviral therapy, the half-life of these cells is instead on the order of two weeks. We present two models explaining the wide disparity in the on- and off-treatment half-lives of the quiescent infected T cells. In the first model, generalized (antigen non-specific) immune activation due to the high HIV viral loads explains the high latent reservoir turnover rates in the absence of treatment. If this mechanism dominates, we demonstrate that reduction of the latent reservoir size is possible, either through the administration of exogenous antigen or through the use of timed treatment interruptions. In the second model, direct killing of reservoir cells by HIV drives the increased turnover off-treatment. If this mechanism dominates, modulation of the reservoir size is not possible by the methods described above. Previously published models of the immune response to HIV show the possibility of inducing post-treatment control by reducing the latent reservoir size; by incorporating the same immune response dynamics in our first model, it is shown that it may be possible to induce post-treatment control using either exogenous antigen administration or timed treatment interruptions.
RNA polymerases from Low G+C Gram Positive Bacteria
Authors: Miller Michael , Oakley Aaron J. , Lewis Peter J. 
Published: June 2021

SummaryThe low G+C Gram positive bacteria represent some of the most medically and industrially important microorganisms. They are relied on for the production of food and dietary supplements, enzymes and antibiotics, as well as being responsible for the majority of nosocomial infections and serving as a reservoir for antibiotic resistance. Control of gene expression in this group is more highly studied than in any bacteria other than the Gram negative model Escherichia coli, yet until recently no structural information on RNA polymerase (RNAP) from this group was available. This review will summarise recent reports on the high resolution structure of RNAP from the model low G+C representative Bacillus subtilis, including the role of auxiliary subunits δ and ε, and outline approaches for the development of antimicrobials to target RNAP from this group.
TRIB1 regulates tumour growth via controlling tumour-associated macrophage phenotypes and is associated with breast cancer survival and treatment response
Authors: Kim Taewoo , Johnston Jessica , Felipe Francisco J. C. , Hamby Stephen , Castillo-Lluva Sonia ,   The Cardiogenics Consortium, Goodall Alison H , Velasco Guillermo , Ocana Alberto , Muthana Munitta , Kiss-Toth Endre 
Published: June 2021

SummaryMolecular mechanisms that regulate tumour-associated macrophage (TAM) phenotype and function are incompletely understood. Here, we show that the pseudokinase TRIB1 is highly expressed by TAMs in breast cancer and that its expression correlates with response to chemotherapy and patient survival. We used immune-competent murine models of breast cancer to characterise the consequences of altered (reduced or elevated) myeloid Trib1 expression on tumour growth and composition of stromal immune cells. We found that both overexpression and knockout of myeloid Trib1 promote tumour growth, albeit through distinct molecular mechanisms. Myeloid Trib1 deficiency resulted in an early accelearation of tumour growth, paired with a selective reduction in perivascular macrophage numbers in vivo and enhanced oncogenic cytokine expression in vitro. In contrast, elevated levels of Trib1 in myeloid cells led to an increase in mammary tumour volume at late stages, together with a reduction of NOS2 expressing macrophages and an overall reduction of these cells in hypoxic tumour regions. In addition, we show that myeloid Trib1 is a previously unknown, negative regulator of the anti-tumour cytokine IL-15 and that increased expression of myeloid Trib1 leads to reduced IL-15 levels in mammary tumours, with a consequent reduction in the number of T-cells, that are key to anti-tumour immune responses.Together, these results define the different roles of TRIB1 in human breast cancer and provide a mechanistic understanding for the importance of myeloid TRIB1 expression levels in the development of this disease.SignificanceTRIB1 expression is strongly associated with response to chemotherapy in breast cancer patients with aggressive tumours. This protein is also highly expressed by tumour-associated macrophages. Thus, we used myeloid-specific alterations of Trib1 expression in mice (Trib1mKO and Trib1mTg), and characterised consequent changes in the growth rate and tumour microenvironment of mammary tumours. Both Trib1mKO and Trib1mTg enhanced tumour growth, but at different stages of tumour growth and via distinct mechanisms. Trib1mKO significantly increased the expression of oncogenic cytokines, such as IL6, IL10, CCL20, PD-L1, and VEGF. In contrast, Trib1mTg accelerated at the later stage of tumour growth via inhibition of hypoxic TAMs in the TME, as well as by reduced IL-15 expression thus leading to impaired naïve and cytotoxic T cell infiltration. These data define TRIB1 as a potential novel marker of therapeutic responses in breast cancer, as well as a key mechanistic regulator of the anti-tumour cytokine, IL-15 in myeloid cells.
DNA transposon expansion is associated with genome size increase in mudminnows
Authors: Lehmann Robert , Kovařík Aleš , Ocalewicz Konrad , Kirtiklis Lech , Zuccolo Andrea , Tegner Jesper N. , Wanzenböck Josef , Bernatchez Louis , Lamatsch Dunja K. , Symonová Radka 
Published: June 2021

AbstractGenome sizes of eukaryotic organisms vary substantially, with whole genome duplications (WGD) and transposable element expansion acting as main drivers for rapid genome size increase. The two North American mudminnows, Umbra limi and U. pygmaea, feature genomes about twice the size of their sister lineage Esocidae (e.g., pikes and pickerels). However, it is unknown whether all Umbra species share this genome expansion and which causal mechanisms drive this expansion. Using flow cytometry, we find that the genome of the European mudminnow is expanded similarly to both North American species, ranging between 4.5-5.4 pg per diploid nucleus. Observed blocks of interstitially located telomeric repeats in Umbra limi suggest frequent Robertsonian rearrangements in its history. Comparative analyses of transcriptome and genome assemblies show that the genome expansion in Umbra is driven by extensive DNA transposon expansion without WGD. Furthermore, we find a substantial ongoing expansion of repeat sequences in the Alaska blackfish Dallia pectoralis, the closest relative to the family Umbridae, which might mark the beginning of a similar genome expansion. Our study suggests that the genome expansion in mudminnows, driven mainly by transposon expansion, but not WGD, occurred before the separation into the American and European lineage.Significance StatementNorth American mudminnows feature genomes about twice the size of their sister lineage Esocidae (e.g., pikes and pickerels). However, neither the mechanism underlaying this genome expansion, nor whether this feature is shared amongst all mudminnows is currently known. Using cytogenetic analyses, we find that the genome of the European mudminnow also expanded and that extensive chromosome fusion events have occurred in some Umbra species. Furthermore, comparative genomics based on de-novo assembled transcriptomes and genome assemblies, which have recently become available, indicates that DNA transposon activity is responsible for this expansion.
Evidence of subjective, but not objective, cognitive deficit in new mothers at one-year postpartum
Authors: Orchard Edwina R , Ward Phillip GD , Egan Gary F , Jamadar Sharna D 
Published: June 2021

AbstractThe experience and even existence of cognitive deficits in the postpartum period is uncertain, with only a few scientific studies, reporting inconsistent results. Here we investigate cognition in 86 women (43 first-time mothers one year postpartum, and 43 non-mothers). Mothers and non-mothers showed no significant differences on measures of objective cognition (verbal memory, working memory, processing speed or theory of mind). Despite the absence of objective differences, mothers self-reported significantly worse subjective memory than non-mothers. To interpret the difference between objective and subjective measures of memory, we investigated relationships between subjective memory, objective memory, and wellbeing. Mothers, but not non-mothers, showed a positive correlation between subjective and objective measures of memory, indicating mothers are ‘in-tune’ with their memory performance. Mothers also demonstrated a positive relationship between subjective memory and wellbeing (sleep, anxiety and depression), where better wellbeing correlated with higher subjective memory. This relationship was not apparent in non-mothers. The results suggest that poorer sleep, higher anxiety and higher depression are related to reports of poorer self-reported memory in mothers. Our results add to our growing understanding of maternal cognition at one year postpartum, with no evidence of cognitive differences between mothers and non-mothers.
Lying in a 3T MRI Scanner Induces Neglect-Like Spatial Attention Bias
Authors: Lindner Axel , Wiesen Daniel , Karnath Hans-Otto 
Published: June 2021

SummaryThe static magnetic field of MRI scanners can induce a magneto-hydrodynamic stimulation of the vestibular organ (MVS). In common fMRI settings, this MVS effect leads to a vestibular ocular reflex (VOR). We asked whether – beyond inducing a VOR – putting a healthy subject in a 3T MRI scanner would also alter goal-directed spatial behavior, as is known from other types of vestibular stimulation. We investigated 17 healthy volunteers, all of which exhibited a rightward VOR inside the MRI-scanner as compared to outside-MRI conditions. More importantly, when probing the distribution of overt spatial attention inside the MRI using a visual search task, subjects scanned a region of space that was significantly shifted towards the right. An additional estimate of subjective straight-ahead orientation likewise exhibited an MVC-induced rightward shift. Hence, putting a subject in a 3T MRI-scanner induces a bias of spatial attention, which closely mimics that of stroke patients with spatial neglect.
Immuno-EM characterization of vasopressin neurons in macaques by use of formaldehyde-fixed tissues stored for several years
Authors: Otubo Akito , Maejima Sho , Oti Takumi , Satoh Keita , Ueda Yasumasa , Morris John F. , Sakamoto Tatsuya , Sakamoto Hirotaka 
Published: June 2021

AbstractTranslational research often requires the testing of experimental therapies in primates, but research in non-human primates is now stringently controlled by law around the world. Tissues fixed in formaldehyde without glutaraldehyde have been thought to be inappropriate for use in electron microscopic analysis, particularly those of the brain. Here we report the immunoelectron microscopic characterization of arginine vasopressin (AVP)-producing neurons in macaque hypothalamo-pituitary axis tissues fixed with 4% formaldehyde and stored at –25°C for several years. The size difference of dense-cored vesicles between magnocellular and parvocellular AVP neurons was detectable in their cell bodies and perivascular nerve endings located, respectively, in the posterior pituitary and median eminence. Furthermore, glutamate and the vesicular glutamate transporter 2 were colocalized with AVP in perivascular nerve endings of both the posterior pituitary and the external layer of the median eminence, suggesting that both magnocellular and parvocellular AVP neurons are glutamatergic in primates. Both ultrastructure and immunoreactivity can therefore be sufficiently preserved in macaque brain tissues stored long-term for light microscopy. Taken together, these results suggest that this methodology could be applied to the human post-mortem brain and be very useful in translational research.
In-vitro Reconstitution of Membrane Contact Sites between the Endoplasmic Reticulum and Lipid Droplets
Authors: Kamerkar Sukrut , Singh Jagjeet , Tripathy Subham , Bhonsle Hemangi , Kumar Mukesh , Mallik Roop 
Published: June 2021

ABSTRACTCoordinated cell function requires inter-organelle communication across Membrane Contact Sites (MCS). Here we deposit ER-enriched microsomes purified from rat liver or from cultured cells on a coverslip in the form of a continuous planar membrane. We visualize real-time protein and lipid exchanges across MCS that form between this ER-mimicking membrane and lipid droplets purified from rat liver. An Optical trap is used to demonstrate physical tethering of individual lipid droplets to the ER-mimicking membrane at MCS, and to directly measure the strength of this tether. In-vitro MCS formation changes dramatically in response to metabolic state and immune activation in the animal. Surprisingly, we find that the Rab18 GTPase and Phosphatidic acid are common molecular factors to control both of these pathways. This assay could possibly be adapted to interrogate MCS formation between other membranes (e.g. mitochondria, peroxisomes, endosomes etc.), and abnormalities therein that cause neurological, metabolic and pathogenic diseases.
Modelling Porcine NAFLD by Deletion of Leptin and defining the role of AMPK in hepatic fibrosis
Authors: Tan Tan , Song Zhiyuan , Wang Runming , Jiang Shuheng , Liang Zuoxiang , Wang Qi , Hu Xiaoxiang , Li Ning , Xing Yiming 
Published: June 2021

AbstractLiver fibrosis occurs during chronic liver disease. Advanced liver fibrosis results in cirrhosis, liver failure and often requires liver transplantation. However, due to the lack of human models, mechanisms underlining the pathogenesis of liver fibrosis remain unclear. Recent studies implicated a central role of deranged lipid metabolism in its pathogenesis. In this study, we generated LEPTIN-deficient (LEPTIN-/-) pigs using zinc finger nuclease technology to investigate the mechanisms of liver fibrosis associated with obesity. The LEPTIN-/- pigs showed increased body fat and significant insulin resistance by 12 months of age. To resemble non-alcoholic fatty liver disease (NAFLD) patients, LEPTIN-/- pig developed the phenotypic features of fatty liver, non-alcoholic steatohepatitis (NASH) and hepatic fibrosis with age. Meanwhile, LEPTIN absence reduced phosphorylation of JAK2-STAT3 and AMPK. The alteration of JAK2-STAT3 enhanced fatty acid β-oxidation, whereas inactivation of AMPK led to mitochondrial autophagy, and both contributed to increased oxidative stress in hepatocytes. Although Leptin deletion in the rat liver altered JAK2-STAT3 phosphorylation, it activated the AMPK pathway and prevented liver fibrogenesis in contrast with the LEPTIN-/- pig. To our knowledge, the LEPTIN-/- pig provides the first model recapitulating the full pathogenesis of NAFLD and its progression toward liver fibrosis. The activity of AMPK signaling pathway suggests a potential target for development of new strategies for the diagnosis and treatment of NAFLD.
Effects of early life adversity on immediate early gene expression: systematic review and 3-level meta-analysis of rodent studies
Authors: Schuler Heike , Bonapersona Valeria , Joëls Marian , Sarabdjitsingh R. Angela 
Published: June 2021

AbstractEarly-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced multiple negative life events. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naïve, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.
Organizational career management and turnover intentions: mediating role of trust in management
Authors: Haridas Jyothilakshmy , Ture Rameshwar Shivadas , Nayanpally Ajith Kumar 
Published: June 2021

PurposeThe contemporary career development models argued more for self-management of careers, yet few researchers emphasized importance of organizational career management. The purpose of this paper is to check association between perceived organizational career management practices, trust in management and turnover intentions.Design/methodology/approachIn this study, authors proposed a model based on social exchange theory. Data for this study were collected from 405 IT professionals employed in India. The proposed model was tested using structural equation modelling.FindingsResults showed significant direct and indirect negative effect of perceived informal organizational career management on turnover intention. In case of perceived formal organizational career management only indirect effect was significant. Trust in management mediated relationship between both types of organizational career management and turnover intentions.Originality/valueFirst, this study delineated effect of formal and informal perceived organizational career management practices on turnover intentions. Second, this study introduced trust in management as mediator to explain relationship between organizational career management practice and outcome.
The curvilinear relationship between servant leadership and work-family conflict: the moderating role of age in Chinese female workers
Authors: Xie Lei , Qiu Shaoping , Bian Xinyi 
Published: June 2021

Purpose
Building on social exchange theory and selection, optimization and compensation theory, this study aims to examine a moderated curvilinear relationship between servant leadership (SL) and work-family conflict (WFC).

Design/methodology/approach
Participants were 329 female workers recruited from a Chinese small business in the service Industry. A three-step hierarchical regression was conducted to examine the relationships among the variables and the incremental contribution of SL and age and the squared term of SL.

Findings
Study results confirmed a curvilinear relationship between SL and WFC and the moderating effect of age. When younger female employees perceived a moderate range of SL from their supervisors, they reported higher WFC compared to the low or high level of perceived SL. On the contrary, senior female employees reported a lower level of WFC when they perceived a moderate level of SL than when they perceived very low or high levels.

Originality/value
SL research has experienced a period of exponential growth in the past decade. This study advanced the field of leadership by arguing that SL perceived by female employees is curvilinearly related to WFC and the curvilinear relationship is moderated by age.
Destination image through social media analytics and survey method
Authors: Lin Michael S. , Liang Yun , Xue Joanne X. , Pan Bing , Schroeder Ashley 
Published: June 2021

Purpose
Recent tourism research has adopted social media analytics (SMA) to examine tourism destination image (TDI) and gain timely insights for marketing purposes. Comparing the methodologies of SMA and intercept surveys would provide a more in-depth understanding of both methodologies and a more holistic understanding of TDI than each method on their own. This study aims to investigate the unique merits and biases of SMA and a traditional visitor intercept survey.

Design/methodology/approach
This study collected and compared data for the same tourism destination from two sources: responses from a visitor intercept survey (n = 1,336) and Flickr social media photos and metadata (n = 11,775). Content analysis, machine learning and text analysis techniques were used to analyze and compare the destination image represented from both methods.

Findings
The results indicated that the survey data and social media data shared major similarities in the identified key image phrases. Social media data revealed more diverse and more specific aspects of the destination, whereas survey data provided more insights in specific local landmarks. Survey data also included additional subjective judgment and attachment towards the destination. Together, the data suggested that social media data should serve as an additional and complementary source of information to traditional survey data.

Originality/value
This study fills a research gap by comparing two methodologies in obtaining TDI: SMA and a traditional visitor intercept survey. Furthermore, within SMA, photo and metadata are compared to offer additional awareness of social media data’s underlying complexity. The results showed the limitations of text-based image questions in surveys. The findings provide meaningful insights for tourism marketers by having a more holistic understanding of TDI through multiple data sources.
Investigating factors that influence Malaysian auditors’ ethical sensitivity
Authors: Johari Razana Juhaida , Alam Md. Mahmudul , Said Jamaliah 
Published: June 2021

Purpose
The primary role of auditors is to offer fiduciary services to society and users of financial reporting. With this role, users placed their trust and depend on the ability and judgement made by the auditors during their auditing works. However, recent financial scandals involving high profile companies frustrated the public’s expectations, particularly in Malaysia. It is claimed that auditors are not having ethical sensitivity while executing their task in mitigating fraudulent financial reporting. Therefore, this study aims to examine the influences of ethical orientation, locus of control and the firm’s ethical culture on the auditors’ ethical sensitivity in Malaysia.

Design/methodology/approach
This study collected primary data based on a questionnaire survey among audit firms in the Klang Valley area and registered with Malaysian Institutes of Accountants.

Findings
The results showed ethical sensitivity has a significant negative relationship with relativism and in some cases has a significant positive relationship with idealism. Moreover, it found a significant positive relationship between ethical sensitivity and ethical culture.

Originality/value
This paper provides benefit to the audit firms, professional bodies, policymakers and academia in understanding the factors that might increase the sensitivity of auditors in dealing with ethical issues that could lead to fraudulent financial reporting in the company.