bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population fraction of Parkinson’s disease attributable to preventable risk factors
Authors: Payami Haydeh , Cohen Gwendolyn , Murchison Charles F , Sampson Timothy R , Standaert David G , Wallen Zachary D 
Published: May 2023

AbstractParkinson’s disease is the fastest growing neurologic disease with seemingly no means for prevention. Intrinsic risk factors (age, sex, genetics) are inescapable, but environmental factors are not. We studied population attributable fraction and estimated fraction of PD that could be reduced if modifiable risk factors were eliminated. Assessing several known risk factors simultaneously in one study, we demonstrate that all were operative and independent, underscoring etiological heterogeneity within a single population. We investigated repeated blows to head in sports or combat as a potential new risk factor, and found it was associated with two-fold increased risk of PD. Considering modifiable risk factors, 23% of PD cases in females were attributable to pesticides/herbicides exposure, and 30% of PD cases in males was attributable to pesticides/herbicides, Agent Orange/chemical warfare, and repeated blows to the head. Thus, one-in-three cases of PD in males, and one-in-four cases in females could have potentially been prevented.
HepG2 cells with knockouts ofCYP51A1,DHCR24orSC5Dfrom cholesterol synthesis accumulate sterols influencing distinct regulatory pathways
Authors: Skubic Cene , Trček Hana , Nassib Petra , Walakira Andrew , Pohar Katka , Petek Sara , Režen Tadeja , Ihan Alojz , Rozman Damjana 
Published: May 2023

ABSTRACTSterol intermediates of cholesterol synthesis are largely dedicated to cholesterol. Here we assess how they influence downstream gene regulatory pathways by developing knockouts (KOs) for consecutive enzymes of cholesterol synthesis in human hepatoma HepG2 cells. The KO ofCYP51,DHCR24, andSC5Dled to the build-up of specific sterols. The shared differentially expressed genes accounted for only 9% with regards to steroid metabolism and proliferation control, with majority of pathways changed in just one KO. TheCYP51KO cells with highly elevated 24,25-dihydrolanosterol exhibited a significant increase in G2+M phase along with enhanced cancer and cell cycle pathways, likely driven by elevated LEF1 through modulation of WNT/NFKB signalling. In contrast,SC5DandDHCR24KO cells with elevated lathosterol or desmosterol, slowed cell proliferation and promoted apoptosis with downregulated E2F, mitosis, cell cycle transition, and enriched HNF1A tumor suppressor. These findings demonstrate that sterols from cholesterol synthesis control distinct gene regulatory pathways, while only early sterols can promote cell proliferation.
Autoreactive B cells in rheumatoid arthritis consist of activated CXCR3+ memory B cells and plasmablasts
Authors: Reijm Sanne , Kwekkeboom Joanneke C. , Blomberg Nienke J. , Suurmond Jolien , van der Woude Diane , Toes Rene E.M. , Scherer Hans U. 
Published: May 2023

AbstractMany autoimmune diseases (AIDs) are characterized by persistence of autoreactive B cell responses which is often directly implicated in disease pathogenesis. How and why these cells are generated or how they are maintained for years is largely unknown. Rheumatoid arthritis is among the most common AIDs and characterized by autoantibodies recognizing proteins with post-translational modifications (PTMs). This PTM-directed, autoreactive B cell compartment is ill defined. Here, we visualized the B cell response against the three main types of PTM antigens implicated in RA by spectral flow cytometry. Our results show extensive cross-reactivity of autoreactive B cells against all three PTM antigens (citrulline, homocitrulline and acetyllysine). Unsupervised clustering revealed several distinct memory B cell (mBC) populations. Autoreactive cells clustered with the most recently activated, class-switched mBC phenotype, expressing high CD80, low CD24 and low CD21. Notably, patients also harbored large fractions of autoreactive plasmablasts (PB). Both PTM-directed mBC and PB showed high expression of CXCR3, a receptor for chemokines abundantly present in arthritic joints. Together, our data provide novel, detailed insight into the biology of B cell autoreactivity and its remarkable, seemingly exhaustless persistence in a prominent human AID.
Incorporating uncertainty within dynamic interoceptive learning
Authors: Brand Katja , Wise Toby , Hess Alexander J. , Russell Bruce R. , Stephan Klaas E. , Harrison Olivia K. 
Published: May 2023

ABSTRACTInteroception, the perception of the internal state of the body, has been shown to be closely linked to emotions and mental health. Of particular interest are interoceptive learning processes that capture associations between environmental cues and body signals as a basis for making homeostatically relevant predictions about the future. Here we extended an interoceptive Breathing Learning Task (BLT) to incorporate continuous measures of prediction certainty, and tested its application using a Rescorla Wagner (RW) associative learning model. Sixteen healthy participants completed the continuous version of the BLT, where they were asked to predict the likelihood of breathing resistances. The task was modified from a previous version and required continuous, rather than binary predictions, in order to include a more precise measure of prediction certainty. The RW model was used to fit a learning rate to each participant’s continuous and binarised predictions, and was additionally extended to test whether learning rates differed according to stimuli valence. The empirical task data demonstrated excellent replicability compared to previously collected data using binary predictions, and the continuous model fits closely captured participant behaviour at the group level. The model extension to estimate different learning rates for negative (i.e. breathing resistance) and positive (i.e. no breathing resistance) trials indicated that learning rates did not significantly differ according to stimuli nature. Furthermore, examining the relationship between estimates of prediction certainty and learning rates with interoceptive and mental health questionnaires demonstrated that fatigue severity was related to both prediction certainty and learning rate, and anxiety sensitivity was related to prediction certainty. The updated task and model show promise for future investigations into interoceptive learning and potential links to mental health.
A Hypothalamic Circuit Underlying the Dynamic Control of Social Homeostasis
Authors: Liu Ding , Rahman Mostafizur , Johnson Autumn , Tsutsui-Kimura Iku , Pena Nicolai , Talay Mustafa , Logeman Brandon L. , Finkbeiner Samantha , Choi Seungwon , Capo-Battaglia Athena , Abdus-Saboor Ishmail , Ginty David D. , Uchida Naoshige , Watabe-Uchida Mitsuko , Dulac Catherine 
Published: May 2023

SummarySocial grouping increases survival in many species, including humans1,2. By contrast, social isolation generates an aversive state (loneliness) that motivates social seeking and heightens social interaction upon reunion3-5. The observed rebound in social interaction triggered by isolation suggests a homeostatic process underlying the control of social drive, similar to that observed for physiological needs such as hunger, thirst or sleep3,6. In this study, we assessed social responses in multiple mouse strains and identified the FVB/NJ line as exquisitely sensitive to social isolation. Using FVB/NJ mice, we uncovered two previously uncharacterized neuronal populations in the hypothalamic preoptic nucleus that are activated during social isolation and social rebound and that orchestrate the behavior display of social need and social satiety, respectively. We identified direct connectivity between these two populations of opposite function and with brain areas associated with social behavior, emotional state, reward, and physiological needs, and showed that animals require touch to assess the presence of others and fulfill their social need, thus revealing a brain-wide neural system underlying social homeostasis. These findings offer mechanistic insight into the nature and function of circuits controlling instinctive social need and for the understanding of healthy and diseased brain states associated with social context.
Restoration of mitochondrial structure and function withinHelicobacter pyloriVacA intoxicated cells
Authors: Holland Robin L. , Bosi Kristopher D. , Seeger Ami , Blanke Steven R. 
Published: May 2023

ABSTRACTTheHelicobacter pylorivacuolating cytotoxin (VacA) is an intracellular, mitochondrial-targeting exotoxin that rapidly causes mitochondrial dysfunction and fragmentation. Although VacA targeting of mitochondria has been reported to alter overall cellular metabolism, there is little known about the consequences of extended exposure to the toxin. Here, we describe studies to address this gap in knowledge, which have revealed that mitochondrial dysfunction and fragmentation are followed by a time-dependent recovery of mitochondrial structure, mitochondrial transmembrane potential, and cellular ATP levels. Cells exposed to VacA also initially demonstrated a reduction in oxidative phosphorylation, as well as increase in compensatory aerobic glycolysis. These metabolic alterations were reversed in cells with limited toxin exposure, congruent with the recovery of mitochondrial transmembrane potential and the absence of cytochromecrelease from the mitochondria. Taken together, these results are consistent with a model that mitochondrial structure and function are restored in VacA-intoxicated cells.
Prognostic Gene Signature for lung adenocarcinoma with a Higher Risk for Treatment Failure and Accelerated cell cycle and cell proliferation Pathway Activity
Authors: Li Zhen-Qing , Li Zheng , Meng Yu-Qi , Li Xuan , Zhai Ke-Rong , Wei Shi-Lin , Li Bin 
Published: May 2023

AbstractLung cancer is the most common of malignant cancers which represents poor prognosis and high invasive. However, the reliable prognosis genes signature and the differential between the genetic and epigenetic are remain unclear. Here, we confirmed 78 genes of signature A to construct a model to predicted the prognosis and the activity of tumorigenesis-related pathways. The score based on the 78 genes expression is high correlation with the cell cycle and cell proliferation activity. Based on the median of score, the lung adenocarcinoma patients were divided into two cohorts which presents different prognosis, tumorigenesis-related pathways activity. The high score group was enriched in the E2F target, mtorc1 signaling and MYC targets. The low score group can be identified as better prognosis subtype. Also, we used the GDSC data to predicted the PIM inhibitor (AZD1208) as the effective compounds for high score group patients, which is supported by a higher PIM1 and PIM2 expression in the score group. An integrative analysis of multi-omics data identified ECT2 as key nodes in a regulatory network related to the prognostic phenotype. In conclusion, our data identified a molecular classifier for the different score groups patients, and the high score group patients might benefit from treatment with PIM inhibitor.
Functional brain connectivity during social attention predicts individual differences in social skill
Authors: Brindley Samantha R. , Skyberg Amalia M. , Graves Andrew J. , Connelly Jessica J. , Puglia Meghan H. , Morris James P. 
Published: May 2023

AbstractSocial attention involves selectively attending to and encoding socially relevant information. We investigated the neural systems underlying the wide range of variability in both social attention ability and social experience in a neurotypical sample. Participants performed a selective social attention task while undergoing fMRI and completed self-report measures of social functioning. Using connectome-based predictive modeling, we demonstrated that individual differences in whole-brain functional connectivity patterns during selective attention to faces predicted task performance. Individuals with more cerebellar-occipital connectivity performed better on the social attention task, suggesting more efficient social information processing. Then, we estimated latent communities of autistic and socially anxious traits using exploratory graph analysis to decompose heterogeneity in social functioning between individuals. Connectivity strength within the identified social attention network was associated with social skills, such that more temporal-parietal connectivity predicted fewer challenges with social communication and interaction. These findings demonstrate that individual differences in functional connectivity strength during a selective social attention task are related to varying levels of self-reported social skill.
Prime editing of the β1adrenoceptor in the brain reprograms mouse behavior
Authors: Böck Desirée , Tidecks Lisa , Wilhelm Maria , Weber Yanik , Ioannidi Eleonora , Mumenthaler Jonas , Rothgangl Tanja , Schmidheini Lukas , Janjuha Sharan , Patriarchi Tommaso , Schwank Gerald 
Published: May 2023

SummaryPrime editing is a highly versatile genome editing technology that holds great potential for treating genetic diseases1, 2. Whilein vivoprime editing has recently been conducted in the brain, liver, heart, and retina3–6, application of this technology to modulate neural circuits in the brain has not been reported yet. Here, we employ adeno-associated viral vectors to deliver optimized intein-split prime editors into the brain of mice. Delivery into newborn pups via intracerebroventricular injection resulted in up to 44.0% editing at theDnmt1locus in the cortex (on average 34.8±9.8% after 6 months). In addition, we obtained up to 28.1% editing at theAdrb1locus in the cortex (on average 14.7±11.6% after 6 months). The introducedAdrb1A187Vmutation is a naturally occurring variant of the β1-adrenergic receptor, which has previously been linked to increased activity and natural short sleep7. Similarly, we observed an increase in the activity and exploratory behavior of treated animals. This study demonstrates the potential of prime editing for treating genetic diseases in the central nervous system and for reprogramming molecular pathways that modulate animal behavior.
Molecular archaeology: individual human DNA and infection profiles from 100 year old mosquitoes
Authors: Crombe Florence , Nagi Sanjay C , Tomás Elsa VE , Charlwood J. Derek , Donnelly Martin J , Weetman David 
Published: May 2023

AbstractNatural history collections represent a vast biological and genetic resource, which has remained largely untapped. We revisit mosquito collections of varying ages; some made by early tropical medicine pioneers over 100 years ago. By applying species-specific primers, a panel of forensic short tandem repeat (STR) markers, andPlasmodiumdiagnostics, we were able to obtain the unique genetic profile andPlasmodiuminfection status of the individual from whom each mosquito obtained their final bloodmeal. We show evidence of long-dead mosquitoes feeding on multiple individuals in the same gonotrophic cycle, and how the human hosts are likely to have been infected with malaria at the time of blood-feeding. This approach may be used to track the host-fidelity of vectors over an evolutionary time scale.
MutantPpbbx24-delgene positively regulates light-induced anthocyanin accumulation in the red pear
Authors: Li Shuran , Ou Chunqing , Wang Fei , Zhang Yanjie , Ismail Omayma , Elaziz Yasser S.G. Abd , Edris Sherif , Jiang Shuling , Li He 
Published: May 2023

AbstractAnthocyanins are pigments and nutrients in red pears regulated by BBX family genes. Herein, we characterized a 14-nucleotide deletion mutation in the coding region of thePpBBX24gene from ‘Red Zaosu’ pear (Pyrus pyrifoliaWhite Pear Group), namedPpbbx24-del. Genetic and biochemical approaches were used to compare the roles of PpBBX24 and Ppbbx24-del in anthocyanin accumulation.Ppbbx24-delplayed a positive role in anthocyanin biosynthesis of the ‘Red Zaosu’ pear peel by light treatment. Functional analyses based on overexpression in tobacco and transient overexpression in pear fruit peels showed thatPpbbx24-delpromoted anthocyanin accumulation. Cyanidin and peonidin were major differentially expressed anthocyanins, and transcript levels of some structural genes in the anthocyanin biosynthesis pathway were significantly increased. Protein interaction assays showed that PpBBX24 was located in the nucleus and interacted with PpHY5, whereas Ppbbx24-del was colocalized in the nucleoplasm and did not interact with PpHY5. PpHY5 and Ppbbx24-del had positive regulatory effects on the expression ofPpCHS,PpCHI, andPpMYB10when acting alone, but had cumulative effects on gene activation when acting simultaneously. Alone, PpBBX24 had no significant effect on the expression ofPpCHS,PpCHI, orPpMYB10, whereas it inhibited the activation effects of PpHY5 on downstream genes when it existed with PpHY5. Our study demonstrated that mutant Ppbbx24-del positively regulates the anthocyanin accumulation in pear. The results of this study clarify the mechanism and enrich the regulatory network of anthocyanin biosynthesis, which lays a theoretical foundation forPpbbx24-deluse to create red pear cultivars.
Buyer–supplier collaboration's commitment. An antecedent for procurement performance of large manufacturing entities in Tanzania
Authors: Kimario Honest F. , Mwagike Leonada R. 
Published: May 2023

PurposeThis study was steered to establish how buyer–supplier collaboration's commitment attributes serve as an antecedent for procurement performance in large manufacturing entities in Tanzania.Design/methodology/approachA parallel, concurrent, mixed method was used in the study. Quantitatively, 52 firms were surveyed from Temeke Municipality, Tanzania, using questionnaire that specified 1 procurement manager and 1 store manager from those firms, totaling a sample size of 104 respondents. Qualitatively, expressive opinions to supplement the numeric data were gathered from supply chain managers using the saturation principle. Explanatory design analyzed the existing cause–effect relationship, and the null hypotheses were tested using binary logistic regression at p values < 0.05 and ExpB > 1.FindingsFidelity and enthusiasm to suggest improvements to suppliers and the duration of the collaboration antecede the procurement performance of the manufacturing firms in Tanzania, while devotion to invest resources and initiatives on joint problem solving have no significant impact.Research limitations/implicationsThe causality between buyer–supplier collaboration and procurement performance has been revealed. Since there might be third party logistics in collaborations, future research should center on their moderating effect.Practical implicationsA framework has been developed for liberating procurement performance in the context of large manufacturing firms in Tanzania.Originality/valueBased on Transaction Cost Economics and Resource Dependency Theories, the study revealed the root cause of procurement performance in the context of Tanzanian manufacturing firms, while also considering commitment to buyer–supplier collaboration as a prerequisit for the commendable target.
The directional spillover effects and time-frequency nexus between stock markets, cryptocurrency, and investor sentiment during the COVID-19 pandemic
Authors: Soltani Hayet , Taleb Jamila , Boujelbène Abbes Mouna 
Published: May 2023

PurposeThis paper aims to analyze the connectedness between Gulf Cooperation Council (GCC) stock market index and cryptocurrencies. It investigates the relevant impact of RavenPack COVID sentiment on the dynamic of stock market indices and conventional cryptocurrencies as well as their Islamic counterparts during the onset of the COVID-19 crisis.Design/methodology/approachThe authors rely on the methodology of Diebold and Yilmaz (2012, 2014) to construct network-associated measures. Then, the wavelet coherence model was applied to explore co-movements between GCC stock markets, cryptocurrencies and RavenPack COVID sentiment. As a robustness check, the authors used the time-frequency connectedness developed by Barunik and Krehlik (2018) to verify the direction and scale connectedness among these markets.FindingsThe results illustrate the effect of COVID-19 on all cryptocurrency markets. The time variations of stock returns display stylized fact tails and volatility clustering for all return series. This stressful period increased investor pessimism and fears and generated negative emotions. The findings also highlight a high spillover of shocks between RavenPack COVID sentiment, Islamic and conventional stock return indices and cryptocurrencies. In addition, we find that RavenPack COVID sentiment is the main net transmitter of shocks for all conventional market indices and that most Islamic indices and cryptocurrencies are net receivers.Practical implicationsThis study provides two main types of implications: On the one hand, it helps fund managers adjust the risk exposure of their portfolio by including stocks that significantly respond to COVID-19 sentiment and those that do not. On the other hand, the volatility mechanism and investor sentiment can be interesting for investors as it allows them to consider the dynamics of each market and thus optimize the asset portfolio allocation.Originality/valueThis finding suggests that the RavenPack COVID sentiment is a net transmitter of shocks. It is considered a prominent channel of shock spillovers during the health crisis, which confirms the behavioral contagion. This study also identifies the contribution of particular interest to fund managers and investors. In fact, it helps them design their portfolio strategy accordingly.
Genetic algorithm modeling of European Union firms' competitive advantage
Authors: Dias Alexandre Teixeira , Martins Henrique Cordeiro , Santos Valdeci Ferreira , Verga Matos Pedro , Morais Greiciele Macedo 
Published: May 2023

PurposeThis research aims to identify the optimal configuration of investment which leads firms to their best competitive positions, considering the degree of concentration in the market.Design/methodology/approachThe methodology was quantitative and based on secondary data with samples of 124, 106 and 90 firms from competitive environment classified as perfect competition, monopolistic competition and oligopoly, respectively. Proposed models' parameters were estimated by means of genetic algorithms.FindingsAdjustments on firm's investment are contingent on the degree of competition they face. Results are in line with existing academic research affirmation that the purpose of investments is to create and exploit opportunities for positive economic rents and that investments allow firms to protect from rivals' competitive actions and reinforce the need for investment decision makers to consider the environment in which the firm is competing, when defining the amount of investment that must be done to achieve and maintain a favorable competitive advantage position.Originality/valueThis research brings two main original contributions. The first one is the identification of the optimal amount of capital and R&D investments which leads firms to their best competitive positions, contingent to the degree of concentration of the competitive environment in which they operate, and the size of the firm. The second one is related to the use of genetic algorithms to estimate optimization models that considers the three competitive environments studied (perfect competition, monopolistic competition and oligopoly) and the investment variables in the linear and quadratic forms.