bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amyloid-β toxicity modulates tau phosphorylation through the PAX6 signalling pathway
Authors: Zhang Yalun , Zhang Yi , Aman Yahyah , Ng Cheung Toa , Chau Wing-Hin , Zhang Zhigang , Yue Ming , Bohm Christopher , Jia Yizhen , Li Siwen , Yuan Qiuju , Griffin Jennifer , Chiu Kin , Wong Dana S M , Wang Binbin , Jin Dongyan , Rogaeva Ekaterina , Fraser Paul E , Fang Evandro F , St George-Hyslop Peter , Song You-Qiang 
Published: June 2021

Abstract
The molecular link between amyloid-β plaques and neurofibrillary tangles, the two pathological hallmarks of Alzheimer’s disease, is still unclear. Increasing evidence suggests that amyloid-β peptide activates multiple regulators of cell cycle pathways, including transcription factors CDKs and E2F1, leading to hyperphosphorylation of tau protein. However, the exact pathways downstream of amyloid-β-induced cell cycle imbalance are unknown. Here, we show that PAX6, a transcription factor essential for eye and brain development which is quiescent in adults, is increased in the brains of patients with Alzheimer’s disease and in APP transgenic mice, and plays a key role between amyloid-β and tau hyperphosphorylation. Downregulation of PAX6 protects against amyloid-β peptide-induced neuronal death, suggesting that PAX6 is a key executor of the amyloid-β toxicity pathway. Mechanistically, amyloid-β upregulates E2F1, followed by the induction of PAX6 and c-Myb, while Pax6 is a direct target for both E2F1 and its downstream target c-Myb. Furthermore, PAX6 directly regulates transcription of GSK-3β, a kinase involved in tau hyperphosphorylation and neurofibrillary tangles formation, and its phosphorylation of tau at Ser356, Ser396 and Ser404. In conclusion, we show that signalling pathways that include CDK/pRB/E2F1 modulate neuronal death signals by activating downstream transcription factors c-Myb and PAX6, leading to GSK-3β activation and tau pathology, providing novel potential targets for pharmaceutical intervention.
Action Observation Responses Are Influenced by Movement Kinematics and Target Identity
Authors: Savaki Helen E , Kavroulakis Eleftherios , Papadaki Efrosini , Maris Thomas G , Simos Panagiotis G 
Published: June 2021

AbstractIn order to inform the debate whether cortical areas related to action observation provide a pragmatic or a semantic representation of goal-directed actions, we performed 2 functional magnetic resonance imaging (fMRI) experiments in humans. The first experiment, involving observation of aimless arm movements, resulted in activation of most of the components known to support action execution and action observation. Given the absence of a target/goal in this experiment and the activation of parieto-premotor cortical areas, which were associated in the past with direction, amplitude, and velocity of movement of biological effectors, our findings suggest that during action observation we could be monitoring movement kinematics. With the second, double dissociation fMRI experiment, we revealed the components of the observation-related cortical network affected by 1) actions that have the same target/goal but different reaching and grasping kinematics and 2) actions that have very similar kinematics but different targets/goals. We found that certain areas related to action observation, including the mirror neuron ones, are informed about movement kinematics and/or target identity, hence providing a pragmatic rather than a semantic representation of goal-directed actions. Overall, our findings support a process-driven simulation-like mechanism of action understanding, in agreement with the theory of motor cognition, and question motor theories of action concept processing.
Differential Effects of the Inactivation of Anterior and Posterior Orbitofrontal Cortex on Affective Responses to Proximal and Distal Threat, and Reward Anticipation in the Common Marmoset
Authors: Stawicka Zuzanna M , Massoudi Roohollah , Oikonomidis Lydia , McIver Lauren , Mulvihill Kevin , Quah Shaun K L , Cockcroft Gemma J , Clarke Hannah F , Horst Nicole K , Wood Christian M , Roberts Angela C 
Published: June 2021

Abstract
Structural and functional abnormalities of the orbitofrontal cortex (OFC) have been implicated in affective disorders that manifest anxiety-related symptoms. However, research into the functions of primate OFC has predominantly focused on reward-oriented rather than threat-oriented responses. To redress this imbalance, the present study performed a comprehensive analysis of the independent role of 2 distinct subregions of the central OFC (anterior area 11; aOFC and posterior area 13; pOFC) in the processing of distal and proximal threat. Temporary inactivation of both aOFC and pOFC heightened responses to distal threat in the form of an unknown human, but not to proximal threat assessed in a discriminative Pavlovian conditioning task. Inactivation of the aOFC, however, did unexpectedly blunt conditioned threat responses, although the effect was not valence-specific, as conditioned appetitive responses were similarly blunted and appeared restricted to a discriminative version of the task (when both CS− and CS+ are present within a session). Inactivation of the pOFC did not affect conditioned responses to either proximal threat or reward and basal cardiovascular activity was unaffected by manipulations of activity in either subregion. The results highlight the contribution of aOFC and pOFC to regulation of responses to more distal uncertain but not proximal, certain threat and reveal their opposing contribution to that of the immediately adjacent medial OFC, area 14.
Rpsa Signaling Regulates Cortical Neuronal Morphogenesis via Its Ligand, PEDF, and Plasma Membrane Interaction Partner, Itga6
Authors: Blazejewski Sara M , Bennison Sarah A , Ha Ngoc T , Liu Xiaonan , Smith Trevor H , Dougherty Kimberly J , Toyo-Oka Kazuhito 
Published: June 2021

Abstract
Neuromorphological defects underlie neurodevelopmental disorders and functional defects. We identified a function for Rpsa in regulating neuromorphogenesis using in utero electroporation to knockdown Rpsa, resulting in apical dendrite misorientation, fewer/shorter extensions, and decreased spine density with altered spine morphology in upper neuronal layers and decreased arborization in upper/lower cortical layers. Rpsa knockdown disrupts multiple aspects of cortical development, including radial glial cell fiber morphology and neuronal layering. We investigated Rpsa’s ligand, PEDF, and interacting partner on the plasma membrane, Itga6. Rpsa, PEDF, and Itga6 knockdown cause similar phenotypes, with Rpsa and Itga6 overexpression rescuing morphological defects in PEDF-deficient neurons in vivo. Additionally, Itga6 overexpression increases and stabilizes Rpsa expression on the plasma membrane. GCaMP6s was used to functionally analyze Rpsa knockdown via ex vivo calcium imaging. Rpsa-deficient neurons showed less fluctuation in fluorescence intensity, suggesting defective subthreshold calcium signaling. The Serpinf1 gene coding for PEDF is localized at chromosome 17p13.3, which is deleted in patients with the neurodevelopmental disorder Miller–Dieker syndrome. Our study identifies a role for Rpsa in early cortical development and for PEDF-Rpsa-Itga6 signaling in neuromorphogenesis, thus implicating these molecules in the etiology of neurodevelopmental disorders like Miller–Dieker syndrome and identifying them as potential therapeutics.
Predictors of Cell-Associated Human Immunodeficiency Virus (HIV)-1 DNA Over 1 Year in Very Early Treated Infants
Authors: Kuhn Louise , Paximadis Maria , Da Costa Dias Bianca , Shen Yanhan , Mncube Sizanani , Strehlau Renate , Shiau Stephanie , Patel Faeezah , Burke Megan , Technau Karl-Günter , Sherman Gayle , Loubser Shayne , Abrams Elaine J , Tiemessen Caroline T 
Published: June 2021

Abstract

Background
Younger age of antiretroviral therapy (ART) initiation is associated with smaller viral reservoirs in perinatally acquired HIV-1 infection, but there is wide variability among early-treated infants. Predictors of this variability are not fully described.

Methods
Sixty-three neonates diagnosed with HIV-1 &lt;48 hours after birth in Johannesburg, South Africa, were started on ART as soon as possible. Fifty-nine (94%) infants received nevirapine prophylaxis from birth until ART start. Viably preserved peripheral blood mononuclear cells (PBMCs) collected at regular intervals to 48 weeks, and from mothers at enrollment, were tested using integrase-targeted, semi-nested, real-time quantitative hydrolysis probe (TaqMan) PCR assays to quantify total HIV-1 subtype C viral DNA (vDNA). Predictors were investigated using generalized estimating equation regression.

Results
Thirty-one (49.2%) infants initiated ART &lt;48 hours, 24 (38.1%) &lt;14 days, and 8 (12.7%) &gt;14 days of birth. Three-quarters were infected despite maternal antenatal ART (however, only 9.5% of women had undetectable viral load closest to delivery) and 86% were breastfed. Higher infant CD4+ T-cell percentage and viral load &lt;100 000 copies/mL pre-ART were associated with lower vDNA in the first 48 weeks after ART start. No antenatal maternal ART and breastfeeding were also associated with lower vDNA. Older age at ART initiation had a discernible negative impact when initiated &gt;14 days.

Conclusions
Among very early treated infants, higher CD4+ T-cell percentage and viral load &lt;100 000 copies/mL pre-ART, infection occurring in the absence of maternal antenatal ART, and breastfeeding were associated with lower levels of HIV-1 DNA in the first 48 weeks of treatment.
Clinical Trials Registration. clinicaltrials.gov (NCT02431975).
How to modulate the formation of negative volatile sulfur compounds during wine fermentation?
Authors: Jimenez-Lorenzo Rafael , Bloem Audrey , Farines Vincent , Sablayrolles Jean-Marie , Camarasa Carole 
Published: June 2021

ABSTRACTBeyond the production of positive aromas during alcoholic fermentation, Saccharomyces cerevisiae metabolism also results in the formation of volatile compounds detrimental to wine quality, including a wide range of volatile sulfur compounds (VSCs). The formation of these VSCs during wine fermentation is strongly variable and depends on biological and environmental factors. First, the comparison of the VSCs profile of 22 S. cerevisiae strains provided a comprehensive overview of the intra-species diversity in VSCs production: according to their genetic background, strains synthetized from 1 to 6 different sulfur molecules, in a 1- to 30-fold concentration range. The impact of fermentation parameters on VSCs production was then investigated. We identified yeast assimilable nitrogen, cysteine, methionine and pantothenic acid contents – but not SO2 content – as the main factors modulating VSCs production. In particular, ethylthioacetate and all the VSCs deriving from methionine catabolism displayed a maximal production at yeast assimilable nitrogen concentrations around 250 mg/L; pantothenic acid had a positive impact on compounds deriving from methionine catabolism through the Ehrlich pathway but a negative one on the production of thioesters. Overall, these results highlight those factors to be taken into account to modulate the formation of negative VSCs and limit their content in wines.
Evolution of recombination landscapes in diverging populations of bread wheat
Authors: Danguy des Déserts Alice , Bouchet Sophie , Sourdille Pierre , Servin Bertrand 
Published: June 2021

Abstract
Reciprocal exchanges of DNA (crossovers) that occur during meiosis are mandatory to ensure the production of fertile gametes in sexually reproducing species. They also contribute to shuffle parental alleles into new combinations thereby fuelling genetic variation and evolution. However, due to biological constraints, the recombination landscape is highly heterogeneous along the genome which limits the range of allelic combinations and the adaptability of populations. An approach to better understand the constraints on the recombination process is to study how it evolved in the past. In this work we tackled this question by constructing recombination profiles in four diverging bread wheat (Triticum aestivum L.) populations established from 371 landraces genotyped at 200,062 SNPs. We used linkage disequilibrium (LD) patterns to estimate in each population the past distribution of recombination along the genome and characterize its fine-scale heterogeneity. At the megabase scale, recombination rates derived from LD patterns were consistent with family-based estimates obtained from a population of 406 recombinant inbred lines. Among the four populations, recombination landscapes were positively correlated between each other and shared a statistically significant proportion of highly recombinant intervals. However, this comparison also highlighted that the similarity in recombination landscapes between populations was significantly decreasing with their genetic differentiation in most regions of the genome. This observation was found to be robust to SNPs ascertainment and demography and suggests a relatively rapid evolution of factors determining the fine-scale localization of recombination in bread wheat.
Do not put eggs in one basket: related variety and export resilience in the post-crisis era
Authors: He Canfei , Chen Tao , Zhu Shengjun 
Published: June 2021

AbstractRegion’s capability to retain economic growth and resist external shocks is important, particularly in the increasingly globalized economy with a plethora of political and economic uncertainties. This paper uses Chinese custom data to investigate the ways in which regional export resilience has been affected by related variety in the post-crisis era. The hypothesis is that regions with a large number of related industries are more vulnerable to external shocks due to the risk-spreading effect, where the negative effects of external shocks on certain industries may be easily transferred to other related industries. Empirical results support our hypothesis that cities with many related industries are often less economically resilient to external shocks and tend to face greater economic decline in the post-crisis era. We also find that industries with high levels of related variety are also vulnerable to external demand shocks.
An evaluation of prophylactic and therapeutic antibiotic prescribing in Lebanese dental practice
Authors: Chehabeddine Nadine , Lahoud Nathalie , Noujeim Ziad E F , Zeidan Rouba K , El Toum Sami , Maison Patrick , Saleh Nadine 
Published: June 2021

Abstract

Objectives
To evaluate antibiotic prescribing patterns and correlates among Lebanese dentists.

Methods
A descriptive observational study was conducted, from the first of April to the end of May 2017. Dentists who specialized in oral dental surgery or general dental practitioners were eligible to participate in this study. All patients who sought consultation with the selected dentists over a 1 month period were included.

Key findings
A total of 2323 oral and dental procedures were performed by 60 dentists; 553 antibiotic prescriptions were prescribed, representing 23.8% (52.35% for prophylactic purposes and 47.65% for curative purposes). Prophylactic indications were mainly for implant surgery (36.3%) with only 1% appropriate. Curative use was mainly for periodontal abscesses/abscesses (indeterminate) (22.8%), followed by pulpal diseases and periradicular complications (20.5%); it was appropriate in only 1.7 and 1.9% of cases respectively. Amoxicillin–clavulanic acid was the antibiotic that was mostly prescribed for both curative and prophylactic uses (57.6 and 55.9%, respectively), followed by amoxicillin for prophylactic purposes and a combination of spiramycin plus metronidazole for curative purposes. Adherence to guidelines was low for both curative and prophylactic purposes (17.4 and 21.8%, respectively), but was better in patients who were younger [adjusted odds ratio
(aOR) = 0.96], male (aOR = 0.40), or had cardiac disease with moderate or high infective endocarditis risk (aOR = 21.72), and when prescribed by oral surgeons (aOR = 0.15).

Conclusions
This study showed evidence of the overuse of antibiotics among Lebanese dentists. It can serve as a basis for future studies to optimize antibiotic use among dentists in Lebanon.
Dietary supplementation of aSaccharomyces cerevisiaefermentation product attenuates exercise-induced stress markers in young horses
Authors: Valigura Hannah C , Leatherwood Jessica L , Martinez Rafael E , Norton Sharon A , White-Springer Sarah H 
Published: June 2021

AbstractMitigation of exercise-induced stress is of key interest in determining ways to optimize performance horse health. To test the hypothesis that dietary supplementation of a Saccharomyces cerevisiae fermentation product would decrease markers of exercise-induced stress and inflammation in young horses, Quarter Horse yearlings (mean ± SD; 9 ± 1 mo) were randomly assigned to receive either no supplementation (CON; n = 8) or 21 g/d S. cerevisiae fermentation product (10.5 g/feeding twice daily; SCFP; n = 10) top-dressed on a basal diet of custom-formulated grain as well as ad libitum Coastal bermudagrass hay. After 8 wk of dietary treatments, horses underwent a 2-h submaximal exercise test (SET) on a free-stall mechanical exerciser. Serum was collected before dietary treatment supplementation (week 0), at week 8 pre-SET, and 0, 1, and 6 h post-SET and analyzed for concentrations of cortisol and serum amyloid A (SAA) by commercial enzyme-linked immunosorbent assay (ELISA) and for cytokine concentrations by commercial bead-based ELISA. Data were analyzed using linear models with repeated measures in SAS v9.4. From week 0 to 8 (pre-SET), serum cortisol decreased (P = 0.01) and SAA did not change, but neither were affected by diet. Serum concentrations of all cytokines decreased from week 0 to 8 (P ≤ 0.008), but granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, and interleukin-8 (IL-8) decreased to a greater extent in CON than in SCFP horses (P ≤0.003). In response to the week 8 SET, serum cortisol increased in all horses (P &lt; 0.0001) but returned to pre-SET levels by 1 h post-SET in horses receiving SCFP. At 6 h post-SET, cortisol concentrations in CON horses returned to pre-SET concentrations, whereas cortisol declined further in SCFP horses to below pre-SET levels (P = 0.0002) and lower than CON (P = 0.003) at that time point. SAA increased at 6 h post-SET in CON (P &lt; 0.0001) but was unchanged through 6 h in SCFP horses. All cytokines except G-CSF increased in response to the SET (P &lt; 0.0001) but showed differing response patterns. Concentrations of IL-1β, IL-6, and tumor necrosis factor-alpha were lesser (P ≤ 0.05), and concentrations of G-CSF and IL-18 tended to be lesser (P ≤ 0.09) in SCFP compared with CON horses throughout recovery from the SET. In summary, 8 wk of dietary supplementation with 21 g/d of SCFP may mitigate cellular stress following a single, prolonged submaximal exercise bout in young horses.
Ectopic BH3-only protein Bim acts as a cochaperone to positively regulate Hsp70 in yeast
Authors: Pan Hao , Song Ting , Wang Ziqian , Guo Yafei , Zhang Hong , Ji Tong , Cao Keke , Zhang Zhichao 
Published: June 2021

Abstract
The chaperone heat shock protein 70 (Hsp70) is conserved from bacteria to humans and is crucial for avoiding protein misfolding under stress. Bim functions, mainly as one of the B-cell lymphoma 2 (Bcl-2) family proapoptotic members, were identified to be a cochaperone of Hsp70. Herein, we reported that ectopic Bim could constitute the interactions with intrinsic Hsp70 and translate its positive cochaperone activity in vitro to the yeast growth promotion and help Hsp70 to fold its client Ras-like protein. With the help of a specific Hsp70/Bim disruptor, we illustrated that Hsp70/Bim dimers rescue yeast from heat shock. In an organism lacks apoptotic Bcl-2 factors, the proapoptotic Bim in mammalian cells exhibits prosurvival functions.
The Impact of Roads on the Redistribution of Plants and Associated Arthropods in a Hyper-Arid Ecosystem
Authors: Cohen Shahar , Groner Elli , Peeters Aviva , Segoli Michal 
Published: June 2021

Abstract
The construction of vehicular roads likely affects the distribution of natural resources. Although the effects of roads on different ecosystem aspects have been extensively studied, studies in arid and, particularly, in hyper-arid ecosystems are scarce. In drylands, where water is the main limiting factor, the effect of roads on the redistribution of water may have strong subsequent effects on the ecosystem, especially when roads cross natural water flow paths. To fill this knowledge gap, we studied the effects of a road that runs across a slope on the distribution of plants and animals in a hyper-arid environment. Changes in shrub cover, below and above the road, were quantified by remote sensing and image classification, while plant-associated arthropods were vacuum-sampled from shrub canopies and from open (inter-shrub) areas. We found that the spatial distribution of shrubs, a vital resource facilitating many other organisms, was affected by the road, with an increase in the shrub cover immediately above the road and a decrease below it. Arthropod abundance generally followed shrub cover, but the exact pattern depended on the specific group sampled. While some arthropod groups (e.g., aphids, parasitic wasps and barklice) thrived under the disturbed conditions above the road, other arthropod groups (e.g., mites and true bugs) were less abundant in the disturbed patches. Our results highlight the strong effects of human-made structures on the distribution of flora and fauna in arid ecosystems.