bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic link between right prefrontal cortical activity and anxious arousal revealed using transcranial magnetic stimulation in healthy subjects
Authors: Balderston Nicholas L. , Beydler Emily M. , Roberts Camille , Deng Zhi-De , Radman Thomas , Lago Tiffany , Luber Bruce , Lisanby Sarah H. , Ernst Monique , Grillon Christian 
Published: December 2019

AbstractMuch of the mechanistic research on anxiety focuses on subcortical structures such as the amygdala; however, less is known about the distributed cortical circuit that also contributes to anxiety expression. One way to learn about this circuit is to probe candidate regions using transcranial magnetic stimulation (TMS). In this study, we tested the involvement of the dorsolateral prefrontal cortex (dlPFC), in anxiety expression using 10 Hz repetitive TMS (rTMS). In a within-subject, crossover experiment, the study measured anxiety in healthy subjects before and after a session of 10 Hz rTMS to the right dorsolateral prefrontal cortex (dlPFC). It used threat of predictable and unpredictable shock to induce anxiety and anxiety potentiated startle to assess anxiety. Counter to our hypotheses, results showed an increase in anxiety-potentiated startle following active but not sham rTMS. These results suggest a mechanistic link between right dlPFC activity and physiological anxiety expression. This result supports current models of prefrontal asymmetry in affect, and lays the groundwork for further exploration into the cortical mechanisms mediating anxiety, which may lead to novel anxiety treatments.
Macrophage-associated pro-inflammatory state in human islets from obese individuals
Authors: He Wei , Yuan Ting , Maedler Kathrin 
Published: December 2019

AbstractObesity is associated with inflammatory macrophages in insulin responsive tissues and the resulting inflammatory response is a major contributor to insulin resistance. In insulin-producing pancreatic islets, the intra-islet accumulation of macrophages is observed in patients of type 2 diabetes (T2D), but such has not been investigated in obese individuals. Here, we show that pro-inflammatory cytokines (IL-1β, IL-6, and TNF), anti-inflammatory cytokines (IL-10 and TGF-β) and macrophage polarization markers (CD11c, CD163, and NOS2) were expressed in isolated human islets from non-diabetic donors. Clodronate-mediated depletion of resident macrophages revealed expression of IL1B and IL10 mostly from macrophages, while IL6, TNF, and TGFB1 came largely from a non-macrophage origin in human islets. NOS2 expression came exclusively from non-macrophage cells in non-obese individuals, while it originated also from macrophages in obese donors. Macrophage marker expression of CD68, CD163, and ITGAX was unchanged in islets of non-obese control and obese cohorts. In contrast, IL1B and NOS2 were significantly increased in islets from obese, compared to non-obese individuals, implying a more inflammatory macrophage phenotype in islets in obesity. Our study shows elevated macrophage-associated inflammation in human islets in obesity, which could be an initiating factor to the pro-inflammatory intra-islet milieu and contribute to the higher susceptibility to T2D in obese individuals.
Bcl-2-associated athanogene 5 (BAG5) regulates Parkin-dependent mitophagy and cell death
Authors: De Snoo Mitchell L. , Friesen Erik L. , Zhang Yu Tong , Earnshaw Rebecca , Dorval Geneviève , Kapadia Minesh , O’Hara Darren M. , Agapova Victoria , Chau Hien , Pellerito Ornella , Tang Matthew Y. , Wang Xinzhu , Schmitt-Ulms Gerold , Durcan Thomas M. , Fon Edward A. , Kalia Lorraine V. , Kalia Suneil K. 
Published: December 2019

AbstractAs pathogenic Parkin mutations result in the defective clearance of damaged mitochondria, Parkin-dependent mitophagy is thought to be protective against the dopaminergic neurodegeneration observed in Parkinson’s disease. Recent studies, however, have demonstrated that Parkin can promote cell death in the context of severe mitochondrial damage by degrading the pro-survival Bcl-2 family member, Mcl-1. Therefore, Parkin may act as a ‘switch’ that can shift the balance between protective or pro-death pathways depending on the degree of mitochondrial damage. Here, we report that the Parkin interacting protein, Bcl-2-associated athanogene 5 (BAG5), impairs mitophagy by suppressing Parkin recruitment to damaged mitochondria and reducing the movement of damaged mitochondria into the lysosomes. BAG5 also enhanced Parkin-mediated Mcl-1 degradation and cell death following severe mitochondrial insult. These results suggest that BAG5 may regulate the bi-modal activity of Parkin, promoting cell death by suppressing Parkin-dependent mitophagy and enhancing Parkin-mediated Mcl-1 degradation.
Superplume mantle tracked isotopically the length of Africa from the Indian Ocean to the Red Sea
Authors: O’Connor John M. , Jokat Wilfried , Regelous Marcel , Kuiper Klaudia F. , Miggins Daniel P. , Koppers Anthony A. P. 
Published: December 2019

AbstractSeismological findings show a complex scenario of plume upwellings from a deep thermo-chemical anomaly (superplume) beneath the East African Rift System (EARS). It is unclear if these geophysical observations represent a true picture of the superplume and its influence on magmatism along the EARS. Thus, it is essential to find a geochemical tracer to establish where upwellings are connected to the deep-seated thermo-chemical anomaly. Here we identify a unique non-volatile superplume isotopic signature (‘C’) in the youngest (after 10 Ma) phase of widespread EARS rift-related magmatism where it extends into the Indian Ocean and the Red Sea. This is the first sound evidence that the superplume influences the EARS far from the low seismic velocities in the magma-rich northern half. Our finding shows for the first time that superplume mantle exists beneath the rift the length of Africa from the Red Sea to the Indian Ocean offshore southern Mozambique.
3D designed and printed chemical generators for on demand reagent synthesis
Authors: Zalesskiy Sergey S. , Kitson Philip J. , Frei Przemyslaw , Bubliauskas Andrius , Cronin Leroy 
Published: December 2019

AbstractModern science has developed well-defined and versatile sets of chemicals to perform many specific tasks, yet the diversity of these reagents is so large that it can be impractical for any one lab to stock everything they might need. At the same time, isssues of stability or limited supply mean these chemicals can be very expensive to purchase from specialist retailers. Here, we address this problem by developing a cartridge -oriented approach to reactionware-based chemical generators which can easily and reliably produce specific reagents from low-cost precursors, requiring minimal expertise and time to operate, potentially in low infrastructure environments. We developed these chemical generators for four specific targets; transition metal catalyst precursor tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3], oxidising agent Dess-Martin periodinane (DMP), protein photolinking reagent succinimidyl 4,4’-azipentanoate (NHS-diazirine), and the polyoxometalate cluster {P8W48}. The cartridge synthesis of these materials provides high-quality target compounds in good yields which are suitable for subsequent utilization.
A family of Type VI secretion system effector proteins that form ion-selective pores
Authors: Mariano Giuseppina , Trunk Katharina , Williams David J. , Monlezun Laura , Strahl Henrik , Pitt Samantha J. , Coulthurst Sarah J. 
Published: December 2019

AbstractType VI secretion systems (T6SSs) are nanomachines widely used by bacteria to deliver toxic effector proteins directly into neighbouring cells. However, the modes of action of many effectors remain unknown. Here we report that Ssp6, an anti-bacterial effector delivered by a T6SS of the opportunistic pathogen Serratia marcescens, is a toxin that forms ion-selective pores. Ssp6 inhibits bacterial growth by causing depolarisation of the inner membrane in intoxicated cells, together with increased outer membrane permeability. Reconstruction of Ssp6 activity in vitro demonstrates that it forms cation-selective pores. A survey of bacterial genomes reveals that genes encoding Ssp6-like effectors are widespread in Enterobacteriaceae and often linked with T6SS genes. We conclude that Ssp6 and similar proteins represent a new family of T6SS-delivered anti-bacterial effectors.
Components of the ribosome biogenesis pathway underlie establishment of telomere length set point in Arabidopsis
Authors: Abdulkina Liliia R. , Kobayashi Callie , Lovell John T. , Chastukhina Inna B. , Aklilu Behailu B. , Agabekian Inna A. , Suescún Ana V. , Valeeva Lia R. , Nyamsuren Chuluuntsetseg , Aglyamova Galina V. , Sharipova Margarita R. , Shippen Dorothy E. , Juenger Thomas E. , Shakirov Eugene V. 
Published: December 2019

AbstractTelomeres cap the physical ends of eukaryotic chromosomes to ensure complete DNA replication and genome stability. Heritable natural variation in telomere length exists in yeast, mice, plants and humans at birth; however, major effect loci underlying such polymorphism remain elusive. Here, we employ quantitative trait locus (QTL) mapping and transgenic manipulations to identify genes controlling telomere length set point in a multi-parent Arabidopsis thaliana mapping population. We detect several QTL explaining 63.7% of the total telomere length variation in the Arabidopsis MAGIC population. Loss-of-function mutants of the NOP2A candidate gene located inside the largest effect QTL and of two other ribosomal genes RPL5A and RPL5B establish a shorter telomere length set point than wild type. These findings indicate that evolutionarily conserved components of ribosome biogenesis and cell proliferation pathways promote telomere elongation.
Impacts of past abrupt land change on local biodiversity globally
Authors: Jung Martin , Rowhani Pedram , Scharlemann Jörn P. W. 
Published: December 2019

AbstractAbrupt land change, such as deforestation or agricultural intensification, is a key driver of biodiversity change. Following abrupt land change, local biodiversity often continues to be influenced through biotic lag effects. However, current understanding of how terrestrial biodiversity is impacted by past abrupt land changes is incomplete. Here we show that abrupt land change in the past continues to influence present species assemblages globally. We combine geographically and taxonomically broad data on local biodiversity with quantitative estimates of abrupt land change detected within time series of satellite imagery from 1982 to 2015. Species richness and abundance were 4.2% and 2% lower, respectively, and assemblage composition was altered at sites with an abrupt land change compared to unchanged sites, although impacts differed among taxonomic groups. Biodiversity recovered to levels comparable to unchanged sites after >10 years. Ignoring delayed impacts of abrupt land changes likely results in incomplete assessments of biodiversity change.
Myc controls a distinct transcriptional program in fetal thymic epithelial cells that determines thymus growth
Authors: Cowan Jennifer E. , Malin Justin , Zhao Yongge , Seedhom Mina O. , Harly Christelle , Ohigashi Izumi , Kelly Michael , Takahama Yousuke , Yewdell Jonathan W. , Cam Maggie , Bhandoola Avinash 
Published: December 2019

AbstractInteractions between thymic epithelial cells (TEC) and developing thymocytes are essential for T cell development, but molecular insights on TEC and thymus homeostasis are still lacking. Here we identify distinct transcriptional programs of TEC that account for their age-specific properties, including proliferation rates, engraftability and function. Further analyses identify Myc as a regulator of fetal thymus development to support the rapid increase of thymus size during fetal life. Enforced Myc expression in TEC induces the prolonged maintenance of a fetal-specific transcriptional program, which in turn extends the growth phase of the thymus and enhances thymic output; meanwhile, inducible expression of Myc in adult TEC similarly promotes thymic growth. Mechanistically, this Myc function is associated with enhanced ribosomal biogenesis in TEC. Our study thus identifies age-specific transcriptional programs in TEC, and establishes that Myc controls thymus size.
Declines in HIV incidence among men and women in a South African population-based cohort
Authors: Vandormael Alain , Akullian Adam , Siedner Mark , de Oliveira Tulio , Bärnighausen Till , Tanser Frank 
Published: December 2019

AbstractOver the past decade, there has been a massive scale-up of primary and secondary prevention services to reduce the population-wide incidence of HIV. However, the impact of these services on HIV incidence has not been demonstrated using a prospectively followed, population-based cohort from South Africa—the country with the world’s highest rate of new infections. To quantify HIV incidence trends in a hyperendemic population, we tested a cohort of 22,239 uninfected participants over 92,877 person-years of observation. We report a 43% decline in the overall incidence rate between 2012 and 2017, from 4.0 to 2.3 seroconversion events per 100 person-years. Men experienced an earlier and larger incidence decline than women (59% vs. 37% reduction), which is consistent with male circumcision scale-up and higher levels of female antiretroviral therapy coverage. Additional efforts are needed to get more men onto consistent, suppressive treatment so that new HIV infections can be reduced among women.
Estimation of Bladder Pressure and Volume from the Neural Activity of Lumbosacral Dorsal Horn Using a Long-Short-Term-Memory-based Deep Neural Network
Authors: Jabbari Milad , Erfanian Abbas 
Published: December 2019

AbstractIn this paper, we propose a deep recurrent neural network (DRNN) for the estimation of bladder pressure and volume from neural activity recorded directly from spinal cord gray matter neurons. The model was based on the Long Short-Term Memory (LSTM) architecture, which has emerged as a general and effective model for capturing long-term temporal dependencies with good generalization performance. In this way, training the network with the data recorded from one rat could lead to estimating the bladder status of different rats. We combined modeling of spiking and local field potential (LFP) activity into a unified framework to estimate the pressure and volume of the bladder. Moreover, we investigated the effect of two-electrode recording on decoding performance. The results show that the two-electrode recordings significantly improve the decoding performance compared to single-electrode recordings. The proposed framework could estimate bladder pressure and volume with an average normalized root-mean-squared (NRMS) error of 14.9 ± 4.8% and 19.7 ± 4.7% and a correlation coefficient (CC) of 83.2 ± 3.2% and 74.2 ± 6.2%, respectively. This work represents a promising approach to the real-time estimation of bladder pressure/volume in the closed-loop control of bladder function using functional electrical stimulation.
Gene activation by dCas9-CBP and the SAM system differ in target preference
Authors: Sajwan Suresh , Mannervik Mattias 
Published: December 2019

AbstractGene overexpression through the targeting of transcription activation domains to regulatory DNA via catalytically defective Cas9 (dCas9) represents a powerful approach to investigate gene function as well as the mechanisms of gene control. To date, the most efficient dCas9-based activator is the Synergistic Activation Mediator (SAM) system whereby transcription activation domains are directly fused to dCas9 as well as tethered through MS2 loops engineered into the gRNA. Here, we show that dCas9 fused to the catalytic domain of the histone acetyltransferase CBP is a more potent activator than the SAM system at some loci, but less efficient at other locations in Drosophila cells. Our results suggest that different rate-limiting steps in the transcription cycle are affected by dCas9-CBP and the SAM system, and that comparing these activators may be useful for mechanistic studies of transcription as well as for increasing the number of hits in genome-wide overexpression screens.
Integrin alpha-5 subunit is critical for the early stages of human pluripotent stem cell cardiac differentiation
Authors: Neiman Gabriel , Scarafía María Agustina , La Greca Alejandro , Santín Velazque Natalia L. , Garate Ximena , Waisman Ariel , Möbbs Alan M. , Kasai-Brunswick Tais Hanae , Mesquita Fernanda , Martire-Greco Daiana , Moro Lucía N. , Luzzani Carlos , Bastos Carvalho Adriana , Sevlever Gustavo E. , Campos de Carvalho Antonio , Guberman Alejandra S. , Miriuka Santiago G. 
Published: December 2019

AbstractThe stem cell niche has a strong influence in the differentiation potential of human pluripotent stem cells with integrins playing a major role in communicating cells with the extracellular environment. However, it is not well understood how interactions between integrins and the extracellular matrix are involved in cardiac stem cell differentiation. To evaluate this, we performed a profile of integrins expression in two stages of cardiac differentiation: mesodermal progenitors and cardiomyocytes. We found an active regulation of the expression of different integrins during cardiac differentiation. In particular, integrin α5 subunit showed an increased expression in mesodermal progenitors, and a significant downregulation in cardiomyocytes. To analyze the effect of α5 subunit, we modified its expression by using a CRISPRi technique. After its downregulation, a significant impairment in the process of epithelial-to-mesenchymal transition was seen. Early mesoderm development was significantly affected due to a downregulation of key genes such as T Brachyury and TBX6. Furthermore, we observed that repression of integrin α5 during early stages led to a reduction in cardiomyocyte differentiation and impaired contractility. In summary, our results showed the link between changes in cell identity with the regulation of integrin α5 expression through the alteration of early stages of mesoderm commitment.
Pegylated liposomal doxorubicin plus cyclophosphamide followed by docetaxel as neoadjuvant chemotherapy in locally advanced breast cancer (registration number: ChiCTR1900023052)
Authors: Li Ruoyang , Tian Fuguo , Qi Yixin , Ma Li , Zhou Tao , Li Yuntao , Hui Tianli , Zhang Lina , Wang Shuo , Song Zhenchuan 
Published: December 2019

AbstractAnthracyclines have a profound effect on breast cancer. However, at higher dosages, there are many toxic side effects associated with their use; these include bone marrow suppression, alopecia, gastrointestinal reactions and cardiotoxicity. Pegylated liposomal doxorubicin (PEG-LG) has been demonstrated to achieve equivalent efficacy to conventional doxorubicin, with significantly lower cardiotoxicity. We conducted an open-label, multicenter, single-armed clinical trial useing an NAC regimen based on four cycles of PEG-LD 40 mg/m2 plus cyclophosphamide (CPM) 600 mg/m2 on day 1 of a 21 day schedule, followed by four cycles of docetaxel (DTX) 85 mg/m2 on day 1 of a 21 day schedule. The primary endpoint analysed was the pathological complete response rate (pCR) in the breast, while treatment toxicities and safety were also assessed. The results showed that the breast pCR rate was 18.75% (95% CI 11.5–26.0%). Among the different molecular cancer types, the triple negative breast cancer patients had the highest pCR, at 43.75%. No significant decrease in left ventricular ejection fraction was observed. Our data tends to draw the conclusion that this regimen is a viable option for the neoadjuvant treatment of patients with LABC, especially in the triple-negative subtype and patients with heart abnormalities. We believe the efficacy and the safety of this regimen is likely to be the same based on published data from other studies but that this cannot be certain without a randomized trial.
Evaluation of Diffusion-Weighted MRI and FDG-PET/CT to Assess Response to AdCD40L treatment in Metastatic Melanoma Patients
Authors: Schiza Aglaia , Irenaeus Sandra , Ortiz-Nieto Francisco , Loskog Angelica , Tötterman Thomas , Sundin Anders , Ullenhag Gustav J. , Ahlström Håkan 
Published: December 2019

AbstractThe purpose was to evaluate the potential of diffusion-weighted-magnetic resonance imaging (DW-MRI) and 18F-fludeoxy-glucose-positron emission tomography integrated with CT (FDG-PET/CT) for prediction of overall survival (OS) following AdCD40L-immunotherapy in patients with metastatic malignant melanoma (MMM). Twenty-four patients with refractory MMM were treated with immunostimulatory AdCD40L gene therapy in a phase I/IIa study. Pre-therapeutic DW-MRI and FDG-PET/CT were performed and then repeated at 5 and 9 weeks post-treatment. Evaluation was conducted according to RECIST 1.1 and EORTC criteria. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), maximum standardized uptake value (SUVmax) were measured in the injected lesions. Fold changes (F) in ADC (F ADC), D (F D), SUVmax (F SUVmax) were statistically assessed. F D ≥ 1 and F ADC ≥ 1 were associated with better OS in scans at week 5 and 9 respectively. F SUVmax was not correlated to OS. F ADC ≥ 1 in both post-treatment scans and F D ≥ 1 at week 5 were related to a significant decrease of size of the injected lesions. These results suggest that in patients with MMM treated with AdCD40l, functional parameters of DW-MRI are better early predictors of OS than the established metabolic and morphologic criteria for FDG-PET/CT and MRI, respectively.
Succession in arbuscular mycorrhizal fungi can be attributed to a chronosequence of Cunninghamia lanceolata
Authors: Lu Nini , Xu Xuelei , Wang Ping , Zhang Peng , Ji Baoming , Wang Xinjie 
Published: December 2019

AbstractArbuscular mycorrhizal (AM) fungi play an important role in plant-fungi communities. It remains a central question of how the AM fungal community changes as plants grow. To establish an understanding of AM fungal community dynamics associated with Chinese fir, Chinese fir with five different growth stages were studied and 60 root samples were collected at the Jiangle National Forestry Farm, Fujian Province. A total of 76 AM fungal operational taxonomic units (OTUs) were identified by high-throughput sequencing on an Illumina Miseq platform. The genera covered by OTUs wereGlomus,Archaeospora,Acaulospora,GigasporaandDiversispora. Glomusdominated the community in the whole stage. The number and composition of OTUs varied along with the host plant growth. The number of OTUs showed an inverted V-shaped change with the host plant age, and the maximum occurred in 23-year. Overall, the basic species diversity and richness in this study were stable. Non-metric multi-dimensional scaling (NMDS) analysis based on bray-curtis distance revealed that there were remarkable differentiations between the 9-year and other stages. Besides, AM fungal community in 32-year had a significant difference with that of 23-year, while no significant difference with that of 45-year, suggesting that 32-year may be a steady stage for AM fungi associated with Chinese fir. The cutting age in 32-year may be the most favorable for microbial community. The pH, total N, total P, total K, available N, available P, available K, organic matter and Mg varied as the Chinese fir grows. According to Mantel test and redundancy analysis, available N, available P, K and Mg could exert significant influence on AM fungal communities, and these variables explained 31% of variance in the composition of AM fungal communities.