Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing cerebellar-cortical connectivity using concurrent TMS-EEG: A Feasibility Study

Background Combined single-pulse transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to probe the features of local networks in the cerebral cortex. Here we investigate whether we can use this approach to explore long-range connections between the cerebellum and cerebral cortex. Objective To assess the feasibility of using cerebellar TMS-EEG for the exploration of cerebellar-cerebral network dynamics. Methods Ten healthy adults received single-pulse suprathreshold TMS to the cerebellum and an occipital/parietal control site with double-cone and figure-of-eight coils while cerebral activity was recorded. A multisensory electrical control condition was used to simulate the sensation of the double-cone coil at the cerebellar site. Two cleaning pipelines were compared, and the spatiotemporal relationships of the EEG output between conditions were examined at sensor and source levels. Results Cerebellar stimulation with the double-cone coil resulted in large artefacts in the EEG trace. The addition of SOUND filtering to the cleaning pipeline improved the signal such that further analyses could be undertaken. The cortical potentials evoked by the active TMS conditions showed strong relationships with the responses to the multisensory control condition after ~50 ms. A distinct parietal component at ~42 ms was found following cerebellar double-cone stimulation. Conclusions Cerebellar double-cone stimulation produces large artefacts in the EEG. Cerebellar-specific responses could not be reliably differentiated from sensory evoked potentials after ~50 ms. While evoked potentials differed across conditions at early latencies, it is unclear as to whether these represented TMS-related network activation of the cerebellarthalamocortical tract, or whether components were dominated by sensory contamination and/or coil-driven artefacts. Further work will be required to clarify the specific contribution of cerebellar-cortical connectivity to the observed early latency signals.
Auxin guides germ-cell specification in Arabidopsis anthers

Significance Germ cells (GCs) (i.e., the cells that are committed to meiosis and gametogenesis) are key carriers for eukaryotes to complete their life cycle, transmitting their genetic information from one generation to the next while generating variations to integrate environmental changes. Compared to what has been known in animals, very little is known about how the GCs in plants are segregated from somatic cells. This work demonstrates that auxin is a key factor guiding GC specification in Arabidopsis anthers. Local auxin biosynthesis interacts with the transcription of SPOROCYTELESS/NOZZLE and a progressive GC specification itself to form a dynamic feedback circuit that ensures the completion of GC specification. Germ cells (GCs) are the key carriers delivering genetic information from one generation to the next. In a majority of animals, GCs segregate from somatic cells during embryogenesis by forming germlines. In land plants, GCs segregate from somatic cells during postembryonic development. In a majority of angiosperms, male GCs (archesporial cells) initiate at the four corners of the anther primordia. Little is known about the mechanism underlying this initiation. Here, we discovered that the dynamic auxin distribution in developing anthers coincided with GC initiation. A centripetal auxin gradient gradually formed toward the four corners where GCs will initiate. Local auxin biosynthesis was necessary for this patterning and for GC specification. The GC determinant protein SPOROCYTELESS/NOZZLE (SPL/NZZ) mediated the effect of auxin on GC specification and modified auxin biosynthesis to maintain a centripetal auxin distribution. Our work reveals that auxin is a key factor guiding GC specification in Arabidopsis anthers. Moreover, we demonstrate that the GC segregation from somatic cells is not a simple switch on/off event but rather a complicated process that involves a dynamic feedback circuit among local auxin biosynthesis, transcription of SPL/NZZ, and a progressive GC specification. This finding sheds light on the mystery of how zygote-derived somatic cells diverge into GCs in plants.
Towards a Systems Immunology Approach to Unravel Responses to Cancer Immunotherapy

Immunotherapy, particularly immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, holds a great promise against cancer. These treatments have markedly improved survival in solid as well as in hematologic tumors previously considered incurable. However, durable responses occur in a fraction of patients, and existing biomarkers (e.g. PD-L1) have shown limited prediction power. This scenario highlights the need to dissect the complex interplay between immune and tumor cells to identify reliable biomarkers of response to be used for patients’ selection. In this context, systems immunology represents indeed the new frontier to address important clinical challenges in biomarker discovery. Through the integration of multiple layers of data obtained with several high-throughput approaches, systems immunology may give insights on the vast range of inter-individual differences and on the influences of genes and factors that cooperatively shape the individual immune response to a given treatment. In this Mini Review, we give an overview of the current high-throughput methodologies, including genomics, epigenomics, transcriptomics, metabolomics, proteomics, and multi-parametric phenotyping suitable for systems immunology as well as on the key steps of data integration and biological interpretation. Additionally, we review recent studies in which multi-omics technologies have been used to characterize mechanisms of response and to identify powerful biomarkers of response to checkpoint inhibitors, CAR-T cell therapy, dendritic cell-based and peptide-based cancer vaccines. We also highlight the need of favoring the collaboration of researchers with complementary expertise and of integrating multi-omics data into biological networks with the final goal of developing accurate markers of therapeutic response.
Bacterial and Archaeal Diversity and Abundance in Shallow Subsurface Clay Sediments at Jianghan Plain, China

Clay layers are common in subsurface where microbial activities play an important role in impacting the biogeochemical properties of adjacent aquifers. In this study, we analyzed the community structure and abundance of bacteria and archaea in response to geochemical properties of six clay sediments at different depths in a borehole (112°34′0″E, 30°36′21″N) of Jianghan Plain (JHP), China. Our results suggested that the top two clay layers were oxic, while the remaining bottom four clay layers were anoxic. Both high-throughput sequencing and qPCR of 16S rRNA gene showed relatively high abundance of archaea (up to 60%) in three of the anoxic clay layers. Furthermore, microbial communities in these clay sediments showed distinct vertical stratification, which may be impacted by changes in concentrations of sulfate, HCl-extractable Fe2+ and total organic carbon (TOC) in the sediments. In the upper two oxic clay layers, identification of phyla Thaumarchaeota (11.2%) and Nitrosporales (1.2%) implied nitrification in these layers. In the two anoxic clay layers beneath the oxic zone, high abundances of Anaeromyxobacter, Chloroflexi bacterium RBG 16_58_14 and Deltaproteobacteria, suggested the reductions of nitrate, iron and sulfate. Remarkably, a significant portion of Bathyarchaeota (∼25%) inhabited in the bottom two anoxic clay layers, which may indicate archaeal anaerobic degradation of TOC by these organisms. The results of this study provide the first systematic understandings of microbial activities in subsurface clay layers at JHP, which may help develop microorganism-based solutions for mitigating subsurface contaminations.
CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells

T cells recognize mycobacterial glycolipid (mycolipid) antigens presented by CD1b molecules, but the role of CD4 and CD8 co-receptors in mycolipid recognition is unknown. Here we show CD1b-mycolipid tetramers reveal a hierarchy in which circulating T cells expressing CD4 or CD8 co-receptor stain with a higher tetramer mean fluorescence intensity than CD4-CD8- T cells. CD4+ primary T cells transduced with mycolipid-specific T cell receptors bind CD1b-mycolipid tetramer with a higher fluorescence intensity than CD8+ primary T cells. The presence of either CD4 or CD8 also decreases the threshold for interferon-γ secretion. Co-receptor expression increases surface expression of CD3ε, suggesting a mechanism for increased tetramer binding and activation. Targeted transcriptional profiling of mycolipid-specific T cells from individuals with active tuberculosis reveals canonical markers associated with cytotoxicity among CD8+ compared to CD4+ T cells. Thus, expression of co-receptors modulates T cell receptor avidity for mycobacterial lipids, leading to in vivo functional diversity during tuberculosis disease. CD4 and CD8 co-receptors are routinely used to define distinct functional and phenotypic lineages of T cells. Here the authors show CD4 and CD8 also modulate the functional avidity of the CD1b-restricted response to mycobacterial lipid antigens
Identification and validation of a ferroptosis-related genes based prognostic signature for prostate cancer

Ferroptosis, an iron-dependent form of selective cell death, involves in the development of many cancers. However, systematic analysis of ferroptosis related genes (FRGs) in prostate cancer (PCa) remains to be clarified. In our research, we collected the mRNA expression profiles and clinical information of PCa patients from TCGA and MSKCC databases. The univariate, LASSO and multivariate Cox regression method were performed to construct prognostic signature in TCGA cohort. Seven FRGs, AKR1C3, ALOXE3, ATP5MC3, CARS1, MT1G, PTGS2, TFRC, were included to establish the risk model, which was validated in MSKCC dataset. Subsequently, we found that high risk group was strongly correlated with copy number alteration load, tumor burden mutation, immune cell infiltration, mRNAsi, immuetherapy and bicalutamide response. Finally, it was identified that overexpression of TFRC could induce proliferation and invasion in PCa cell lines in vitro. These results demonstrated that this risk model based on recurrence free survival (RFS) could accurately predict prognosis in PCa patients, suggesting that FRGs are promising prognostic biomarkers and drug target genes for PCa patients.
Identification of novel quantitative trait loci associated with tolerance to phytophthora root rot in the soybean cultivar Hefeng 25 using two recombinant inbred line populations

Abstract: The objective of this study was to identify quantitative trait loci (QTL) related to phytophthora root rot (PRR) tolerance and to analyze their genetic effects through two recombinant inbred line populations between tolerance cultivar Hefeng 25 and two susceptible cultivars (Dongnong 93046 for the HD population, including 140 F5:9 lines, and Maple Arrow for the HM population, including 149 F5:10 lines) based on greenhouse evaluation of PRR. A total of five and seven QTL underlying tolerance to PRR were identified in the HD and HM populations, respectively. Phenotypic variation explained by the QTL ranged from 1.27% to 10.41% in the HD population and from 1.68% to 12.65% in the HM population. Of these QTL, three (qHDPRR-4 in the HD population and qHMPRR-1 and qHMPRR-3 in the HM population) were identified in similar genomic regions reported previously. Nine new QTL contributed by Hefeng 25 were found in the present study (four in the HD population and five in the HM population). Three QTL in the HD and five QTL in the HM populations had higher additive effects that were likely to be stable across multiple environments or genetic backgrounds. Moreover, four and five epistatic pairwise QTL were found to underlie tolerance to PRR in the HD and HM populations, respectively.
Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine

In 2019, the United States Food and Drug Administration accorded restricted approval to Sanofi Pasteur's Dengvaxia, a live attenuated vaccine (LAV) for dengue fever, a mosquito-borne viral disease, caused by four antigenically distinct dengue virus serotypes (DENV 1-4). The reason for this limited approval is the concern that this vaccine sensitized some of the dengue-naïve recipients to severe dengue fever. Recent knowledge about the nature of the immune response elicited by DENV viruses suggests that all LAVs have inherent capacity to predominantly elicit antibodies (Abs) against the pre-membrane (prM) and fusion loop epitope (FLE) of DENV. These antibodies are generally cross-reactive among DENV serotypes carrying a higher risk of promoting Antibody-Dependent Enhancement (ADE). ADE is a phenomenon in which suboptimal neutralizing or non-neutralizing cross-reactive antibodies bind to virus and facilitate Fcγ receptor mediated enhanced entry into host cells, followed by its replication, and thus increasing the cellular viral load. On the other hand, antibody responses directed against the host-cell receptor binding domain of DENV envelope domain-III (EDIII), exhibit a higher degree of type-specificity with lower potential of ADE. The challenges associated with whole DENV-based vaccine strategies necessitate re-focusing our attention toward the designed dengue vaccine candidates, capable of inducing predominantly type-specific immune responses. If the designed vaccines elicited predominantly EDIII-directed serotype specific antibodies in the absence of prM and FLE antibodies, this could avoid the ADE phenomenon largely associated with the prM and FLE antibodies. The generation of type-specific antibodies to each of the four DENV serotypes by the designed vaccines could avoid the immune evasion mechanisms of DENVs. For the enhanced vaccine safety, all dengue vaccine candidates should be assessed for the extent of type-specific (minimal ADE) vs. cross-reactive (ADE promoting) neutralizing antibodies. The type-specific EDIII antibodies may be more directly related to protection from disease in the absence of ADE promoted by the cross-reactive antibodies.
Air Transport and Its Impact on the Tourism Industry in Rwanda: Case of RwandAir

The study focused on the air transportation and its impact on the tourism industry in Rwanda; the case of RwandAir. The study objectives were to identify the contributions of air transportation to the development of tourism industry in Rwanda; to establish the challenges facing the air transport sector and to propose strategic measures to mitigate the challenges. The study used a cross-sectional survey thus both the qualitative and quantitative approaches were applied. The study used closed-ended questionnaires, structured interview, as well as document review. Purposive sampling was used on the key managers of both RwandAir and Rwanda Development Board. The study targeted 700 international tourists and 200 domestic tourists (conveniently selected), as well as structured interview with 30 senior officers of RwandAir and 20 senior officers of RDB, hence making the total population to be 950 respondents. The study sample size was 274 respondents. However, after validating the returned questionnaires, only 240 questionnaires were found to be valid. It was revealed that RwandAir greatly contributes to tourism development in many ways such as marketing, job creation, transporting tourists, providing a convenient, quick and safe way to get into the country among others. It was revealed by the world bank that international tourism arrivals in 2016 was 932000 tourists bringing in 25.85 % of total exports and total imports and expenditure on travel service es was 11.99 % in Rwanda. The number of tourists’ arrivals was limited to arrivals by air. However, RwandAir and air transport in general faces changing oil prices, expensive jets, terrorism in neighbouring countries, limited funding, skills gap in aviation sector (lack of technical engineers and pilots), geographical location, inadequate infrastructure and to a great extent, lack of safety compliance. The strategies that can be adopted to improve air transport sector are: more funding to air transport industry by government; oil and energy negotiations with oil-producing countries; skills enhancement like training local pilots and engineers; improved airport infrastructure in Rwanda e.g. at Kigali international airport and other domestic airports; space agreements as well as benchmarking best airline companies like Qatar and emirates and others in the region. The study recommends tax concessions for the air transport, oil negotiations, opening up and re-development of the domestic airports in the country, reduced prices for incoming tourists using RwandAir, partnerships between government and private sector in developing air transport, increased training of aviation staff among others. It is believed that when these are done, then air transport will continue to positively transform tourism into a better and developing sector with sustained customer base hence national development.
PIP2 promotes conformation-specific dimerization of the EphA2 membrane region

The impact of the EphA2 receptor on cancer malignancy hinges on the two different ways it can be activated. EphA2 induces anti-oncogenic signaling after ligand binding, but ligand-independent activation of EphA2 is pro-oncogenic. It is believed that the transmembrane (TM) domain of EphA2 adopts two alternate conformations in the ligand-dependent and the ligand-independent states. However, it is poorly understood how the difference in TM helical crossing angles found in the two conformations impacts the activity and regulation of EphA2. We devised a method that uses hydrophobic matching to stabilize two conformations of a peptide comprising the EphA2 TM domain and a portion of the intracellular juxtamembrane (JM) segment. The two conformations exhibit different TM crossing angles, resembling the ligand-dependent and ligand-independent states. We developed a single-molecule technique using SMALPs to measure dimerization in membranes. We observed that the signaling lipid PIP2 promotes TM dimerization, but only in the small crossing angle state, which we propose corresponds to the ligand-independent conformation. In this state the two TM are almost parallel, and the positively charged JM segments are expected to be close to each other, causing electrostatic repulsion. The mechanism PIP2 uses to promote dimerization might involve alleviating this repulsion due to its high density of negative charges. Our data reveal a conformational coupling between the TM and JM regions, and suggest that PIP2 might directly exert a regulatory effect on EphA2 activation in cells that is specific to the ligand-independent conformation of the receptor.
Hedera caerulescens (Alcyonacea : Alcyoniidae), a new genus and species of soft coral from the temperate North Atlantic: invasive in its known range?

Abstract. We describe a novel alcyoniid species of stoloniferous octocoral found off the coast of North Carolina, USA. Colonies have an encrusting morphology with pale to bright blue monomorphic polyps connected by spongy, sclerite-dense stolons that often form mats. Sclerites are colourless and sparsely tubercled. Sclerites of the stolons are predominantly spindles and rods with rare irregular fused forms, butterflies, and crosses. Polyps have a crown and points formation that consists of rods and spindles that can be curved or irregularly branched. Tentacles contain short flattened rods and rare crosses. Both the mitochondria-encoded COI-5P and mtMutS were sequenced and BLAST searches revealed no close homology with any previously sequenced species. Phylogenetic analyses of the sequence data suggested a closest relationship with species of Alcyonium Linnaeus, 1758 (Alcyoniidae) and Gersemia Marenzeller, 1877 (Nephtheidae) and supported the recognition of a new genus. This species was not previously reported in the Carolinas region despite extensive historical sampling and a recently published key to octocorals of the South Atlantic Bight. Reports and photographs from local divers suggest that this species may have been introduced in North Carolina waters ∼2002–04, where it has been found on both shipwrecks and hard bottom ledges, at 13–34 m depth.
Using Messy, Authentic Data to Promote Data Literacy & Reveal the Nature of Science

Abstract Authentic, “messy data” contain variability that comes from many sources, such as natural variation in nature, chance occurrences during research, and human error. It is this messiness that both deters potential users of authentic data and gives data the power to create unique learning opportunities that reveal the nature of science itself. While the value of bringing contemporary research and messy data into the classroom is recognized, implementation can seem overwhelming. We discuss the importance of frequent interactions with messy data throughout K–16 science education as a mechanism for students to engage in the practices of science, such as visualizing, analyzing, and interpreting data. Next, we describe strategies to help facilitate the use of messy data in the classroom while building complexity over time. Finally, we outline one potential sequence of activities, with specific examples, to highlight how various activity types can be used to scaffold students' interactions with messy data.
Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery

Abstract We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210 nm and −14 mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12 nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.