Miracle-dz/UniFAR-FTUs huggingface dataset:
A comparative study of hybrid and internet-based educational technology course modules

The purpose o f this study was to examine students’ attitudes and performance toward the teaching methods in an educational technology course. Undergraduate students enrolled in the Educational Technology course ETEC 2002L at the University o f Arkansas had been exposed to both on-line modules and in-class instruction. The sample size for this study was 155. The results included 110 valid surveys completed by the students on paper. The data collected from the survey were analyzed using percentages, means, and t test o f paired samples to find if there was a significant difference in students’ attitudes toward on-line versus hybrid instruction. Four two-way ANOVAs were performed to test whether there was a significant difference between students’ attitude toward the on-line vs. hybrid teaching methods. The independent variables in this study were students’ age, gender, computer experience, and prior experience with on-line courses. An independent sample t test was completed to investigate if there was a significant relationship between the students’ performance and the teaching method. A Pearson Correlation Coefficient test was made to test whether there was a significant relationship between students’ performance and their attitude toward on-line versus hybrid instruction. Findings indicated that students agreed that participating in the on-line as well as the in-class lectures positively impacted their attitude toward the instructional technology. However, the results indicated that there was no difference in the students’ Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. attitudes toward either hybrid or on-line teaching methods. The ANOVA results showed that age, gender, computer experience, and prior experience with on line courses were not significant factors in defining an attitude toward either hybrid or on-line method. When comparing students’ performance, the only difference between the two teaching methods was found in one assignment out o f the four assignments that students submitted. When looking for a relationship between students’ performance and their attitude toward any o f the teaching methods, results showed that there was a significant correlation between the students’ performance and their attitude in the on-line method in one out o f the four lessons given to the students. In general, this study outlines the importance o f studying the various factors that affect students’ attitude and their performance in educational technology courses. Recommendations to enhance the students’ performance and perception toward educational technology courses were given after the conclusions are presented. Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. To the soul of my brother, Ahmed.
Profiling the proximal proteome of the mu opioid receptor identifies novel regulators of receptor signaling and trafficking

The mu opioid receptor (μOR), a prototypic member of the large G protein-coupled receptor (GPCR) family, represents an important target of therapeutic and abused drugs. To date, most of our understanding of μOR activity has focused on signal transducers and regulatory molecules including G proteins, GPCR kinases, and beta-arrestins. Yet it is clear that signaling through the μOR is coordinated by additional proteins recruited into the proximal interaction network of the activated receptor, which have largely remained invisible given the lack of technologies to interrogate these networks systematically. Here, we implement a quantitative proteomics pipeline leveraging the chemical diversity of μOR agonists and APEX-based proximity labeling to investigate the protein networks that underlie μOR signaling. We leverage a novel computational framework to extract subcellular location, trafficking, and functional partners of GPCR activity from the proximity labeling datasets. Applying this unbiased, systematic approach to the μOR, we demonstrate that opioid agonists exert differences in the μOR proximal proteome mediated by endocytosis and subsequent endosomal sorting, exemplified by VPS35 and COMMD3. Moreover, we identify two novel μOR network components, EYA4 and KCTD12, that are recruited into the receptor proximal network irrespective of the activating ligand and independent of receptor trafficking but based on receptor-triggered G protein activation. We provide functional evidence that these network components form a previously unrecognized buffering system for G protein activity which broadly modulates cellular GPCR signaling.
Activation of the CA2-vCA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice

Social memory dysfunction is a feature of several neuropsychiatric and neurodevelopmental disorders. Mutation or deletion of the SHANK3 gene, which codes for a synaptic scaffolding protein, has been linked to autism spectrum disorder (ASD) and Phelan-McDermid syndrome, conditions associated with impairments in social memory. Shank3B knockout (KO) mice exhibit several behavioral abnormalities that may be analogous to symptoms of ASD, including social discrimination deficits. The CA2 region of the hippocampus integrates numerous afferents and sends a major output to the ventral CA1 (vCA1), circuitry that plays an important role in social memory. Despite finding few differences in excitatory afferents to the CA2 in Shank3B KO mice, chemogenetic activation of CA2 excitatory neurons restored social recognition function to wildtype (WT) levels. Specific activation of the CA2-vCA1 circuitry had a similar effect. Neuronal oscillations in the theta, gamma and, sharp wave ripple ranges have been linked to social memory, but we observed no differences in these measures between WT and Shank3B KO mice in the vCA1 in response to social stimuli. However, activation of CA2 excitatory neurons enhanced vCA1 theta power in Shank3B KO mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can be sufficient to invoke latent function, particularly with respect to social memory dysfunction. The extent to which vCA1 network oscillations in the theta range are responsible for rescued behavioral function remains unknown.
Multimodal microscale mechanical mapping of cancer cells in complex microenvironments

The mechanical phenotype of the cell is critical for survival following deformations due to confinement and fluid flow. One idea is that cancer cells are plastic and adopt different mechanical phenotypes under different geometries that aid in their survival. Thus, an attractive goal, is to disrupt the cancer cells’ ability to adopt multiple mechanical states. To begin to address this question, we aimed to quantify the diversity of these mechanical states using in vitro biomimetics to mimic in vivo 2D and 3D extracellular matrix environments. Here, we used two modalities Brillouin microscopy (∼GHz) and broadband frequency (3-15kHz) optical tweezer microrheology to measure microscale cell mechanics. We measured the response of intracellular mechanics of cancer cells cultured in 2D and 3D environments where we modified substrate stiffness, dimensionality (2D versus 3D), and presence of fibrillar topography. We determined that there was good agreement between two modalities despite the difference in timescale of the two measurements. These findings on cell mechanical phenotype in different environments confirm a correlation between modalities that employ different mechanisms at different temporal scales (Hz-kHz vs. GHz). We also determined that observed heterogeneity in cell shape that is more closely linked to the cells’ mechanical state. We also determined that individual cells in multicellular spheroids exhibit a lower degree of mechanical heterogeneity when compared to single cells cultured in monodisperse 3D cultures. Moreover, the observed decreased heterogeneity among cells in spheroids suggested that there is mechanical cooperativity between cells that make up a single spheroid.
The connection between the gut mycobiome community of natural black soldier fly populations and their environment

In contrast to interactions between prokaryotic organisms (e.g. bacteria) and insects, an understanding of the interactions between eukaryotic microorganisms (e.g. fungi) and insects is lacking. In this study, black soldier fly larvae were collected from natural populations in household composts. The mycobiome composition of the larval gut and environment was identified using next generation sequencing. The nutrient composition of the larvae’s environment was analyzed. The mycobiome composition was divided into three groups: the first included larvae from Kfar HaHoresh that comprised mostly Meyerozyma and were influenced by the fiber and carbohydrate composition of the compost; the second included the compost samples from Kfar HaHoresh and Misgav Am that mainly comprised the Dipodascaceae family and were influenced by the fiber composition of the compost. The third group contained all the remaining compost and larvae samples and mainly comprised the genus Candida. Candida spp. are the most common in the environment and may thus affect their abundance in the insect gut. However, this species may be adapted to the insect’s gut, providing the insect with a benefit that allows the insect to disperse Candida to new resource patches and thereby help increase its abundance in the environment. In cases where dominant species are not present, it seems that the important factor determining fungal composition in the insect gut is its diet. Understanding the metabolic effect of fungi, e.g. Candida, on the BSF larvae is still a black box which requires further study. IMPORTANCE The research analyzed the mycobiome composition of BSF larvae from natural environments. It was found that the most dominant fungi in these communities is the Candida genus, which was found also dominant in the BSF environment (household compost) that differ in its nutrient composition. Understanding the metabolic effect of these fungi on the BSF larvae have the potential to dramatically affect the physiological condition of the insect. Revealing these metabolic interactions may help to increase the rearing efficiency of insects, such as the BSF, which is currently being reared at large scales as an alternative protein source.
Sorting of mitochondrial and plastid heteroplasmy in Arabidopsis is extremely rapid and depends on MSH1 activity

The fate of new mitochondrial and plastid mutations depends on their ability to persist and spread among the numerous organellar genome copies within a cell (heteroplasmy). The extent to which heteroplasmies are transmitted across generations or eliminated through genetic bottlenecks is not well understood in plants, in part because their low mutation rates make these variants so infrequent. Disruption of MutS Homolog 1 (MSH1), a gene involved in plant organellar DNA repair, results in numerous de novo point mutations, which we used to quantitatively track the inheritance of single nucleotide variants in mitochondrial and plastid genomes in Arabidopsis. We found that heteroplasmic sorting (the fixation or loss of a variant) was rapid for both organelles, greatly exceeding rates observed in animals. In msh1 mutants, plastid variants sorted faster than those in mitochondria and were typically fixed or lost within a single generation. Effective transmission bottleneck sizes for plastids and mitochondria were N ≈ 1 and 4, respectively. Restoring MSH1 function further increased the rate of heteroplasmic sorting in mitochondria (N ≈ 1.3), potentially due to its hypothesized role in promoting gene conversion as a mechanism of DNA repair, which is expected to homogenize genome copies within a cell. Heteroplasmic sorting also favored GC base pairs. Therefore, recombinational repair and gene conversion in plant organellar genomes can potentially accelerate the elimination of heteroplasmies and bias the outcome of this sorting process. Significance statement Mitochondria and plastids play essential roles in eukaryotic life; thus, mutations in these organellar genomes can have severe consequences. In animals, early germline sequestration creates genetic “bottlenecks” providing cell-to-cell variance in mitochondrial mutations upon which selection can act. However, the dynamics of organellar mutations in plants and other organisms that lack early germline segregation remain unclear. Here, we show that sorting of mutations in plant organellar genomes proceeds very rapidly – much faster than in animals. In mitochondria, this process is accelerated by MSH1, a gene involved in recombination and repair of organellar genomes. This suggests that in plants, recombinational repair creates cell-to-cell variance in the frequency of organellar mutations, facilitating selection in the absence of a classical germline bottleneck.
Slc9a6 mutation causes Purkinje cell loss and ataxia in the spontaneous shaker rat

Background The shaker rat carries a naturally occurring mutation leading to progressive ataxia characterized by Purkinje cell (PC) loss. We previously reported on fine-mapping the shaker locus to the long arm of the rat X chromosome. In this work, we sought to identify the mutated gene underlying the shaker phenotype and confirm its identity by functional complementation. Methods We fine-mapped the candidate region and analyzed cerebellar transcriptomes to identify deleterious variants. We generated an adeno-associated virus (AAV) targeting solute carrier family 9, member A6 (Slc9a6) expression to PCs using a mouse L7-6 (L7) promoter, as well as a control green fluorescent protein (GFP)-expressing virus. We administered AAVs prior to the onset of PC degeneration through intracerebroventricular injection and evaluated the molecular, cellular, and motor phenotypes. Results We identified a XM_217630. 9 (Slc9a6):c. [191_195delinsA] variant in the Slc9a6 gene that segregated with disease. This mutation is predicted to generate a truncated sodium-hydrogen exchanger 6 (NHE6) protein, p.(Ala64Glufs*23). Administration of AAV9-PHP.eB expressing rat Slc9a6 prior to symptom onset reduced the shaker motor, molecular, and cellular phenotypes. Interpretation Slc9a6 is mutated in shaker and also in human Christianson syndrome, an epileptic encephalopathy. AAV-based gene therapy may be a viable therapeutic strategy for Christianson syndrome, and the shaker rat model may aid in therapeutic development.
News sharing on Twitter: A nationally comparative study

The utility of Twitter as a medium for public engagement with news events has been well documented. Research has particularly highlighted the importance of Twitter as a space for the rapid assembly of ad hoc publics (Bruns & Burgess, 2015) around breaking news events, aided also by the availability of hashtags as a flexible mechanism for collecting all tweets marked as relevant to a specific topic (Rambukkana, 2015). In this, Twitter arguably even surpasses Facebook, as its flat, non- reciprocal, weak -tie network facilitates the dissemination of news more effectively than the hierarchical, reciprocal, strong -tie structure implemented by Facebook (Dewan & Kumaraguru, 2014).
TOR acts as a metabolic gatekeeper for auxin‐dependent lateral root initiation in Arabidopsis thaliana

Plant organogenesis requires matching the available metabolic resources to developmental programs. In Arabidopsis, the root system is determined by primary root‐derived lateral roots (LRs), and adventitious roots (ARs) formed from non‐root organs. Lateral root formation entails the auxin‐dependent activation of transcription factors ARF7, ARF19, and LBD16. Adventitious root formation relies on LBD16 activation by auxin and WOX11. The allocation of shoot‐derived sugar to the roots influences branching, but how its availability is sensed for LRs formation remains unknown. We combine metabolic profiling with cell‐specific interference to show that LRs switch to glycolysis and consume carbohydrates. The target‐of‐rapamycin (TOR) kinase is activated in the lateral root domain. Interfering with TOR kinase blocks LR initiation while promoting AR formation. The target‐of‐rapamycin inhibition marginally affects the auxin‐induced transcriptional response of the pericycle but attenuates the translation of ARF19, ARF7, and LBD16. TOR inhibition induces WOX11 transcription in these cells, yet no root branching occurs as TOR controls LBD16 translation. TOR is a central gatekeeper for root branching that integrates local auxin‐dependent pathways with systemic metabolic signals, modulating the translation of auxin‐induced genes.
Comprehensive profiling of antibody responses to the human anellome using programmable phage display

Viruses belonging to the diverse Anelloviridae family represent a major constituent of the commensal human virome. Aside from their widespread prevalence and persistence in humans and their absence of detectable pathologic associations, little is known about the immunobiology of the human anellome. In this study, we employed the Phage ImmunoPrecipitation Sequencing (PhlP-Seq) assay for comprehensive analyses of antibody binding to 56 amino acid long anellovirus peptides. We designed and constructed a large and diverse “AnelloScan” T7 phage library comprising more than 32,000 non-redundant peptides representing the ORF1, ORF2, ORF3 and TTV-derived apoptosis-inducing protein (TAIP) sequences of more than 800 human anelloviruses (spanning three genera). We used this library to profile the antibody reactivities of serum samples from 156 subjects. The vast majority of anellovirus peptides were not reactive in any of the subjects tested (n=~28,000; ~85% of the library). Antibody reactive peptides were largely restricted to the C-terminal region of the putative capsid protein, ORF1. To characterize antibody responses to newly acquired anellovirus infections, we screened a longitudinal cohort of matched blood-transfusion donors and recipients. Most transmitted anelloviruses did not elicit detectable antibody reactivity in the recipient (29 out of a total of 40 transmitted anelloviruses) and the remainder demonstrated delayed reactivity (~100-150 days after transfusion). This study represents the first large-scale epitope-level serological survey of the antibody response to the human anellome. Graphical Abstract
Systemic Ablation of Camkk2 Impairs Metastatic Colonization and Improves Insulin Sensitivity in TRAMP Mice: Evidence for Cancer Cell-Extrinsic CAMKK2 Functions in Prostate Cancer

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2’s effects on whole body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of Camkk2 slows, but does not stop, primary prostate tumorigenesis in the TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) genetic mouse model. Consistent with prior epidemiological reports supporting a link between obesity and prostate cancer aggressiveness, TRAMP mice fed a high-fat diet exhibited a pronounced increase in the colonization of lung metastases. We demonstrated that this effect on metastatic spread was dependent on CAMKK2. Notably, diet-induced lung metastases exhibited a highly aggressive neuroendocrine phenotype. Concurrently, Camkk2 deletion improved insulin sensitivity in the same mice. Histological analyses revealed that cancer cells were smaller in the TRAMP;Camkk2-/- mice compared to TRAMP;Camkk2+/+ controls. Given the differences in circulating insulin levels, a known regulator of cell growth, we hypothesized that systemic CAMKK2 could promote prostate cancer cell growth and disease progression in part through cancer cell-extrinsic mechanisms. Accordingly, host deletion of Camkk2 impaired the growth of syngeneic murine prostate tumors in vivo, confirming nonautonomous roles for CAMKK2 in prostate cancer. Cancer cell size and mTOR signaling was diminished in tumors propagated in Camkk2-null mice. Together, these data indicate that, in addition to cancer cell-intrinsic roles, CAMKK2 promotes prostate cancer progression via tumor-extrinsic mechanisms. Further, we propose that CAMKK2 inhibition may also help combat common metabolic comorbidities in men with advanced prostate cancer.
PinR as a Stress Inducible Inhibitory Transcription Factor in Stopping Stress-induced Mutagenesis Bacterial Evolution of Antibiotic Resistance

PinR is a lambdoid prophage Rac existing in many different bacteria, but its function is yet to be discovered. Here, we report PinR as an effective “anti-evolution” target towards 16 combating antibiotic resistant bacteria. We show the function of PinR as a stress 17 inducible inhibitory transcription factor in the bacterial evolution of antibiotic resistance, 18 which represses the transcriptions of many oxidative stress response genes and 19 consequently orchestrate the ROS burst-induced evolution of antibiotic resistance. We 20 show that deletion of pinR gene can avoid the accelerated evolution of antibiotic resistance 21 induced by the deficiency of DNA repair, while the strategies to target RecA, e.g., the 22 deletion of recA gene, can be safely implemented to disarm the bacterial resistances to a 23 variety of antibiotics.
De novo mutations in KIF1A-associated neuronal disorder (KAND) dominant-negatively inhibit motor activity and axonal transport of synaptic vesicle precursors

KIF1A is a kinesin superfamily molecular motor that transports synaptic vesicle precursors in axons. Mutations in Kif1a lead to a group of neuronal diseases called KIF1A-associated neuronal disorder (KAND). KIF1A forms a homodimer and KAND mutations are mostly de novo and autosomal dominant; however, it is not known whether the function of wild-type KIF1A is inhibited by disease-associated KIF1A when they are dimerized. No reliable in vivo model systems to analyze the molecular and cellular biology of KAND caused by loss of function mutations have been developed; therefore, here, we established Caenorhabditis elegans models for KAND using CRISPR/cas9 technology and analyzed defects in axonal transport. In the C. elegans models, heterozygotes and homozygotes exhibited reduced axonal transport phenotypes. Suppressor screening using the disease model worm identified a mutation that recovers the motor activity of disease-associated human KIF1A. In addition, we developed in vitro assays to analyze the motility of single heterodimers composed of wild-type KIF1A and disease-associated KIF1A. Disease-associated KIF1A significantly inhibited the motility of wild-type KIF1A when heterodimers were formed. These data indicate the molecular mechanism underlying the dominant nature of de novo KAND mutations. Significance Statement KIF1A is a molecular motor that transports synaptic vesicle precursors in axons. Recent studies have identified many KIF1A mutations in congenital neuropathy patients; however, the molecular mechanism of pathogenesis remains largely elusive. This study established loss of function models for KIF1A-associated neuronal disorder (KAND) in Caenorhabditis elegans to analyze the molecular and cell biology of the disease in vivo. Genetic screening using the disease model could find a mutation that recovers the motor activity of disease-associated KIF1A. This study also established in vitro single-molecule assays to quantitatively analyze the effect of KAND mutations when mutant KIF1A forms heterodimers with wild-type KIF1A. Our findings provide a foundation for future genetic screening and for drug screening to search for KAND treatments.