Miracle-dz/UniFAR-FTUs huggingface dataset:
Cacna2d2 is an hnRNP H target of the striatal mRNA targetome and regulates methamphetamine behavior

Methamphetamine addiction remains a major public health concern in the United States that has paralleled the opioid epidemic. Psychostimulant use disorders have a heritable genetic component that remains unexplained. Methamphetamine targets membrane and vesicular transporters to increase synaptic dopamine, norepinephrine, and serotonin. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying methamphetamine behavioral sensitivity. Hnrnph1 encodes the RNA-binding protein hnRNP H1 that is ubiquitously expressed in neurons throughout the brain. Gene-edited mice with a heterozygous frameshift deletion in the first coding exon of Hnrnph1 showed reduced methamphetamine-induced dopamine release and behaviors. To inform the mechanism linking hnRNP H dysfunction with reduced methamphetamine neurobehavioral effects, we surveyed the mRNA targetome of hnRNP H via cross-linking immunoprecipitation coupled with RNA-sequencing in striatal tissue at baseline and at 30 min post-methamphetamine. Methamphetamine induced opposite changes in RNA-binding targets of hnRNP H in Hnrnph1 mutants versus wild-types, including 3’UTR targets in mRNAs enriched for synaptic proteins involved in dopamine release and excitatory synaptic plasticity. Targetome, transcriptome, and spliceome analyses triangulated on a methamphetamine-induced upregulation of the calcium channel subunit transcript Cacna2d2 and decreased its 3’UTR usage in hyposensitive Hnrnph1 mutants. Pretreatment with pregabalin, an inhibitor of α2δ2 and α2δ1 voltage-gated calcium channel subunits attenuated methamphetamine-induced locomotor activity in wild-type females but not in Hnrnph1 mutants, supporting Cacna2d2 as a hnRNP H target. Our study identifies a dynamic hnRNP H RNA targetome that can rapidly and adaptively respond to methamphetamine to regulate gene expression and likely synaptic plasticity and behavior. SIGNIFICANCE STATEMENT The genetic risks mediating psychostimulant addiction are unknown and there are no FDA-approved treatments. We identified Hnrnph1 in modulating methamphetamine behavioral sensitivity in mice. Hnrnph1 codes for hnRNP H1, an RNA-binding protein. Here, we asked whether an Hnrnph1 mutation and methamphetamine treatment would change the hnRNP H RNA targets and whether these targets could tell us how Hnrnph1 is linked to behavior. We identified a calcium channel subunit that is a primary target of the FDA-approved drug pregabalin (a.k.a. Lyrica®). Like the Hnrnph1 mutation, pregabalin reduced methamphetamine behaviors in wild-type mice. We propose hnRNP H regulates calcium channels in response to methamphetamine-induced perturbations in neurotransmitter release. Accordingly, pregabalin could represent a novel treatment to restore synaptic function following methamphetamine administration.
Distinct Differences in Gene Expression Profiles in Early and Late Stage Rhodesiense HAT Individuals in Malawi

T. b. rhodesiense is the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between the different foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected with T. b. rhodesiense was used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease focus. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 25 healthy controls and 23 r-HAT case samples of which 3 case samples were excluded for downstream analysis as outliers. 4519 genes were significantly differentially expressed (p adjusted <0.05) in individuals with early stage 1 r-HAT disease (n = 12) and 1824 genes in individuals with late stage 2 r-HAT disease (n = 8). Enrichment of innate immune response genes through neutrophil activation was identified in individuals with both early and late stages of the disease. Additionally, lipid metabolism genes were enriched in late stage 2 disease. We further identified uniquely upregulated genes (log2 Fold Change 1.4 - 2.0) in stage 1 (ZNF354C) and stage 2 (TCN1 and MAGI3) blood. Our data brings new insight into the human transcriptome landscape during T. b. rhodesiense infection. We have further identified key biological pathways and transcripts during stage 1 and stage 2 r-HAT. Lastly, we have identified potential diagnostic biomarkers that may be used for staging of r-HAT disease.
PTPN1 Deficiency Modulates BMPR2 Signaling and Induces Endothelial Dysfunction in Pulmonary Arterial Hypertension

Bone morphogenic protein receptor 2 (BMPR2) expression and signaling are impaired in pulmonary arterial hypertension (PAH). How BMPR2 signaling is decreased in PAH is poorly understood. Protein tyrosine phosphatases (PTPs) play important roles in vascular remodeling in PAH. To identify whether PTPs modify BMPR2 signaling we used a siRNA-mediated high throughput screening of 22,124 murine genes in mouse myoblastoma reporter cells using ID1 expression as read-out for BMPR2 signaling. We further experimentally validated the top hit, PTPN1 (PTP1B), in human healthy pulmonary arterial endothelial cells (PAECs) either silenced by siRNA or exposed to hypoxia and confirmed its relevance to PAH by measuring PTPN1 levels in blood and PAECs collected from PAH patients. We identified PTPN1 as a novel regulator of BMPR2 signaling in PAECs, which is downregulated in the blood of PAH patients and documented that downregulation of PTPN1 is linked to endothelial dysfunction in PAECs. These findings point to a potential involvement for PTPN1 in PAH and will aid in our understanding of the molecular mechanisms involved in the disease.
Extracellular disintegration of viral proteins as an innovative strategy for developing broad-spectrum antivirals against coronavirus

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed millions of lives worldwide, not to mention innumerable losses in the global economy and disruptions in social relationships. Unfortunately, state-of-the-art treatments still lag behind the fast emergence of new variants of concern. The key to resolve this issue is to develop broad-spectrum antivirals with innovative antiviral mechanisms in which coronaviruses are deactivated regardless of their variant development. Herein, we report a new antiviral strategy involving extracellular disintegration of viral proteins that are indispensable for viral infection with hyperanion-grafted enediyne molecules. The sulfate groups ensure low cellular permeability and rather low cytotoxicity of the molecules, while the core enediyne generates reactive radical species and causes significant damage to the spike (S) protein of coronavirus. The enediyne compounds exhibit antiviral activity at micromolar to nanomolar concentrations, and the selectivity index of up to 20,000 against four kinds of human coronaviruses, including the SARS-CoV-2 omicron variant, suggesting the high potential of this new strategy in combating the COVID-19 pandemic.
Synaptic weights that correlate with presynaptic selectivity increase decoding performance

The activity of neurons in the visual cortex is often characterized by tuning curves, which are thought to be shaped by Hebbian plasticity during development and sensory experience. This leads to the prediction that neural circuits should be organized such that neurons with similar functional preference are connected with stronger weights. In support of this idea, previous experimental and theoretical work have provided evidence for a model of the visual cortex characterized by such functional subnetworks. A recent experimental study, however, have found that the postsynaptic preferred stimulus was defined by the total number of spines activated by a given stimulus and independent of their individual strength. While this result might seem to contradict previous literature, there are many factors that define how a given synaptic input influences postsynaptic selectivity. Here, we designed a computational model in which postsynaptic functional preference is defined by the number of inputs activated by a given stimulus. Using a plasticity rule where synaptic weights tend to correlate with presynaptic selectivity, and is independent of functional-similarity between pre- and postsynaptic activity, we find that this model can be used to decode presented stimuli in a manner that is comparable to maximum likelihood inference.
Harnessing the Power of Defaults Now and Forever? The Effects of Mood and Personality

ABSTRACT Opt-in, opt-out, and forced choice are the three policies most frequently used to engage consumers’ willingness to receive e-mail communication. This research examines the effectiveness and the persistence of these policies in engaging consumer consent to receive e-mail communication, while the effects of consumer mood and personality traits are embedded in the research framework. Three experiments served as the vehicle for data collection. Interaction effects between the default policies and consumer mood and personality traits are examined using logit and multiple regression models. Results show that opt-out is more effective than opt-in and forced choice in engaging consumer consent to receive e-mail communication. Interestingly, opt-in is the most effective policy in engaging a more permanent consumer consent. Although negative mood results in a higher consumer consent rate for e-mail notifications, positive mood results in a higher consent rate for future engagement. Higher levels of neuroticism lead to higher willingness to receive e-mail notifications, but higher extraversion leads to higher future engagement. The article contributes to the literature on defaults, mood, and personality traits. The findings advance the theory and have important managerial implications.
How do the framing effects, environmental factors and personal risk perceptions influence our decision about a hypothetical COVID-19 pill?

ABSTRACT This study investigates the willingness to pay for the real COVID-19 vaccine and the framing effect for a hypothetical COVID-19 pill. The way how a message concerning a risky situation is formulated impacts decisions. However, personal characteristics, like attitude to risk, also strongly impact this decision. In this study, risk attitudes are measured with the DOSPERT Scale. As many studies proved, the intention to be vaccinated is not just related to risk preferences, but also strongly influenced by socioemotional factors. The extent to which friends and relatives are vaccinated in our social circles as well as the concern for both others and for ourselves influence this decision. Using an online survey, personal pricing and acceptance of both real and hypothetical COVID-19 medicines were studied. The results of the descriptive and inference statistics concerning how the message frame impacts pricing are ambiguous, but the significant effects of environmental and individual factors are confirmed.
The Seeds of Industrial Hemp (Cannabis Sativa L.) a Source of Minerals and Biologically Active Compounds

ABSTRACT The study aims to investigate industrial hemp growing potential in the Nordic-Baltic region, to assess the impact of various agrotechnological measures on macro: calcium, magnesium, potassium, phosphorus, and micronutrient: boron, iron, manganese, copper, zinc accumulation in hemp seeds, and to determine biologically active compounds and beneficial elements: elements cobalt, aluminum, sodium accumulation trends. Obtained results indicate that hemp seeds are rich in K (0.69–0.90%) followed by P (0.41–0.51%), Mg (0.42–0.46%), and Ca (0.10–0.19%). It was determined that Fe (181–334 mg/kg) was the main abundant microelement followed by Mn (58–81 mg/kg), Zn (55–68 mg/kg), Cu (13–20 mg/kg), and B (7–16 mg/kg) independently from applied agrotechnological measures. The amount of biologically active compounds ranged from 6.55 to 12.39 mg/gRUE and from 2.52 to 4.74 mg/gRUE, respectively, for TPC and TFC. A significant amount of beneficial elements Al (6.0–12.6 mg/kg) and Na (0.90–16.1 mg/kg) except Co were obtained. Results presented in this study indicate that seeds of industrial hemp grown in the Nordic-Baltic region could be considered as an important source of essential minerals and biologically active compounds.
A restricted Liu estimator for binary regression models and its application to an applied demand system

In this article, we propose a restricted Liu regression estimator (RLRE) for estimating the parameter vector, β, in the presence of multicollinearity, when the dependent variable is binary and it is suspected that β may belong to a linear subspace defined by Rβ = r. First, we investigate the mean squared error (MSE) properties of the new estimator and compare them with those of the restricted maximum likelihood estimator (RMLE). Then we suggest some estimators of the shrinkage parameter, and a simulation study is conducted to compare the performance of the different estimators. Finally, we show the benefit of using RLRE instead of RMLE when estimating how changes in price affect consumer demand for a specific product.
Critical state of bubbles in liquid‐gas solutions

According to homogeneous nucleation theory, the spontaneous formation of a bubble occurs in a liquid when a thermodynamic fluctuation of sufficient magnitude occurs to form a bubble of at least the critical size. Here we report the results of an experimental study of bubbles near the critical state. We examine both the stability of this state and the predicted value of the critical radius. Photographs of two bubbles simultaneously present in a liquid, one slightly larger than the critical size and the other slightly smaller, are presented. Subsequent photographs show the larger one to grow and the smaller one to dissolve. Hence the critical state is unstable and the critical radius lies between the initial radii of the two bubbles. A second series of tests was conducted to examine more carefully the value of the critical radius.
Are all Frames Equal? Active Sparse Labeling for Video Action Detection

Video action detection requires annotations at every frame, which drastically increases the labeling cost. In this work, we focus on efﬁcient labeling of videos for action detection to minimize this cost. We propose active sparse labeling (ASL) , a novel active learning strategy for video action detection. Sparse labeling will reduce the annotation cost but poses two main challenges; 1) how to estimate the utility of annotating a single frame for action detection as detection is performed at video level? , and 2) how these sparse labels can be used for action detection which require annotations on all the frames? This work attempts to address these challenges within a simple active learning framework. For the ﬁrst challenge, we propose a novel frame-level scoring mechanism aimed at selecting most informative frames in a video. Next, we introduce a novel loss formulation which enables training of action detection model with these sparsely selected frames. We evaluate the proposed approach on two different action detection benchmark datasets, UCF-101-24 and J-HMDB-21, and observed that active sparse labeling can be very effective in saving annotation costs. We demonstrate that the proposed approach performs better than random selection, outperforming all other baselines, with performance comparable to supervised approach using merely 10% annotations. Project details available at https://www.crcv. ucf.edu/research/projects/active-sparse-labeling-for-video-action-detection/
Compton scattering in strong magnetic fields

The relativistic cross section for Compton scattering by electrons in strong magnetic fields is derived. The results confirm and extend earlier work which has treated only transitions to the lowest or first excited Landau levels. For the teragauss field strengths expected in neutron star magnetospheres, the relative rates for excited state transitions are found to be significant, especially for incident photon energies several times the cyclotron frequency. Since these transitions must result in the rapid emission of one or more cyclotron photons as well as the Compton-scattered photon, the scattering process actually becomes a photon splitting mechanism which acts to soften hard photon spectra, and also provides a specific mechanism for populating higher Landau levels in the electron distribution function. The results should be significant for models of gamma-ray bursters and pulsating X-ray sources. 15 references.
Influencing factors of users’ shift to buying expensive virtual gifts in live streaming: Empirical evidence from China

The market size of live streaming on the Internet, in which the streamer earns profit by prompting users to give virtual gifts through emotional labor, is getting bigger and bigger. However, most users will only buy cheap virtual gifts in live streaming, therefore exploring how to promote users to buy expensive virtual gifts is a valuable topic in live commerce research. Based on social presence theory and information overload theory, this study used the PLS-SEM method to investigate the factors influencing live streaming users to shift from buying cheap virtual gifts to buying expensive virtual gifts, and analyzed the moderating role of information overload in these relationships. The results show that immediate interaction anxiety, verbal intimacy, and virtual physical intimacy positively influence users’ shift to purchasing expensive virtual gifts, and that perceived network size and perceived financial risk are negative factors in users’ shift to purchasing expensive virtual gifts. Information overload has a moderating role in the relationship between immediate interaction anxiety and switch intention, and it also plays a moderating role in the relationship between perceived network size and perceived financial risk on users’ switch intention.
2.5D mass spectrometry imaging of N-glycans in esophageal adenocarcinoma and precursor lesions

Glycosylation plays an important role in the progression of esophageal adenocarcinoma (EAC). Being able to image these glycosylation changes directly in endoscopic resection specimens could provide useful insights into the molecular mechanisms of the disease progression and potential markers for EAC staging. For this purpose, both 3D and 2.5D matrix-assisted laser/desorption ionization (MALDI) mass spectrometry imaging (MSI) have been employed in this study to investigate glycosidase-cleaved N-glycans in a total of 24 formalin-fixed paraffin-embedded esophageal local excision specimens spanning all stages of disease progression, namely from non-dysplastic Barrett’s esophagus to metastatic EAC. 3D-MSI was first used to estimate the number of sections needed to sufficiently cover the molecular heterogeneity of each stage of progression. This analysis showed that a total of four sections out of 20 were sufficient. This subset of four sections was measured for all remaining specimens and is called 2.5D-MSI. Subsequent analyses of the 2.5D-MSI datasets revealed significant elevations of five high-mannose N-glycans (Man3, Man4, Man6, Man7, and Man8) in EAC and three complex (Hex6HexNAc5, Hex6HexNAc5NeuAc1, Hex7HexNAc6) N-glycans in metastatic EAC as compared to previous stages of the disease. The augmented levels of these glycans in EAC could be explained by publically available gene expression data of enzymes involved in glycan synthesis and processing. As the role of glycosylation is gaining more interest in MSI and cancer research, our results show the added value of combining localized N-glycan levels, as provided by MSI, with gene expression to gain a deeper understanding of the mechanisms behind N-glycan changes. This gives evidence at multiple levels that specific N-glycosylation plays an important role during progression of dysplasia to EAC and could play a role in patient surveillance.
Fecal microbiota transplantation restores normal fecal composition and delays malignant development of mild chronic kidney disease in rats

Chronic kidney disease (CKD) is associated with gut microbiome dysbiosis, but the role of intestinal flora in CKD treatment remains to be elucidated. Fecal microbiota transplantation (FMT) can be utilized to re-establish healthy gut microbiota for a variety of diseases, which offers new insight for treating CKD. First, 5/6 nephrectomy rats (Donor CKD) and sham rats (Donor Sham) were used as donors for FMT, and fecal metagenome were analyzed to explore potential therapeutic targets. Then, to assess the effect of FMT on CKD, sterilized 1/2 nephrectomy rats were transplanted with fecal microbiota from Donor sham (CKD/Sham) or Donor CKD (CKD/CKD) rats, and 1/2 nephrectomy rats without FMT (CKD) or no nephrectomy (Sham) were used as model control or normal control. Results showed that Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 were enriched in Donor CKD, while Lactobacillus johnsonii and Lactobacillus intestinalis were reduced. In addition, the increased abundance of microbial functions included tryptophan metabolism and lysine degradation contributing to the accumulation of protein-bound uremic toxins (PBUTs) in Donor CKD. Genome analysis indicated that FMT successfully differentiated groups of gut microbes and altered specific gut microbiota after 1 week of treatment, with Bacteroides uniformis and Anaerotruncus sp. 1XD22-93 increasing in CKD/CKD group as well as Lactobacillus johnsonii and Lactobacillus intestinalis being improved in CKD/Sham group. In comparison to CKD group, substantial PBUT buildup and renal damage were observed in CKD/CKD. Interestingly, compared to CKD or CKD/CKD group, tryptophan metabolism and lysine degradation were efficiently suppressed in CKD/Sham group, while lysine biosynthesis was promoted. Therefore, FMT considerably reduced PBUTs accumulation. After FMT, PBUTs and renal function in CKD/Sham rats remained the same as in Sham group throughout the experimental period. In summary, FMT could delay the malignant development of CKD by modifying microbial amino acid metabolism through altering the microenvironment of intestinal flora, thereby providing a novel potential approach for treating CKD.