Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulatory effects of post-translational modifications on zDHHC S-acyltransferases

The human zDHHC S-acyltransferase family comprises 23 enzymes that mediate the S-acylation of a multitude of cellular proteins, including channels, receptors, transporters, signaling molecules, scaffolds, and chaperones. This reversible post-transitional modification (PTM) involves the attachment of a fatty acyl chain, usually derived from palmitoyl-CoA, to specific cysteine residues on target proteins, which affects their stability, localization, and function. These outcomes are essential to control many processes, including synaptic transmission and plasticity, cell growth and differentiation, and infectivity of viruses and other pathogens. Given the physiological importance of S-acylation, it is unsurprising that perturbations in this process, including mutations in ZDHHC genes, have been linked to different neurological pathologies and cancers, and there is growing interest in zDHHC enzymes as novel drug targets. Although zDHHC enzymes control a diverse array of cellular processes and are associated with major disorders, our understanding of these enzymes is surprisingly incomplete, particularly with regard to the regulatory mechanisms controlling these enzymes. However, there is growing evidence highlighting the role of different PTMs in this process. In this review, we discuss how PTMs, including phosphorylation, S-acylation, and ubiquitination, affect the stability, localization, and function of zDHHC enzymes and speculate on possible effects of PTMs that have emerged from larger screening studies. Developing a better understanding of the regulatory effects of PTMs on zDHHC enzymes will provide new insight into the intracellular dynamics of S-acylation and may also highlight novel approaches to modulate S-acylation for clinical gain.
A Shared TCR Bias toward an Immunogenic EBV Epitope Dominates in HLA-B*07:02–Expressing Individuals

Key Points Shared bias of TRBV4-1 dominates the HLA-B7 EBVRPP–specific CD8+ T cell response. Key residues of TRBV4-1 CDR1/2 loops interact with the HLA-B7/EBVRPP complex. EBV is one of the most common viruses found in humans and is prototypic of a persistent viral infection characterized by periods of latency. Across many HLA class I molecules, the latent-specific CD8+ T cell response is focused on epitopes derived from the EBNA-3 protein family. In the case of HLA-B*07:02 restriction, a highly frequent class I allele, the T cell response is dominated by an epitope spanning residues 379–387 of EBNA-3 (RPPIFIRRL [EBVRPP]). However, little is known about either the TCR repertoire specific for this epitope or the molecular basis for this observed immunodominance. The EBVRPP CD8+ T cell response was common among both EBV-seropositive HLA-B*07:02+ healthy and immunocompromised individuals. Similar TCRs were identified in EBVRPP–specific CD8+ T cell repertoires across multiple HLA-B7+ individuals, indicating a shared Ag-driven bias in TCR usage. In particular, TRBV4-1 and TRAV38 usage was observed in five out of six individuals studied. In this study, we report the crystal structure of a TRBV4-1+ TCR–HLA-B*07:02/EBVRPP complex, which provides a molecular basis for the observed TRBV4-1 bias. These findings enhance our understanding of the CD8+ T cell response toward a common EBV determinant in HLA-B*07:02+ individuals.
Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics

SUMMARY: Deep brain stimulation is an established therapy for multiple brain disorders, with rapidly expanding potential indications. Neuroimaging has advanced the field of deep brain stimulation through improvements in delineation of anatomy, and, more recently, application of brain connectomics. Older lesion-derived, localizationist theories of these conditions have evolved to newer, network-based “circuitopathies,” aided by the ability to directly assess these brain circuits in vivo through the use of advanced neuroimaging techniques, such as diffusion tractography and fMRI. In this review, we use a combination of ultra-high-field MR imaging and diffusion tractography to highlight relevant anatomy for the currently approved indications for deep brain stimulation in the United States: essential tremor, Parkinson disease, drug-resistant epilepsy, dystonia, and obsessive-compulsive disorder. We also review the literature regarding the use of fMRI and diffusion tractography in understanding the role of deep brain stimulation in these disorders, as well as their potential use in both surgical targeting and device programming.
A three-gene signature based on MYC, BCL-2 and NFKBIA improves risk stratification in diffuse large B-cell lymphoma

Recent randomized trials focused on gene expression-based determination of the cell of origin in diffuse large B-cell lymphoma could not show significant improvements by adding novel agents to standard chemoimmunotherapy. The aim of this study was the identification of a gene signature able to refine current prognostication algorithms and applicable to clinical practice. Here we used a targeted gene expression profiling panel combining the Lymph2Cx signature for cell of origin classification with additional targets including MYC, BCL-2 and NFKBIA, in 186 patients from two randomized trials (discovery cohort) (clinicaltrials gov. Identifier: NCT00355199 and NCT00499018). Data were validated in three independent series (two large public datasets and a real-life cohort). By integrating the cell of origin, MYC/BCL-2 double expressor status and NFKBIA expression, we defined a three-gene signature combining MYC, BCL-2 and NFKBIA (MBN-signature), which outperformed the MYC/BCL-2 double expressor status in multivariate analysis, and allowed further risk stratification within the germinal center B-cell/unclassified subset. The high-risk (MBN Sig-high) subgroup identified the vast majority of double hit cases and a significant fraction of activated B-cell-derived diffuse large B-cell lymphomas. These results were validated in three independent series including a cohort from the REMoDL-B trial, where, in an exploratory ad hoc analysis, the addition of bortezomib in the MBN Sig-high subgroup provided a progression free survival advantage compared with standard chemoimmunotherapy. These data indicate that a simple three-gene signature based on MYC, BCL-2 and NFKBIA could refine the prognostic stratification in diffuse large B-cell lymphoma, and might be the basis for future precision-therapy approaches.
SARS-CoV-2 Community Transmission disproportionately affects Latinx population during Shelter-in-Place in San Francisco

Abstract Background There is urgent need to understand the dynamics and risk factors driving ongoing SARS-CoV-2 transmission during shelter-in-place mandates. Methods We offered SARS-CoV-2 reverse transcription-PCR and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (≥4 years) and workers in a San Francisco census tract (population: 5,174) at outdoor, community-mobilized events over four days. We estimated SARS-CoV-2 point prevalence (PCR-positive) and cumulative incidence (antibody or PCR-positive) in the census tract and evaluated risk factors for recent (PCR-positive/antibody-negative) versus prior infection (antibody-positive/PCR-negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions. Results We tested 3,953 persons: 40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black. Overall, 2.1% (83/3,871) tested PCR-positive: 95% were Latinx and 52% asymptomatic when tested. 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR-positive. Among 2,598 tract residents, estimated point prevalence of PCR-positives was 2.3% (95%CI: 1.2-3.8%): 3.9% (95%CI: 2.0-6.4%) among Latinx vs. 0.2% (95%CI: 0.0-0.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95%CI: 4.0-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter-in-place and maintain income, frontline service work, unemployment, and household income &$50,000/year. Five SARS-CoV-2 phylogenetic lineages were detected. Conclusion SARS-CoV-2 infections from diverse lineages continued circulating among low-income, Latinx persons unable to work from home and maintain income during San Francisco’s shelter-in-place ordinance.
Age and Genetic Background Modify Hybrid Male Sterility in House Mice

Hybrid male sterility (HMS) contributes to reproductive isolation commonly observed among house mouse (Mus musculus) subspecies, both in the wild and in laboratory crosses. Incompatibilities involving specific Prdm9 alleles and certain Chromosome (Chr) X genotypes are known determinants of fertility and HMS, and previous work in the field has demonstrated that genetic background modifies these two major loci. We constructed hybrids that have identical genotypes at Prdm9 and identical X chromosomes, but differ widely across the rest of the genome. In each case, we crossed female PWK/PhJ mice representative of the M. m. musculus subspecies to males from a classical inbred strain representative of M. m. domesticus: 129S1/SvImJ, A/J, C57BL/6J, or DBA/2J. We detected three distinct trajectories of fertility among the hybrids using breeding experiments. The PWK129S1 males were always infertile. PWKDBA2 males were fertile, despite their genotypes at the major HMS loci. We also observed age-dependent changes in fertility parameters across multiple genetic backgrounds. The PWKB6 and PWKAJ males were always infertile before 12 weeks and after 35 weeks. However, some PWKB6 and PWKAJ males were transiently fertile between 12 and 35 weeks. This observation could resolve previous contradictory reports about the fertility of PWKB6. Taken together, these results point to multiple segregating HMS modifier alleles, some of which have age-related modes of action. The ultimate identification of these alleles and their age-related mechanisms will advance understanding both of the genetic architecture of HMS and of how reproductive barriers are maintained between house mouse subspecies.
Time trends in incidence, comorbidity, and mortality of ischemic stroke in Denmark (1996–2016)

Objective To examine whether the incidence, comorbidity, and mortality of first-time ischemic stroke changed in Denmark between 1996 and 2016 overall and according to age and sex using a nationwide cohort design. Methods In this cohort study, 224,617 individuals ≥18 years of age admitted with first-time ischemic stroke between 1996 and 2016 were identified through Danish nationwide registries. We calculated annual age-standardized incidence rates and absolute 30-day and 1-year mortality risks. Furthermore, we calculated annual incidence rate ratios using Poisson regression, odds ratios for 30-day mortality using logistic regression, and hazard ratios for 1-year mortality using Cox regression. Results The overall age-standardized incidence rates of ischemic stroke per 1,000 person-years increased from 1996 (2.70 [95% confidence interval [CI] 2.65–2.76]) to 2002 (3.25 [95% CI 3.20–3.31]) and then gradually decreased to below the initial level until 2016 (1.99 [95% CI 1.95–2.02]). Men had higher incidence rates than women in all age groups except 18 to 34 and ≥85 years. Absolute mortality risk decreased between 1996 and 2016 (30-day mortality from 17.1% to 7.6% and 1-year mortality from 30.9% to 17.3%). Women between 55 and 64 and ≥85 years of age had higher mortality than men. Similar trends were observed for all analyses after multivariable adjustment. The prevalence of atrial fibrillation, hypertension, diabetes mellitus, and use of lipid-lowering medication increased during the study period. Conclusions The age-standardized incidence of first-time hospitalization for ischemic stroke increased from 1996 to 2002 and then gradually decreased to below the initial level until 2016. Absolute 30-day and 1-year mortality risks decreased between 1996 and 2016. These findings correspond to increased stroke prevention awareness and introduction of new treatments during the study period.
Detection of Luminous Vibrio harveyi in Penaeid Shrimp Through Nested PCR Using Haemolysin Gene Primer

Whiteleg shrimp ( Litopenaeus vannamei ) is one of the most important aquaculture commodity in Indonesia. However, the luminous disease primarily caused by Vibrio harveyi bacteria still becomes an obstacle in penaeid shrimp farming, especially in shrimp hatchery. This study was aimed to identify the presence of V. harveyi in L. vannamei through nested PCR using haemolysin gene primer. First, initial primers were designed using V. harveyi VIB 391 haemolysin gene sequence (accession number: DQ640264), flanking the position 133 to 756. This primer pairs were used to identify haemolysin gene in both V. harveyi MR5339 and V. harveyi 275 strain. Sequencing results from each sample showed 99% similarity with haemolysin gene sequence in Genebank. Furthermore, the sequence of V. harveyi MR5339 haemolysin gene was used to design the nested PCR primers. The first primer pairs of nested PCR have successfully amplified the haemolysin gene fragment of all V. harveyi strains samples from position 52 to 405. The second primer pairs of nested PCR have amplified position 204 to 405 where it can detect all of V. harveyi strains used as sample sources in this study. The application of nested PCR technique in this study was able to identify V. harveyi strains at serial dilution of cells density as low as 10 0 cfu/mL, which is equal to a single cell or at DNA concentration up to 10 1 fg/µL.
A Near-Infrared-Induced Contractile Proteinosome Microreactor with A Fast Control on Enzymatic Reaction.

Inspired by the compartmentalized structure of cells, a self-regulating responsive hollow microcapsule is highly desirable for the modulation of enzymatic reactions. Here, we report a way to fabricate gold nanorod embedded proteinosomes by covalently grafting gold nanorod onto the surface of proteinosome. The excellent photothermal conversion efficiency of the embedded gold nanorod and the thermal phase transition of the grafted PNIPAAm allow the constructed hybrid proteinosomes to show reversible contraction behaviours triggered by near-infrared light with the molecular weight cutoff of the membrane decreased to be ca. 50 kDa, and importantly, the contraction frequency of the constructed proteinosomes could be as fast as 1 min and lasted for at least 15 cycles. Then the effective encapsulation of three cascade enzymes into the proteinosomes realizes the construction of a near-infrared responsive microreactor that allows control of the cascade reaction by near-infrared illumination, thereby enabling reversible opening and closing of the enzymatic reaction. Such microcapsule-based reactors demonstrate the potential to alter membrane molecular weight cutoff, and it is believed that the development of such responsive microcapsules will have great potential for studying cellular responses and provide a platform for the future applications in biosensing and drug delivery.
Audit of Carotid Doppler Sonography: Spectrum of Findings at a Tertiary Hospital in Northwestern Nigeria

Introduction: Doppler sonography of the cervical segment of the carotid arteries is becoming a popular tool for evaluating atherosclerosis of the carotid artery. We present the audit of findings on carotid ultrasound examination among patients with clinical suspicion and risks for cerebrovascular disease and possible correlates in Northern Nigeria. Materials and Methods: We performed carotid ultrasound examination on all patients referred for screening and clinical suspicion of cerebrovascular disease within the year 2017. The patients' characteristics, risk factors, presence of atheroma and characteristic of the atheroma, degree of stenotic disease as well as the presence of incidental ultrasound findings were reviewed and documented. Results: Out of the 62 patients, 55 (88.7%) of them had various degrees and types of atheromatous plaques in different segments of the cervical carotid arteries, whereas 7 (11.3%) were normal. The predominant risk factor was smoking followed by diabetes mellitus, whereas the highest indication for the scan was transient ischemic attack. Incidental thyroid lesions such as nodules and cysts were encountered in 14 (22.6%) of the patients. There is a statistically significant difference between sex and age with the side of lesion, degree of stenosis, segment involved, and type of atheromatous plaque. Conclusion: There is a statistically significant difference between sex and age with the side of lesion, degree of stenosis, segment involved, and type of atheromatous plaque. About one-fifth of our patients had incidental thyroid lesions. Therefore, routine screening of population at risk is highly recommended.
What Happens When COVID-19 Collides With Flu Season?

At a February 26 press conference, President Donald J. Trump said of the novel coronavirus, “This is like a flu,” and expressed surprise that as many as 69 000 people in the US die of influenza every year. However, the ensuing 51⁄2 months have shown that coronavirus disease 2019 (COVID-19) is far deadlier and less predictable than seasonal influenza. Unlike influenza, COVID-19 does not appear to be seasonal, given the ever-increasing numbers of US cases this summer. So beginning this fall, the US for the first time will have to deal with a flu season wrapped in a global pandemic. Or, as the headline on a recent editorial by Edward Belongia, MD, and Michael Osterholm, PhD, MPH, described it, “a perfect storm. ” Many questions remain about how flu season might affect the pandemic, and vice versa. For example, would coinfection with influenza worsen the course of COVID-19? Experts also aren’t certain whether influenza vaccinat ion could help protect against COVID-19 or whether steps taken to mitigate COVID-19 will reduce the burden of the coming flu season. Some hints have come from preliminary research conducted in China, where influenza was still widely circulating when the first novel coronavirus infections emerged, and in the southern hemisphere, which is currently in the midst of its flu season. At least 2 things are clear: Quicker and more widely available testing is needed to distinguish between COVID-19 and influenza, which have similar symptoms, at least at first, but require different treatments. On top of that, a severe influenza season—the result of more virulent strains, inadequate vaccination rates, or a combination of both— coupled with a COVID-19 pandemic that shows no signs of abating, could overwhelm already taxed emergency departments and intensive care units. As pulmonary and critical care specialist Benjamin Singer, MD, wrote in a recent editorial, influenza and other causes of pneumonia represent the eighth leading cause of US deaths in nonpandemic years. “We can expect that the new reality of COVID-19 will only complicate the next influenza season,” Singer, of the Northwestern University Feinberg School of Medicine, concluded in his editorial.
Resting theta activity is associated with specific coding levels in event‐related theta activity during conflict monitoring

Brain electrical activity in the theta frequency band is essential for cognitive control (e.g., during conflict monitoring), but is also evident in the resting state. The link between resting state theta activity and its relevance for theta‐related neural mechanisms during cognitive control is still undetermined. Yet, theoretical considerations suggest that there may be a connection. To examine the link between resting state theta activity and conflict‐related theta activity, we combined temporal EEG signal decomposition methods with time‐frequency decomposition and beamforming methods in N = 86 healthy participants. Results indicate that resting state theta activity is closely associated with the strength of conflict‐related neural activity at the level of ERPs and total theta power (consisting of phase‐locked and nonphase‐locked aspects of theta activity). The data reveal that resting state theta activity is related to a specific aspect of conflict‐related theta activity, mainly in superior frontal regions and in the supplemental motor area (SMA, BA6) in particular. The signal decomposition showed that only stimulus‐related, but not motor‐response‐related coding levels in the EEG signal and the event‐related total theta activity were associated with resting theta activity. This specificity of effects may explain why the association between resting state theta activity and overt conflict monitoring performance may not be as strong as often assumed. The results suggest that resting state theta activity is particularly important to consider for input integration processes during cognitive control.
Hepatitis E Virus Genotype 7 RNA and Antibody Kinetics in Naturally Infected Dromedary Calves, United Arab Emirates

Orthohepevirus A genotype 7 is a novel zoonotic variant of hepatitis E virus. To clarify infection in the animal reservoir, we virologically monitored 11 dromedary dam–calf pairs. All calves became infected during the first 6 months of life and cleared the virus after an average of 2 months. Dams did not become infected.
Enhancing oxidative stability of sunflower oil by supplementation with prickled broom (Pterospartum tridentatum) ethanolic extract.

This study aimed to evaluate the effect of ethanolic extract of Pterospartum tridentatum flowers in the stability of sunflower oil. The extract was characterized regarding to its antioxidant activity by the 2,2,1-diphenyl-1-picrylhydrazyl (DPPH) scavenging method (EC50 = 76.3 ± 2.6 µg/mL) and total phenolic content (200 ± 8 mg GAE/g). Extracts were added at 500 mg/L (E1) and 1,000 mg/L (E2), and after 30 days of storage at room temperature, E2 oil showed improved quality parameters, with a reduction of 22.4%, 17.2%, and 45.6% in the values of acidity, peroxide, and p-anisidine, respectively. The extract also increased oil stability at 180 °C. After 27 hr, the acidity (0.216 ± 0.016 mg KOH/g) and the total oxidation value (TOTOX) (69.30 ± 0.26) values of E2 oil were significantly lower than the control. These results showed that P. tridentatum effectively improved the shelf-life and thermal stability of sunflower oil, being a promising source of antioxidants for edible oils processing. PRACTICAL APPLICATION: Pterospartum tridentatum ethanolic extracts increased stability of sunflower oil during storage at room temperature and at 180 °C. Oil stability increased with extract concentration, being highest for 1,000 mg/L. Therefore, P. tridentatum may be a promising source of antioxidants for edible oils processing.
Severe Fever with Thrombocytopenia Syndrome Virus in Ticks and SFTS Incidence in Humans, South Korea

During 2016–2018, we collected 3,193 ticks from rural areas in South Korea to investigate the prevalence of severe fever with thrombocytopenia syndrome virus (SFTSV). We detected SFTSV in ticks at an infection rate (IR) of 11.1%. We noted increases in the human IR associated with the monthly SFTSV IR in ticks.