Miracle-dz/UniFAR-FTUs huggingface dataset:
CRISPR-Cas9 enables efficient genome engineering of the strictly lytic, broad host-range staphylococcal bacteriophage K

Staphylococcus aureus is an important opportunistic pathogen, responsible for a range of diseases that often prove challenging to treat due to resistance to methicillin, vancomycin, and other antimicrobials. Bacteriophages present a promising alternative to target such pathogens, particularly when conventional drugs are ineffective. The antimicrobial efficacy of phage therapeutics can be further improved through genetic engineering. Among S. aureus phages, members of the Twortvirinae subfamily, characterized by their strictly lytic nature and broad host range, are considered the most promising therapeutic candidates. However, their large genome sizes make them notoriously difficult to engineer. In this study, we utilized Twortvirus K as a model to develop an efficient phage engineering platform, leveraging homologous recombination and CRISPR-Cas9-assisted counterselection. As proof of principle, this platform was utilized to construct a nanoluciferase (nluc)-encoding reporter phage (K::nluc) and tested as a preliminary, bioluminescence-based approach for identifying viable Staphylococcus cells. Independent of their phage-resistance profile, 100% of tested clinical S. aureus isolates emitted bioluminescence upon K::nluc challenge. This diagnostic assay was further adapted to complex matrices such as human whole blood and bovine raw milk, simulating S. aureus detection scenarios in bacteremia and bovine mastitis. Beyond reporter phage-based diagnostics, our engineering technology opens avenues for the design and engineering of therapeutic Twortvirinae phages to combat drug-resistant S. aureus strains.
Gene-language models are whole genome representation learners

The language of genetic code embodies a complex grammar and rich syntax of interacting molecular elements. Recent advances in self-supervision and feature learning suggest that statistical learning techniques can identify high-quality quantitative representations from inherent semantic structure. We present a gene-based language model that generates whole-genome vector representations from a population of 16 disease-causing bacterial species by leveraging natural contrastive characteristics between individuals. To achieve this, we developed a set-based learning objective, AB learning, that compares the annotated gene content of two population subsets for use in optimization. Using this foundational objective, we trained a Transformer model to backpropagate information into dense genome vector representations. The resulting bacterial representations, or embeddings, captured important population structure characteristics, like delineations across serotypes and host specificity preferences. Their vector quantities encoded the relevant functional information necessary to achieve state-of-the-art genomic supervised prediction accuracy in 11 out of 12 antibiotic resistance phenotypes. Teaser Deep transformers capture and encode gene language content to derive versatile latent embeddings of microbial genomes.
Binding of SARS-CoV-2 nucleocapsid protein to uninfected epithelial cells induces antibody-mediated complement deposition

SARS-CoV-2 infection triggers strong antibody response toward Nucleocapsid-Protein (NP), suggesting extracellular presence beyond its intra-virion RNA binding. Interestingly, NP was found to decorate infected and proximal uninfected cell-surfaces. Here, we propose a new mechanism through which extracellular NP on uninfected cells contributes to COVID-19 pathogenicity. We show that NP binds to cell-surface sulfated linear-glycosaminoglycans by spatial rearrangement of its RNA-binding sites facilitated by the flexible, positively charged, linker. Coating of uninfected lung-derived cells with purified NP attracted anti-NP-IgG from lung fluids and sera collected from COVID-19 patients. The magnitude of this immune recognition was significantly elevated in moderate compared to mild COVID-19 cases. Importantly, binding of anti-NP-IgG present in sera generated clusters that triggered C3b deposition by the classical complement pathway. Heparin analog enoxaparin outcompeted NP-binding, rescuing cells from anti-NP IgG-mediated complement deposition. Our findings unveil how extracellular NP may exacerbate COVID-19 tissue damage, and suggest leads for preventative therapy. Highlights IgG from patients’ sera target NP-bound cells resulting in complement activation The flexible linker allows NP to both bind linear sulfated GAGs and wrap around RNA Heparin analogs prevent NP surface binding and alleviate complement activation Cell-ELISA anti-NP IgG levels differ between mild and moderate COVID-19
Large-Scale Assessment of the Iranian population structure of Mitochondrial and Y-chromosome Haplogroups

The Iranian plateau, strategically positioned as a corridor for population diffusion across Eurasia, holds a pivotal role in elucidating the dynamics of human migrations originating from Africa around 60,000 years ago. Both prehistoric and historic movements of populations between Africa, Asia, and Europe may have been influenced by the unique geographical features of the Iranian plateau. Iran boasts ancient cultures and urban settlements predating some of the earliest civilizations, including the Neolithic revolution in neighboring Mesopotamia. Spanning from the Balkans and Egypt in the west to the Indus Valley in Pakistan and northern India in the southeast, the Iranian plateau encompasses a vast area characterized by incredible ethnocultural diversity. This region served as the origin for numerous mt-DNA/Y-DNA haplogroups that expanded to West Asia, Europe, Siberia, Central Asia, and South Asia. By examining both maternal and paternal haplogroups within the Iranian context, we aim to contribute to the broader narrative of human dispersals and elucidate the role those specific regions, such as the Iranian plateau, played in shaping the observed genetic diversity today. Due to the lack of comprehensive studies on mt-DNA /Y-DNA haplogroups in the Iranian population, our study sought to uncover the distribution of haplogroups among Iranian peoples using a large sample size. Our analysis focused on the frequency of ancestral haplogroups in Iran through the examination of large-scale whole-exome sequencing (WES) and SNP microarray data from 18,184 individuals. In our study, we observed 24 mt-DNA super haplogroups in the Iranian population, with the most common haplogroups belonging to West-Eurasian lineages U (20.73%), H (18.84%), J (12.10%), HV (9.22%), and T (8.98%), collectively comprising 69.70% of all Iranian samples. Notably, subclades J1 and U7 emerged as the two most frequent subclades, with frequencies of 11.24% and 7.30%, respectively. We also revealed the presence of 14 distinct Y-DNA haplogroups, with J, R, G, T, and Q emerging as the five predominant lineages. Notably, J2 (including J-L26) exhibited the highest frequency at 35.64%, followed by R1a at 14.68%. also, The detected mtDNA and Y-chromosome haplogroups were clustered into distinct groups that confirmed the heterogenicity of the Iranian population because of various factors including geographic or linguistic ethnic groups.
Identification of a Conserved B-Cell Epitope on the Capsid Protein of Porcine Circovirus Type 4

Porcine circovirus type 4 (PCV4), a recently identified circovirus, is prevalent in numerous provinces in China, as well as in South Korea, Thailand, and Europe. PCV4 virus rescued from an infectious clone showed pathogenicity, suggesting the economic impact of PCV4. However, there remains a lack of understanding regarding the immunogenicity and epitopes of PCV4. This study generated a monoclonal antibody (MAb) 1D8 by immunizing mice with PCV4 virus-like particles (VLPs). Subsequently, the epitope recognized by the MAb 1D8 was identified by truncated protein expression and alanine scanning mutagenesis analysis. Results showed that the 225PKQG228 located at the C-terminus of the PCV4 Cap protein is the minimal motif binding to the MAb. Homology modeling analysis and immunoelectron microscopy revealed that the epitope extends beyond the outer surface of the PCV4 VLP. Moreover, the epitope is highly conserved among PCV4 strains and does not react with other PCVs. Together, the MAb 1D8 recognized epitope shows potential for detecting PCV4. These findings significantly contribute to the design of antigens for PCV4 detection and control strategies. IMPORTANCE Porcine circovirus type 4 (PCV4) is a novel circovirus. Although PCV4 has been identified in several countries, including China, Korea, Thailand, and Spain, no vaccine is available. Given the potential pathogenic effects of PCV4 on pigs, PCV4 could threaten the global pig farming industry, highlighting the urgency for further investigation. Thus, epitopes of PCV4 remain to be determined. Our finding of a conserved epitope significantly advances vaccine development and pathogen detection.
Minimally Invasive Surgical Versus Catheter Ablation for the Long-Lasting Persistent Atrial Fibrillation

Objective To assess the efficacy of video-assisted minimally invasive surgical vs. catheter ablation for the long-standing persistent AF. Methods We performed a retrospective comparative analysis in a series of 166 long-standing persistent AF patients treated between 2006 and 2009 with either video-assisted minimally invasive ablation (83 patients), or catheter ablations (83 patients). The catheter group was screened using a ‘pair-matched case-control’ methodology in order to select appropriate statistical comparison candidates out of 169 long-standing persistent AF patients which were potentially suitable for surgery, but have been treated with catheter approaches in order to balance major prognostic factors between the two groups. Follow-up for all patients ranged from 1 to 3.6 years. Results No patient died postoperatively. One patient suffered from stroke in the surgical group but recovered before discharge. Freedom from AF was obtained in 59.0% and 74.7% during follow-up in the catheter group and the surgical group respectively (P = 0.047). Patients in the catheter group had a significantly higher rate of recurrent arrhythmia (P = 0.011, hazard ratio: 0.555, 95% CI: 0.354 to 0.872) compared with the surgically treated group. The freedom from antiarrhythmic drugs was 44.6% in the catheter group and 61.4% in the surgical group (P = 0.043). Conclusions The video-assisted minimally invasive ablation was safe and effective, and had an optimistic success rate for patients with long-standing persistent AF in our retrospective comparative study. Thus, further randomized studies addressing this issue seem to be justified.
The EndoPredict Gene-Expression Assay in Clinical Practice - Performance and Impact on Clinical Decisions

The validated EndoPredict assay is a novel tool to predict the risk of metastases of patients with estrogen receptor positive, HER2 negative breast cancer treated with endocrine therapy alone. It has been designed to integrate genomic and clinical information and includes clinico-pathological factors such as tumor size and nodal status. The test is feasible in a decentral setting in molecular pathology laboratories. In this project, we investigated the performance of this test in clinical practice, and performed a retrospective evaluation of its impact on treatment decisions in breast cancer. During one year, EndoPredict assays from 167 patients could be successfully performed. For retrospective evaluation of treatment decisions, a questionnaire was sent to the clinical partner. Regarding the molecular EP class, samples from 56 patients (33.5%) had a low-risk, whereas 111 patients (66.5%) showed a high-risk gene profile. After integration of the clinicopathological factors the combined clinical and molecular score (EPclin) resulted in a low-risk group of 77 patients (46.4%), while 89 (53.6%) had a high risk EPclin score. The EPclin-based estimated median 10-year-risk for metastases with endocrine therapy alone was 11% for the whole cohort. The median handling time averaged three days (range: 0 to 11 days), 59.3% of the tests could be performed in three or less than three days. Comparison of pre- and post-test therapy decisions showed a change of therapy in 37.7% of patients. 16 patients (12.3%) had a change to an additional chemotherapy while 25.4% of patients (n = 33) changed to an endocrine therapy alone. In 73 patients (56.2%) no change of therapy resulted. In 6.1% of patients (n = 8), the patients did not agree to the recommendation of the tumor board. Our results show that the EndoPredict assay could be routinely performed in decentral molecular pathology laboratories and the results markedly change treatment decisions.
Role of Potassium Ions in the Vascular Response to a Brief Tetanus

Changes in the plasma potassium ion (K+) concentration in the venous effluent of isolated dog tibialis cranialis and extensor digitorum longus muscles were measured following 1 second of tetanic exercise (32 impulses/sec) during constant-flow perfusion. After a brief delay, venous plasma K+ concentration increased to a peak change of 0.23 ± 0.02 mEq/liter and then returned to the control level within 1.5 minutes after the beginning of stimulation, representing a net K+ loss of 1.7 μEq/100 g muscle. These experiments indicate a very short period of actual tissue-blood K+ transfer, since the time course of the venous efflux can be explained almost entirely by the distribution of vascular transit times. Our best estimate is that a 1-second tetanus produces an immediate 1.3–2.4-mEq/liter increase in interstitial K+ concentration which then returns to its control level with a time constant of 6–8 seconds due to rapid cellular reuptake. These K+ concentration changes have sufficient magnitude and the correct time course to play a significant role in the production of the vascular response to a brief tetanus.
On the Use of Magnetically Coupled Resonators for Chirp-Based Timestamping

The knowledge of the time value at which an event of interest occurred is the typical feature needed to perform many kinds of postprocessing in distributed sensor networks. Consequently, network-based distributed systems must support time dissemination in order to ensure that relative clock errors among nodes remain below a certain threshold. Despite many protocols being well established for wired connections, the wireless sensor network paradigm required a new approach to address adverse characteristics of the wireless medium. In this paper, the adoption of low-frequency signaling is proposed for overcoming some issues of radio frequency transmissions when used for timestamping events. The proposed approach is characterized using numerical simulations and an experimental prototype, based on inductive coupling of tuned resonators. Experimental tests confirm the effectiveness and feasibility of this approach that achieves microsecond-order time recovery performance in practical system configurations.
MirageTable: freehand interaction on a projected augmented reality tabletop

Instrumented with a single depth camera, a stereoscopic projector, and a curved screen, MirageTable is an interactive system designed to merge real and virtual worlds into a single spatially registered experience on top of a table. Our depth camera tracks the user's eyes and performs a real-time capture of both the shape and the appearance of any object placed in front of the camera (including user's body and hands). This real-time capture enables perspective stereoscopic 3D visualizations to a single user that account for deformations caused by physical objects on the table. In addition, the user can interact with virtual objects through physically-realistic freehand actions without any gloves, trackers, or instruments. We illustrate these unique capabilities through three application examples: virtual 3D model creation, interactive gaming with real and virtual objects, and a 3D teleconferencing experience that not only presents a 3D view of a remote person, but also a seamless 3D shared task space. We also evaluated the user's perception of projected 3D objects in our system, which confirmed that the users can correctly perceive such objects even when they are projected over different background colors and geometries (e.g., gaps, drops).
Influence of Motor Operating Parameters on Discharge Bearing Current Activity

While the cause-and-effect chains of inverter-induced bearing currents have been well understood today, not much is known about the damage mechanism inside the bearings. Research has suggested that the bearing degradation is approximately proportional to the frequency of occurrence of the bearing currents. For bearing currents that occur statistically distributed-such as discharge bearing currents-this parameter has not been thoroughly researched yet. In this paper, we present an analysis of the influence of different motor operating parameters on the frequency of occurrence (“discharge activity”) of discharge bearing currents, using a non-intrusive detection method. When analyzed individually, the motor speed, motor shaft temperature, inverter switching frequency, and inverter dc-link voltage influence the discharge activity. However, the overall running time of the motor, the state-steady-state versus instantaneous-and the “operating history” on the time-scale of several days have the strongest effect on the frequency of the discharge bearing current occurrence.
Oropharyngeal and Sputum Microbiomes Are Similar Following Exacerbation of Chronic Obstructive Pulmonary Disease

Growing evidence suggests that the airway microbiota might be involved in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Understanding this relationship requires examination of a large-scale population for a long duration to accurately monitor changes in the microbiome. This type of longitudinal study requires an appropriate sampling strategy; two options are the collection of sputum or oropharyngeal swabs. Comparative analysis of the changes that occur in these two specimen types has not been previously performed. This observational study was conducted to explore oropharyngeal microbial community dynamics over time and to examine the relationship between oropharyngeal swabs and sputum. A total of 114 samples were collected from four patients suffering from severe AECOPD. Bacterial and fungal communities were evaluated using 16S rRNA and ITS sequencing. Inter-individual differences were found in bacterial community structure, but the core genera were shared by both sample types and included 32 lineages. Most of the core genera were members of the phyla Proteobacteria, Firmicutes and Ascomycota. Although the oropharyngeal samples showed higher bacterial alpha diversity, the two sample types generated rather similar taxonomic profiles. These results suggest that the sputum microbiome is remarkably similar to the oropharyngeal microbiome. Thus, oropharyngeal swabs can potentially be used instead of sputum samples for patients with exacerbation of COPD.
Identification of a novel CRYAB mutation associated with autosomal recessive juvenile cataract in a Saudi family

Purpose To describe the first cataract-causing recessive mutation in the crystalline, alpha-b gene CRYAB. Methods Homozygosity mapping complemented by linkage analysis was performed in a family with autosomal recessive juvenile cataract. Results A homozygous missense mutation in CRYAB was identified. The mutation replaces a highly conserved amino acid residue in a dual function domain of the protein. None of the patients has clinically significant myopathy, but the oldest patient (the mother) has retinal pathology. Conclusions This is the first report of a recessive mutation in CRYAB causing cataract. Based on recent knowledge of the structure and function of this small heat shock protein, we speculate on the potential mutational mechanism.
X-rays from α Centauri – The darkening of the solar twin

We present first results from five XMM-Newton observations of the binary system α Centauri, which has been observed in snapshot like exposures of roughly two hours each during the last two years. In all our observations the X-ray emission of the system is dominated by α Cen B, a K1 star. The derived light curves of the individual components reveal variability on short timescales and a flare was discovered on α Cen B during one observation. A PSF fitting algorithm is applied to the event distribution to determine the brightness of each component during the observations. We perform a spectral analysis with multi-temperature models to calculate the X-ray luminosities. We investigate long term variability and possible activity cycles of both stars and find the optically brighter component α Cen A, a G2 star very similar to our Sun, to have fainted in X-rays by at least an order of magnitude during the observation program, a behaviour never observed before on α Cen A, but rather similar to the X-ray behaviour observed with XMM-Newton on HD 81809. We also compare our data with earlier spatially resolved observations performed over the last 25 years.
REVIEW ARTILCE: Cell therapy and stem cells in animal models of motor neuron disorders

Amyotrophic lateral sclerosis (ALS), spinal bulbar muscular atrophy (or Kennedy's disease), spinal muscular atrophy and spinal muscular atrophy with respiratory distress 1 are neurodegenerative disorders mainly affecting motor neurons and which currently lack effective therapies. Recent studies in animal models as well as primary and embryonic stem cell models of ALS, utilizing over‐expression of mutated forms of Cu/Zn superoxide dismutase 1, have shown that motor neuron degeneration in these models is in part a non cell‐autonomous event and that by providing genetically non‐compromised supporting cells such as microglia or growth factor‐excreting cells, onset can be delayed and survival increased. Using models of acute motor neuron injury it has been shown that embryonic stem cell‐derived motor neurons implanted into the spinal cord can innervate muscle targets and improve functional recovery. Thus, a rationale exists for the development of cell therapies in motor neuron diseases aimed at either protecting and/or replacing lost motor neurons, interneurons as well as non‐neuronal cells. This review evaluates approaches used in animal models of motor neuron disorders and their therapeutic relevance.
Buffering of Ocean Export Production by Flexible Elemental Stoichiometry of Particulate Organic Matter

One of the most important factors that determine the ocean‐atmosphere carbon partitioning is the sinking of particulate organic matter (POM) from the surface ocean to the deep ocean. The amount of carbon (C) removed from the surface ocean by this POM export production depends critically on the elemental ratio in POM of C to nitrogen (N) and phosphorus (P), two essential elements that limit productivity. Recent observations indicate that P:N:C in marine POM varies both spatially and temporally due to chemical, physical, and ecological dynamics. In a new approach to predicting a flexible P:C ratio, we developed a power law model with a stoichiometry sensitivity factor, which is able to relate P:C of POM to ambient phosphate concentration. The new factor is robust, measurable, and biogeochemically meaningful. Using the new stoichiometry sensitivity factor, we present a first‐order estimate that P:C plasticity could buffer against a generally expected future reduction in global carbon export production by up to 5% under a future warming scenario compared to a fixed, Redfield P:C. Further, we demonstrate that our new stoichiometry model can be implemented successfully and easily in a global model to reproduce the large‐scale P:N:C variability in the ocean.