Miracle-dz/UniFAR-FTUs huggingface dataset:
In depth characterization of the Staphylococcus aureus phosphoproteome reveals new targets of Stk1.

Staphylococcus aureus is a major cause of infections worldwide and infection results in a variety of diseases. As of no surprise, protein phosphorylation is an important game player in signaling cascades and has been shown to be involved in S. aureus virulence. Albeit long neglected, eukaryotic-type serine/threonine kinases in S. aureus have been implicated in this complex signaling cascades. Due to the sub-stoichiometric nature of protein phosphorylation and a lack of suitable analysis tools, the knowledge of these cascades is however, to date, still limited.Here, were apply an optimized protocol for efficient phosphopeptide enrichment via Fe3+-IMAC followed by LC-MS/MS to get a better understanding of the impact of protein phosphorylation on the complex signaling networks involved in pathogenicity. By profiling a serine/threonine kinase and phosphatase mutant from a methicillin-resistant S. aureus mutant library, we generated the most comprehensive phosphoproteome dataset of S. aureus to date, aiding a better understanding of signaling in bacteria. With the identification of 3800 class I p-sites we were able to increase the number of identifications by more than 21 times compared to recent literature. In addition, we were able to identify 74 downstream targets of the only reported eukaryotic-type Ser/Thr kinase of the S. aureus strain USA300, Stk1. This work allowed an extensive analysis of the bacterial phosphoproteome and indicates that Ser/Thr kinase signaling is far more abundant than previously anticipated in S. aureus.
3D Modeling of craniofacial ontogeny and sexual dimorphism in children

The range of normal variation of growth and development of the craniofacial region is of direct clinical interest but incompletely understood. Here we develop a statistical model of craniofacial growth and development to compare craniofacial ontogeny between age groups and sexes and pilot an approach to modeling that is relatively straightforward to apply in the context of clinical research and assessment.
Utility of certain π-acceptors for the spectrophotometric determination of norfloxacin

Simple, rapid, accurate and sensitive spectrophotometric methods are described for the determination of norfloxacin. The methods are based on the reaction of this drug as a π-electron donor with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), 7,7,8,8-tetracyanoquinodimethane (TCNQ), p-chloranil (CL) or chloranilic acid (CLA) as π-acceptors to give highly coloured complex species. The coloured products are measured spectrophotometrically at 460, 843, 550 and 531 nm for DDQ, TCNQ, CL and CLA, respectively. Optimization of the different experimental conditions is described. Beer's law is obeyed in the range 10–400 µg ml–1 and colours were produced in non-aqueous media and were stable for at least 3 h. Applications of the suggested methods to representative pharmaceutical dosage forms are presented and compared with the official method. Interferences from additives and common degradation products were investigated.
An overview on the molecular diagnosis of animal leptospirosis

The most common presentation of animal leptospirosis is the subclinical and silent chronic form, that can lead to important reproductive disorders. The diagnosis of this chronic form remains a challenge. The aim of the present study is to gather and critically analyse the current information about molecular tools applied to animal leptospirosis diagnosis, particularly the silent chronic presentation of the infection. Regarding clinical specimens, samples from urinary tract were the most used (69/102, 67·7%), while few studies (12/102, 11·8%) investigated samples from reproductive tract. Concerning the molecular methods applied, the most used is still the conventional polymerase chain reaction (PCR) (46/102, 45%), followed by real‐time PCR (38/102, 37·2%). The lipL32 gene is currently the most common target used for Leptospira detection, with 48% of studies applying this genetic marker. From all the studies, only few (21/102, 20·5%) performed gene sequencing. According to the majority of authors, current evidence suggests that lipL32‐PCR is useful for an initial screening for Leptospira DNA detection in animal clinical samples. Posteriorly, if DNA sequencing could be performed on positive lipL32‐PCR samples, we encourage the use of secY gene as a genetic marker. The molecular methods appear as the most important tools for the diagnosis of the chronic silent leptospirosis on domestic animals, reinforcing its evident impact not only on animal reproduction but also on a One Health context.
Salivary Carbohydrate-Deficient Transferrin in Alcohol- and Nicotine-Dependent Males

Serum carbohydrate-deficient transferrin (CDT), an 80 kDa glycoprotein, is one of the most commonly employed biomarkers to detect alcohol dependence. Some salivary glycoproteins such as α-amylase, clusterin, haptoglobin, light/heavy-chain immunoglobulin, and transferrin, which alter glycosylation in alcohol-dependent persons, have been suggested to be potential alcohol markers. However, their identification is based on indirect analysis of lectin glycosidic bonds and molecular weight. We investigated the CDT content in the saliva of alcohol- and nicotine-dependent men. The CDT concentration (ng/mL, ng/mg protein) was determined by an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit in 55 men: 20 healthy social drinkers (C), 10 chronic cigarette smokers (S), 10 alcohol-dependent non-smokers (A), and 15 alcohol-dependent smokers (AS). Surprisingly, there were no differences in the concentrations of CDT between the studied groups. Salivary pH was the lowest in the AS and the highest in the A group. Therefore, salivary CDT cannot be used as an alcohol dependence marker as measured by ELISA. We suggest that direct identification of glycoproteins is necessary to search for potential salivary alcohol biomarkers. Molecules smaller than 40 kDa, which easily translocate from blood to the saliva, might be preferred as salivary alcohol markers.
EDTD-SC: An IoT Sensor Deployment Strategy for Smart Cities

A smart city is a geographical area that uses modern technologies to facilitate the lives of its residents. Wireless sensor networks (WSNs) are important components of smart cities. Deploying IoT sensors in WSNs is a challenging aspect of network design. Sensor deployment is performed to achieve objectives like increasing coverage, strengthening connectivity, improving robustness, or increasing the lifetime of a given WSN. Therefore, a sensor deployment method must be carefully designed to achieve such objective functions without exceeding the available budget. This study introduces a novel deployment algorithm, called the Evaluated Delaunay Triangulation-based Deployment for Smart Cities (EDTD-SC), which targets not only sensor distribution, but also sink placement. Our algorithm utilizes Delaunay triangulation and k-means clustering to find optimal locations to improve coverage while maintaining connectivity and robustness with obstacles existence in sensing area. The EDTD-SC has been applied to real-world areas and cities, such as Midtown Manhattan in New York in the United States of America. The results show that the EDTD-SC outperforms random and regular deployments in terms of area coverage and end-to-end-delay by 29.6% and 29.7%, respectively. Further, it exhibits significant performance in terms of resilience to attacks.
Microbial sulfate reduction and organic sulfur formation in sinking marine particles

Where they can't breathe Climate warming is causing the expansion of marine oxygen-deficient zones, which are regions in which dissolved oxygen concentrations are so low that many marine animals cannot survive. This phenomenon also might affect the global cycles of carbon, sulfur, nitrogen, and trace metals in the oceans. Raven et al. show how ocean anoxia affects microbial sulfur processing in sinking marine particles. They observed cryptic microbial sulfate reduction, which forms organic sulfur that is resistant to acid hydrolysis, a process that could enhance carbon preservation in sediments underlying oxygen-deficient water columns. This may help explain some of the more extreme episodes of organic carbon preservation associated with marine anoxia in Earth's history. Science, this issue p. 178 Cryptic sulfur cycling may enhance organic carbon preservation in sediments below marine oxygen–deficient zones. Climate change is driving an expansion of marine oxygen-deficient zones, which may alter the global cycles of carbon, sulfur, nitrogen, and trace metals. Currently, however, we lack a full mechanistic understanding of how oxygen deficiency affects organic carbon cycling and burial. Here, we show that cryptic microbial sulfate reduction occurs in sinking particles from the eastern tropical North Pacific oxygen-deficient zone and that some microbially produced sulfide reacts rapidly to form organic sulfur that is resistant to acid hydrolysis. Particle-hosted sulfurization could enhance carbon preservation in sediments underlying oxygen-deficient water columns and serve as a stabilizing feedback between expanding anoxic zones and atmospheric carbon dioxide. A similar mechanism may help explain more-extreme instances of organic carbon preservation associated with marine anoxia in Earth history.
Nanocellulose‐Reinforced Hydroxyapatite Nanobelt Membrane as a Stem Cell Multi‐Lineage Differentiation Platform for Biomimetic Construction of Bioactive 3D Osteoid Tissue In Vitro

Severe bone defects, especially accompanied by vascular and peripheral nerve injuries, remain a massive challenge. Most studies related to bone tissue engineering have focused on osteogenic differentiation of mesenchymal stem cells (MSCs), and ignored the formation of blood vessels and nerves in the newly generated bone owing to the lack of proper materials and methodology for tuning stem cells differentiated into osteogenic, neuronal, and endothelial cells (ECs) in the same scaffold system. Herein, a nanocellulose‐reinforced hybrid membrane with good mechanical properties and control over biodegradation by assembling ultralong hydroxyapatite nanobelts in a bacterial nanocellulose hydrogel is designed and synthesized. Osteogenic, neuronal cells are successfully differentiated on this hybrid membrane. Based on the multi‐lineage differentiation property of the membrane, a bioactive 3D osteoid tissue (osteogenic, neural, and ECs) is mimetically constructed in vitro using layer‐by‐layer culture and integration. The bone regeneration ability of the as‐prepared bioactive osteoid tissue is assessed in vivo via heterotopic osteogenesis experiments for eight weeks. The rapid new bone growth and formation of blood capillaries and nerve fibers prove that the hybrid membrane can be universally applied as a stem cell multi‐lineage differentiation platform, which has significant applications in bone tissue engineering.
Finding food in a novel environment: The diet of a reintroduced endangered meso-predator to mainland Australia, with notes on foraging behaviour

Translocated captive-bred predators are less skilled at hunting than wild-born predators and more prone to starvation post-release. Foraging in an unfamiliar environment presents many further risks to translocated animals. Knowledge of the diet and foraging behaviour of translocated animals is therefore an important consideration of reintroductions. We investigated the diet of the endangered meso-predator, the eastern quoll Dasyurus viverrinus. We also opportunistically observed foraging behaviour, enabling us to examine risks associated with foraging. Sixty captive-bred eastern quolls were reintroduced to an unfenced reserve on mainland Australia (where introduced predators are managed) over a two year period (2018, 2019). Quolls were supplementary fed macropod meat but were also able to forage freely. Dietary analysis of scats (n = 56) revealed that quolls ate macropods, small mammals, birds, invertebrates, fish, reptiles and frogs, with some between-year differences in the frequency of different diet categories. We also observed quolls hunting live prey. Quolls utilised supplementary feeding stations, indicating that this may be an important strategy during the establishment phase. Our study demonstrated that, in a novel environment, captive-bred quolls were able to locate food and hunt live prey. However, foraging was not without risks; with the ingestion of toxic substances and foraging in dangerous environments found to be potentially harmful. Knowledge of the diet of reintroduced fauna in natural landscapes is important for understanding foraging behaviour and evaluating habitat suitability for future translocations and management.
Large Multidomain Protein NMR: HIV-1 Reverse Transcriptase Precursor in Solution

NMR studies of large proteins, over 100 kDa, in solution are technically challenging and, therefore, of considerable interest in the biophysics field. The challenge arises because the molecular tumbling of a protein in solution considerably slows as molecular mass increases, reducing the ability to detect resonances. In fact, the typical 1H-13C or 1H-15N correlation spectrum of a large protein, using a 13C- or 15N-uniformly labeled protein, shows severe line-broadening and signal overlap. Selective isotope labeling of methyl groups is a useful strategy to reduce these issues, however, the reduction in the number of signals that goes hand-in-hand with such a strategy is, in turn, disadvantageous for characterizing the overall features of the protein. When domain motion exists in large proteins, the domain motion differently affects backbone amide signals and methyl groups. Thus, the use of multiple NMR probes, such as 1H, 19F, 13C, and 15N, is ideal to gain overall structural or dynamical information for large proteins. We discuss the utility of observing different NMR nuclei when characterizing a large protein, namely, the 66 kDa multi-domain HIV-1 reverse transcriptase that forms a homodimer in solution. Importantly, we present a biophysical approach, complemented by biochemical assays, to understand not only the homodimer, p66/p66, but also the conformational changes that contribute to its maturation to a heterodimer, p66/p51, upon HIV-1 protease cleavage.
Lipid alterations in human frontal cortex in ALS‐FTLD‐TDP43 proteinopathy spectrum are partly related to peroxisome impairment

Peroxisomes play a key role in lipid metabolism, and peroxisome defects have been associated with neurodegenerative diseases such as X‐adrenoleukodystrophy and Alzheimer's disease. This study aims to elucidate the contribution of peroxisomes in lipid alterations of area 8 of the frontal cortex in the spectrum of TDP43‐proteinopathies. Cases of frontotemporal lobar degeneration‐TDP43 (FTLD‐TDP), manifested as sporadic (sFTLD‐TDP) or linked to mutations in various genes including expansions of the non‐coding region of C9ORF72 (c9FTLD), and of sporadic amyotrophic lateral sclerosis (sALS) as the most common TDP43 proteinopathies, were analysed.
An Integrative Review of Self-Management Interventions for Treatment Sequelae in Adult Survivors.

PROBLEM IDENTIFICATION Self-management interventions support cancer survivors in addressing the consequences of treatment. With post-treatment survivors living longer, it is critical to know how research responds to their changing needs. LITERATURE SEARCH A comprehensive search of the CINAHL®, PsycINFO®, and PubMed® databases was performed. Articles were included if the self-management intervention was conducted on cancer-free adult survivors after completing primary treatment. DATA EVALUATION Each study was evaluated using the Critical Appraisal Skills Programme checklist. SYNTHESIS 38 articles were included. The majority of the interventions were designed for short-term survivors, with limited interventions found to support the self-management of long-term cancer survivors. When implementing self-management support, there is a need to use theoretical frameworks that can respond to the changing needs of cancer survivors over time. IMPLICATIONS FOR PRACTICE Future research should provide support for long-term survivors. Oncology nurses can use the results of this review to identify gaps in the self-management education provided to cancer survivors.
Splicing at the phase-separated nuclear speckle interface: a model

Abstract Phase-separated membraneless bodies play important roles in nucleic acid biology. While current models for the roles of phase separation largely focus on the compartmentalization of constituent proteins, we reason that other properties of phase separation may play functional roles. Specifically, we propose that interfaces of phase-separated membraneless bodies could have functional roles in spatially organizing biochemical reactions. Here we propose such a model for the nuclear speckle, a membraneless body implicated in RNA splicing. In our model, sequence-dependent RNA positioning along the nuclear speckle interface coordinates RNA splicing. Our model asserts that exons are preferentially sequestered into nuclear speckles through binding by SR proteins, while introns are excluded through binding by nucleoplasmic hnRNP proteins. As a result, splice sites at exon-intron boundaries are preferentially positioned at nuclear speckle interfaces. This positioning exposes splice sites to interface-localized spliceosomes, enabling the subsequent splicing reaction. Our model provides a simple mechanism that seamlessly explains much of the complex logic of splicing. This logic includes experimental results such as the antagonistic duality between splicing factors, the position dependence of splicing sequence motifs, and the collective contribution of many motifs to splicing decisions. Similar functional roles for phase-separated interfaces may exist for other membraneless bodies.
Introduction of a Simplified Psoriatic Arthritis Magnetic Resonance Imaging Score (sPsAMRIS): A Potential Tool for Treatment Monitoring in Peripheral Psoriatic Arthritis

Background: To evaluate whether a simplified (s) version of the psoriatic arthritis magnetic resonance imaging score (PsAMRIS), sPsAMRIS, is a potential tool for therapy monitoring in psoriatic arthritis (PsA). Methods: Seventeen patients with active psoriatic arthritis (PsA) underwent magnetic resonance imaging (MRI) at 3 T of the clinically dominant hand at baseline and after 6 months. Scoring was performed by two musculoskeletal radiologists in terms of the PsAMRIS and sPsAMRIS, which is a simplified version with reduced item numbers based on prior evaluation of responsiveness to change by standardized response means (SRMs). Both scores were compared by calculation of overall and each sub-score’s SRMs and relative efficacy (RE) after bootstrapping. Results: PsAMRIS sub-scores of MCP joints 3 and 4, and proximal interphalangeal (PIP) joint 4 had the highest SRM (−0.07 each), indicating highest responsiveness to change, and were, therefore, included in sPsAMRIS. Compared to PsAMRIS, sPsAMRIS was characterized by higher SRMs (sPsAMRIS: −0.13 vs. PsAMRIS: −0.02) and higher RE (29.46). sPsAMRIS and PsAMRIS were highly correlated at baseline (r = 0.75, p < 0.01 (Pearson’s correlation)) and at 6-month follow-up (r = 0.64, p = 0.01). Mean time burden for completion of scoring per MRI study was significantly reduced when using PsAMRIS (469 ± 87.03 s) as compared to sPsAMRIS (140.1 ± 21.25 s) (p < 0.001). Conclusion: Due to its similar responsiveness to change compared to standard PsAMRIS, and time efficiency, sPsAMRIS might be a potential diagnostic tool to quantitatively assess and monitor therapy in PsA.
The optimized drug delivery systems of treating cancer bone metastatic osteolysis with nanomaterials

Abstract Some cancers such as human breast cancer, prostate cancer, and lung cancer easily metastasize to bone, leading to osteolysis and bone destruction accompanied by a complicated microenvironment. Systemic administration of bisphosphonates (BP) or denosumab is the routine therapy for osteolysis but with non-negligible side effects such as mandibular osteonecrosis and hypocalcemia. Thus, it is imperative to exploit optimized drug delivery systems, and some novel nanotechnology and nanomaterials have opened new horizons for scientists. Targeted and local drug delivery systems can optimize biodistribution depending on nanoparticles (NPs) or microspheres (MS) and implantable biomaterials with the controllable property. Drug delivery kinetics can be optimized by smart and sustained/local drug delivery systems for responsive delivery and sustained delivery. These delicately fabricated drug delivery systems with special matrix, structure, morphology, and modification can minimize unexpected toxicity caused by systemic delivery and achieve desired effects through integrating multiple drugs or multiple functions. This review summarized recent studies about optimized drug delivery systems for the treatment of cancer metastatic osteolysis, aimed at giving some inspiration in designing efficient multifunctional drug delivery systems.
TikTok, Tide Pods and Tiger King: health implications of trends taking over pediatric populations

Supplemental Digital Content is available in the text Purpose of review With children and adolescents constantly connected to their devices in an ever-changing technological landscape, new and emerging trends in entertainment media have created potential health implications for pediatric patients. The purpose of this review is to provide pediatricians with explanations of specific trends on streaming services, the popular new mobile application TikTok, recent widespread ‘Internet Challenges’ that include pediatric participants, and new technologies. These emerging trends can pose potential harms to the health and wellbeing of children and adolescents. Recent findings Recent reports and news articles have discussed popular technological trends and the adverse effects that can occur. Although technology provides access to information and social connection for youth, it also creates platforms where children can be exposed to disturbing content, peer pressure, cyberbullying, and encouragement to participate in activities that could cause potential physical harm or even death. Summary Pediatricians need to be aware of trends to best understand the implications of these technologies, especially in clinical practice. Pediatricians play an important role in educating parents and patients about the risks of these trends, in facilitating conversations about related topics including self-esteem, cyberbullying and peer pressure to promote healthy internet use, and providing necessary resources.