Miracle-dz/UniFAR-FTUs huggingface dataset:
Tankyrase 1-Dependent pADPr Modification of DNA-PKcs is Essential for Holoenzyme Formation and Function

Intrigued by the dynamics of the seemingly contradictory yet integrated cellular responses to the requisites of preserving telomere integrity while also efficiently repairing damaged DNA, we investigated roles of the telomere associated poly(adenosine diphosphate [ADP]‐ribose) polymerase (PARP) tankyrase 1 in both telomere function and the DNA damage response following exposure to ionizing radiation [1]. Tankyrase 1 siRNA knockdown in human cells significantly elevated recombination specifically within telomeres, hotspots for sister chromatid exchange (T‐SCE), a phenotype that quantitative modeling suggests has the potential of accelerating cellular senescence [2, 3]. We have also observed high T‐SCE rates in cells with deficiencies in WRN and BLM, the genes defective in Werner’s and Bloom’s syndromes, supporting a connection to premature aging [4]. Much more unexpected was the observation that depletion of tankyrase 1 resulted in concomitant and rapid reduction of the nonhomologous end‐joining (NHEJ) protein DNA dependent protein kinase catalytic subunit (DNA‐PKcs), while Ku86 and ATM protein levels remained unchanged; DNA‐PKcs mRNA levels were also unaffected. We demonstrated that depletion of tankyrase 1 resulted in proteasome‐mediated DNA‐PKcs degradation, thereby explaining the associated defective damage response observed; i.e., increased sensitivity to ionizing radiation‐induced cell killing, mutagenesis, chromosome aberration and telomere fusion, regardless of radiation quality. These studies were consistent with identification of DNA-PKcs amongst poly(ADP-ribose) protein complexes [5], and provided the first evidence for regulation of DNA-PKcs by tankyrase 1 PARP activity [1, 6]. However, any potential role of PARsylated DNA-PKcs in processes such as NHEJ remained to be elucidated. Here, we investigated the role of PARsylated DNA-PKcs in NHEJ-mediated double-strand break (DSB) repair in human cells. We found that tankyrase 1 PARP catalytic activity is required for recruitment to and function of DNA-PKcs at ionizing radiation-induced DSB sites, and so provide the first insights into the relevance of regulation of DNA-PKcs protein stability by pADPr modification. Our results demonstrate that inhibition of telomere-associated tankyrase 1 catalytic activity compromises DSB-repair kinetics as a consequence of abrogated DNA-PK holoenzyme assembly, and so provide new understanding into basic mechanisms of DNA repair following radiation injury. We propose a model in which the stepwise pADPr modification of DNA-PK subunits provides plausible explanation for the ‘DNA-dependent’ nature of the functional holoenzyme.
Safety, Biodistribution, and Radiation Dosimetry of 18F-rhPSMA-7.3 in Healthy Adult Volunteers

This first-in-humans study investigated the safety, biodistribution, and radiation dosimetry of a novel 18F-labeled radiohybrid prostate-specific membrane antigen (rhPSMA) PET imaging agent, 18F-rhPSMA-7.3. Methods: Six healthy volunteers (3 men, 3 women) underwent multiple whole-body PET acquisitions at scheduled time points up to 248 min after the administration of 18F-rhPSMA-7.3 (mean activity, 220; range, 210–228 MBq). PET scans were conducted in 3 separate sessions, and subjects were encouraged to void between sessions. Blood and urine samples were collected for up to 4 h after injection to assess metabolite-corrected radioactivity in whole blood, plasma, and urine. Quantitative measurements of 18F radioactivity in volumes of interest over target organs were determined directly from the PET images at 8 time points, and normalized time–activity concentration curves were generated. These normalized cumulated activities were then inputted into the OLINDA/EXM package to calculate the internal radiation dosimetry and the subjects’ effective dose. Results: 18F-rhPSMA-7.3 was well tolerated. One adverse event (mild headache, not requiring medication) was considered possibly related to 18F-rhPSMA-7.3. The calculated effective dose was 0.0141 mSv/MBq when using a 3.5-h voiding interval. The organs with the highest mean absorbed dose per unit of administered radioactivity were the adrenals (0.1835 mSv/MBq), the kidneys (0.1722 mSv/MBq), the submandibular glands (0.1479 mSv), and the parotid glands (0.1137 mSv/MBq). At the end of the first scanning session (mean time, 111 min after injection), an average of 7.2% (range, 4.4%–9.0%) of the injected radioactivity of 18F-rhPSMA-7.3 was excreted into urine. Conclusion: The safety, biodistribution, and internal radiation dosimetry of 18F-rhPSMA-7.3 are considered favorable for PET imaging.
Plastid DNA Sequence Diversity in a Worldwide Set of Grapevine Cultivars (Vitis vinifera L. subsp. vinifera)

DNA sequence diversity was investigated at two plastid regions (the trnH-psbA intergenic spacer and the rpl16 intron) in a geographically diverse group of 113 cultivated grape samples. This group included 40 samples from the Republic of Georgia, home to over 500 grape cultivars and the earliest archaeological evidence of grape domestication. The greater Caucasus region in which Georgia lies is widely believed to be the area in which grape domestication began, and the study of genetic diversity in this region is viewed as key to understanding grape domestication in general. Four plastid haplotypes are evident in the 113 samples, and are designated by their character-states at each of the 3 polymorphic positions: (AAA) – 23 samples, (ATT) – 29 samples, (GTA) – 26 samples, and (ATA) – 35 samples. The AAA haplotype was only observed in Georgian samples. The observation that the Georgian cultivars exhibited both unique plastid DNA variation (the AAA haplotype) and all other observed plastid haplotypes is consistent with previous studies that have observed both unique and high levels of genetic variation in wild grapes (V. vinifera subsp. sylvestris) in the greater Caucasus region.
CELL MOVEMENT, RATE OF REGENERATION, AND THE AXIAL GRADIENT IN TUBULARIA

1. The regeneration process in Tubularia is divisible into two phases. There is a period of tissue movement, during which extra cells are provided to the presumptive regeneration site, followed directly by the period of differentiation of the new hydranth.2. Differences in rate of regeneration between narrow versus wide stems, the distal versus the proximal ends of stems ligated in the middle, and apical versus basal stem levels are all due to differences in the time occupied by the tissue movement.3. Narrow and wide stems differentiate at the same rate, as do the distal and proximal ends of stems ligated in the middle. However, pieces from basal stem levels differentiate, in these experiments, at a significantly greater rate than pieces from apical stem levels.4. Both rate of regeneration considered as a whole and rate of differentiation vary from colony to colony and between comparable stems taken from the same colony.5. Neither the tissue movement nor the process of differentiation is always continuous.
Sol-Gel Derived Hydroxyapatite Coatings for Titanium Implants: A Review

With the growing demands for bone implant therapy, titanium (Ti) and its alloys are considered as appropriate choices for the load-bearing bone implant substitutes. However, the interaction of bare Ti-based implants with the tissues is critical to the success of the implants for long-term stability. Thus, surface modifications of Ti implants with biocompatible hydroxyapatite (HAp) coatings before implantation is important and gained interest. Sol-gel is a potential technique for deposition the biocompatible HAp and has many advantages over other methods. Therefore, this review strives to provide widespread overview on the recent development of sol-gel HAp deposition on Ti. This study shows that sol-gel technique was able to produce uniform and homogenous HAp coatings and identified the role of surface pretreatment of Ti substrate, optimizing the sol-gel parameters, substitution, and reinforcement of HAp on improving the coating properties. Critical factors that influence on the characteristics of the deposited sol-gel HAp films as corrosion resistance, adhesion to substrate, bioactivity, morphological, and structural properties are discussed. The review also highlights the critical issues, the most significant challenges, and the areas requiring further research.
Assessment of Retinoblastoma Capacity in the Middle East, North Africa, and West Asia Region

PURPOSE We aimed to evaluate the capacity to treat retinoblastoma in the Middle East, North Africa, and West Asia region. METHODS A Web-based assessment that investigated retinoblastoma-related pediatric oncology and ophthalmology infrastructure and associated capacity at member institutions of the Pediatric Oncology East and Mediterranean group was distributed. Data were analyzed in terms of availability, location, and confidence of use for each resource needed for the management of retinoblastoma. Resources were categorized by diagnostics, focal therapy, chemotherapy, advanced treatment, and supportive care. Responding institutions were further divided into an asset-based tiered system. RESULTS In total, responses from 23 institutions were obtained. Fifteen institutions reported the availability of an ophthalmologist, 12 of which held primary off-site appointments. All institutions reported the availability of a pediatric oncologist and systemic chemotherapy A significant portion of available resources was located off site. Green laser was available on site at seven institutions, diode laser at six institutions, cryotherapy at 12 institutions, and brachytherapy at nine institutions. There existed marked disparity between the availability of some specific ophthalmic resources and oncologic resources. CONCLUSION The assessment revealed common themes related to the treatment of retinoblastoma in low- and- middle-income countries, including decentralization of care, limited resources, and lack of multidisciplinary care. Resource disparities warrant targeted intervention in the Middle East, North Africa, and West Asia region to advance the management of retinoblastoma in the region.
Meios de diagnóstico das principais afecções testiculares em cães: revisão de literatura Diagnostics tools of testicular disorders in dogs: review

Testes are responsible for producing sperm and the hormone testosterone and are directly related to male sexual behavior and the ability to fertilize the female. Studies related to the normal pattern of the testes of dogs as well as the testicular changes and consequently its influence on soil fertility are scarce. Knowledge of the best diagnostic method for detection of testicular disorders is important for the evaluation and selection of potential players that can be used in breeding schemes. Our intention is, therefore, this review describes the main diseases found in the testicles of dogs and diagnostics in the evaluation.
Influences of Multilayer Graphene and Boron Decoration on the Structure and Combustion Heat of Al3Mg2 Alloy

To improve the engine-driven performance of propellants, high-energy alloys such as Al and Mg are usually adopted as annexing agents. However, there is still room for improvement in the potential full utilization of alloy energy. In this study, we investigated how to improve combustion efficiency by decorating Al3Mg2 alloy with multilayer graphene and amorphous boron. Scanning electron microscopy and Raman tests showed that decorating with multilayer graphene and amorphous boron promoted the dispersion of Al3Mg2 alloy. The results showed that decorating with 1% boron and 2% multilayer graphene improved the combustion heat of Al3Mg2 alloy to 32.8 and 30.5 MJ/kg, respectively. The coexistence of two phases improved the combustion efficiency of the matrix Al3Mg2 alloy.
Exploring the Use of Helicogenic Amino Acids for Optimising Single Chain Relaxin-3 Peptide Agonists

Relaxin-3 is a highly conserved two-chain neuropeptide that acts through its endogenous receptor the Relaxin Family Peptide-3 (RXFP3) receptor. The ligand/receptor system is known to modulate several physiological processes, with changes in food intake and anxiety-levels the most well studied in rodent models. Agonist and antagonist analogues based on the native two-chain peptide are costly to synthesise and not ideal drug leads. Since RXFP3 interacting residues are found in the relaxin B-chain only, this has been the focus of analogue development. The B-chain is unstructured without the A-chain support, but in single-chain variants structure can be induced by dicarba-based helical stapling strategies. Here we investigated whether alternative helical inducing strategies also can enhance structure and activity at RXFP3. Combinations of the helix inducing α-aminoisobutyric acid (Aib) were incorporated into the sequence of the relaxin-3 B-chain. Aib residues at positions 13, 17 and 18 partially reintroduce helicity and activity of the relaxin-3 B-chain, but other positions are generally not suited for modifications. We identify Thr21 as a putative new receptor contact residue important for RXFP3 binding. Cysteine residues were also incorporated into the sequence and cross-linked with dichloroacetone or α, α’-dibromo-m-xylene. However, in contrast to previously reported dicarba variants, neither were found to promote structure and RXFP3 activity.
Improving Prosthetic Selection and Predicting BMD from Biometric Measurements in Patients Receiving Total Hip Arthroplasty

There are two surgical approaches to performing total hip arthroplasty (THA): a cemented or uncemented type of prosthesis. The choice is usually based on the experience of the orthopaedic surgeon and on parameters such as the age and gender of the patient. Using machine learning (ML) techniques on quantitative biomechanical and bone quality data extracted from computed tomography, electromyography and gait analysis, the aim of this paper was, firstly, to help clinicians use patient-specific biomarkers from diagnostic exams in the prosthetic decision-making process. The second aim was to evaluate patient long-term outcomes by predicting the bone mineral density (BMD) of the proximal and distal parts of the femur using advanced image processing analysis techniques and ML. The ML analyses were performed on diagnostic patient data extracted from a national database of 51 THA patients using the Knime analytics platform. The classification analysis achieved 93% accuracy in choosing the type of prosthesis; the regression analysis on the BMD data showed a coefficient of determination of about 0.6. The start and stop of the electromyographic signals were identified as the best predictors. This study shows a patient-specific approach could be helpful in the decision-making process and provide clinicians with information regarding the follow up of patients.
Differential Protein Expression in Striatal D1- and D2-Dopamine Receptor-Expressing Medium Spiny Neurons

Many neurological disorders and diseases including drug addiction are associated with specific neuronal cell types in the brain. The striatum, a region that plays a critically important role in the development of addictive drug-related behavior, provides a good example of the cellular heterogeneity challenges associated with analyses of specific neuronal cell types. Such studies are needed to identify the adaptive changes in neuroproteomic signaling that occur in response to diseases such as addiction. The striatum contains two major cell types, D1 and D2 type dopaminoceptive medium spiny neurons (MSNs), whose cell bodies and processes are intermingled throughout this region. Since little is known about the proteomes of these two neuronal cell populations, we have begun to address this challenge by using fluorescence-activated nuclear sorting (FANS) to isolate nuclei-containing fractions from striatum from D1 and D2 “Translating Ribosome Affinity Purification” (TRAP) mice. This approach enabled us to devise and implement a robust and reproducible workflow for preparing samples from specific MSN cell types for mass spectrometry analyses. These analyses quantified at least 685 proteins in each of four biological replicates of 50 K sorted nuclei from two D1 mice/replicate and from each of four biological replicates of 50 K sorted nuclei from two D2 mice/replicate. Proteome analyses identified 87 proteins that were differentially expressed in D1 versus D2 MSN nuclei and principal component analysis (PCA) of these proteins separated the 8 biological replicates into specific cell types. Central network analysis of the 87 differentially expressed proteins identified Hnrnpd and Hnmpa2b1 in D1 and Cct2 and Cct7 in D2 as potential central interactors. This workflow can now be used to improve our understanding of many neurological diseases including characterizing the short and long-term impact of drugs of abuse on the proteomes of these two dopaminoceptive neuronal populations.
Age‐Related Effects on Social Cognition in Adults with Autism Spectrum Disorder: A Possible Protective Effect on Theory of Mind

Impaired social cognition has been suggested to underlie the social communication difficulties that define autism spectrum disorder (ASD). In typical development, social cognition may deteriorate in older age, but age effects in ASD adults have been little explored. In the present study, we compared groups of younger and older adults with and without ASD (n = 97), who completed a set of social cognition tasks assessing theory of mind (ToM), and self‐report measures of empathy and alexithymia. While typically developing (TD) younger adults outperformed elderly TD and younger ASD participants, younger and older ASD adults did not differ in their ToM performance, and the elderly ASD and TD groups performed equivalently. By contrast, ASD adults reported lower empathy scores and higher levels of alexithymia symptoms compared to TD adults regardless of age. The difference between ASD and TD groups in self‐reported empathy scores was no longer significant when alexithymia was covaried (with the exception of the Perspective Taking subscore). Results suggest a possible age‐protective effect on ToM in the ASD group. In addition, empathy difficulties appear to be associated with alexithymia rather than ASD per se. Possible interpretations are discussed, and future directions for autism aging research are proposed.
Probiotic Lactobacilli Limit Avian Influenza Virus Subtype H9N2 Replication in Chicken Cecal Tonsil Mononuclear Cells

Low pathogenic avian influenza virus (LPAIV) H9N2 poses significant threat to animal and human health. The growing interest in beneficial effects of probiotic bacteria on host immune system has led to research efforts studying their interaction with cells of host immune system. However, the role of lactobacilli in inducing antiviral responses in lymphoid tissue cells requires further investigation. The objective of the present study was to examine the antiviral and immunostimulatory effects of lactobacilli bacteria on chicken cecal tonsils (CT) cells against H9N2 LPAIV. CT mononuclear cells were stimulated with probiotic Lactobacillus spp mixture either alone or in combination with a Toll-like receptor (TLR)21 ligand, CpG oligodeoxynucleotides (CpG). Pre-treatment of CT cells with probiotic lactobacilli, alone or in combination with CpG, significantly reduced H9N2 LPAIV replication. Furthermore, lactobacilli alone elicited cytokine expression, including IL-2, IFN-γ, IL-1β, IL-6, and IL-12, and IL-10, while when combined with CpG, a significantly higher expression of (interferon-stimulated gene (viperin)), IL-12, IL-6, CXCLi2, and IL-1β was observed. However, none of these treatments induced significant changes in nitric oxide production by CT cells. In conclusion, probiotic lactobacilli demonstrated a modulatory effect on CT cells, and this correlated with enhanced antiviral immunity and reduced H9N2 LPAIV viral replication.
Investigation of the relationship between the pelvic floor and sexual dysfunction in women with Sjögren’s syndrome

Women with Sjögren's syndrome (SS) may have sexual dysfunctions due to vaginal dryness and may also have pelvic floor problems. The aim of this study was to examine the pelvic floor distress of women with SS with a self‐reported questionnaire, to compare this group with healthy individuals, and to examine the relationship between pelvic floor problems and sexual dysfunction.
Work-Related Psychosocial Stress in Small and Medium-Sized Enterprises: An Integrative Review

Background: Work-related psychosocial stress can cause mental and physical illnesses resulting in high costs for the individual, the economy and society. Small and medium-sized enterprises (SMEs) employ the majority of the world’s workforce and often have fewer financial and human resources compared to larger businesses. The aim of this review is to summarize current knowledge on work-related stress in SMEs according to well-established guidelines categorizing psychosocial factors at work. Methods: A systematic database search was carried out in PubMed, PsycINFO, PSYNDEX and Business Source Premiere from March to June 2019, updated in January 2020. Data of included studies were analyzed and mapped into five themes: “work content and task”, “organization of work”, “social relations”, “working environment” and “new forms of work”. Results: After full-text screening, 45 out of 116 studies were included for data extraction. Studies were very heterogeneous and of varying quality, mostly applying a cross-sectional study design. Psychosocial factors in SMEs have been researched with a focus on the work patterns “work organization” and “work content and task”. Conclusions: This review underlines the need for more and better quality research of psychosocial factors in SMEs, particularly in relation to ongoing and new challenges in the workplace, including stressors related to the process of digitalization or the development of safe working conditions during the emerge of new infectious diseases.
Plasma free fatty acid is associated with ischemic cardiomyopathy and cardiac dysfunction severity in systolic heart failure patients with diabetes

Heart failure (HF) is a worldwide problem due to the substantial morbidity and mortality of patients with cardiovascular diseases. Recently, the PARADIGM-HF trial (the Prospective comparison of angiotensin receptorneprilysin inhibitor [ARNI] with angiotensin-converting enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure trial) showed that ischemic heart disease is the most common etiology of HF, which accounts for 60% of HF with reduced ejection fraction (HFrEF). However, effective predictors are still in urgent need to predict ischemic cardiomyopathy (ICM) in HF patients.
Platelet aggregates, a marker of severe COVID-19 disease

Thrombocytopenia is common in an intensive care unit (ICU) setting due to endogenous and iatrogenic factors. Despite that, thrombocytopenia in patients with severe COVID-19 infections is surprisingly uncommon. By examining the blood film of 20 ICU patients with COVID-19, we observed the presence of platelet aggregates and macrothrombocytes indicating increased platelet activity. We compared these findings with 20 blood films of non-severe COVID-19 cases where these findings were absent. These morphology features could be consistent with severe COVID-19 infection and is further evidence of the important role that platelets play when COVID-19 manifests with thrombotic complications or respiratory failure.