Miracle-dz/UniFAR-FTUs huggingface dataset:
Associations between immune competence phenotype and feedlot health and productivity in Angus cattle.

Genetic strategies aimed at improving general immune competence (IC) have the potential to reduce the incidence and severity of disease in beef production systems, with resulting benefits of improved animal health and welfare and reduced reliance on antibiotics to prevent and treat disease. Implementation of such strategies first requires that methodologies be developed to phenotype animals for IC and demonstration that these phenotypes are associated with health outcomes. We have developed methodology to identify IC phenotypes in beef steers during the yard weaning period, which is both practical to apply on-farm and does not restrict the future sale of tested animals. In the current study, a total of 838 Angus steers, previously IC phenotyped at weaning, were categorised as low (n=98), average (n=653) or high (n=88) for the IC phenotype. Detailed health and productivity data were collected on all steers during feedlot finishing and associations between IC phenotype, health outcomes and productivity were investigated. A favourable association between IC phenotype and number of mortalities during feedlot finishing was observed with higher mortalities recorded in low IC steers (6.1%) as compared to average (1.2%, P < 0.001) or high (0%, P = 0.018) IC steers. Disease incidence was numerically highest in low IC steers (15.3 cases / 100 animals) and similar in average IC steers (10.1 cases / 100 animals) and high IC steers (10.2 cases / 100 animals); however, differences between groups were not significant. No significant influence of immune competence phenotype on average daily gain was observed, suggesting that selection for improved IC is unlikely to incur a significant penalty to production. The potential economic benefits of selecting for IC in the feedlot production environment were calculated. Health-associated costs were calculated as the sum of lost production costs, lost capital investment costs and disease treatment costs. Based on these calculations, health associated costs were estimated at $103/head in low IC steers, $25/head in average IC steers and $4/head in high IC steers, respectively. These findings suggest that selection for IC has the potential to reduce mortalities during feedlot finishing and, as a consequence, improve the health and welfare of cattle in the feedlot production environment and reduce health-associated costs incurred by feedlot operators.
Monitoring of endogenous nitric oxide exhaled by pig lungs during ex-vivo lung perfusion

In the context of organ shortage for transplantation, new criteria for better organ evaluation should be investigated. Ex-vivo lung perfusion (EVLP) allows extra-corporal lung re-conditioning and evaluation, under controlled parameters of the organ reperfusion and mechanical ventilation. This work reports on the interest of exhaled gas analysis during the EVLP procedure. After a 1 h cold ischemia, the endogenous gas production by an isolated lung of nitric oxide and carbon monoxide is simultaneously monitored in real time. The exhaled gas is analysed with two very sensitive and selective laser spectrometers developed upon the technique of optical-feedback cavity-enhanced absorption spectroscopy. Exhaled gas concentration measured for an ex-vivo lung is compared to the corresponding production by the whole living pig, measured before euthanasia. On-line measurements of the fraction of nitric oxide in exhaled gas (FENO) in isolated lungs are reported here for the first time, allowing to resolve the respiratory cycles. In this study, performed on 9 animals, FENO by isolated lungs range from 3.3 to 10.6 ppb with a median value of 4.4 ppb. Pairing ex-vivo lung and pig measurements allows to demonstrate a systematic increase of FENO in the ex-vivo lung as compared to the living animal, by a factor of 3 ± 1.2. Measurements of the fraction of carbon monoxide in exhaled gas (FECO) confirm levels recorded during previous studies driven to evaluate FECO as a potential marker of ischemia reperfusion injuries. FECO production by ex-vivo lungs ranges from 0.31 to 2.3 ppm with a median value of 0.8 ppm. As expected, these FECO values are lower than the production by the corresponding whole pig body, by a factor of 6.9 ± 2.7.
Application of Tissue Aspirate Parathyroid Hormone Assay for Imaging Suspicious Neck Lesions in Patients with Complicated Recurrent or Persistent Renal Hyperparathyroidism

Background: Comprehensive pre-reoperative localization is essential in complicated persistent or recurrent renal hyperparathyroidism. The widely used imaging studies sometimes lead to ambiguous results. Our study aimed to clarify the role of tissue aspirate parathyroid hormone (PTH) assay with a new positive assay definition for imaging suspicious neck lesions in these challenging scenarios. Methods: All patients with complicated recurrent or persistent renal hyperparathyroidism underwent parathyroid sonography and scintigraphy. Echo-guided tissue aspirate PTH assay was performed in suspicious lesions revealed by localization imaging studies. The tissue aspirate PTH level was determined by an immunoradiometric assay. We proposed a newly-developed definition for positive assay as a washout level higher than one-thirtieth of the serum PTH level obtained at the same time. The final diagnosis after re-operation was confirmed by the pathologists. Results: In total, 50 tissue aspirate PTH assays were performed in 32 patients with imaging suspicious neck lesions, including discrepant results between scintigraphy and sonography in 47 lesions (94%), unusual locations in 19 lesions (38%), multiple foci in 28 lesions (56%), and locations over previously explored areas in 31 lesions (62%). Among 39 assay-positive lesions, 13 lesions (33.3%) were not identified by parathyroid scintigraphy, and 28 lesions (71.8%) had uncertain parathyroid sonography findings. The final pathology in patients who underwent re-operative surgery proved the tissue aspirate PTH assays had a 100% positive predictive value. Conclusions: Our findings suggest tissue aspirate PTH assay with this new positive assay definition is beneficial to clarify the nature of imaging suspicious lesions in patients with complicated persistent or recurrent renal hyperparathyroidism.
Human umbilical cord mesenchymal stem cell-derived exosomal miR-146a-5p reduces microglial-mediated neuroinflammation via suppression of the IRAK1/TRAF6 signaling pathway after ischemic stroke

To investigate the therapeutic mechanism of action of transplanted stem cells and develop exosome-based nanotherapeutics for ischemic stroke, we assessed the effect of exosomes (Exos) produced by human umbilical cord mesenchymal stem cells (hUMSCs) on microglia-mediated neuroinflammation after ischemic stroke. Our results found that injected hUMSC-Exos were able to access the site of ischemic damage and could be internalized by cells both in vivo and in vitro. In vitro, treatment with hUMSC-Exos attenuated microglia-mediated inflammation after oxygen-glucose deprivation (OGD). In vivo results demonstrated that treatment with hUMSC-Exos significantly reduced infarct volume, attenuated behavioral deficits, and ameliorated microglia activation, as measured three days post-transient brain ischemia. Furthermore, miR-146a-5p knockdown (miR-146a-5p k/d Exos) partially reversed the neuroprotective effect of hUMSC-Exos. Our mechanistic study demonstrated that miR-146a-5p in hUMSC-Exos reduces microglial-mediated neuroinflammatory response through IRAK1/TRAF6 pathway. We conclude that miR-146a-5p derived from hUMSC-Exos can attenuate microglia-mediated neuroinflammation and consequent neural deficits following ischemic stroke. These results elucidate a potential therapeutic mechanism of action of mesenchymal stem cells and provide evidence that hUMSC-Exos represent a potential cell-free therapeutic option for ischemic stroke.
Synthetic and catalytic investigations of ruthenium(III) complexes with triphenylphosphine/triphenylarsine and tridentate Schiff base

The synthesis and characterization of several hexa-coordinated ruthenium(III) complexes of the type [RuCl(PPh3)2(L)] (L = dibasic tridentate ligand derived by the condensation of salicylaldehyde/o-vanillin with o-aminophenol/o-aminothiophenol) are reported. IR, electronic, EPR spectral data and redox bahaviour of the complexes are discussed. An octahedral geometry has been tentatively proposed for all the complexes. The new complexes were found to be effective catalysts for the oxidation of benzyl alcohol and cyclohexanol to benzaldehyde and cyclohexanone respectively using N-methylmorpholine-N-oxide as a co-oxidant. Copyright © 2007 John Wiley & Sons, Ltd.
Generation of enzymatically competent SARS‐CoV‐2 decoy receptor ACE2‐Fc in glycoengineered Nicotiana benthamiana

Human angiotensin‐converting enzyme 2 (ACE2) is the primary host cell receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) binding and cell entry. Administration of high concentrations of soluble ACE2 can be utilized as a decoy to block the interaction of the virus with cellular ACE2 receptors and potentially be used as a strategy for treatment or prevention of coronavirus disease 2019. Human ACE2 is heavily glycosylated and its glycans impact on binding to the SARS‐CoV‐2 spike protein and virus infectivity. Here, we describe the production of a recombinant soluble ACE2‐fragment crystallizable (Fc) variant in glycoengineered Nicotiana benthamiana. Our data reveal that the produced dimeric ACE2‐Fc variant is glycosylated with mainly complex human‐type N‐glycans and functional with regard to enzyme activity, affinity to the SARS‐CoV‐2 receptor‐binding domain, and wild‐type virus neutralization.
The Role of Polyphosphate in Motility, Adhesion, and Biofilm Formation in Sulfolobales

Polyphosphates (polyP) are polymers of orthophosphate residues linked by high-energy phosphoanhydride bonds that are important in all domains of life and function in many different processes, including biofilm development. To study the effect of polyP in archaeal biofilm formation, our previously described Sa. solfataricus polyP (−) strain and a new polyP (−) S. acidocaldarius strain generated in this report were used. These two strains lack the polymer due to the overexpression of their respective exopolyphosphatase gene (ppx). Both strains showed a reduction in biofilm formation, decreased motility on semi-solid plates and a diminished adherence to glass surfaces as seen by DAPI (4′,6-diamidino-2-phenylindole) staining using fluorescence microscopy. Even though arlB (encoding the archaellum subunit) was highly upregulated in S. acidocardarius polyP (−), no archaellated cells were observed. These results suggest that polyP might be involved in the regulation of the expression of archaellum components and their assembly, possibly by affecting energy availability, phosphorylation or other phenomena. This is the first evidence indicating polyP affects biofilm formation and other related processes in archaea.
A New Mouse Model Related to SCA14 Carrying a Pseudosubstrate Domain Mutation in PKCγ Shows Perturbed Purkinje Cell Maturation and Ataxic Motor Behavior

Spinocerebellar ataxias (SCAs) are diseases characterized by cerebellar atrophy and loss of Purkinje neurons caused by mutations in diverse genes. In SCA14, the disease is caused by point mutations or small deletions in protein kinase C γ (PKCγ), a crucial signaling protein in Purkinje cells. It is still unclear whether increased or decreased PKCγ activity may be involved in the SCA14 pathogenesis. In this study, we present a new knock-in mouse model related to SCA14 with a point mutation in the pseudosubstrate domain, PKCγ-A24E, known to induce a constitutive PKCγ activation. In this protein conformation, the kinase domain of PKCγ is activated, but at the same time the protein is subject to dephosphorylation and protein degradation. As a result, we find a dramatic reduction of PKCγ protein expression in PKCγ-A24E mice of either sex. Despite this reduction, there is clear evidence for an increased PKC activity in Purkinje cells from PKCγ-A24E mice. Purkinje cells derived from PKCγ-A24E have short thickened dendrites typical for PKC activation. These mice also develop a marked ataxia and signs of Purkinje cell dysfunction making them an interesting new mouse model related to SCA. Recently, a similar mutation in a human patient was discovered and found to be associated with overt SCA14. RNA profiling of PKCγ-A24E mice showed a dysregulation of related signaling pathways, such as mGluR1 or mTOR. Our results show that the induction of PKCγ activation in Purkinje cells results in the SCA-like phenotype indicating PKC activation as one pathogenetic avenue leading to a SCA. SIGNIFICANCE STATEMENT Spinocerebellar ataxias (SCAs) are hereditary diseases affecting cerebellar Purkinje cells and are a one of neurodegenerative diseases. While mutation in several genes have been identified as causing SCAs, it is unclear how these mutations cause the disease phenotype. Mutations in PKCγ cause one subtype of SCAs, SCA14. In this study, we have generated a knock-in mouse with a mutation in the pseudosubstrate domain of PKCγ, which keeps PKCγ in the constitutive active open conformation. We show that this mutation leading to a constant activation of PKCγ results in a SCA-like phenotype in these mice. Our findings establish the constant activation of PKC signaling as one pathogenetic avenue leading to an SCA phenotype and a mechanism causing a neurodegenerative disease.
Characterisation of geometric isomers of europium chlorides with 2,2′-bipyridine based on X-ray diffraction, luminescence and quantum chemical data

A low-temperature high-resolution luminescence study of the EuCl3bpy2(H2O) n isomers has been carried out. The Eu3+ luminescence spectra of all geometric isomers were recorded over the spectral range which includes transitions from the 5D0 excited state to the 7F0–4 ground state manifolds and from the 5D1 excited state to the 7F0–2 ground state manifolds. Analysis of the Eu3+ transitions observed in the luminescence spectra shows that the Eu3+ ion occupies a spectroscopic site symmetry that approaches a C2 v symmetry with distortion towards C2 or lower symmetry. The structural features and distortions of the Eu3+ coordination polyhedron in these geometric isomers were described based on the X-ray crystallographic data as well. The splitting patterns and energies found of the 7F0–4 manifolds have been used to calculate the crystal field parameters (CFPs) of the Eu3+ ions in these geometric isomers. In addition the mutual influence of the ligands as well as the relative stability of geometric isomers of the [EuCl3bpy2(H2O)2]+ cation in the gas phase was analyzed within DFT calculations.
Is the Antimicrobial Activity of Hydrolates Lower than that of Essential Oils?

Among the top five human infections requiring medical treatment is dermatitis. Treatment of bacterial and fungal skin infections is usually based on antibiotic therapy, which is often ineffective due to the involvement of antibiotic-resistant microbial strains. The aim of this study was to compare the antimicrobial activity of essential oils (EOs) and hydrolates (Hys) extracted from six aromatic plants grown in Italy (Lavandula angustifolia, Lavandula intermedia, Origanum hirtum, Satureja montana, Monarda didyma, and Monarda fistulosa) towards fungal (Candida albicans, Candida parapsilosis, Candida glabrata and Candida tropicalis; Trichophyton soudanense, Trichophyton tonsurans, Trichophyton rubrum, Trichophyton violaceum and Microsporum canis) and bacterial strains (Staphylococcus aureus MRSA, Staphylococcus aureus MSSA, Streptococcus pyogenes, E. faecalis, Enterococcus faecalis VRE, and Enterococcus faecium) potentially pathogenic for human skin. The composition and antimicrobial activity of EOs and Hys were evaluated using the Gas-chromatography mass spectrometry and micro dilution-broth test, respectively. The volatiles’ conversion factors (CFs) were calculated to compare the activity of Hys with that of the corresponding EOs. Data show that, although the minimum inhibitory concentration values of EOs are lower than the corresponding Hys, the volatiles contained in Hys are more effective at inhibiting microbial growth because they are active at lower concentrations.
Gonoactivity of Culex (Culex) (Diptera: Culicidae) Mosquitoes During Winter in Temperate Argentina

Abstract The subgenus Culex L. includes species involved in summer–autumn arbovirus transmission but studies during winter are scarce in temperate Argentina. Female specimens were collected host-seeking at dry-ice-baited traps during autumn–winter–spring at two sites in Córdoba City during 2016 and 2017. The specimens were morphologically identified and dissected to determine the follicular developmental stage (gonotrophic activity). Females with advanced follicular stages (≥III) were subjected to molecular procedures to confirm or re-identify previous morphological identification. Five species (Culex apicinus Philippi (Diptera: Culicidae), Culex dolosus (Lynch-Arribálzaga) (Diptera: Culicidae), Culex maxi Dyar (Diptera: Culicidae), Culex pipiens pipiens L. (Diptera: Culicidae), and Culex quinquefasciatus Say (Diptera: Culicidae)) were collected and found gonoactive during winter; showing that a high proportion of Culex (Culex) females remain reproductively active during the unfavorable season for mosquito populations. Among them, it is worth noting the collection of Cx. quinquefasciatus, vector of the St. Louis encephalitis virus (endemic in the city), a specimen of Cx. p. pipiens, and a hybrid of Cx. p. pipiens/Cx. quinquefasciatus (during autumn). The study of this community during winter should continue because a high gonoactive female proportion with advanced follicular stages was found: 29.12 and 13.07% in 2016 and 2017, respectively. Local studies such as this one provide evidence about ornithophilic Culex species with active year-round life cycles, species that could favor arbovirus overwintering.
A Selective Competitive Inhibitor of Aldehyde Dehydrogenase 1A3 Hinders Cancer Cell Growth, Invasiveness and Stemness In Vitro

Simple Summary The aldehyde dehydrogenases enzymes (ALDHs) are promising drug targets in cancer therapy. ALDHs are members of an enzymatic superfamily composed by 19 isoforms involved in the oxidation of aldehydes, with a scavenger role. Among them, the isoform ALDH1A3 is a cancer biomarker since it is highly expressed in cancer stem cells characterized by a marked drug resistance and the capacity to promote self-renewal, clonogenic growth and tumour-initiating capacity. In this paper, we present the first highly potent and selective ALDH1A3 inhibitor able to induce cytotoxic effects and to reduce cell migration and stemness of ALDH1A3-positive cancer cells. We propose the targeting of the ALDH1A3 enzyme as a promising approach for improving the treatments outcomes of patients affected by ALDH1A3-positive cancers. Abstract Aldehyde dehydrogenase 1A3 (ALDH1A3) belongs to an enzymatic superfamily composed by 19 different isoforms, with a scavenger role, involved in the oxidation of a plethora of aldehydes to the respective carboxylic acids, through a NAD+-dependent reaction. Previous clinical studies highlighted the high expression of ALDH1A3 in cancer stem cells (CSCs) correlated to a higher risk of cancer relapses, chemoresistance and a poor clinical outcome. We report on the structural, biochemical, and cellular characterization of NR6, a new selective ALDH1A3 inhibitor derived from an already published ALDH non-selective inhibitor with cytotoxic activity on glioblastoma and colorectal cancer cells. Crystal structure, through X-Ray analysis, showed that NR6 binds a non-conserved tyrosine residue of ALDH1A3 which drives the selectivity towards this isoform, as supported by computational binding simulations. Moreover, NR6 shows anti-metastatic activity in wound healing and invasion assays and induces the downregulation of cancer stem cell markers. Overall, our work confirms the role of ALDH1A3 as an important target in glioblastoma and colorectal cells and propose NR6 as a promising molecule for future preclinical studies.
Urodynamic and morphometric characteristics of the lower urogenital tract of male Beagle littermates from four months to two years of age.

OBJECTIVE To describe functional and anatomic changes of the lower urogenital tract of healthy male dogs during the sexually immature period and up to 2 years of age by urodynamic and morphometric assessment. ANIMALS 6 sexually intact male Beagle littermates. PROCEDURES Dogs underwent electromyography-coupled urodynamic tests, CT-assisted retrograde urethrography, prostatic washes, and blood sampling monthly from 4 through 12 months of age and then at 3-month intervals. Urodynamic and morphometric variables and serum canine prostate-specific esterase concentrations were analyzed by statistical methods. RESULTS Integrated pressure of the urethra was significantly increased beginning at 8 months of age, compared with earlier time points. Urethral pressure peak amplitudes varied among anatomic regions. During bladder filling, few electromyographic signals were concurrent with urethral pressure peaks; these were most commonly detected in the penile portion of the urethra. Urethral length and prostate gland volume were significantly greater from 7 to 24 months of age than at younger ages. Urethral length was approximately 26 to 27 cm after 9 months, and prostate gland volume was approximately 11 to 12 cm3 after 11 months of age. Serum canine prostate-specific esterase concentrations correlated with prostate gland volume. Urinary bladder threshold volume was significantly increased at 6 months of age, compared with that at 4 months, with a maximum of 197.7 mL at 24 months. CONCLUSIONS AND CLINICAL RELEVANCE Urethral resistance was acquired at approximately 8 months of age, when growth of the lower urinary tract was incomplete. Electromyographic and integrated pressure measurement results and the distribution and amplitude of urethral pressure peaks highlighted the potential role of the prostate gland and possibly the bulbocavernosus muscles in control of continence.
Novel anti-PD-L1 peptide selected from combinatorial phage library inhibits tumor cell growth and restores T-cell activity

Abstract PD-L1 overexpression on tumour cells forms a protective shield against cytotoxic T-cell killing, which consequently leads to immune evasion. Engagement of PD-1 in tumour infiltrating T cells with PD-L1 results in an exhausted T-cell phenotype, thus preventing an effective immune response against tumour cells. In the present study, we employed phage display combinatorial peptide library to discover anti-PD-L1 peptides. The peptides discovered here, could computationally exhibit specific interactions with PD-L1 at residues with which PD-1 also interacts. Binding affinity and specificity of the peptides were examined by flow cytometry. Anti- tumour activity of peptides was also investigated using several cell-based assays. Surprisingly, we demonstrated that Pep-39 can inhibit PDL-1, and reduce MDA-MB-231, CT-26, and DU-145 cells survival. In co-culture experiments, Pep-39 restored proliferation of Jurkat cells cultured in the presence of MDA-MB-231 cells. In addition, Jurkat cells apoptosis was impeded, indicating blocking potential of Pep-39 against PD-1/PD-L1 interaction.