Diastereomeric Recognition of 5',8-cyclo-2'-Deoxyadenosine Lesions by Human Poly(ADP-ribose) Polymerase 1 in a Biomimetic Model.

5',8-Cyclo-2'-deoxyadenosine (cdA), in the 5' and 5'diastereomeric forms, are typical non strand-break oxidative DNA lesions, induced by hydroxyl radicals, with emerging importance as a molecular marker. These lesions are exclusively repaired by the nucleotide excision repair (NER) mechanism with a low efficiency, thus readily accumulating in the genome. Poly(ADP-ribose) polymerase1 (PARP1) acts as an early responder to DNA damage and plays a key role as a nick sensor in the maintenance of the integrity of the genome by recognizing nicked DNA.

Fluoride and azide binding to ferric human hemoglobin:haptoglobin complexes highlights the ligand-dependent inequivalence of the α and β hemoglobin chains.

Haptoglobin (Hp) binds human hemoglobin (Hb), contributing to prevent extra-erythrocytic Hb-induced damage. Hp forms preferentially complexes with αβ dimers, displaying heme-based reactivity. Here, kinetics and thermodynamics of fluoride and azide binding to ferric human Hb (Hb(III)) complexed with the human Hp phenotypes 1-1 and 2-2 (Hp1-1:Hb(III) and Hp2-2:Hb(III), respectively) are reported (pH 7.

Protein Profiling of Arabidopsis Roots Treated With Humic Substances: Insights Into the Metabolic and Interactome Networks.

Humic substances (HSs) influence the chemical and physical properties of the soil, and are also known to affect plant physiology and nutrient uptake. This study aimed to elucidate plant metabolic pathways and physiological processes influenced by HS activity. Arabidopsis roots were treated with HS for 8 h.

Nucleotide Excision Repair and Impact of Site-Specific 5',8-Cyclopurine and Bulky DNA Lesions on the Physical Properties of Nucleosomes.

The nonbulky 5',8-cyclopurine DNA lesions (cP) and the bulky, benzo[ a]pyrene diol epoxide-derived stereoisomeric cis- and trans- N-guanine adducts (BPDE-dG) are good substrates of the human nucleotide excision repair (NER) mechanism. These DNA lesions were embedded at the In or Out rotational settings near the dyad axis in nucleosome core particles reconstituted either with native histones extracted from HeLa cells (HeLa-NCP) or with recombinant histones (Rec-NCP). The cP lesions are completely resistant to NER in human HeLa cell extracts.

[Cu(TPMA)(Phen)](ClO): Metallodrug Nanocontainer Delivery and Membrane Lipidomics of a Neuroblastoma Cell Line Coupled with a Liposome Biomimetic Model Focusing on Fatty Acid Reactivity.

The use of copper complexes for redox and oxidative-based mechanisms in therapeutic strategies is an important field of multidisciplinary research. Here, a novel Cu(II) complex [Cu(TPMA)(Phen)](ClO) (Cu-TPMA-Phen, where TPMA = tris-(2-pyridylmethyl)amine and Phen = 1,10-phenanthroline) was studied using both the free and encapsulated forms. A hollow pH-sensitive drug-delivery system was synthesized, characterized, and used to encapsulate and release the copper complex, thus allowing for the comparison with the free drug.

Human nitrobindin: the first example of an all-β-barrel ferric heme-protein that catalyzes peroxynitrite detoxification.

Nitrobindins (Nbs), constituting a heme-protein family spanning from bacteria to , display an all-β-barrel structural organization. Human Nb has been described as a domain of the nuclear protein named THAP4, whose physiological function is still unknown. We report the first evidence of the heme-Fe(III)-based detoxification of peroxynitrite by the all-β-barrel -terminal Nb-like domain of THAP4.

Can we downstage locally advanced pancreatic cancer to resectable? A phase I/II study of induction oxaliplatin and 5-FU chemoradiation.

Background: Half of patients with pancreatic adenocarcinoma (PC) present with regionally advanced disease. This includes borderline resectable and locally advanced unresectable tumors as defined by current NCCN guidelines for resectability. Chemoradiation (CH-RT) is used in this setting in attempt to control local disease, and possibly downstage to resectable disease.

Are DNA damage response kinases a target for the differentiation treatment of acute myeloid leukemia?

Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy characterized by the expansion of hematopoietic stem/progenitor cells (HPCs) blocked at different stages of maturation/differentiation. The poor outcome of AMLs necessitates therapeutic improvement. In AML, genes encoding for myeloid transcription factors, signaling receptors regulating cell proliferation, and epigenetic modifiers can be mutated by somatically acquired genetic mutations or altered by chromosomal translocations.

Anal High-Grade Squamous Intraepithelial Lesions in Pharmacologically Immunocompromised Patients Followed in a Referral Center.

Background: Information is lacking regarding anal/perianal precancerous lesions in referral cohorts of pharmacologically immunocompromised patients.

Objective: The aim of this study is to evaluate the prevalence of anal/perianal high-grade squamous intraepithelial lesions in a referral cohort of patients on immunomodulator/immunosuppressive medications, who were assessed and followed with high-resolution anoscopy.

Design: This is a retrospective study.

Nitrate affects transcriptional regulation of UPBEAT1 and ROS localisation in roots of Zea mays L.

Nitrogen (N) is an indispensable nutrient for crops but its availability in agricultural soils is subject to considerable fluctuation. Plants have developed plastic responses to external N fluctuations in order to optimise their development. The coordinated action of nitric oxide and auxin seems to allow the cells of the root apex transition zone (TZ) of N-deprived maize to rapidly sense nitrate (NO ).

Study protocol for the Australian autism biobank: an international resource to advance autism discovery research.

Background: The phenotypic and genetic heterogeneity of autism spectrum disorder (ASD) presents considerable challenges in understanding etiological pathways, selecting effective therapies, providing genetic counselling, and predicting clinical outcomes. With advances in genetic and biological research alongside rapid-pace technological innovations, there is an increasing imperative to access large, representative, and diverse cohorts to advance knowledge of ASD. To date, there has not been any single collective effort towards a similar resource in Australia, which has its own unique ethnic and cultural diversity.

Anticonvulsant and Neuroprotective Effects of the Thyroid Hormone Metabolite 3-Iodothyroacetic Acid.

Background: 3-Iodothyroacetic acid (TA1) is among the thyroid hormone (T3) metabolites that can acutely modify behavior in mice. This study aimed to investigate whether TA1 is also able to reduce neuron hyper-excitability and protect from excitotoxic damage.

Methods: CD1 male mice were treated intraperitoneally with saline solution or TA1 (4, 7, 11, or 33 μg/kg) before receiving 90 mg/kg pentylenetrazole subcutaneously.

Hypoalbuminemia as a predictor of acute kidney injury during colistin treatment.

This study aimed to assess the predictors of acute kidney injury (AKI) during colistin therapy in a cohort of patients with bloodstream infections (BSI) due to colistin-susceptible Gram-negative bacteria, focusing on the role of serum albumin levels. The study consisted of two parts: (1) a multicentre retrospective clinical study to assess the predictors of AKI during colistin therapy, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and (2) bioinformatic and biochemical characterization of the possible interaction between human serum albumin and colistin. Among the 170 patients included in the study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively.

^{7}Be(n,p)^{7}Li Reaction and the Cosmological Lithium Problem: Measurement of the Cross Section in a Wide Energy Range at n_TOF at CERN.

We report on the measurement of the ^{7}Be(n,p)^{7}Li cross section from thermal to approximately 325 keV neutron energy, performed in the high-flux experimental area (EAR2) of the n_TOF facility at CERN. This reaction plays a key role in the lithium yield of the big bang nucleosynthesis (BBN) for standard cosmology. The only two previous time-of-flight measurements performed on this reaction did not cover the energy window of interest for BBN, and they showed a large discrepancy between each other.

Naphthalene diimide-derivatives G-quadruplex ligands induce cell proliferation inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG glioma cells.

In the present paper, the biological effects of three different naphthalene diimides (NDIs) G-quadruplex (G4) ligands (H-NDI-Tyr, H-NDI-NMe2, and tetra-NDI-NMe2) were comparatively evaluated to those exerted by RHPS4, a well-characterized telomeric G4-ligand, in an in vitro model of glioblastoma. Data indicated that NDIs were very effective in blocking cell proliferation at nanomolar concentrations, although displaying a lower specificity for telomere targeting compared to RHPS4. In addition, differently from RHPS4, NDIs failed to enhance the effect of ionizing radiation, thus suggesting that additional targets other than telomeres could be involved in the strong NDI-mediated anti-proliferative effects.

Biomechanical properties of low back myofascial tissue in younger adult ankylosing spondylitis patients and matched healthy control subjects.

Background: Ankylosing spondylitis is a degenerative and inflammatory rheumatologic disorder that primarily affects the spine. Delayed diagnosis leads to debilitating spinal damage. This study examines biomechanical properties of non-contracting (resting) human lower lumbar myofascia in ankylosing spondylitis patients and matched healthy control subjects.

Human Serum Albumin Is an Essential Component of the Host Defense Mechanism Against Clostridium difficile Intoxication.

Background: The pathogenic effects of Clostridium difficile are primarily attributable to the production of the large protein toxins (C difficile toxins [Tcd]) A (TcdA) and B (TcdB). These toxins monoglucosylate Rho GTPases in the cytosol of host cells, causing destruction of the actin cytoskeleton with cytotoxic effects. Low human serum albumin (HSA) levels indicate a higher risk of acquiring and developing a severe C difficile infection (CDI) and are associated with recurrent and fatal disease.

The acceptability of high resolution anoscopy examination in patients attending a tertiary referral centre.

Background: High resolution anoscopy (HRA) examination is regarded as the best method for the management of anal high grade squamous intraepithelial lesions to prevent anal squamous carcinoma. However, little is known about the acceptability of this procedure. This analysis looks at patient experience of HRA examination and ablative treatment under local anaesthetic.

CfPDIP1, a novel secreted protein of Colletotrichum falcatum, elicits defense responses in sugarcane and triggers hypersensitive response in tobacco.

Colletotrichum falcatum, a hemibiotrophic fungal pathogen, causes one of the major devastating diseases of sugarcane-red rot. C. falcatum secretes a plethora of molecular signatures that might play a crucial role during its interaction with sugarcane.

Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology in Women With Lower Anogenital Tract Neoplasia.

Background: Information on the performance of anal cytology in women who are high risk for human papillomavirus-related lesions and the factors that might influence cytology are largely lacking.

Methods: Retrospective study including all new referrals of women with a previous history of anogenital neoplasia from January 2012 to July 2017, with concomitant anal cytology and high-resolution anoscopy with or without biopsies.

Results: Six hundred and thirty six anal cytology samples and 323 biopsies obtained from 278 women were included.

δ C values in archaeological C-AMS dated charcoals: assessing mid-Holocene climate fluctuations and human response from a high-resolution isotope record (Arslantepe, Turkey).

Rationale: Past climate has always influenced human adaptation to the environment. In order to reconstruct palaeoclimate fluctuations and their role in the evolution of Near Eastern societies during the mid-Holocene, high-resolution Δ C records from fossil wood remains at the archaeological site of Arslantepe (eastern Turkey) have been developed.

Methods: After chemical treatment, δ C values were measured by sample combustion flow using a FLASH EA-CHNS instrument interfaced with a Delta V isotope ratio mass spectrometer via a CONFLO III.

Arterial stiffness and left ventricular performance in elderly patients with persistent atrial fibrillation.

Background: The prevalence of atrial fibrillation (AF) and arterial stiffness (AS) increases with age.

Aims: To evaluate if AS is correlated to longitudinal strain (LS), a marker of left ventricular (LV) function, in elderly AF patients with preserved ejection fraction (EF) undergoing external cardioversion.

Methods: AS was measured using the cardio-ankle vascular index (CAVI), LS was calculated from echocardiographic data of three consecutive cardiac cycles.

Magnetic Metal-Organic Framework Composite by Fast and Facile Mechanochemical Process.

Magnetic porous metal-organic framework nanocomposite was obtained by an easy, efficient, and environmentally friendly fabrication method. The material consists in magnetic spinel iron oxide nanoparticles incorporated in an iron(III) carboxylate framework. The magnetic composite was fabricated by a multistep mechanochemical approach.