Bottom-up hierarchical self-assembly of chiral porphyrins through coordination and hydrogen bonds

A series of chiral synthetic compounds is reported that show intricate but specific hierarchical assembly because of varying positions of coordination and hydrogen bonds. The evolution of the aggregates (followed by absorption spectroscopy and temperature-dependent circular dichroism studies in solution) reveal the influence of the proportion of stereogenic centers in the side groups connected to the chromophore ring in their optical activity and the important role of pyridyl groups in the self-assembly of these chiral macrocycles. The optical activity spans two orders of magnitude depending on composition and constitution. Two of the aggregates show very high optical activity even though the isolated chromophores barely give a circular dichroism signal. Molecular modeling of the aggregates, starting from the pyridine-zinc(II) porphyrin interaction and working up, and calculation of the circular dichroism signal confirm the origin of this optical activity as the chiral supramolecular organization of the molecules. The aggregates show a broad absorption range, between approximately 390 and 475 nm for the transitions associated with the Soret region alone, that spans wavelengths far more than the isolated chromophore. The supramolecular assemblies of the metalloporphyrins in solution were deposited onto highly oriented pyrolitic graphite in order to study their hierarchy in assembly by atomic force microscopy. Zero and one-dimensional aggregates were observed, and a clear dependence on deposition temperature was shown, indicating that the hierarchical assembly took place largely in solution. Moreover, scanning electron microscopy images of porphyrins and metalloporphyrins precipitated under out-of-equilibrium conditions showed the dependence of the number and position of chiral amide groups in the formation of a fibrillar nanomaterial. The combination of coordination and hydrogen bonding in the complicated assembly of these molecules - where there is a clear hierarchy for zinc(II)-pyridyl interaction followed by hydrogen-bonding between amide groups, and then van der Waals interactions - paves the way for the preparation of molecular materials with multiple chromophore environments

Academic Service Learning Benefits Diverse, Urban Community College Students

Urban community college students are a vulnerable population, often carrying one or more risk factors that predict they will not graduate or transfer to a four-year institution. This article presents evidence that academic service learning can provide support for urban community college students, increasing retention and providing multiple positive benefits. After participating in service learning, urban community college students report increased confidence in their ability to learn and apply course content knowledge, general education knowledge, and workplace skills as well as an interest in civic engagement

Comparative genomic mapping of the bovine Fragile Histidine Triad (FHIT) tumour suppressor gene: characterization of a 2 Mb BAC contig covering the locus, complete annotation of the gene, analysis of cDNA and of physiological expression profiles

BACKGROUND: The Fragile Histidine Triad gene (FHIT) is an oncosuppressor implicated in many human cancers, including vesical tumors. FHIT is frequently hit by deletions caused by fragility at FRA3B, the most active of human common fragile sites, where FHIT lays. Vesical tumors affect also cattle, including animals grazing in the wild on bracken fern; compounds released by the fern are known to induce chromosome fragility and may trigger cancer with the interplay of latent Papilloma virus. RESULTS: The bovine FHIT was characterized by assembling a contig of 78 BACs. Sequence tags were designed on human exons and introns and used directly to select bovine BACs, or compared with sequence data in the bovine genome database or in the trace archive of the bovine genome sequencing project, and adapted before use. FHIT is split in ten exons like in man, with exons 5 to 9 coding for a 149 amino acids protein. VISTA global alignments between bovine genomic contigs retrieved from the bovine genome database and the human FHIT region were performed. Conservation was extremely high over a 2 Mb region spanning the whole FHIT locus, including the size of introns. Thus, the bovine FHIT covers about 1.6 Mb compared to 1.5 Mb in man. Expression was analyzed by RT-PCR and Northern blot, and was found to be ubiquitous. Four cDNA isoforms were isolated and sequenced, that originate from an alternative usage of three variants of exon 4, revealing a size very close to the major human FHIT cDNAs. CONCLUSION: A comparative genomic approach allowed to assemble a contig of 78 BACs and to completely annotate a 1.6 Mb region spanning the bovine FHIT gene. The findings confirmed the very high level of conservation between human and bovine genomes and the importance of comparative mapping to speed the annotation process of the recently sequenced bovine genome. The detailed knowledge of the genomic FHIT region will allow to study the role of FHIT in bovine cancerogenesis, especially of vesical papillomavirus-associated cancers of the urinary bladder, and will be the basis to define the molecular structure of the bovine homologue of FRA3B, the major common fragile site of the human genome

Comparación de parámetros metabólicos en pacientes adultos y ancianos sometidos a cirugía bariátrica: Una cohorte prospectiva

Introduction: The aim was to evaluate metabolic parameters in a group of patients older than 65 years old compared to younger adults at three and six months after bariatric surgery (BS). Materials and methods: Prospective analytic study of a cohort of 40 patients under BS since 2015 to 2018. Participants were divided into two groups (Group A: ≥65; B: <65 years old). Anthropometrics and metabolic parameters were assessed before and 3 and 6 months after BS. The excess weight loss percentage (EWLP) and the Triglycerides/HDLc ratio, as a marker of insulin resistance, were also evaluated. A p <0.05 was statistically significant. Results: Forty patients were under BS, we included thirty six: 21 patients were at group A (Median age: 59, RIQ: 48-61 years old) and 15 at group B (median age 67, RIQ: 66-69 years old), the prevalence of patients with type 2 diabetes was 53% (n=8) in group B vs 43% (n=9) at group A. After 3 and 6 months of BS, we found no statistical difference between groups in WL and the EWLP and the decrease in fasting blood glucose (FBG), HbAc1 % levels but a significant rise in the levels of HDLc in group B. We observed a statistically decrease in the TAG/HDLc ratio and a positive correlation between HbA1c% and levels of FBG, HDLc and the TAG/HDLc ratio in group B. Moreover, we found a reduction in the use of antidiabetics and lipid lowering drugs in this age group.Conclusion: We found a significant benefit in metabolic effects of BS in the≥65 y/o cohort, especially by decreasing insulin resistance, even in those patients without diagnosis of DM2. We need more studies and a greater sample size to generalize these results.Introducción: El Objetivo fue evaluar los parámetros metabólicos en pacientes adultos ≥ 65 años en comparación con adultos < 65 años sometidos a CB pre y post intervención.Materiales y métodos: Estudio analítico de cohorte prospectiva en 40 pacientes sometidos a CB durante el periodo julio de 2015 y marzo de 2018. Los pacientes fueron divididos en dos grupos (A: ≥65 años; B: < 65 años) y se evaluaron previo a la cirugía (basal), y a los 3 y 6 meses posteriores al acto quirúrgico parámetros antropométricos y parámetros bioquímicos. Se calculó el porcentaje de peso perdido (PEPP) y se evaluó el índice Triglicéridos/HDLc (TAG/HDLc) como marcador de insulinorresistencia.Resultados: De los 40 pacientes sometidos a la CB, se incluyeron 36: 21 pacientes eran del grupo A (mediana de edad: 59, RIQ: 48-61 años) y 15 pacientes del grupo B (mediana de edad: 67, RIQ: 66-69 años), el porcentaje de pacientes con diabetes mellitus tipo 2 era de 53%(n=8) en B vs 43% (n=9) en A. Luego de 3 y 6 meses post CB se observó en el grupo B un descenso en el peso, índice de masa corporal y porcentaje de exceso de peso perdido (PEPP) no significativo, disminución en los niveles de glucemia y HbA1c sumado a un aumento significativo en los niveles de HDLc, además de un descenso significativo del índice TAG/HDLc en el grupo B. Se encontró una correlación positiva entre los niveles de HbA1c y PEPP, HDLc y el índice TAG/HDLc así como el descenso del uso de antidiabéticos e hipolipemiantes en el grupo B. Conclusiones: la CB logró similares resultados antropométricos en el grupo de pacientes ≥ de 65 años presentando una mejoría significativa en los paramétricos metabólicos a los 3 y 6 meses, principalmente en la insulinorresistencia, lo cual apoyaría el beneficio de la CB en este grupo etario

Analysis of plasma indices of redox homeostasis in dairy cows reared in polluted areas of Piedmont (northern Italy)

Steel manufacturing is responsible for the emission of pollutants, including dioxins and transition metals, inducing reactive oxygen species generation and DNA damage. Dioxin pollution represents the major cause of milk and dairy product contamination, in Italy, and is associated with oxidative stress-related processes, that may impair health and performance of cows.We evaluated the effect of exposure to different concentrations of pollutants derived from steel manufacturing on blood redox homeostasis of bovine cows. We analyzed two groups of dairy cows (A, B), reared in two different polluted areas, and a control group of cows bred in an industry free area. The extent of exposure to contaminants was defined by measuring dioxin level in bulk milk samples collected from animals of each farm. This level was lower in milk of group A than in group B. Plasma concentrations of retinol, alpha-tocopherol and ascorbate, the total antioxidant capacity, and the activities of superoxide dismutase and glutathione peroxidase were higher in control group than in exposed groups. In particular, retinol and tocopherol levelswere higher in the groupwith lower milk dioxin level. Plasma titers of protein-bound carbonyls (PC), nitro-tyrosine, and hydroperoxideswere lower in control group than in A or B. Hydroperoxides and PC plasmaconcentrationswere increased in the groupwith higher milk concentration of dioxin. Our results demonstrate that, irrespective of the nature of chemicals inducing oxidativemodifications, the extent of damage to plasmaprotein and lipid, is correlatedwith the concentration of dioxin in milk. So, the characterization of blood redox status might be a useful tool for identifying animals exposed to environmental pollutants. Plasma concentrations of retinol, alpha-tocopherol, PC and hydroperoxides could therefore represent good indices of the extent of animal exposure, as they significantly change in groups with different milk concentrations of dioxi

Constraints on the χ_(c1) versus χ_(c2) polarizations in proton-proton collisions at √s = 8 TeV

The polarizations of promptly produced χ_(c1) and χ_(c2) mesons are studied using data collected by the CMS experiment at the LHC, in proton-proton collisions at √s=8  TeV. The χ_c states are reconstructed via their radiative decays χ_c → J/ψγ, with the photons being measured through conversions to e⁺e⁻, which allows the two states to be well resolved. The polarizations are measured in the helicity frame, through the analysis of the χ_(c2) to χ_(c1) yield ratio as a function of the polar or azimuthal angle of the positive muon emitted in the J/ψ → μ⁺μ⁻ decay, in three bins of J/ψ transverse momentum. While no differences are seen between the two states in terms of azimuthal decay angle distributions, they are observed to have significantly different polar anisotropies. The measurement favors a scenario where at least one of the two states is strongly polarized along the helicity quantization axis, in agreement with nonrelativistic quantum chromodynamics predictions. This is the first measurement of significantly polarized quarkonia produced at high transverse momentum

Acetyl-4'-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency

CITATION: Di Meo, I., et al. 2017. Acetyl-4′-phosphopantetheine is stable in serum and prevents phenotypes induced by pantothenate kinase deficiency. Scientific Reports, 7:11260, doi:10.1038/s41598-017-11564-8.The original publication is available at https://www.nature.comCoenzyme A is an essential metabolite known for its central role in over one hundred cellular metabolic reactions. In cells, Coenzyme A is synthesized de novo in five enzymatic steps with vitamin B5 as the starting metabolite, phosphorylated by pantothenate kinase. Mutations in the pantothenate kinase 2 gene cause a severe form of neurodegeneration for which no treatment is available. One therapeutic strategy is to generate Coenzyme A precursors downstream of the defective step in the pathway. Here we describe the synthesis, characteristics and in vivo rescue potential of the acetyl-Coenzyme A precursor S-acetyl-4′-phosphopantetheine as a possible treatment for neurodegeneration associated with pantothenate kinase deficiency.https://www.nature.com/articles/s41598-017-11564-8Publisher's versio

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population