Effectiveness of the combined use of an inactivated vaccine and a proteolysis inhibitor in the prevention of experimental influenza

The prophylactic effects produced by different types of antiviral preparations, used separately or in combination, in experimental lethal infection induced by influenza virus AO/32 (H0N1) in mice are compared. The use of inactivated vaccine and E-aminocaproic acid (E-ACA), a proteolysis-inhibiting agent, was studied. The qualitative characterization and quantitative evaluation of the anti-influenza effect were carried out by the method of multifactor analysis with the use of a computer after the optimum second-order plan based on the mathematical theory of experiment. This made it possible to determine the best combination of the preparations and their doses, to establish the time of the formation of reliable protection from influenza in mice. The prophylactic effect produced by the use of E-ACA alone and the capacity of this preparation for enhancing the protective action of inactivated influenza vaccine were established. Mathematical analysis revealed the optimum value of the four factors under study: the dose of the vaccine, the dose of E-ACA, the lapse of time between the injection of the preparations and the challenge of the animals, as well as the infective dose of the pathogenic virus. A special experiment made in the study of these data confirmed that the specific formation of a high level of anti-influenza protection in mice can be achieved by the combined use of the vaccine and the inhibitor of proteolysis.     

Biomechanical properties of breast tissue,a state-of-the-art review

Biomechanics and Modeling in Mechanobiology - This paper reviews the existing literature on the tests used to determine the mechanical properties of women breast tissues (fat, glandular and tumour...     

DAZAP2 acts as specifier of the p53 response to DNA damage

The DNA damage-responsive tumor suppressors p53 and HIPK2 are well established regulators of cell fate decision-making and regulate the cellular sensitivity to DNA-damaging drugs. Here, we identify Deleted in Azoospermia-associated protein 2 (DAZAP2), a small adaptor protein, as a novel regulator of HIPK2 and specifier of the DNA damage-induced p53 response. Knock-down or genetic deletion of DAZAP2 strongly potentiates cancer cell chemosensitivity both in cells and in vivo using a mouse tumour xenograft model. In unstressed cells, DAZAP2 stimulates HIPK2 polyubiquitination and degradation through interplay with the ubiquitin ligase SIAH1. Upon DNA damage, HIPK2 site-specifically phosphorylates DAZAP2, which terminates its HIPK2-degrading function and triggers its re-localization to the cell nucleus. Interestingly, nuclear DAZAP2 interacts with p53 and specifies target gene expression through modulating a defined subset of p53 target genes. Furthermore, our results suggest that DAZAP2 co-occupies p53 response elements to specify target gene expression. Collectively, our findings propose DAZAP2 as novel regulator of the DNA damage-induced p53 response that controls cancer cell chemosensitivity.     

The Effect of Obesity and Cardiometabolic Risk Factors on Expenditures and Productivity in the United States

Objective: To examine the effect of obesity and cardiometabolic risk factors on medical expenditures and missed work days. Methods and Procedures: The 2000 and 2002 Medical Expenditure Panel Survey (MEPS), a nationally representative survey of the US population, was used to estimate the marginal effect of obesity (BMI ≥ 30) on annual per‐person medical expenditures and missed work days for patients with diabetes, dyslipidemia, or hypertension using multivariate regression methods controlling for age, sex, race, ethnicity, education, income, insurance, and smoking status. Maximum Likelihood Heckman Selection with Smearing retransformation was used to assess medical expenditures, and Negative Binomial regression was used for missed work days. Results: Normal weight individuals with diabetes, dyslipidemia, or hypertension had significantly greater medical expenditures than those without the respective condition ($6,006 (5,124–6,887), $4,760 (4,102–5,417), $3,911 (3,345–4,476)) and obesity significantly exacerbated this effect ($7,986 (7,397–8,574), $7,636 (7,072–8,200), $6,197 (5,745–6,649); $2007; all P < 0.05). In addition, diabetes, dyslipidemia, and hypertension resulted in greater missed work days (3.1 (0.94–6.21), 3.2 (0.42–7.91), 1.4 (0.0–3.52)) (all P < 0.05 except hypertension), which resulted in greater lost productivity ($433, $451, $199) and obesity significantly exacerbated the deleterious effect on work days (8.7 (4.44–15.2), 5.5 (2.18–10.5), 4.5 (2.92–6.34)) and lost productivity ($1,217, $763, $622) (all P < 0.05). In addition, medical expenditures increased for increasing weight category and increasing number of risk factors. Discussion: Obesity significantly exacerbates the deleterious effect of diabetes, dyslipidemia, and hypertension on medical expenditures and productivity loss in the United States. Obesity is preventable and public health efforts need to be undertaken to prevent its alarming increase in order to reduce the incidence and effect of cardiometabolic risk factors.     

Effects of neutral salts on the circular dichroism spectra of ribonuclease a and ribonuclease s

The circular dichroism (CD) spectra of ribonuclease A, ribonuclease S, and N-acetyltyrosineamide were recorded as a function of pH in the presence of various concentrations of inorganic salts. Above pH 9.0 salting-in of tyrosine residues increases their intramolecular associations. This association enhances the contribution from these residues to the CD spectrum leading to an apparent titration curve that is shifted toward lower pH. The data indicate that unfolding of ribonuclease A and S by inorganic salts does not begin with disrupting existing electrostatic interactions. But, as the unfolding process progresses, disruption of electrostatic interactions may take place. This is consistent with our previous calorimetric studies which suggest that unfolding of ribonuclease A by salts proceeds initially by energetically favorable solvation of the folded protein. An increase in ellipiticity at 275 nm of partially unfolded protein in salt was observed as the pH was changed from 7.0 to 4.0. This observation may suggest that the isothermal unfolding of the protein by salts at low pH proceeds through an intermediate step which involves histidine residues and causes a conformational change in the tyrosine's asymmetric environment.     

Protocatechuic acid reverses myocardial infarction mediated by β-adrenergic agonist via regulation of Nrf2/HO-1 pathway,inflammatory, apoptotic,and fibrotic events

Myocardial infarction (MI) is an instant ischemic death of cardiomyocytes that remains a major global cause of mortalities. MI is accompanied by oxidative, inflammatory, apoptotic, and fibrotic insults. Protocatechuic acid (PCA) is a polyphenolic compound with various potent biological activities. In this study, we explored the possible cardioprotective role of PCA against isoproterenol (ISO)-mediated MI. Rats were either injected with ISO (85 mg/kg, subcutaneously) or pretreated with PCA (100 or 200 mg/kg, orally). PCA supplementation markedly normalized ISO-induced disturbed cardiac function markers (creatine kinase-MB, lactate dehydrogenase, and troponin T). Notably, PCA administration exerted remarkable increases in glutathione and its derived enzymes, superoxide dismutase, and catalase, as well as decreases in malondialdehyde and nitric oxide levels in the injured cardiac tissue. The molecular findings validated the augmented cellular antioxidative capacity by PCA via increasing the gene expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. The cardioprotective efficacy of PCA extended to suppress cardiac inflammation as demonstrated by the decreased levels of tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B. Additionally, PCA prevented cardiomyocyte loss and fibrosis by decreasing Bax, caspase-3, transforming growth factor-β1 and matrix metalloproteinase-9, and enhancing B-cell lymphoma 2 and tissue inhibitors of metalloproteinase-3. The cardiac histological screening further confirmed the PCA's protective action. The obtained data recommend PCA as an alternative therapeutic agent to attenuate the molecular, biochemical, and histological alterations associated with MI development.     

A hyperparasite of coccids develops as a primary parasite of fly puparia

Species ofPachyneuron (Hym.: Pteromalidae) have been recorded as either primary parasites or hyperparasites.P. concolor (Foerster) is a polyphagous secondary parasite, attacking encyrtid primary parasites in soft scales, mealy bugs and coccinellid larvae. It also develops as a tertiary parasite. We now report thatP. concolor may also develop as a primary parasite of aphidophagous fly puparia. Host selection in this species appears to be based on locating a soft-bodied host within a hard, dry shell, independent of whether the host is a dipterous pupa in its puparium or a primary parasite in its mummified host. The overall effect ofP. concolor is detrimental. Its introduction into new areas should definitely be avoided.     

Axonal Accumulation of Lysosomal-Associated Membrane Protein 1 (LAMP1) Accompanying Alterations of Autophagy Dynamics in the Rat Hippocampus Upon Seizure-Induced Injury

We found a dramatic upregulation in the expression of LC3 in the hippocampus of rats upon status epilepticus (SE). However, the enhancement in LC3 expression might be caused by a reduction in lysosomal activity or by alterations in autophagosome-lysosome fusion leading to a cytosolic vesicular retention. In order to dissect this aspect, we monitored the spatial and temporal expression of LC3 and LAMP1 in the hippocampus of rats with SE. The Western blot analysis showed that the expression of LAMP1 was slightly increased in hippocampal cells at 6, 24, and 48 h post-SE. However, immunofluorescence analysis showed dramatic spatial changes in LAMP1 distribution within the hippocampus. LAMP1 in controls was localised only in cytosol as dot like staining, however at 24 h post-SE LAMP1 was not only highly expressed, but accumulated in mossy fibers of dentate gyrus. In parallel, we found few scattered LC3-positive-dots in neurites of dentate gyrus which co-localise with LAMP1-positive structures. We conclude that SE not only increased autophagosomal abundance, but also lysosomal activities and a massive accumulation of LAMP1 in axons of dentate gyrus. This could support the hypothesis that the marked increased autophagosomal abundance in cytosol reflects an increase in the autophagic activity more than an inhibition of autophagosomal clearance. Although LAMP1 may have contributed to cell damage in the selective vulnerable hippocampal CA1-subfield, it is also possible that lysosomal/autophagic mechanisms in mossy fibers were compensatory and reflected an attempt to survive the epileptic insult by breaking down non-essential components.