Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair

Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.     

Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

A New Criteria Decision Applied on the Primary Synchronization in the DS-WCDMA Interface of the UMTS System

In DS-WCDMA mobile systems such the UMTS, asynchronous cell site operation,assigning different long spreading code to each cell, yields the advantageof flexible system deployment. We can design an indoor system basedon an outdoor one. However, in general, much longer search time isrequired in asynchronous operation than in synchronous. This paperproposes three techniques to take decisions about synchronizationbased on observation of correlated signals. Classical decision criterialike maximum and threshold criterion are presented. A new decisioncriteria that we call Threshold&Max combined decision criteriais analyzed. The results of this new introduced technique is comparedwith the classical ones.     

Epidemiology of Trauma and Posttraumatic Stress Disorder in Mexico.

Prevalence rates of trauma and posttraumatic stress disorder (PTSD) were estimated from a probability sample of 2,509 adults from 4 cities in Mexico. PTSD was assessed according to Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) criteria using the Composite International Diagnostic Interview (CIDI; WHO, 1997). Lifetime prevalence of exposure and PTSD were 76% and 11.2%, respectively. Risk for PTSD was highest in Oaxaca (the poorest city), persons of lower socioeconomic status, and women. Conditional risk for PTSD was highest following sexual violence, but nonsexual violence and traumatic bereavement had greater overall impact because of their frequency. Of lifetime cases, 62% became chronic; only 42% received medical or professional care. The research demonstrates the importance of expanding the epidemiologic research base on trauma to include developing countries around the world. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynamical modelling of an activated sludge system of a petrochemical plant operating at high temperatures.

The Mexican petrochemical industry, Morelos S.A. de C.V., is one of the biggest and more important petroleum industries in Mexico and Latin America. It has an activated sludge system to treat its wastewater flow, which is approximately 7,000 m3/d. The wastewater contains volatile organic carbon substances classified as toxics. The old surface aeration system was changed for fine bubble diffusers; however, one major drawback of the new aeration system is that the temperature in the bioreactor has increased due to the compression of the air, which at the compressor exit reaches 85 degrees C. This effect results in the temperature in the bioreactor attaining 32 degrees C during the fall, whereas in the spring and summer, the bioreactor temperature reaches higher values than 40 degrees C. The high temperatures reduce the microorganism activity and cause a higher volatilisation rate of volatile compounds, among other effects, which affect the performance of the biological treatment. This work was performed to obtain a better modelling of the wastewater treatment from the petrochemical industry. The model describes the effect of the temperature on the performance of the biological treatment. The model was obtained from tests that were carried out in laboratory reactors with 14 L capacity, which were operated at different temperatures (from 30 to 45 degrees C), with the same wastewater and conditions as the actual system.     

Hydrogen adsorption studies in micro-size cobalt dots

Hydrogen desorption curves were obtained from a sample composed of a square arrangement of Co dots with average diameter of 4.4 μm, separated by a distance of 11.6 μm. A macroscopic sample of Co dots grown on a 2.5 × 2.5 cm Si substrate was made by standard lithographic techniques and used in these experiments. Thermal programmed desorption (TPD) was performed under ultra-high vacuum conditions. Hydrogen TPD curves were obtained from a 1 × 1 cm Co dots samples displaying a maximum of intensity at 425 K. Hydrogen TPD curve was also obtained from 1 cm× 1 cm samples of Co films and Co foils for comparison. The hydrogen TPD curves have decreasing intensity from the Co foils to the Co dots and finally to the Co films. This indicates that there are more sites for hydrogen adsorption on the Co dots than in the Co films. This is a surprising result because there is approximately 8.7 times less Co atoms exposed in the Co dots that in the Co film sample. A desorption energy of 27 kcal/mol was obtained for the Co dots suggesting that hydrogen is adsorbed on an hcp hollow site of the Co dot crystalline structure.