Pseudo High-Throughput Development and Optimization of the Electrochemical Oxidation of Sensitive Propargylic Benzylic Alco-hols

The electrochemical oxidation of sensitive propargylic benzylic alcohols having varying substituents is reported. The ther-mal oxidation of propargylic benzylic alcohols presents an acute challenge in the synthesis of complex molecules and various traditional oxidation methods proceed with low efficiency or not at all. We describe the convenient preparation and charac-terization of N-hydroxytetrafluorophthalimide (TFNHPI) and a practical, green electrochemical oxidation protocol that em-ploys TFNHPI as a stable, efficient electrochemical mediator. The electrochemical method employing TFNHPI to oxidize propargylic benzylic alcohols was developed and optimized in pseudo high-throughput fashion using a bank of inexpensive two-electrode power supplies. The electrochemical oxidation of propargylic benzylic alcohol was also leveraged to develop efficient synthetic pathways to prepare gram quantities of resveratrol natural products such as the pauciflorols.

Evolution of an Increased Performance Under Acute Challenge Does Not Exacerbate Vulnerability to Chronic Stress

An adequate stress response plays a vital role in coping with challenges. However, if selection for improved coping with an acute challenge affects the entire stress response system, susceptibility to adverse effects of chronic stressors can be deepened. Here, we used bank voles from lines selected for high swim-induced aerobic metabolism (A) and unselected control (C), and asked if the selection affected sensitivity to chronic mild stress (CMS). The voles were first habituated to daily weighing and feces collection for three weeks, and then for two weeks were exposed to CMS or remained undisturbed. The habituation itself resulted in an increased swim-induced oxygen consumption in both line types, and a decreased body mass. The CMS treatment caused reduction of food consumption in the second week of the experiment, and, in males, a decline in the metabolic rate. Paradoxically, fecal corticosterone metabolites decreased in the CMS-treated group. The response to CMS did not differ between the line types. Thus, the selection for increased performance was not traded off by increased vulnerability to chronic stress. However, the unexpected decrease in corticosterone suggests that bank voles – and perhaps also other animals – prefer experiencing unpredictable, unpleasant stressors over the monotony of standard laboratory housing.

Teamwork Approach in Lifestyle Modification in a Health Clinic: A Perspective Study

Chronic diseases have become an acute challenge in health. Providing a framework for the transformation of services could be very helpful. In this study, the teamwork services based on lifestyle modification used in a series of Health Clinics in Isfahan (Iran); have been reported as a desirable method in the treatment of metabolic Syndromes. "Iranian Health Clinics" have been providing services in the fields of lifestyle modification, promoting healthy lifestyles, diagnosing and treating metabolic syndromes such as diabetes, hypertension, hyperlipidemia, as well as weight regulation and stabilization. This clinic series offers its services as a team of psychologists, nutritionists, physical trainers, and physicians. Treatment of metabolic syndromes by the team-based method as well as continuing contact with patients in the courses of treatment, stabilization, and training of health ambassadors can be instrumental in consolidating the results using this framework in the control of metabolic syndromes.

The Challenges of Implementing Temporal Shifts in Temporary Organizations: Implications of a Situated Temporal View

We apply a situated temporal view to reveal the acute challenge actors face in making changes when their project moves toward its final deadline. A situated temporal view takes account not just of the dwindling time left to change the future but also the lingering past, the combination of which poses particular challenges to organizers. We discuss aspects of temporary organizing that make such temporal shifts challenging: the complex interplay between temporal structures and practices, multiple temporal orientations, and deferred timing of temporal shifts. We suggest ideas for further research to apply a situated temporal view to temporary organizing.

TO THE ISSUE OF THE DEVELOPMENT OF INTERNATIONAL LEGAL COOPERATION OF STATES IN THE FIELD OF THE RATIONAL USE AND PROTECTION OF RESOURCES OF THE WORLD OCEAN

Over the decades, attempts were made to elaborate a legally binding single document on ocean resource management that would be acceptable to all countries. The culmination of this process was the adoption of the 1982 UN Convention on the law of sea. Since its entry into force, the Convention has become an important legal basis for ensuring the rational use of the world's ocean resources and their long-term conservation on behalf of future generations. At the same time, there remains the very acute challenge associated with finding a balance between reaching a global consensus on issues that are common to all and identifying topics that can be addressed and resolved by leaders at the global level. As humankind continues to postpone the adoption of urgent measures to prevent the effects of climate change, the environment deteriorates, while measures to mitigate these effects get more expensive and complex.

Virus-like vesicles expressing multiple antigens for immunotherapy of chronic hepatitis B

ABSTRACTInfection with hepatitis B virus (HBV) can initiate chronic hepatitis and liver injury, eventually progressing to liver fibrosis or cancer and causing more than 600,000 deaths each year worldwide. Current treatments for chronic hepatitis B, relying on nucleoside antivirals and interferon, are inadequate and leave an unmet need for immunotherapeutic approaches. This report describes virus-like vesicles (VLV), a form of self-amplifying RNA replicons, which express multiple HBV antigens (polymerase, core, and middle surface) from a single vector (HBV-VLV). The HBV-VLV induces HBV-specific T cell responses to all three HBV antigens. Immunization of naive mice with the multiantigen HBV-VLV renders them resistant to acute challenge with HBV delivered by adeno-associated virus (AAV). Using a chronic model of HBV infection by AAV delivery of HBV, we demonstrate immunotherapeutic potential of the multiantigen HBV-VLV in combination with DNA booster immunization, as 40% of the HBV-VLV-treated mice showed a decline of the serum HBV surface antigen below the detection limit and marked reduction in liver HBV RNA accompanied by induction of HBsAg-specific CD8 T cells. These results warrant further evaluation of multiantigen HBV-VLV for immunotherapy of chronic hepatitis B.IMPORTANCEMore than 240 million people worldwide are chronically infected with hepatitis B virus. Current therapies are not sufficiently effective and are often beyond reach in the developing world. We describe a virus-like vesicle-based immunotherapeutic vaccine that expresses three major antigens of hepatitis B virus as a self-amplifying RNA replicon. By incorporating three HBV antigens in a single vaccine, we ensure broad T cell responses. We demonstrate that immunization with this vaccine protects mice from hepatitis B virus in a model of acute challenge. Importantly, treatment with this vaccine shows 40% efficacy in a mouse model of chronic hepatitis B. Thus, this study paves the way for evaluation of the multi-antigen virus-like vesicles as a tool for immunotherapy of chronic hepatitis B.

Anti-OspA DNA-Encoded Monoclonal Antibody Prevents Transmission of Spirochetes in Tick Challenge Providing Sterilizing Immunity in Mice

We recently developed anti-OspA human immunoglobulin G1 monoclonal antibodies (HuMAbs) that are effective in preventing Borrelia transmission from ticks in a murine model. Here, we investigated a novel approach of DNA-mediated gene transfer of HuMAbs that provide protection against Lyme disease. Plasmid DNA-encoded anti-OspA HuMAbs inoculated in mice achieved a serum antibody concentration of >6 μg/mL. Among mice injected with DNA-encoded monoclonal antibodies, 75%–77% were protected against an acute challenge by Borrelia-infected ticks. Our results represent the first demonstration of employing DNA transfer as a delivery system for antibodies that block transmission of Borrelia in animal models.