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2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Joseph Kanyi Kihika ◽  
Susanna A. Wood ◽  
Lesley Rhodes ◽  
Kirsty F. Smith ◽  
Lucy Thompson ◽  
...  

AbstractDinoflagellates are among the most diverse group of microalgae. Many dinoflagellate species have been isolated and cultured, and these are used for scientific, industrial, pharmaceutical, and agricultural applications. Maintaining cultures is time-consuming, expensive, and there is a risk of contamination or genetic drift. Cryopreservation offers an efficient means for their long-term preservation. Cryopreservation of larger dinoflagellate species is challenging and to date there has been only limited success. In this study, we explored the effect of cryoprotectant agents (CPAs) and freezing methods on three species: Vulcanodinium rugosum, Alexandrium pacificum and Breviolum sp. A total of 12 CPAs were assessed at concentrations between 5 and 15%, as well as in combination with dimethyl sulfoxide (DMSO) and other non-penetrating CPAs. Two freezing techniques were employed: rapid freezing and controlled-rate freezing. Breviolum sp. was successfully cryopreserved using 15% DMSO. Despite exploring different CPAs and optimizing the freezing techniques, we were unable to successfully cryopreserve V. rugosum and A. pacificum. For Breviolum sp. there was higher cell viability (45.4 ± 2.2%) when using the controlled-rate freezing compared to the rapid freezing technique (10.0 ± 2.8%). This optimized cryopreservation protocol will be of benefit for the cryopreservation of other species from the family Symbiodiniaceae.


2022 ◽  
Author(s):  
Fei-Yu Zhou ◽  
Lei Jiao

Carbon-fluorine bond activation reaction of the trifluoromethyl group represent an important approach to fluorine-containing molecules. While selective defluorofunctionalization reactions of CF3-containing substrates have been achieved by invoking difluorocarbocation, difluorocarboradical, or difluoroorganometallic species as the key intermedi-ate, the transformations via fluorocarbanion mechanism remained a limited success. Furthermore, the enantioselective defluorotransformation of CF3 group has not yet been realized. Herein, we report a defluorofunctionalization reaction of 4-trifluoromethylpyridines involving pyridyldifluoromethyl anion as the key intermediate, which was developed based upon our previous studies on the N-boryl pyridyl anion chemistry. When combined with Ir-catalysis, asymmetric defluoroallylation of 4-trifluoromethylpyridines could be achieved to forge a difluoroalkyl-substituted chiral center. The present work opens up a new opportunity for the defluorofunctionalization of CF3 group, and provides new insights into the N-boryl pyridyl anion chemistry.


2022 ◽  
pp. 107780122110706
Author(s):  
Sarah E. Ullman ◽  
Emily A. Waterman ◽  
Katie M. Edwards ◽  
Jania Marshall ◽  
Christina M. Dardis ◽  
...  

The current arricle describes a novel recruitment protocol for collecting data from sexual assault and intimate partner violence survivors referred to research studies by individuals to whom they had previously disclosed. Challenges in both recruiting participants and interpreting data are described. Only 35.8% of cases had usable data for both survivors and disclosure recipients, suggesting that this referral method had limited success in recruiting matched pairs. Suggestions for modifications to improve the protocol for future research are offered. Potential advantages and drawbacks of various methods for recruiting dyads are described in order to facilitate future research on survivors’ disclosure processes, social reactions, and the influence of social reactions on survivor recovery.


2022 ◽  
Vol 12 ◽  
Author(s):  
Rajkumar Venkatadri ◽  
Vikram Sabapathy ◽  
Murat Dogan ◽  
Rahul Sharma

Lupus glomerulonephritis (LN) is a complex autoimmune disease characterized by circulating autoantibodies, immune-complex deposition, immune dysregulation and defects in regulatory T cell (Tregs). Treatment options rely on general immunosuppressants and steroids that have serious side effects. Approaches to target immune cells, such as B cells in particular, has had limited success and new approaches are being investigated. Defects in Tregs in the setting of autoimmunity is well known and Treg-replacement strategies are currently being explored. The aim of this minireview is to rekindle interest on Treg-targeting strategies. We discuss the existing evidences for Treg-enhancement strategies using key cytokines interleukin (IL)-2, IL-33 and IL-6 that have shown to provide remission in LN. We also discuss strategies for indirect Treg-modulation for protection from LN.


Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6317
Author(s):  
Nathan Karin

Over the last decade, monoclonal antibodies to immune checkpoint inhibitors (ICI), also known as immune checkpoint blockers (ICB), have been the most successful approach for cancer therapy. Starting with mAb to cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors in metastatic melanoma and continuing with blockers of the interactions between program cell death 1 (PD-1) and its ligand program cell death ligand 1 (PDL-1) or program cell death ligand 2 (PDL-2), that have been approved for about 20 different indications. Yet for many cancers, ICI shows limited success. Several lines of evidence imply that the limited success in cancer immunotherapy is associated with attempts to treat patients with “cold tumors” that either lack effector T cells, or in which these cells are markedly suppressed by regulatory T cells (Tregs). Chemokines are a well-defined group of proteins that were so named due to their chemotactic properties. The current review focuses on key chemokines that not only attract leukocytes but also shape their biological properties. CXCR3 is a chemokine receptor with 3 ligands. We suggest using Ig-based fusion proteins of two of them: CXL9 and CXCL10, to enhance anti-tumor immunity and perhaps transform cold tumors into hot tumors. Potential differences between CXCL9 and CXCL10 regarding ICI are discussed. We also discuss the possibility of targeting the function or deleting a key subset of Tregs that are CCR8+ by monoclonal antibodies to CCR8. These cells are preferentially abundant in several tumors and are likely to be the key drivers in suppressing anti-cancer immune reactivity.


2021 ◽  
Vol 2 (2) ◽  
pp. 22-40
Author(s):  
Lasha Tchantouridze

The two-decade-long U.S.-led military mission in Afghanistan ended in August 2021 after a chaotic departure of the NATO troops. Power in Kabul transferred back to the Taliban, the political force the United States and its allies tried to defeat. In its failure to achieve a lasting change, the Western mission in Afghanistan is similar to that of the Soviet Union in the 1980s. These two missions in Afghanistan had many things in common, specifically their unsuccessful counterinsurgency efforts. However, both managed to achieve limited success in their attempts to impose their style of governance on Afghanistan as well. The current study compares and contrasts some of the crucial aspects of counterinsurgency operations conducted by the Soviet and Western forces during their respective missions, such as special forces actions, propaganda activities, and dealing with crucial social issues. Interestingly, when the Soviets withdrew in 1988, they left Afghanistan worse off, but the US-backed opposition forces subsequently made the situation even worse. On the other hand, the Western mission left the country better off in 2021, and violence subsided when power in the country was captured by the Taliban, which the United States has opposed.


2021 ◽  
Vol 11 ◽  
Author(s):  
Sagun Parakh ◽  
Joseph Nicolazzo ◽  
Andrew M Scott ◽  
Hui Kong Gan

Glioblastoma (GBM) is an aggressive and fatal malignancy that despite decades of trials has limited therapeutic options. Antibody drug conjugates (ADCs) are composed of a monoclonal antibody which specifically recognizes a cellular surface antigen linked to a cytotoxic payload. ADCs have demonstrated superior efficacy and/or reduced toxicity in a range of haematological and solid tumors resulting in nine ADCs receiving regulatory approval. ADCs have also been explored in patients with brain tumours but with limited success to date. While earlier generations ADCs in glioma patients have had limited success and high toxicity, newer and improved ADCs characterised by low immunogenicity and more effective payloads have shown promise in a range of tumour types. These newer ADCs have also been tested in glioma patients, however, with mixed results. Factors affecting the effectiveness of ADCs to target the CNS include the blood brain barrier which acts as a physical and biochemical barrier, the pro-cancerogenic and immunosuppressive tumor microenvironment and tumour characteristics like tumour volume and antigen expression. In this paper we review the data regarding the ongoing the development of ADCs in glioma patients as well as potential strategies to overcome these barriers to maximise their therapeutic potential.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Timothy M. Caradonna ◽  
Aaron G. Schmidt

AbstractAntibody immunodominance refers to the preferential and asymmetric elicitation of antibodies against specific epitopes on a complex protein antigen. Traditional vaccination approaches for rapidly evolving pathogens have had limited success in part because of this phenomenon, as elicited antibodies preferentially target highly variable regions of antigens, and thus do not confer long lasting protection. While antibodies targeting functionally conserved epitopes have the potential to be broadly protective, they often make up a minority of the overall repertoire. Here, we discuss recent protein engineering strategies used to favorably alter patterns of immunodominance, and selectively focus antibody responses toward broadly protective epitopes in the pursuit of next-generation vaccines for rapidly evolving pathogens.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 124-125
Author(s):  
Qiong Nie ◽  
Daniel Morrow ◽  
Maurita Harris ◽  
Wendy Rogers

Abstract Health technology has the potential to support behavior change by measuring performance and providing users with visualizations of this performance as feedback. Such visual feedback has had limited success in changing health behaviors, but it is not clear why. We conducted a systematic review of the visual feedback literature to develop an organizational framework representing the visual feedback-action process. We identified the components that have been investigated in the context of visual feedback. These components are classified into four categories: visualization types (e.g., bar graph) and variables (e.g., color); feedback characteristics (e.g., social comparison); psychological processes (e.g., motivation) and action (e.g., exercise). The insights will inform the design of feedback visualizations in a smartphone application to support medication adherence for older adults. More broadly, this integrative perspective will yield principles of feedback visualization techniques and components that influence the behavior change process and develop a roadmap to facilitate the design.


2021 ◽  
Author(s):  
Vladimir G. Ivanov

The author analyses the principles and regularities of the competition of soft power strategies of different states as an actual problem of comparative politics. The article addresses the question of determining principles and key elements of competing soft power strategies in the system of international relations, which is of current interest in comparative political science. As a methodological foundation of the analysis is used the H. Hotelling’s law of spatial competition and its political implications, formulated by A. Downs. The author examines two contrasting tendencies: drift of the content and strategies of soft power of different states towards unification and convergence of communicated values and standards or on the contrary increase of ideological and value polarization in the wake of escalating international and global tensions. The principles and rules of spatial competition of H. Hotelling and A. Downs have been applied for typology of national strategies of soft power to evaluate their effectiveness and segmentation of potential audience for maximum impact. It was concluded that, due to the polymodality and civilizational diversity of the world, universalist soft-power projects today can only have limited success, with significant costs and reputational losses, while attracting value-close countries and pushing away the others. This division provides the basis for the international clustering by interests and values


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