Generation of High Quality Memory B Cells

Protection against pathogen re-infection is mediated, in large part, by two humoral cellular compartments, namely, long-lived plasma cells and memory B cells. Recent data have reinforced the importance of memory B cells, particularly in response to re-infection of different viral subtypes or in response with viral escape mutants. In regard to memory B cell generation, considerable advancements have been made in recent years in elucidating its basic mechanism, which seems to well explain why the memory B cells pool can deal with variant viruses. Despite such progress, efforts to develop vaccines that induce broadly protective memory B cells to fight against rapidly mutating pathogens such as influenza virus and HIV have not yet been successful. Here, we discuss recent advances regarding the key signals and factors regulating germinal center-derived memory B cell development and activation and highlight the challenges for successful vaccine development.

Systemic Mobilization of Breast Cancer Resistance Protein in Response to Oncogenic Stress

The breast cancer resistance protein (BCRP or ABCG2) involved in cancer multidrug resistance (MDR), transports many hydrophobic compounds, including a number of anti-cancer drugs. Our comprehensive study using a mouse model reveals that a subcutaneously growing tumor strongly affects the expression of BCRP in the host’s normal organs on both the transcriptional and translational level. Additionally, the efflux of BCRP substrates is markedly enhanced. The levels of BCRP and its transcript in normal tissues distant from the tumor site correlate with tumor growth and the levels of cytokines in the peripheral blood. Thus, oncogenic stress causes transient systemic upregulation of BCRP in the host’s normal tissues and organs, which is possibly mediated via cytokines. Because BCRP upregulation takes place in many organs as early as the initial stages of tumor development, it reveals a most basic mechanism that may be responsible for the induction of primary MDR. We hypothesize that such effects are not tumor-specific responses, but rather constitute a more universal defense strategy. The xenobiotic transporters are systemically mobilized due to various stresses, seemingly in a pre-emptive manner so that the body can be quickly and efficiently detoxified. Our findings shed new light on the biology of cancer and on the complexity of cancer–host interactions and are highly relevant to cancer therapies as well as to the design of new generations of therapeutics and personalized medicine.

Estimation of Gene Action and Interaction for Some Quantitative Characters in Rice (Oryza sativa L.) by Generation Mean Analysis

The present investigation was conducted to understand the genetic action for controlling the inheritance of some quantitative characters. The experimental materials consisted of three rice varieties, i.e., Mahsuri, Bhutmuri, IR36 and F1, F2, and F3 populations of Mahsuri×Bhutmuri (Cross I) and IR36×Bhutmuri (Cross II). To conduct the generation mean analysis, the parents and their F1, F2, and F3 populations were evaluated during June to October month of Kharif 2016 and Kharif 2017. Generation mean analysis was done for eighteen quantitative characters following the five parameter model. The Analysis of Variance revealed significant differences among the five generations for all the characters studied. The results of the scaling tests and joint scaling test revealed that the Simple additive-dominance model was inadequate for days to 50% flowering, days to maturity, number of panicles plant-1, number of primary branches panicle-1, number of secondary branches panicle-1 in Cross I, while it was for plant height, number of tillers plant-1, number of panicles plant-1, number of grains panicle-1, number of filled grains panicle–1 and fertility % in Cross II. Hence, the present studies have revealed that epistasis as a basic mechanism that cannot be ignored. Thus, formulating breeding policies on only main gene effects i.e. additive and dominance could be misleading.

Digital school: Searching for Explanatory Models. Part 1

Introduction. The purpose of this study was to analyze L. S. Vygotsky’s cultural-historical psychology from the perspective of distinguishing the structure of the act of development within its framework and understanding its explanatory potential as a whole. This analysis enables to clarify and understand the essence of the digital and virtual shift. Moreover, it is required in order to overcome the limitations associated with the currently dominant behavioral models, which are used by researchers in their attempts to explain and describe the phenomenon of the influence of digital technologies on people, in particular, on schoolchildren and students. Materials and Methods. The paper considers the concept derived from L. S. Vygotsky’s cultural-historical psychology, which is proposed to be adopted as a basic one in order to build an explanatory model used by the author to describe and comprehend the phenomenon of transformation of the human development process in the new reality of the digital environment. Results. The article introduces the basic principles and provisions, the explanatory model is built on, concerning the role of symbolic-instrumental mediation in human development, the role of an adult as a mediator, the structure of the act of thinking and the act of development, the basic mechanism of mastering a person's behavior, which permeates the formation of higher mental functions. The author compares this explanatory model and the behavioral model used in most modern research investigations that examine the impact of digital technologies on schoolchildren and students. Conclusions. The findings show that the student is presented in the behavioral model as a passive reactive being that reacts to external stimuli. In this sense, a human being is not treated as a personality with highest abilities, but is considered as a function. The proposed model cannot be used to explain and comprehend modern development processes.

Oscillatory movement of a dynein-microtubule complex crosslinked with DNA origami

During repetitive bending of cilia and flagella, axonemal dynein molecules move in an oscillatory manner along a microtubule (MT), but how the minus-end-directed motor dynein can oscillate back and forth is unknown. There are various factors that may regulate the dynein activities, e.g., the nexin-dynein regulatory complex, radial spokes, and central apparatus. In order to understand the basic mechanism of the oscillatory movement, we constructed a simple model system composed of MTs, outer-arm dyneins, and DNA origami that crosslinks the MTs. Electron microscopy (EM) showed patches of dynein molecules crossbridging two MTs in two opposite orientations; the oppositely oriented dyneins are expected to produce opposing forces. The optical trapping experiments showed that the dynein-MT-DNA-origami complex actually oscillate back and forth after photolysis of caged ATP. Intriguingly, the complex, when held at one end, showed repetitive bending motions. The results show that a simple system composed of ensembles of oppositely oriented dyneins, MTs, and inter-MT crosslinkers, without the additional regulatory structures, has an intrinsic ability to cause oscillation and repetitive bending motions.

Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?

Since the discovery of the first MDM2 inhibitors, we have gained deeper insights into the cellular roles of MDM2 and p53. In this review, we focus on MDM2 inhibitors that bind to the p53-binding domain of MDM2 and aim to disrupt the binding of MDM2 to p53. We describe the basic mechanism of action of these MDM2 inhibitors, such as nutlin-3a, summarise the determinants of sensitivity to MDM2 inhibition from p53-dependent and p53-independent points of view and discuss the problems with innate and acquired resistance to MDM2 inhibition. Despite progress in MDM2 inhibitor design and ongoing clinical trials, their broad use in cancer treatment is not fulfilling expectations in heterogenous human cancers. We assess the MDM2 inhibitor types in clinical trials and provide an overview of possible sources of resistance to MDM2 inhibition, underlining the need for patient stratification based on these aspects to gain better clinical responses, including the use of combination therapies for personalised medicine.

Interactions of Coated-Gold Engineered Nanoparticles with Aquatic Higher Plant Salvinia minima Baker

The study investigated the interactions of coated-gold engineered nanoparticles (nAu) with the aquatic higher plant Salvinia minima Baker in 2,7, and 14 d. Herein, the nAu concentration of 1000 µg/L was used; as in lower concentrations, analytical limitations persisted but >1000 µg/L were deemed too high and unlikely to be present in the environment. Exposure of S. minima to 1000 µg/L of citrate (cit)- and branched polyethyleneimine (BPEI)-coated nAu (5, 20, and 40 nm) in 10% Hoagland’s medium (10 HM) had marginal effect on biomass and growth rate irrespective of nAu size, coating type, or exposure duration. Further, results demonstrated that nAu were adsorbed on the plants’ roots irrespective of their size or coating variant; however, no evidence of internalization was apparent, and this was attributed to high agglomeration of nAu in 10 HM. Hence, adsorption was concluded as the basic mechanism of nAu accumulation by S. minima. Overall, the long-term exposure of S. minima to nAu did not inhibit plant biomass and growth rate but agglomerates on plant roots may block cell wall pores, and, in turn, alter uptake of essential macronutrients in plants, thus potentially affecting the overall ecological function.

CRISPER/CAS: A potential tool for genomes editing

The ability to engineer genomes presents a significant opportunity for applied biology research. In 2050, the population of this world is expected to reach 9.6 billion residents; rising food with better quality is the most promising approach to food security. Compared to earlier methodologies including Zinc Finger Nucleases (ZFNs) plus Transcription Activator-Like Effector Nucleases (TALENs), which were expensive as well as time-consuming, innovation in Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and related CRISPR (Cas) protein classifications allowed selective editing of genes for the enhancement of food. The basic mechanism of CRISPR Cas9 process and its applications on genome editing has been summarized in this manuscript. The method relies on Sequence-Specific Nucleases (SSNs) to create Double Stranded Breaks (DSB) of DNA at the locus of genome defined by user, mended by using one of two DNA mending ways: Non-Homologous End Joining (NHEJ) or Homology Directed Repair (HDR). Cas9, an RNA-guided endonuclease, was used to produce stable knock-in and knock-out mutants. The focus of this effort is to explore the CRISPR Cas9 genome editing to manage gene expression and improve future editing success. This adaptable technique can be consumed for a wide range of applications of genome editing requiring high precision. Advances in this technology have sparked renewed interest in the possibilities for editing genome in plants.

Silicon-Based Technologies for Flexible Photovoltaic (PV) Devices: From Basic Mechanism to Manufacturing Technologies

Over the past few decades, silicon-based solar cells have been used in the photovoltaic (PV) industry because of the abundance of silicon material and the mature fabrication process. However, as more electrical devices with wearable and portable functions are required, silicon-based PV solar cells have been developed to create solar cells that are flexible, lightweight, and thin. Unlike flexible PV systems (inorganic and organic), the drawbacks of silicon-based solar cells are that they are difficult to fabricate as flexible solar cells. However, new technologies have emerged for flexible solar cells with silicon. In this paper, we describe the basic energy-conversion mechanism from light and introduce various silicon-based manufacturing technologies for flexible solar cells. In addition, for high energy-conversion efficiency, we deal with various technologies (process, structure, and materials).

Analytical study on the effect of extreme seismic strains on the transverse buckling of ultra-reinforced seismic walls and their environmental design

In the context of the present work, the influence of the degree of tension on the phenomenon of transverse instability of reinforced concrete seismic walls is examined. Useful conclusions are drawn regarding the influence of the degree of elongation on the phenomenon of transverse buckling. These conclusions are substantiated both experimentally and analytically, as the results of the experiments are compared with the corresponding results of the analytical investigation. Moreover, some thoughts on a more environmental design of R/C seismic walls are stated. The present investigation is both experimental and analytical and consists of 4 test specimens. These specimens simulate the extreme boundary edges of structural walls. All columns simulate only the extreme reinforced areas of the walls, in order to study the basic mechanism of the phenomenon. The detailing of the specimens consists of 6 rebars with a diameter of 12 mm for each bar. The geometric dimensions are the same for all specimens. What differentiates the specimens from each other is the degree of tension they have sustained. More specifically, the tensile degrees used are 10‰, 20‰, 30‰ and 50‰. The loading stages of each specimen for all specimens are as follows: (a) Uniaxial central tensile loading on each test specimen apart from the specimen sustained 0‰ degree of tension; (b) Uniaxial central compression loading on each specimen till its failure due to buckling or due to an excess of its cross-section compressive strength. The present study focuses on the tensile loading stage only. Extreme tensile strengths are also used, e.g., 30‰ and 50‰, in order to take into account, the cases of extreme seismic excitations. The experimental study is followed by the numerical investigation of these 4 specimens using appropriate statistical software and finite elements.