Dogmatisms and Catechisms — Ethics and Companion Animals

Abstract

The current reconsideration of the place in nature of human beings unfortunately continues to be an acrimonious one. All too often the debate is more akin to a warlike encounter where each side attempts to gain control or the upper hand than a search for points of agreement. Given this context, it is important to entertain views that emanate from different cultural traditions as a way to infuse the debate with new life. Students of Native American culture have consistently pointed out that the essential concepts of life balance and reciprocity represented there may serve as useful points of consideration as we struggle with the appropriate relationships with animals and nature. This article presents a representative Zuni story, told by Governor Robert E. Lewis, that illustrates these notions.     

Zinc and diabetes — clinical links and molecular mechanisms

Zinc is an essential trace element crucial for the function of more than 300 enzymes and it is important for cellular processes like cell division and apoptosis. Hence, the concentration of zinc in the human body is tightly regulated and disturbances of zinc homeostasis have been associated with several diseases including diabetes mellitus, a disease characterized by high blood glucose concentrations as a consequence of decreased secretion or action of insulin. Zinc supplementation of animals and humans has been shown to ameliorate glycemic control in type 1 and 2 diabetes, the two major forms of diabetes mellitus, but the underlying molecular mechanisms have only slowly been elucidated. Zinc seems to exert insulin-like effects by supporting the signal transduction of insulin and by reducing the production of cytokines, which lead to beta-cell death during the inflammatory process in the pancreas in the course of the disease. Furthermore, zinc might play a role in the development of diabetes, since genetic polymorphisms in the gene of zinc transporter 8 and in metallothionein (MT)-encoding genes could be demonstrated to be associated with type 2 diabetes mellitus. The fact that antibodies against this zinc transporter have been detected in type 1 diabetic patients offers new diagnostic possibilities. This article reviews the influence of zinc on the diabetic state including the molecular mechanisms, the role of the zinc transporter 8 and MT for diabetes development and the resulting diagnostic and therapeutic options.     

Toxoplasmosis and Epilepsy — Systematic Review and Meta Analysis

Background

Toxoplasmosis is an important, widespread, parasitic infection caused by Toxoplasma gondii. The chronic infection in immunocompetent patients, usually considered as asymptomatic, is now suspected to be a risk factor for various neurological disorders, including epilepsy. We aimed to conduct a systematic review and meta-analysis of the available literature to estimate the risk of epilepsy due to toxoplasmosis.

Methods

A systematic literature search was conducted of several databases and journals to identify studies published in English or French, without date restriction, which looked at toxoplasmosis (as exposure) and epilepsy (as disease) and met certain other inclusion criteria. The search was based on keywords and suitable combinations in English and French. Fixed and random effects models were used to determine odds ratios, and statistical significance was set at 5.0%.

Principal findings

Six studies were identified, with an estimated total of 2888 subjects, of whom 1280 had epilepsy (477 positive for toxoplasmosis) and 1608 did not (503 positive for toxoplasmosis). The common odds ratio (calculated) by random effects model was 2.25 (95% CI 1.27–3.9), p = 0.005.

Conclusions

Despite the limited number of studies, and a lack of high-quality data, toxoplasmosis should continue to be regarded as an epilepsy risk factor. More and better studies are needed to determine the real impact of this parasite on the occurrence of epilepsy.     

Heat shock response and autophagy—cooperation and control

Protein quality control (proteostasis) depends on constant protein degradation and resynthesis, and is essential for proper homeostasis in systems from single cells to whole organisms. Cells possess several mechanisms and processes to maintain proteostasis. At one end of the spectrum, the heat shock proteins modulate protein folding and repair. At the other end, the proteasome and autophagy as well as other lysosome-dependent systems, function in the degradation of dysfunctional proteins. In this review, we examine how these systems interact to maintain proteostasis. Both the direct cellular data on heat shock control over autophagy and the time course of exercise-associated changes in humans support the model that heat shock response and autophagy are tightly linked. Studying the links between exercise stress and molecular control of proteostasis provides evidence that the heat shock response and autophagy coordinate and undergo sequential activation and downregulation, and that this is essential for proper proteostasis in eukaryotic systems.     

Excited States and Free Radicals in Biology and Medicine——Contributions from Flash Photolysis and Pulse Radiolysis

Excited states and free radicals are involved in the normal physiology of living systems; in pathological processes including lipid peroxidation, inflammation, Parkinson's disease, cancer, and ageing; in the mechanism of action of drugs, such as quinone antitumour agents, and in photochemotherapies such as the PUVA therapy of skin diseases and PDT of cancer. The chief aim of this text is to introduce the reader to this rapidly expanding field, which lies at the borderlines of physics, chemistry, biology, pharmacology, and medicine, and, in particular, to explore how time—resolved spectroscopic methods have found solutions at the molecular level to biological and medical problems.     

Immunolcocalization of actin in intact and DNA—and histone—depleted nuclei and chromosomes of allium cepa

The presence of actin in eukaryotic nuclei and chromosomes,and especially in higher plant nuclei and chromosomes,has not been well established.We detected actin in meristematic cells of Allium cepa with indirect immunofluorescence technique and observed bright fluorescence in the intact nuclei and chromosomes,indicating that actin is present in the nuclei and chromosomes of the higher plant.We labeld sections of the meristematic cells of A.cepa with immunogold technique,gold parti cles were concentrated in condensed chromatin and nucleoli,confirming the results of the immunofluoresence observations.We traeated the nuclei and chromosomes of A.cepa with DNase I and 2M NaCl and obtained DNA-and histone-depleted nuclei and chromosomes.Indirect immunofluorescence tests showed that the DNA-and histonedepleted nuclei and chromosomes reacted positively with the anti-actin antibodies.These results demonstrate that the anti-actin antibodies.These results demonstrate that actin exists not only in intact nuclei and chromosomes,but also in DNA-and histone-depleted nuclei and chrmosomes of the plant.In addition,our immuno-fluorescence tests indicate that tropomyosin is present in the nuclei and chromosomes of A.cepa.     

Defining and measuring autophagosome flux—concept and reality

The autophagic system is involved in both bulk degradation of primarily long-lived cytoplasmic proteins as well as in selective degradation of cytoplasmic organelles. Autophagic flux is often defined as a measure of autophagic degradation activity, and a number of methods are currently utilized to assess autophagic flux. However, despite major advances in measuring various molecular aspects of the autophagic machinery, we remain less able to express autophagic flux in a highly sensitive, robust, and well-quantifiable manner. Here, we describe a conceptual framework for defining and measuring autophagosome flux at the single-cell level. The concept discussed here is based on the theoretical framework of metabolic control analysis, which distinguishes between the pathway along which there is a flow of material and the quantitative measure of this flow. By treating the autophagic system as a multistep pathway with each step characterized by a particular rate, we are able to provide a single-cell fluorescence live-cell imaging-based approach that describes the accurate assessment of the complete autophagosome pool size, the autophagosome flux, and the transition time required to turn over the intracellular autophagosome pool. In doing so, this perspective provides clarity on whether the system is at steady state or in a transient state moving towards a new steady state. It is hoped that this theoretical account of quantitatively measuring autophagosome flux may contribute towards a new direction in the field of autophagy, a standardized approach that allows the establishment of systematic flux databases of clinically relevant cell and tissue types that serve as important model systems for human pathologies.Abbreviations: CMA, chaperone-mediated autophagy; GFP, green fluorescent protein; J, flux; LC3, microtubule-associated protein 1 light chain 3; n_A, number of autophagosomes; τ, transition time; TEM, transmission electron microscopyThe autophagic system is involved in both bulk degradation of primarily long-lived cytosolic proteins as well as in the selective degradation of cytoplasmic organelles. In the past few years the assessment and evaluation of this complete system including its dynamics has received growing attention, as our understanding of autophagosome turnover and kinetic behavior has progressed. Autophagic flux is often defined as a measure of autophagic degradation activity, and a number of methods are currently suggested for assessing autophagic flux, many of which infer whether or not autophagic flux is occuring.¹ However, although we have advanced in the methodological approach to assess whether or not a change in autophagic flux is occurring, and whether autophagic flux goes up or down, we remain less able to express this change in a sensitive, robust, and well-quantifiable manner. Moreover, although the development of novel reporter assays enabled the identification of pharmacological regulators of autophagy, highly sensitive assays that characterize the extent and dynamics of this regulation quantitatively remain a challenge in the in vitro, and even more so the in vivo, environment. Based on the well-established metabolic control analysis approach,^2,3 where the use of the term flux has been reserved for the rate of flow along a metabolic pathway, we describe a methodological concept that allows the definition and measurement of autophagosome flux at the single cell level in a sensitive and quantifiable manner. Here, we treat the autophagic system as a multistep pathway with each step characterized by a particular rate. We distinguish between the vesicular machinery of the autophagic system, and the cargo that is being degraded within this system. Autophagosome flux, the subject of this paper, is the rate of flow along the vesicular pathway, whereas substrate clearance flux is the rate of cargo degradation within the vesicular system. This distinction makes it possible not only to describe whether or not the vesicular part of the autophagic system is at steady state, but also to quantitatively assess autophagosome flux and to calculate the transition time of the system required to turn over its autophagosome pool. The concept described here makes it possible to quantify and to compare treatment interventions or different cellular systems with one another in terms of change in autophagosome pool size, autophagosome flux, and pool size turnover as well as in the responsiveness and sensitivity to the treatment intervention.We will start with our quantitative definition of autophagosome flux and describe a methodological concept for measuring this flux. We will then briefly describe 3 of the major current and predominantly used approaches to measuring autophagic degradation activity, and, by juxtaposing them against our definition of autophagosome flux, attempt to indicate the major inherent challenges to these techniques. We will then describe a step-by-step methodology that describes the accurate assessment of i) the complete autophagosome pool size, ii) the steady state, iii) autophagosome flux, and iv) the transition time. Since our definition of autophagosome flux requires a dynamic assessment over time, this conceptual approach shows how to acquire data that describe both the existence of a steady state and the variables that characterize the steady state, such as the steady-state number of autophagosomes and the associated flux in terms of the change in this number per time per cell. We hope that this approach will provide a robust tool for generating numerical data that are sensitive enough to allow us to change flux incrementally, say by 5%, that allows a comparison of fluxes and steady states of different cellular systems, with the benefit of using data that directly reflect the intracellular autophagosome pool. It is moreover envisaged that the approach described here may contribute towards a standardized means for the establishment of flux databases of clinically relevant cell and tissue types that serve as important model systems for, for example, neurodegenerative disorders, cancer, or heart disease.^4-6 Finally, this concept may lay the foundation for future control analyses, to unravel the degree of control as opposed to regulation that the different steps in the autophagic pathway exert over the autophagosome flux.     

Lung cancer and oncolytic virotherapy——enemy's enemy

Lung cancer is one of the malignant tumors that seriously threaten human health worldwide, while the covid-19 virus has become people's nightmare after the coronavirus pandemic. There are too many similarities between cancer cells and viruses, one of the most significant is that both of them are our enemies. The strategy to take the advantage of the virus to beat cancer cells is called Oncolytic virotherapy. When immunotherapy represented by immune checkpoint inhibitors has made remarkable breakthroughs in the clinical practice of lung cancer, the induction of antitumor immunity from immune cells gradually becomes a rapidly developing and promising strategy of cancer therapy. Oncolytic virotherapy is based on the same mechanisms that selectively kill tumor cells and induce systemic anti-tumor immunity, but still has a long way to go before it becomes a standard treatment for lung cancer. This article provides a comprehensive review of the latest progress in oncolytic virotherapy for lung cancer, including the specific mechanism of oncolytic virus therapy and the main types of oncolytic viruses, and the combination of oncolytic virotherapy and existing standard treatments. It aims to provide new insights and ideas on oncolytic virotherapy for lung cancer.     

Non-Viral Deoxyribonucleoside Kinases——Diversity and Practical Use

Deoxyribonucleoside kinases(d NKs) phosphorylate deoxyribonucleosides to their corresponding monophosphate compounds. d Nks also phosphorylate deoxyribonucleoside analogues that are used in the treatment of cancer or viral infections. The study of the mammalian d NKs has therefore always been of great medical interest. However, during the last 20 years, research on d NKs has gone into nonmammalian organisms. In this review, we focus on non-viral d NKs, in particular their diversity and their practical applications. The diversity of this enzyme family in different organisms has proven to be valuable in studying the evolution of enzymes. Some of these newly discovered enzymes have been useful in numerous practical applications in medicine and biotechnology, and have contributed to our understanding of the structural basis of nucleoside and nucleoside analogue activation.     

On the origin and evolution of new genes——a genomic and experimental perspective

The inherent interest on the origin of genetic novelties can be traced back to Darwin. But it was not until recently that we were allowed to investigate the fundamental process of origin of new genes by the studies on newly evolved young genes. Two indispensible steps are involved in this process:origin of new gene copies through various mutational mechanisms and evolution of novel functions, which further more leads to fixation of the new copies within populations. The theoretical framework for the former ...     

Analysis of plastid and nuclear DNA data in plant phylogenetics——evaluation and improvement

Correct combination of plastid(cp)and nuclear(nr)DNA data for plant phylogenetic reconstructions is not a new issue,but with an increasing number of nrDNA loci being used,it is of ever greater practical concern.For accurately reconstructing the phylogeny and evolutionary history of plant groups,correct treatment of phylogenetic incongruence is a vital step in the proper analysis of cpDNA and nrDNA data.We first evaluated the current status of analyzing cpDNA and nrDNA data by searching all articles published in the journal Systematic Botany between 2005 and 2011.Many studies combining cpDNA and nrDNA data did not rigorously assess the combinability of the data sets,or did not address in detail possible reasons for incongruence between the two data sets.By reviewing various methods,we outline a procedure to more accurately analyze and/or combine cpDNA and nrDNA data,which includes four steps:identifying significant incongruence,determining conflicting taxa,providing possible interpretations for incongruence,and reconstructing the phylogeny after treating incongruence.Particular attention is given to explanation of the cause of incongruence.We hope that our procedure will help raise awareness of the importance of rigorous analysis and help identify the cause of incongruence before combining cpDNA and nrDNA data.     

Pectin—Its extraction and utilization

This cementing substance between the cells of all plants is economically valuable as a jellifying, stabilizing, emulsifying and binding agent, and is extracted for those purposes principally from apple pomace and citrus peels.     

Time series — information and prediction

A time series Y _t can be transformed into another time series V _t by means of a linear transformation. Should the matrix of that transformation have an inverse, the pair (Y _t, V _t) is called invertible. Based on the decomposition procedure for stationary time series introduced in a previous paper it is shown that a sufficient condition for the invertibility of the pair (Y _t, V _t) is that V _t be the first component of Y _t, i.e. V _t = V _t ¹ . By the invertibility property V _t ¹ can be used for forecasting, that is, predictions are made on V _t ¹ which is then transformed into Y _t. This is accomplished by means of a special kind of predictor permitting to make one-step-ahead forecasts in a straightforward way. Since the first component depends on a parameter i.e. V _t ¹ = V _t ¹ (), a procedure is proposed that allows us to find the optimal parameter value, = ₀. Thus, it is shown that better forecasting accuracy may result by fitting a simple autoregression to the first component V _t ¹ (₀) than if the process Y _t were described by a more elaborate model. Model building is therefore no longer a prerequisite in forecasting. The forecasting procedure is then extended so as to cope with the homogeneous nonstationary case, and examples are given to illustrate the forecasting accuracy as compared to customary model-based approaches. In the light of these results the problem of the information conveyed by the values of the series is discussed in terms of the spreading rate concept, thus highlighting the role of the current time value, as well as that of the remote values of the series, in forecasting stationary and nonstationary time series.