bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochemical detection of cytoskeletal and nucleoskeletal changes during apoptosis
Authors: Van Engeland Manon , Schutte Bert , Hopman Anton H N , Ramaekers Frans C S , Reutelingsperger Chris.P M
Published: November 2023

Apoptosis is an evolutionarily conserved form of physiological cell death by which redundant and damaged cells are eliminated during embryonic development and tissue homeostasis. In diseased tissue the process may be disturbed in such a way that accumulation of cells or increased cell loss may occur. Rapid elimination of the dying cell, without evoking an inflammatory response, is accomplished by disintegration of the cell into apoptotic bodies, which will then be phagocytosed (1). During this process, in which the plasma membrane remains intact, cleavage of cytoskeletal and nucleoskeletal proteins occurs by caspases, a family of cysteine proteases that cleave key proteins at conserved aspartic amino acid residues. The cleavage of cell-cell adhesion molecules leads to loss of contact with neighbouring cells (2), proteolysis of nuclear proteins facilitates nuclear disassembly (3), and the reorganization of actin filaments plays a role in the formation of apoptotic bodies (4).
Methods for detecting proteolysis during apoptosis in intact cells
Authors: Blajeski April L , Kaufmann Scott H
Published: November 2023

Over the past five years it has become clear that protease activation is the single most important event that characterizes the process of apoptosis. In the present chapter, we briefly review the evidence that proteases2014particularly caspases-play an important role in apoptosis. We then discuss various methods that have been applied to the study of caspases and their precursors, including immunoblotting, activity assays, and affinity labelling. We also describe various polypeptides whose cleavage can be used as a marker for caspase activation in situ. Finally, we outline an approach for determining whether a particular cleavage is mediated by caspases, focusing on the potential pitfalls in relying solely upon in vitro cleavage assays or inhibitor studies.
Comparison of protein sequences and practical database searching
Authors: Yona Golan , Brenner* Steven E
Published: November 2023

During the last three decades a considerable effort has been made to develop algorithms that compare sequences of biological macromolecules (proteins, DNA). The purpose of such algorithms is to detect evolutionary, and thus structural and functional, relations among sequences. Successful sequence comparison would allow us to infer the biological properties of new sequences from data accumulated on related genes. For example, a similarity between a translated nucleotide sequence and a known protein sequence suggests a homologous coding region in the corresponding nucleotide sequence. Significant sequence similarity among proteins may imply that the proteins share the same second ary and tertiary structures, and have close biological functions. The prediction of unknown protein structures is often based on the study of known structures of homologous proteins.
Principles of enzyme assay and kinetic studies
Authors: Tipton Keith F
Published: November 2023

The activity of an enzyme may be measured by determining the rate of product formation or substrate used during the enzyme-catalysed reaction. For many enzymes there are several alternative assay procedures available and the choice between them may be made on the grounds of convenience, cost, the availability of appropriate equipment and reagents and the level of sensitivity required. It would not be possible in this account to give detailed descriptions of all the assay mixtures and procedures that have been devised for individual enzymes. The examples that will be presented here are intended to illustrate general features of specific types of assay. Convenient recipes for the assay of individual enzymes can be found in a variety of sources, such as Methods in Enzymology (1), Methods in Enzymatic Analysis (2) and The Enzyme Handbook (3), as well as in the original literature.
Radiometric assays
Authors: Hughes Kelvin T
Published: November 2023

The accurate measurement of enzymatic activity in biological samples is important in many fields of cell biology, not only in routine biochemistry and in fundamental research, but also in clinical and pharmacological studies as well as in drug discovery and development. For an enzyme assay to be ‘fit for purpose’, it should be specific, sensitive, quantitative and, ideally, simple and rapid to perform. It should also allow the assay of enzymatic activity in both crude and purified enzyme preparations.
Cell culture
Authors: Touhey Samantha , Heenan Mary
Published: November 2023

Until animal cell culture emerged as a valuable research tool in the 1940s and 1950s, experimental approaches to the study of cellular physiology were limited to either studies in the whole animal or short-term studies with isolated cells or slices from various tissues. The development of cell culture led to a new experimental approach to cellular physiology in which isolated, functionally differentiated cells could be maintained in culture under conditions that allowed direct manipulations of the environment and measurement of the resulting changes in the function of a single cell type. Today many aspects of research and development involve the use of animal cells as in vitro model systems, substrates for virus replication, and in the production of diagnostic and therapeutic products.
In vitro reconstitution of early to late endosome transport: biogenesis and subsequent fusion of transport intermediates
Authors: Gu Feng , Gruenberg Jean
Published: November 2023

Vesicles formed via invaginations of the plasma membrane are responsible for the internalization and turnover of cell surface proteins and lipids, and for the uptake of extracellular ligands and solutes. Although evidence is accumulating for the existence of more than one internalization pathway, most receptors are internalized via the well characterized clathrin-dependent pathway. The bulk of internalized molecules, including solutes, ligands, and membrane constituents, are then delivered to common early endosomes, at least in most animal cell types. From there, many receptors and lipids, as well as a significant proportion of internalized solutes, are rapidly recycled back to the extracellular medium, via recycling endosomes. In contrast, molecules destined to be degraded, including all down-regulated receptors, are selectively incorporated into transport intermediates destined for late endosomes. Protein sorting thus occurs within these common early endosomes, hence they have been referred to as sorting early endosomes (1). In this chapter, we will describe assays which have been used to study the sequential formation and consumption by fusion of transport intermediates between early and late endosomes.
Functional analysis of ion channels: Planar patch clamp and impedance spectroscopy of tethered lipid membranes
Authors: Mayer Michael , Terrettaz Samuel , Giovangrandi Laurent , Stora Thierry , Vogel Horst
Published: November 2023

Ion channels play essential roles in cellular processes such as maintenance of the membrane potential, signal transduction, and osmoregulation and are therefore directly or indirectly targeted by many clinically used drugs (1). Despite the importance of ion channels, the molecular mechanisms of their function are largely unresolved. A nearly unlimited number of mutant proteins provided by combinatorial genetics (2, 3) and huge libraries of potentially active compounds produced by combinatorial chemistry (4) offer enormous possibilities for unraveling molecular details of channel function and for finding new medicines. Electrical recordings of ion channel activity provide the most detailed insight into the function of these important proteins (1, 5, 6); however, presently available techniques are not ideally suited for efficient screening of the existing large numbers of compounds.
Northern analysis, RT-PCR, RNase protection, cDNA array systems, and in situ hybridization to detect cytokine messenger RNA
Authors: Scotton Chris , Burke Frances
Published: November 2023

There are various methods used to detect cytokine mRNA in tissues and cell lines and the commonly used ones are described in this chapter. The varying degrees of sensitivity and suitability for use are discussed.

Northern analysis of RNA allows the quantitation of specific messenger RNA (mRNA) sequences and the determination of their size. The RNA sample is separated by electrophoresis through a denaturing agarose gel followed by capillary transfer to a membrane to which the RNA is subsequently covalently linked. The mRNA of interest is located by probing the membrane with a labelled complementary nucleotide sequence which, in the case of a radioisotopic label, is revealed by autoradiography. Reprobing for a suitable housekeeping gene allows quantitative comparison between samples on the same gel.
Purification, sequencing, and synthesis of cytokines and chemokines
Authors: Struyf Sofie , Wuyts Anja , Damme Jo Van
Published: November 2023

This chapter describes the purification strategy routinely used in our laboratory to isolate and characterize novel cytokines from natural sources (cell cultures, body fluids) (1-3). The subsequent steps that constitute this strategy can easily be modified for the isolation of a particular cytokine by adapting the characteristics of the chromatography (type of columns and buffers) to the biochemical properties of the protein to be purified. The identification of cytokines through the isolation of natural proteins is a valuable approach in basic cytokine research. Based on relevant biological assays, new molecules can be isolated or new biological properties for a known cytokine might be revealed.
Cytokine signalling
Authors: Foxwell B M J , Hunt A E , Lali F V , Smith C
Published: November 2023

The study of cytokines as a discrete topic has existed for approximately two decades. Initial studies focused on the identification of new cytokines, a process that is still continuing, with approximately 150 having been identified to date. The subsequent characterization of cytokine receptors led to the identification of several supramolecular cytokine receptor families (see Figure 1). As a consequence of these studies the complex nature of cytokine receptor structure also became apparent, with receptors often composed of multiple components. These observations gave an early indication of the complexity of cytokine signalling mechanisms. A general overview of cytokine and cytokine receptor structures can be found in the Cytokinefacts book (1).
Ria, Irma, and Elisa For Cytokines And Their Soluble Receptors
Authors: Meager A
Published: November 2023

The lack of absolute specificity of cultured mammalian cells for the activities of individual cytokines and the often relatively poor reproducibility of cytokine bioassays has created the need for more specific and reproducible, alternative assays. This need has largely been filled by the development of immunoassays for cytokines. Such assays are based on antibodies to each different cytokine and are generally reasonably sensitive and reliable and are quick and easy to perform. Homogeneous cytokines of known protein content can be used to calibrate immunoassays in terms of cytokine concentration (e.g. pg or ng/ml), since the extent of antibody binding is related in a dose-dependent manner to the im­munoreactive mass of cytokine present. While the correlation of immunoassay results with biological activity appears possible, such correlations are dependent on a number of variables, including the specificity of antibodies, immunoassay type, and cytokine preparation used for calibration. It is therefore inadvisable to express immunoassay results in units of biological activity (1).
Quantitative biological assays for individual cytokines
Authors: Wadhwa Meenu , Bird Christopher , Dilger Paula , Mire-Sluis* Tony , Thorpe Robin
Published: November 2023

Cytokines have often been discovered in complex mixtures by observing their effect on a biological system. This usually becomes the definitive property ( or one of several properties) of the cytokine and can become the basis for its bioassay. Cytokine bioassays are based on various biological effects such as cell proliferation, cytotoxic/cytostatic activity, kinetic effects, antiviral activity, colony forma­tion, or induction of secretion of other cytokine/non cytokine molecules (1).
Gap junction-mediated interactions between cells
Authors: Becker David , Green Colin
Published: November 2023

Gap junction channels are expressed in almost all types of cell. Their roles are diverse and are crucial for normal embryonic development and the functioning of adult organs. Point mutations, in a growing number of members of the gap junction family, appear to underlie several human diseases including profound non-syndromic deafness, heart disease, peripheral nerve myopathy, skin disorders, and cataract promotion. This has led to a rapid increase in the number of researchers investigating gap junctional communication in these disease conditions. In order to study gap junctional interactions between cells, there are three basic approaches which, when integrated, provide a rounded picture of communication in any particular system.
Oocyte–granulosa cell interactions
Authors: Vanderhyden Barbara C
Published: November 2023

Oocyte development occurs largely within the context of a complex and continuously changing environment, involving proliferation, differentiation, and apoptosis of the surrounding somatic or granulosa cells. Decades of investigation have resulted in protocols that enable the replication of many aspects of this process in vitro, some of which are able to maintain or enable to some degree the developmental capabilities of the oocyte. While the acquisition of developmental competence relies most heavily on adequate communication between the oocyte and granulosa cells, the process is complicated further by the fact that these cell–cell interactions are strongly influenced by hormones and growth factors generated by the hypothalamic–pituitary–ovarian axis. This chapter describes some of the methods currently used to investigate oocyte–granulosa cell interactions in pre-antral and antral follicles as well as the procedures that enable the study of the influence of each cell type on the other.
Cell–cell interactions in early mammalian development
Authors: Fleming Tom P , Eckert Judith J , Kwong Wing Yee , Thomas Fay C , Miller Daniel J , Fesenko Irina , Mears Andrew , Sheth Bhavwanti
Published: November 2023

Cell–cell interactions during early development prior to implantation play a key role in the morphogenesis of the blastocyst. The essential processes in blastocyst formation that are dependent upon intercellular contact and signalling and which occur concurrantly are the differentiation of the trophectoderm epithelium and the segregation of the inner cell mass (ICM) as a separate cell lineage from the epithelium. The trophectoderm forms the wall of the blastocyst, is responsible for generating the blastocoel cavity by transport processes, and, later in development, gives rise to trophoblast and most placental cell lineages. The ICM is a non-epithelial cell cluster located on the inner surface of the trophectoderm at one pole of the blastocyst from which the entire fetus forms after implantation (Figure 1).
The Importance of Closure
Authors: Walsh Joseph
Published: November 2023

Building on our review of the many types of endings that occur in clinical practice, I focus in this chapter on how positive endings are significant to the wellbeing of both the client and practitioner. I elaborate on this topic with discussions of eight case vignettes. All of them have been provided by clinical practitioners as examples of situations in which the ending turned out unexpectedly to be the most important aspect of the intervention. The closure that was achieved served to resolve the clients’ and practitioners’ work on problem issues, work that had been unsatisfying during the earlier stages of intervention. The chapter concludes with general principles for practitioners and supervisors to follow in maximizing the chances for positive endings.
Why People Volunteer
Authors: Sherr Michael E
Published: November 2023

Although Ava, Raymond, and Duane work in different practice settings, they are each responsible for finding people who want to volunteer. Ava’s and Raymond’s professional roles involve screening, training, and assigning volunteers to work with clients at their agencies. They have each developed extensive processes for screening, training, and assigning volunteers to ensure that people are well prepared; however, their measure of success and effectiveness is determined primarily by their ability to recruit and retain volunteers. Stated differently, Ava and Raymond could have the most elaborate procedures in place for preparing volunteers, but if there are not enough people to volunteer, some women in Ava’s program may not be assigned mentors and some clients in Raymond’s program may not be paired with volunteers.
Jane Addams: Social Worker and Volunteer
Authors: Sherr Michael E
Published: November 2023

Addams is one of the most written-about figures in social work, and there are a number of social work textbooks and biographies that highlight her accomplishments and provide useful analyses of her life and personality. Unlike other texts, this chapter does not focus on the person of Jane Addams and her accomplishments; instead, it examines how Addams accomplished so much. The chapter posits the following thesis regarding her approach and her accomplishments: Jane Addams’s approach to social work practice was to strategically engage the most people possible as potential volunteers to partner with her in addressing social issues. What made her so effective was her ability to recruit, join, and partner with all types of volunteers.
Changing the Context
Authors: Sherr Michael E
Published: November 2023

Recall that the CSOP model consists of two main components-assessing the specific context and creating optimal partnerships. Assessing the context involves collecting information from multiple sources to understand the parameters that define the specific context. The information from the assessment can then be used to develop the optimal mix of professionals and volunteers to address social problems and provide needed services to the community. But what if the assessment shows that the context, at least partially, contributes to the existence of the social problems that need to be addressed? In such cases social workers’ interventions must be aimed at adjusting the context.
Understanding the Systems that Serve Children
Authors: Strom-Gottfried Kim
Published: November 2023

The major child-serving systems—child welfare, juvenile justice, mental health, education, substance abuse, and health—all embrace distinct philosophic orientations, policy mandates, values, and interventions. These variables influence the ways that ethical dilemmas are approached and resolved in those settings. The decision-making framework used in this book encourages multiple grounded perspectives for resolving dilemmas and therefore requires consideration of the unique characteristics of the settings in which decisions are made.
Justice-vs-Mercy Dilemmas
Authors: Strom-Gottfried Kim
Published: November 2023

Dilemmas that involve the enforcement of policies usually come down to tensions between justice and mercy. Policies specifying processes, consequences, requirements, and eligibility standards exist to ensure that decisions are standardized according to certain criteria, rather than left to the whims of an individual. Such rules are intended to guarantee due process, ensuring that relevant facts and qualifications are taken into account and irrelevant variables are not. Thus, if a school has a zero-tolerance policy for alcohol, tobacco, and drug use, the presumption is that the criteria and consequences are handled consistently regardless of what substances are being used, where they are being used, or who is using them. However, the application of rules and policies is not always so clear cut.
Ambassador Wendy R. Sherman:A Social Worker at the Forefront of Foreign Policy
Authors: Lieberman Alice
Published: November 2023

We all go through life hearing the names of people who populate the various realms of our world, but we are often surprised when those people turn out to be closer to us than we imagined. Such is the case with Ambassador Wendy R. Sherman, whom former secretary of state Madeleine Albright (2004) called ‘‘a shrewd and resilient veteran of numerous Washington wars who [can] learn any subject faster than anyone I [know]’’ (p. 233). This is one of the reasons Secretary Albright chose Sherman for the position of State Department counselor, in 1997. In her memoir, Madame Secretary, Albright further details the logic behind her choice: ‘‘The position . . . is of special importance because it has no formal place in the bureaucratic hierarchy and has little staff. To be useful, the [counselor] must give the Secretary better advice than she receives elsewhere, then have the drive to make sure that advice is implemented should it become policy.
Mulu Haile: An Advocate for Ethiopian Women
Authors: Butterfield Alice K , Abye Tigest K
Published: November 2023

The primary author of this chapter has a long-standing interest in international social work and in Ethiopia in particular. In the course of her research, she met Mulu Haile and the second author, a native of Ethiopia, who was able to conduct the interview in their native language. As a young woman starting out, Mulu had some rather unconventional life goals for a woman in Ethiopia. In this chapter, you will see that many female-headed families in Ethiopia’s poorest communities are better off for her success in attaining those goals.
Reverend Debra Trakel: Fighting for Milwaukee’s Hungry, Homeless, and Displaced
Authors: Padgett Deborah
Published: November 2023

Recently, Rev. Debra Trakel’s office was awarded the Hole in the Wall Award by staff at the neighborhood meal program. Large, comfortable, and packed with books, couches, and other accoutrements of her work, Rev. Debra’s office may be a bit out of the way by downtown standards, but it is central to the church and the people she serves. Rev. Debra is an ordained pastor and the rector of St. James Episcopal Church, in the center of the city of Milwaukee. As pastor, Rev. Debra serves her parishioners and the local community in one of the poorest zip codes in the state. She is also an MSW.
Toward Evidence-Based Practice
Authors: Fischer Joel
Published: November 2023

Toward Evidence-Based Practice: Variations on a Theme is an insight¬ful collection of previously published articles by one of social work’s most controversial figures, Joel Fischer, a long time advocate of research and research-based practices. In this book, which includes his groundbreaking 1973 article, “Is casework effective?” and ending with excerpts of his most recent Reflections, Fischer offers insight on the field of social work and the struggle toward evidence-based practice and empirically supported interventions.
Introduction
Authors: Fischer Joel
Published: November 2023

“Interpersonal helping”—the topic of this book—encompasses a wide variety of interventive practices, methods and techniques. In the broadest sense, interpersonal helping can be described as informed, purposeful intervention either directly with, or on behalf of, a given person or persons (client). The goal of such intervention is to bring about positive changes either directly in the client’s functioning, or in environmental factors immediately impinging on the client’s functioning. These interventions are intended to enhance aspects of the client’s feelings, attitudes and/or behaviors in such a way that his personal and social functioning will be more satisfying and beneficial to him.
Introducing New Technology into Social Agencies: The Case of Behavior Modification
Authors: Fischer Joel
Published: November 2023

There seems to be a pattern in the introduction of new practice concepts into social work practice (Carter and Stuart, 1970). First, a few social workers introduce the ideas into practice and the social work literature. As the ideas spread, others in the field may inspect the ideas, often with a negative bias, and achieve consensus in rejecting the new and restating their allegiance to the established. As the number of people who experiment with the approach increase, some in the field begin to rephrase their evaluation in terms of the ideas having some, but limited, applications (Bruck, 1968). Or sometimes, the ideas may be viewed as all right, but nothing really new. Subsequently, the field may bifurcate (as it did in the functional-diagnostic schism) or—as seems to be happening in the case of the introduction of behavior modification—the concepts slowly begin to be infused into the mainstream of social work practice.
An Eclectic Base for Practice
Authors: Fischer Joel
Published: November 2023

Chapter One called for caseworkers to be aware of and use, when appropriate, knowledge from diverse sources, regardless of whether that knowledge is derived from within or outside the profession. Such a stance, though, does suggest some questions regarding the knowledge base for the practice of social casework: (1) Are there any limitations to the types of knowledge caseworkers should use; (2) how should caseworkers select that knowledge; and (3) how can caseworkers organize such knowledge into an integrated, effective approach?
Eclectic Casework
Authors: Fischer Joel
Published: November 2023

The winds of change are blowing on social casework. Since the earliest days of the profession, most caseworkers tended to approach knowledge development for practice in more or less unsystematic, haphazard, and uncritical ways. Criteria for knowledge selection were either vague, undefined, or, when they were available, unrelated to the empirical status of the knowledge. Such criteria included the comfort of the practitioner with new knowledge, the prestige of the proponent of new knowledge, or consensus among experts or peers. Part and parcel of this era was an inability of caseworkers to demonstrate their effectiveness in empirical research (Fischer, 1973, 1976). But the last decade or so has seen major changes in the world view of many caseworkers, changes that have been described elsewhere as—in Kuhn’s (1970) terms—revolutionary (Fischer, 1981). There appears to be a paradigm shift underway in casework involving a movement toward more systematic, rational, and empirically oriented development, selection, and use of knowledge for practice with a concomitant increase in practice effectiveness (Reid & Hanrahan, 1982). For want of better terminology, it appears as though casework is moving toward the development of a practice that could be called scientifically based. This development in social work, or at least its potential, is one that has also been noted by a number of other authors (Mullen, 1978; Thomas, 1977; Reid, 1978; Hepworth & Larsen, 1982; Gambrill, 1983; Wodarski, 1981; Bloom, 1975; Briar, 1978).
Meta-analysis: The Premise, the Problems, the Promise
Authors: Fischer Joel
Published: November 2023

What responsibilities do social workers have when new tools or technologies became available? The possibilities range from uncritical and total adoption of the new technology, to uncritical and total rejection of the new technology. Somewhere in between lies the critical evaluation and assessment of the potentialities of the new technology, and adoption or adaptation of those components that both can withstand careful scrutiny and appear to offer benefits for some aspects of the social work enterprise. With the fairly recent advent of the methods of meta-analysis, social work has the perfect opportunity to engage in this process of careful and critical evaluation of a new technology that may have important implications for the field.
Empirically Based Practice: The End of Ideology
Authors: Fischer Joel
Published: November 2023

It has been a full decade since a series of changes that were occurring in social work were dubbed a “quiet revolution” (Fischer, 1981). The revolution was viewed essentially as a move away from vague, unvalidated, and haphazardly derived knowledge traditionally used in social work toward more systematic, rational, and empirically oriented development and use of knowledge for practice. The changes in the field that were seen as some of the components of the revolution were: (1) work on systematizing the processes of knowledge development in social work;
The Contribution of Mindfulness Practice to the Development of Professional Self-Concept in Students of Social Work
Authors: Birnbaum Liora
Published: November 2023

The use of mindfulness meditation in teaching social work represents a shift in social work education toward a broader holistic approach that utilizes bodily, cognitive, and emotional personal experiences in the learning process (Canda & Smith, 2001). The social work literature tends to be limited to describing the emotional and educational benefits associated with mindfulness meditation, among them emotional regulation, enhanced community and self-awareness, and an enriched teaching curriculum. Although these benefits have been studied and docu- mented, it is not clear how mindfulness produces them.
Mindfulness-Influenced Social Work Practice with Immigrants
Authors: George Miriam
Published: November 2023

When I first met Ms. Nair, I expected my session with her to be no different from those with my other clients. Instead, it turned out to be one of the greatest learning experiences of my life. Ms. Nair came from India and had been physically abused by her husband before and after her migration to Canada and was also adjusting to her new life in this new country. She had recently been involved in a workplace accident and was receiving mental health support. Neither my personal experience as an immigrant nor my professional knowledge as a clinical social worker prepared me for this unusual therapy session.
Mindfulness in Activism: Fighting for Justice as a Self-Reflective Emancipatory Practice
Authors: Lysack Mishka
Published: November 2023

Activism is conceptualized as acting as a change agent to transform society through externalized action. As noted by Dorothy E. Smith (2006), ‘‘an activist sees the world in terms of what people are doing— what he is or she is doing and what others are doing’’ (p. 21). However, activism also embodies a transformative and transcendent personal quality of mindful internalized action, variously called conviction, courage, righteousness, or that ‘‘still small voice within,’’ as articulated by Mahatma Gandhi, the leader of India’s movement for independence from British colonial rule. I see mindfulness as foundational to work devoted to the realization of social justice. An activist’s work has the potential to be either poetic and courageous or destructive and blind in its intent and consequences. Therefore, an activist needs to purposively direct her intent in order for her actions to be congruent with social justice aims. The activist who endeavours’ to integrate her consciousness of self with her awareness of societal injustices maintains her usefulness for realizing fundamental social change. Mindfulness can be seen as a necessary condition for an activist to become mature in her passion and mission to fight for justice.
MET variants with activating N-lobe mutations identified in hereditary papillary renal cell carcinomas still require ligand stimulation
Authors: Guérin Célia , Vinchent Audrey , Fernandes Marie , Damour Isabelle , Laratte Agathe , Tellier Rémi , Estevam Gabriella O. , Meneboo Jean-Pascal , Villenet Céline , Descarpentries Clotilde , Fraser James S. , Figeac Martin , Cortot Alexis B , Rouleau Etienne , Tulasne David
Published: November 2023

In hereditary papillary renal cell carcinoma (HPRCC), the hepatocyte growth factor receptor (MET) receptor tyrosine kinase (RTK) mutations recorded to date are located in the kinase domain and lead to constitutive MET activation. This contrasts with MET mutations identified in non-small cell lung cancer (NSCLC), which lead to exon 14 skipping and deletion of a regulatory domain: in this latter case, the mutated receptor still requires ligand stimulation. Sequencing of MET in samples from 158 HPRCC and 2808 NSCLC patients revealed ten uncharacterized mutations. Four of these, all found in HPRCC and leading to amino acid substitutions in the N-lobe of the MET kinase, proved able to induce cell transformation, which was further enhanced by hepatocyte growth factor (HGF) stimulation: His1086Leu, Ile1102Thr, Leu1130Ser and Cis1125Gly. Similar to the variant resulting in MET exon 14 skipping, the two N-lobe MET variants His1086Leu and Ile1102Thr were found to require stimulation by HGF in order to strongly activate downstream signaling pathways and epithelial cell motility. The Ile1102Thr mutation also displayed transforming potential, promoting tumor growth in a xenograft model. In addition, the N-lobe-mutated MET variants were found to trigger a common HGF-stimulation-dependent transcriptional program, consistent with an observed increase in cell motility and invasion. Altogether, this functional characterization revealed that N-lobe variants still require ligand stimulation, in contrast to other RTK variants. This suggests that HGF expression in the tumor microenvironment is important for tumor growth. The sensitivity of these variants to MET inhibitors opens the way for use of targeted therapies for patients harboring the corresponding mutations.
Differences in transcription initiation directionality underlie distinctions between plants and animals in chromatin modification patterns at genes and cis-regulatory elements
Authors: Silver Brianna D. , Willett Courtney G. , Maher Kelsey A. , Wang Dongxue , Deal Roger B.
Published: November 2023

Transcriptional initiation is among the first regulated steps controlling eukaryotic gene expression. High-throughput profiling of fungal and animal genomes has revealed that RNA Polymerase II (Pol II) often initiates transcription in both directions at the promoter transcription start site (TSS), but generally only elongates productively into the gene body. Additionally, Pol II can initiate transcription in both directions at cis-regulatory elements (CREs) such as enhancers. These bidirectional Pol II initiation events can be observed directly with methods that capture nascent transcripts, and they are also revealed indirectly by the presence of transcription-associated histone modifications on both sides of the TSS or CRE. Previous studies have shown that nascent RNAs and transcription-associated histone modifications in the model plantArabidopsis thalianaaccumulate mainly in the gene body, suggesting that transcription does not initiate widely in the upstream direction from genes in this plant. We compared transcription-associated histone modifications and nascent transcripts at both TSSs and CREs inArabidopsis thaliana, Drosophila melanogaster, andHomo sapiens. Our results provide evidence for mostly unidirectional Pol II initiation at both promoters and gene-proximal CREs ofArabidopsis thaliana, whereas bidirectional transcription initiation is observed widely at promoters in bothDrosophila melanogasterandHomo sapiens, as well as CREs inDrosophila. Furthermore, the distribution of transcription-associated histone modifications around TSSs in theOryza sativa(rice) andGlycine max(soybean) genomes suggests that unidirectional transcription initiation is the norm in these genomes as well. These results suggest that there are fundamental differences in transcriptional initiation directionality between flowering plant and metazoan genomes, which are manifested as distinct patterns of chromatin modifications around RNA polymerase initiation sites.
Applicability of multiple quantitative magnetic resonance methods in genetic brain white matter disorders
Authors: Stellingwerff Menno D. , Al‐Saady Murtadha L. , Chan Kwok‐Shing , Dvorak Adam , Marques José P. , Kolind Shannon , Roosendaal Stefan D. , Wolf Nicole I. , Barkhof Frederik , van der Knaap Marjo S. , Pouwels Petra J. W.
Published: November 2023

Background and purpose

Magnetic resonance imaging (MRI) measures of tissue microstructure are important for monitoring brain white matter (WM) disorders like leukodystrophies and multiple sclerosis. They should be sensitive to underlying pathological changes. Three whole‐brain isotropic quantitative methods were applied and compared within a cohort of controls and leukodystrophy patients: two novel myelin water imaging (MWI) techniques (multi‐compartment relaxometry diffusion‐informed MWI: MCR‐DIMWI, and multi‐echo T2 relaxation imaging with compressed sensing: METRICS) and neurite orientation dispersion and density imaging (NODDI).

Methods

For 9 patients with different leukodystrophies (age range 0.4‐62.4 years) and 15 control subjects (2.3‐61.3 years), T1‐weighted MRI, fluid‐attenuated inversion recovery, multi‐echo gradient echo with variable flip angles, METRICS, and multi‐shell diffusion‐weighted imaging were acquired on 3 Tesla. MCR‐DIMWI, METRICS, NODDI, and quality control measures were extracted to evaluate differences between patients and controls in WM and deep gray matter (GM) regions of interest (ROIs). Pearson correlations, effect size calculations, and multi‐level analyses were performed.

Results

MCR‐DIMWI and METRICS‐derived myelin water fractions (MWFs) were lower and relaxation times were higher in patients than in controls. Effect sizes of MWF values and relaxation times were large for both techniques. Differences between patients and controls were more pronounced in WM ROIs than in deep GM. MCR‐DIMWI‐MWFs were more homogeneous within ROIs and more bilaterally symmetrical than METRICS‐MWFs. The neurite density index was more sensitive in detecting differences between patients and controls than fractional anisotropy. Most measures obtained from MCR‐DIMWI, METRICS, NODDI, and diffusion tensor imaging correlated strongly with each other.

Conclusion

This proof‐of‐concept study shows that MCR‐DIMWI, METRICS, and NODDI are sensitive techniques to detect changes in tissue microstructure in WM disorders.
Cantilever beam bending as a potential method to determine the elasticity of cooked Udon noodles
Authors: Jiang Song , Xu Congmei , Jiang Yiyi , Xu Bin , Liu Shuyi
Published: November 2023

Elasticity is a critical measure of the eating quality of Udon noodles. To characterize the elasticity of Udon noodles, an instrumental method based on the cantilever beam bending test was established. Firstly, the optimum test parameters were determined. Then, texture profile analysis, compression, tension, and cantilever beam bending methods were used to measure the elasticity of 25 commercial Udon noodles with different shapes and sizes, and the correlations between elasticity obtained by the above instrumental methods and sensory evaluation were analyzed. Finally, how the shape and size of Udon noodles influenced their elasticity was discussed in detail. Within the deflection of 2.0 mm, the force increased approximately linearly with increasing deflection, and moderate loading speed (0.5–1.0 mm/s) should be used in the cantilever beam bending experiments to improve the accuracy of results. The bending stiffness obtained by the cantilever beam bending method exhibited a higher coefficient of variation and stronger correlation with the elasticity of sensory evaluation than other instrumental methods. Furthermore, the Udon noodle sample with a higher size, especially the thickness, had higher elasticity, and the Udon noodle sample with a rectangular cross‐section showed higher elasticity than that with a circular cross‐section. In conclusion, the bending stiffness determined by the cantilever beam bending method could be used to characterize the elasticity of cooked Udon noodles.
Promising directions of socio-psychological research (to the 75th anniversary of A.L. Zhuravlev)
Authors: Nestik Timofei A.
Published: November 2023

Background. Te internal logic of the development of social psychology as a science, as well as the rapid changes in society afecting its subject feld, require discussion on the current scientifc problems and prospects for further social psychological research, many of which are related to the development of scientifc directions initiated by A.L. Zhuravlev and his colleagues. Te aim of the study was to describe the contribution of A.L. Zhuravlev to the development of a number of branches of Russian social psychology and, on the basis of the concepts developed by him, to identify some of the most promising areas for further research. Results. Te study singled out the following branches and directions of social psychology, the formation of which in Russia is closely connected with the works of A.L. Zhuravlev: psychology of management, joint activity and collective subject; psychology of morality; economical psychology; social psychology of the city; studies of the psychological state of the Russian society; studies of attitudes to new technologies and the infuence of technologies on socio-psychological phenomena; psychology of nuclear deterrence and strategic security, psychology of global risks. In each of these areas, the prospects for further research are outlined, taking into account the social, economic and technological changes in Russia. Conclusion. Presented analysis allows to consider collective subjectivity as an integral phenomenon that connects promising areas of research in social psychology, and the works of A.L. Zhuravlev can serve as a basis for their further development.
Conscious self-regulation and coping strategies as resources for overcoming difcult life situations
Authors: Vets Irina V.
Published: November 2023

Background. Te relevance of the study is due to the search for regulatory and intrapersonal resources for a successful way out of difcult life situations on the example of the postoperative period afer high-tech operations on the large joints. Objective. Te study had its purpose to scrutinize the contribution of conscious selfregulation and coping strategies to overcoming difcult life situations. Methods. “Self-Regulation Profle Questionnaire by Morosanova — SRPQM 2020”, questionnaire “Methods of Coping Behavior” by R. Lazarus, questionnaire of cognitive regulation of emotions by N. Garnefsky, “Knee Score Scale” modifed by D. Insall, “Hip Joint Assessment System”. Sample of the study consisted of 128 people of them: 80 men, 48 women (average age 55.76 ± 12.7), who underwent high-tech operations on the large joints. Measurements were carried out in two stages: before the operation and 1.5 months later. Results confrm that most people experience difculties in the process of self-recovery afer high-tech operations. Te study revealed a positive contribution of adaptive coping strategies, such as problem-solving planning and reviewing the situation from the positive side to the patients’ recovery. Tese coping strategies make a positive contribution to compliance with standard recovery deadlines and reduce the efect of ineffective cognitive-emotional strategies. Avoidance, denial of the problem, fantasizing and emotional distancing prevent a successful exit from a difcult life situation and delay the recovery process. Te study also showed contribution of self-accusation, exaggeration of occurred events signifcance and blaming others to the difculties that arise during self-rehabilitation. Te research results demonstrate the system-forming resource role of conscious self-regulation in the successful overcoming difcult life situations, where conscious self-regulation acts as a central predictor and mediator of other personality characteristics. Conclusions. Adaptive coping strategies and conscious self-regulation make a signifcant contribution to overcoming difcult life situations. Self-regulation is a predictor and mediator of health indicators and compliance with standard rehabilitation deadlines; it plays a system-forming resource role in restraining inefective ways of cognitive-emotional regulation and coping strategies in the process of overcoming difcult life situations.
Safety culture of young people: phenomenology, assessment methods, typology
Authors: Leоnova Elena V. , Khavylo Alexey V.
Published: November 2023

Background. Te relevance of studying the youth safety culture (SC) in various spheres of life is due to a signifcant change in the structure of risks coming along with the development of Internet and digital technologies. Objective. Te empirical study had its purpose to reveal the intrapersonal and subjective determinants of the youth SC taking into consideration its gender specifcity, as well as to describe the types of youth SC as per the attitude to diferent safety components. Sample. Te study involved 1469 university students (545 boys, 924 girls, mean age 20.34 years). Methods. Te study implemented the standardized questionnaires TIPI-RU, BriefCope, PIL, RFQ, assessments of self-confrmation patterns as well as ad hoc developed technique for evaluating the youth SC and its components (public, personal, fnancial, and data security). Data analysis was carried out using multivariate statistical methods (ANOVA (Analysis of Variance), factor analysis, cluster analysis, correlation analysis), Student’s t-test and Fisher’s F-test. Results of the study revealed certain gender diferences in the youth SC: young women have a signifcantly higher indicator of personal safety, while young men dominate in all other components and the integral indicator of SC. Cluster analysis allowed for identifying 4 types of SC according to the rates of diferent SC components. Te revealed types of SC difer in the personality characteristics, meaningfulness of life, preferred coping strategies, focus of regulation, and self-confrmation patterns. Conclusion. It was established that youth security culture is more a consequence of comprehension (as well as learning) than a personality conditioned phenomenon. Te study substantiated the expediency of individually oriented proactive approach to the formation of the students’ SC.
DNA methylation in poultry: a review
Authors: Ju Xing , Wang Zhijun , Cai Danfeng , Bello Semiu Folaniyi , Nie Qinghua
Published: November 2023

As an important epigenetic modification, DNA methylation is involved in many biological processes such as animal cell differentiation, embryonic development, genomic imprinting and sex chromosome inactivation. As DNA methylation sequencing becomes more sophisticated, it becomes possible to use it to solve more zoological problems. This paper reviews the characteristics of DNA methylation, with emphasis on the research and application of DNA methylation in poultry.