bluuebunny/crossref_metadata_2025 huggingface dataset:
RNA polymerase redistribution supports growth in E. coli strains with a minimal number of rRNA operons
Authors: Fan Jun , El Sayyed Hafez , Pambos Oliver J , Stracy Mathew , Kyropoulos Jingwen , Kapanidis Achillefs N
Published: June 2023

Bacterial transcription by RNA polymerase (RNAP) is spatially organized. RNAPs transcribing highly expressed genes locate in the nucleoid periphery, and form clusters in rich medium, with several studies linking RNAP clustering and transcription of rRNA (rrn). However, the nature of RNAP clusters and their association with rrn transcription remains unclear. Here we address these questions by using single-molecule tracking to monitor the subcellular distribution of mobile and immobile RNAP in strains with a heavily reduced number of chromosomal rrn operons (Δrrn strains). Strikingly, we find that the fraction of chromosome-associated RNAP (which is mainly engaged in transcription) is robust to deleting five or six of the seven chromosomal rrn operons. Spatial analysis in Δrrn strains showed substantial RNAP redistribution during moderate growth, with clustering increasing at cell endcaps, where the remaining rrn operons reside. These results support a model where RNAPs in Δrrn strains relocate to copies of the remaining rrn operons. In rich medium, Δrrn strains redistribute RNAP to minimize growth defects due to rrn deletions, with very high RNAP densities on rrn genes leading to genomic instability. Our study links RNAP clusters and rrn transcription, and offers insight into how bacteria maintain growth in the presence of only 1–2 rrn operons.
Spatially resolved transcriptomic analysis of the germinating barley grain
Authors: Peirats-Llobet Marta , Yi Changyu , Liew Lim Chee , Berkowitz Oliver , Narsai Reena , Lewsey Mathew G , Whelan James
Published: June 2023

Seeds are a vital source of calories for humans and a unique stage in the life cycle of flowering plants. During seed germination, the embryo undergoes major developmental transitions to become a seedling. Studying gene expression in individual seed cell types has been challenging due to the lack of spatial information or low throughput of existing methods. To overcome these limitations, a spatial transcriptomics workflow was developed for germinating barley grain. This approach enabled high-throughput analysis of spatial gene expression, revealing specific spatial expression patterns of various functional gene categories at a sub-tissue level. This study revealed over 14 000 genes differentially regulated during the first 24 h after imbibition. Individual genes, such as the aquaporin gene family, starch degradation, cell wall modification, transport processes, ribosomal proteins and transcription factors, were found to have specific spatial expression patterns over time. Using spatial autocorrelation algorithms, we identified auxin transport genes that had increasingly focused expression within subdomains of the embryo over time, suggesting their role in establishing the embryo axis. Overall, our study provides an unprecedented spatially resolved cellular map for barley germination and identifies specific functional genomics targets to better understand cellular restricted processes during germination. The data can be viewed at https://spatial.latrobe.edu.au/.
Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells
Authors: Doimo Mara , Chaudhari Namrata , Abrahamsson Sanna , L’Hôte Valentin , Nguyen Tran V H , Berner Andreas , Ndi Mama , Abrahamsson Alva , Das Rabindra Nath , Aasumets Koit , Goffart Steffi , Pohjoismäki Jaakko L O , López Marcela Dávila , Chorell Erik , Wanrooij Sjoerd
Published: June 2023

Mitochondrial DNA (mtDNA) replication stalling is considered an initial step in the formation of mtDNA deletions that associate with genetic inherited disorders and aging. However, the molecular details of how stalled replication forks lead to mtDNA deletions accumulation are still unclear. Mitochondrial DNA deletion breakpoints preferentially occur at sequence motifs predicted to form G-quadruplexes (G4s), four-stranded nucleic acid structures that can fold in guanine-rich regions. Whether mtDNA G4s form in vivo and their potential implication for mtDNA instability is still under debate. In here, we developed new tools to map G4s in the mtDNA of living cells. We engineered a G4-binding protein targeted to the mitochondrial matrix of a human cell line and established the mtG4-ChIP method, enabling the determination of mtDNA G4s under different cellular conditions. Our results are indicative of transient mtDNA G4 formation in human cells. We demonstrate that mtDNA-specific replication stalling increases formation of G4s, particularly in the major arc. Moreover, elevated levels of G4 block the progression of the mtDNA replication fork and cause mtDNA loss. We conclude that stalling of the mtDNA replisome enhances mtDNA G4 occurrence, and that G4s not resolved in a timely manner can have a negative impact on mtDNA integrity.
Metallohelices stabilize DNA three-way junctions and induce DNA damage in cancer cells
Authors: Malina Jaroslav , Kostrhunova Hana , Scott Peter , Brabec Viktor
Published: June 2023

DNA three-way junctions (3WJ) represent one of the simplest supramolecular DNA structures arising as intermediates in homologous recombination in the absence of replication. They are also formed transiently during DNA replication. Here we examine the ability of Fe(II)-based metallohelices to act as DNA 3WJ binders and induce DNA damage in cells. We investigated the interaction of eight pairs of enantiomerically pure Fe(II) metallohelices with four different DNA junctions using biophysical and molecular biology methods. The results show that the metallohelices stabilize all types of tested DNA junctions, with the highest selectivity for the Y-shaped 3WJ and minimal selectivity for the 4WJ. The potential of the best stabilizer of DNA junctions and, at the same time, the most selective 3WJ binder investigated in this work to induce DNA damage was determined in human colon cancer HCT116 cells. These metallohelices proved to be efficient in killing cancer cells and triggering DNA damage that could yield therapeutic benefits.
Dna2 removes toxic ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis
Authors: Zhai Binyuan , Zhang Shuxian , Li Bo , Zhang Jiaming , Yang Xuan , Tan Yingjin , Wang Ying , Tan Taicong , Yang Xiao , Chen Beiyi , Tian Zhongyu , Cao Yanding , Huang Qilai , Gao Jinmin , Wang Shunxin , Zhang Liangran
Published: June 2023

During the repair of DNA double-strand breaks (DSBs), de novo synthesized DNA strands can displace the parental strand to generate single-strand DNAs (ssDNAs). Many programmed DSBs and thus many ssDNAs occur during meiosis. However, it is unclear how these ssDNAs are removed for the complete repair of meiotic DSBs. Here, we show that meiosis-specific depletion of Dna2 (dna2-md) results in an abundant accumulation of RPA and an expansion of RPA from DSBs to broader regions in Saccharomyces cerevisiae. As a result, DSB repair is defective and spores are inviable, although the levels of crossovers/non-crossovers seem to be unaffected. Furthermore, Dna2 induction at pachytene is highly effective in removing accumulated RPA and restoring spore viability. Moreover, the depletion of Pif1, an activator of polymerase δ required for meiotic recombination-associated DNA synthesis, and Pif1 inhibitor Mlh2 decreases and increases RPA accumulation in dna2-md, respectively. In addition, blocking DNA synthesis during meiotic recombination dramatically decreases RPA accumulation in dna2-md. Together, our findings show that meiotic DSB repair requires Dna2 to remove ssDNA-RPA filaments generated from meiotic recombination-associated DNA synthesis. Additionally, we showed that Dna2 also regulates DSB-independent RPA distribution.
Gene expressions associated with longer lifespan and aging exhibit similarity in mammals
Authors: Takasugi Masaki , Yoshida Yuya , Nonaka Yoshiki , Ohtani Naoko
Published: June 2023

Although molecular features underlying aging and species maximum lifespan (MLS) have been comprehensively studied by transcriptome analyses, the actual impact of transcriptome on aging and MLS remains elusive. Here, we found that transcriptional signatures that are associated with mammalian MLS exhibited significant similarity to those of aging. Moreover, transcriptional signatures of longer MLS and aging both exhibited significant similarity to that of longer-lived mouse strains, suggesting that gene expression patterns associated with species MLS contribute to extended lifespan even within a species and that aging-related gene expression changes overall represent adaptations that extend lifespan rather than deterioration. Finally, we found evidence of co-evolution of MLS and promoter sequences of MLS-associated genes, highlighting the evolutionary contribution of specific transcription factor binding motifs such as that of E2F1 in shaping MLS-associated gene expression signature. Our results highlight the importance of focusing on adaptive aspects of aging transcriptome and demonstrate that cross-species genomics can be a powerful approach for understanding adaptive aging transcriptome.
Mineral and bone metabolism markers and mortality in diabetic patients on haemodialysis
Authors: Martín-Carro Beatriz , Navarro-González Juan F , Ortiz Alberto , Zoccali Carmine , Floege Jürgen , Ferreira Manuel A , Gorriz-Teruel José L , Carrillo-López Natalia , Panizo Sara , Locatelli Francesco , Ketteler Markus , London Gerard M , Naves-Díaz Manuel , Alonso-Montes Cristina , Cannata-Andía Jorge B , Fernández-Martín José L
Published: June 2023

Background

Diabetic patients on haemodialysis have a higher risk of mortality than non-diabetic patients. The aim of this COSMOS (Current management of secondary hyperparathyroidism: a multicentre observational study) analysis was to assess whether bone and mineral laboratory values [calcium, phosphorus and parathyroid hormone (PTH)] contribute to this risk.

Methods

COSMOS is a multicentre, open-cohort, 3-year prospective study, which includes 6797 patients from 227 randomly selected dialysis centres in 20 European countries. The association between mortality and calcium, phosphate or PTH was assessed using Cox proportional hazard regression models using both penalized splines smoothing and categorization according to KDIGO guidelines. The effect modification of the association between the relative risk of mortality and serum calcium, phosphate or PTH by diabetes was assessed.

Results

There was a statistically significant effect modification of the association between the relative risk of mortality and serum PTH by diabetes (P = .011). The slope of the curve of the association between increasing values of PTH and relative risk of mortality was steeper for diabetic compared with non-diabetic patients, mainly for high levels of PTH. In addition, high serum PTH (>9 times the normal values) was significantly associated with a higher relative risk of mortality in diabetic patients but not in non-diabetic patients [1.53 (95% confidence interval 1.07–2.19) and 1.17 (95% confidence interval 0.91–1.52)]. No significant effect modification of the association between the relative risk of mortality and serum calcium or phosphate by diabetes was found (P = .2 and P = .059, respectively).

Conclusion

The results show a different association of PTH with the relative risk of mortality in diabetic and non-diabetic patients. These findings could have relevant implications for the diagnosis and treatment of chronic kidney disease–mineral and bone disorders.
Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy
Authors: Peters Björn , Beige Joachim , Siwy Justyna , Rudnicki Michael , Wendt Ralph , Ortiz Alberto , Sanz Ana Belen , Mischak Harald , Reich Heather N , Nasic Salmir , Mahmood Dana , Persson Anders , Fernström Anders , Weiner Maria , Stegmayr Bernd ,   the PersTIgAN Working Group, Beige Joachim , Wendt Ralph , Schmidt Ulrike , Siwy Justyna , Zürbig Petra , Mischak Harald , Durban Annika , Raad Julia , Golovko Igor , Reich Heather , Lam Ping , Yang Stuart , Sanz Ana Belen , Fernandez-Fernandez Beatriz , Rojas-Rivera Jorge Enrique , Perez-Gomez Maria Vanessa , Ortiz Alberto , Sanchez-Niño Maria Dolores , Sanchez-Rodriguez Jinny , Rudnicki Michael , Kerschbaum Julia , Leierer Johannes , Mayer Gert , Stegmayr Bernd , Peters Björn
Published: June 2023

Background

Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN.

Methods

Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis–mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as “non-progressors” (IgAN237 ≤0.38) and “progressors” (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin–creatinine ratio slopes were calculated.

Results

Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71–531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = –0.278, P = .02 for score-1; rho = –0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = –0.31, P = .009 and rho = –0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median –5.98 versus –1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; –3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .001).

Conclusion

The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.
“I Get the Flavors and It Makes Me Love Vaping More”: How and Why Youth Users Modify Electronic Nicotine Delivery Systems
Authors: Churchill Victoria , Fairman Robert T , Brown Devon , Massey Zachary B , Ashley David L , Popova Lucy
Published: June 2023

Introduction

Youth in the United States are using electronic nicotine delivery systems (ENDS) at a high rate. Modifications to ENDS by youth can introduce additional health hazards which have not been previously considered. To better understand these risks, we need more information on what these modifications are, the motivations behind them, and the sources of information on modifications.

Aims and Methods

Utilizing a trained moderator, in 2020–2021, we conducted one-on-one interviews with 19 youth ENDS users aged 16–17 living in the United States and analyzed their responses using a qualitative description approach.

Results

The most prominent modification was to the e-liquid; youth indicated they mixed e-juices to create new flavors and added substances not intended for vaping, including illicit drugs such as cannabis and cocaine. Few youths from our sample were interested in achieving a specific nicotine level to vape, and modifications to the battery, coil and wick were less frequently mentioned. Some of these modifications were motivated by a desire to achieve specific experiences with their device. At other times, modifications were made due to necessity because of limited access to ENDS devices and supplies. YouTube and peers were the main sources of information about modifying.

Conclusions

Youth are making modifications that are both intended and unintended by the manufacturer. Adding illicit drugs and other substances not made for vaping is of particular concern. Understanding how youth modify ENDS and how that changes their use is important to guide regulatory policy intended to reduce harm to youth from ENDS use.

Implications

Youth from our study indicated that they make modifications to the ENDS devices, specifically to the e-liquid. These modifications are both intended by the manufacturer, such as changing the e-liquid and replacing coils, and unintended, such as adding substances not meant for vaping. Future policies aimed at reducing youth ENDS use should consider mandating better safeguards against modifications that appeal to youth.
An experimental test of cause-related marketing and charitable giving
Authors: Murphy James J , Conlin Molly , Haugstad Bryan
Published: June 2023

We conducted a natural field experiment at a local toy store in Anchorage, Alaska to estimate the effect on consumer behavior when the firm’s charitable donation is conditional on the total dollar amount of the individual transaction. Results suggest that the donation offer resulted in a modest increase in both the share of transactions exceeding the minimum amount needed to qualify for the donation and sales revenue.
A Thousand Cuts
Authors: Kentikelenis Alexandros , Stubbs Thomas
Published: June 2023

The dominant policy response to economic crises over the past four decades has been the introduction of austerity. How has this mix of budget cuts and reforms to downsize the role of the state evolved over time? What affect has it had on social policies and on people’s lives? This book examines the activities of the world’s leading advocate of austerity: the International Monetary Fund (IMF). This international organization lends to countries facing economic trouble in exchange for the implementation of far-reaching austerity measures. Drawing on new data, the authors reveal that although the precise content of IMF-mandated austerity has changed considerably over time, the organization continues to place a high burden of reform on countries in crisis. These reforms then decrease the availability of important social services, and contribute to rises in income inequality and declines in population health. These findings form the first systematic assessment of how austerity has impacted people’s lives and livelihoods around the world. Will such policy mistakes be avoided in the postpandemic world? The early evidence presented in this book do not raise grounds for optimism. Public expenditure projections reveal that in 2023, 86 out of 189 countries—mostly middle-income ones—face contractions in government spending compared to their 2010s average, thereby exposing a cumulative total of 2.3 billion people to the socioeconomic consequences of budget cuts.
Introduction
Authors: Kentikelenis Alexandros , Stubbs Thomas
Published: June 2023

Austerity measures have been implemented far and wide across the globe in recent decades, commonly as a precondition to access financial assistance from the International Monetary Fund (IMF)—one of the world’s most powerful international organizations. This book seeks to provide a comprehensive account of the scope and diversity of IMF-mandated austerity measures over the past forty years, and to examine how austerity has impacted social policies and outcomes. This introductory chapter covers definitional issues on austerity, describes the roles of the IMF, explains what conditionality is and how it is applied in IMF loans, and outlines how the analysis will unfold throughout the volume.
The IMF and the COVID-19 Response
Authors: Kentikelenis Alexandros , Stubbs Thomas
Published: June 2023

In the aftermath of the COVID-19 pandemic the narrative emerging out of the International Monetary Fund (IMF) stresses avoiding a divergent recovery, whereby some countries steam ahead with high growth rates while others fall behind. In this account, the postcrisis period should not witness budget cuts, but investment in employment and human capital formation. Is austerity a thing of the past? This chapter reviews available evidence, focusing on public spending projections by the IMF and the precise content of IMF lending arrangements. Overall, the chapter shows that the abandonment of austerity argument is partially true now, but questionable in the medium term. An original analysis of public expenditure projections reveals that by 2023, 86 out of 189 countries—mostly middle-income ones—will face contractions in government spending compared to their 2010s average, thereby exposing a cumulative total of 2.3 billion people to the socioeconomic consequences of budget cuts.
The Future of IMF Lending
Authors: Kentikelenis Alexandros , Stubbs Thomas
Published: June 2023

How can the International Monetary Fund (IMF) be reformed so that its lending programs do not have the adverse socioeconomic consequences documented in this volume? This concluding chapter elaborates on what can be done for the IMF to effectively live up to its promise and potential. The chapter first examines how IMF programs impact meeting the goal of universal social protection, a requisite for achieving many of the Sustainable Development Goals. Subsequently, it draws attention to a newer area of IMF engagement: supporting countries in their climate change adaptation and mitigation efforts. As environmental degradation poses an existential challenge to humanity, ensuring that countries have appropriate macroeconomic frameworks in place to facilitate the green transition is of paramount importance, and the IMF has a role to play here too. Finally, the chapter spells out the challenges in the road ahead for the IMF, and what types of practices could underpin a reformed IMF.
Introduction
Authors: Key Aidan
Published: June 2023

The introduction establishes this book’s necessity in a rapidly changing world. This book dismantles some general assumptions about gender and show a path to greater gender inclusion in schools. The primary audience (educators) and secondary audience (parents) for the text are explained. This chapter underscores the crucial need to examine gender inclusion in schools from both systemic and personal perspectives. This chapter hints at the regressive nature of the present historical moment and points to divisive politics that muddy progress toward understanding and celebrating gender diversity. It also champions educators who have made tremendous efforts in embracing change.
Teaching Gender
Authors: Key Aidan
Published: June 2023

Chapter 3 presents a contextual framework for teaching gender in the K–12 classroom. This framework can be introduced in a simple, age-appropriate manner for younger students and modified as students mature and develop over time. The simplicity of this AEIOU (Anatomy, Expression, Identity, Orientation, Universal) framework provides parents and teachers with the clarity they need to meet students where they are, and it helps to avoid overcomplicating discussions of gender identity. The reader will gain greater confidence to engage in discussions with children of all ages about gender and how our gender is uniquely expressed in our daily lives.
Creating an Optimal School Environment
Authors: Key Aidan
Published: June 2023

Chapter 11 considers the following important stakeholders: the gender-diverse student, the rest of the student body, and the parent community. This chapter contains standalone content addressing the fundamentals of creating a student support plan, which is a collaboration between the student and the school. This chapter outlines approaches to student empowerment, such as fostering student leadership and the creation of student alliances. It also provides detailed approaches for parents who want to get more involved in their school community and suggests approaches for how educators can support parents in their involvement.
Bathrooms and Locker Rooms
Authors: Key Aidan
Published: June 2023

Chapter 13 addresses some of the most often expressed areas of contention when considering the successful inclusion of trans students in schools—bathrooms and locker rooms. This chapter dives head long into the questions, ranging from practical to inflammatory, that arise. How do students respond to the presence of gender-diverse students in facilities versus the responses and fears from their adult counterparts. Is a separate bathroom or locker room a diplomatic solution or a way of segregating trans youth from their peers? This chapter offers numerous real-life examples that make evident the experiences, and implications of those experiences, of trans children, their peers, and the educators involved as they strive to optimize safety and privacy for every student.
Experimental psychology and psychopathology on animals
Authors: Yokoyama Olga T.
Published: June 2023

As I believe the language of facts to be the most eloquent one, I shall take the liberty of addressing myself directly to that experimental material which has given me the right to speak on the topic of my presentation today. This will be first of all a story of a physiologist’s turn from purely physiological questions toward the area usually called psychic. This transition was not anticipated, but it occurred quite naturally, and—what seems to me to be especially important in this case—without changing, so to speak, the methodological front lines. Having worked for many years on the normal function of the digestive glands and having analyzed the regular conditions of this function, I encountered here—as had actually been pointed out by others as well—situations of a psychic nature.
On the psychic secretion of the salivary glands
Authors: Yokoyama Olga T.
Published: June 2023

Most recently, the physiology of the salivary glands has especially foregrounded, within their functioning, certain phenomena which are usually called psychic. The latest research on the salivary glands by Glinski?, Vul’fson, Henri and Malloizel, and Borisov has revealed a most perfect adaptability of these glands to external stimulations, as had already been anticipated by Claude Bernard. In response to food that gets into the mouth and is hard and dry, the salivary glands release great quantities of saliva, and mixing with it allows such food to realize its chemical properties and helps its mechanical processing, thus aiding its passage through the esophagus into the stomach. In contrast, saliva is produced in much smaller quantities when the food contains a lot of free water, and less saliva is produced the higher the water content. To be sure, milk causes a decent amount of saliva to flow, but it should be kept in mind that the addition of mucous saliva to milk prevents, by virtue of the mucous layering, the formation in the stomach of a large compact curd mass, and by this it facilitates the digestive effect of gastric juice on the milk. In response to water or to a physiological saline solution, no salivation occurs at all, as saliva is of no use to them. When strong chemical irritants are introduced into the mouth, saliva always flows in quantities strictly proportional to the irritating strength of these substances.
Further steps in the objective analysis of complex-nervous phenomena as contrasted with their subjective understanding
Authors: Yokoyama Olga T.
Published: June 2023

This presentation concerns the so-called conditional reflexes, an area of objective research of the central nervous system of the dog. Let me first remind you of the basic tenets of this theory. From the standpoint of objective research, the dog’s total nervous activity, with no omissions, is understood by us as reflexes, the animal’s reactions to the external world realized by means of the nervous system. We distinguish two kinds of reflexes. The common reflex, the old one, which we dub “unconditional”, is the kind of reaction when given external phenomena correlate with given responses of the organism in a predictable, unchangeable way.
Natural science and the brain
Authors: Yokoyama Olga T.
Published: June 2023

It would be fair to say that the progress of natural science, which had marched on inexorably since the time of Galileo, first noticeably slowed down when it reached the highest parts of the brain, or, to put it more generally, the organ that handles the most complex relations of animals to the external world. And this seemed to be for a reason, it seemed that this was indeed a critical moment for natural science, for the brain—which in its highest form, the human brain, has created and continues to create natural science—has itself become the object of this science.
The principal laws governing central nervous system activity as revealed through conditional reflex research
Authors: Yokoyama Olga T.
Published: June 2023

Our knowledge of the two main components of the nervous system—the peripheral nervous system, i.e. the nerve fibers, and the central nervous system, hence mostly the grey matter, nerve cells—differs a lot in content and significance. In the physiology of the peripheral nervous system, as most of you know, many very precise laws related to both excitability and conductivity have been established. Of course, the nervous process as such remains mysterious and unexplored so far, but this is also true for the central nervous system, since this process is the same in both parts.
Physiology and psychology in the study of the higher nervous activity of animals
Authors: Yokoyama Olga T.
Published: June 2023

Among many, many dogs which have served in our laboratories for experiments with the so-called conditional reflexes, two stood out in certain ways. When a stranger entered the special room where the person conducting these experiments on his animals usually was, the animals normally showed no reaction, except for a slight orientational one. But these two dogs met every new arrival with overt hostility. Not only was it impossible to touch these dogs with impunity, but even extending your hand to the experimenter would cause a strong attacking move of the dogs toward the visitor. It soon became obvious that these dogs displayed a special guarding reaction. Because this reaction was so peculiar and so pronounced, and also because it caused so much inconvenience in the laboratory setting, we decided to subject the problem to special investigation.
The freedom reflex
Authors: Yokoyama Olga T.
Published: June 2023

First of all, I consider it my duty to thank the Philosophical Society for expressing, through its chairman, its willingness to listen to my report. It was not easy for me to gauge how interesting this presentation will be to the esteemed membership. As for me personally, I have a special purpose in doing this, as will become clear at the end of my presentation. I must report to you about the results of a very big project that has been going on for many years. This project was undertaken by me jointly with a dozen or so of my co-workers, who regularly participated in it with their heads as well as their hands. Were it not for them, the results would have been a tenth of what they are now. When I use the word “I”, I hope you will understand it not in the narrow sense of an author, but rather in the sense of, shall we say, a music conductor. What I did was mainly directing and coordinating everything.
A strictly objective study of all the higher manifestations of animal life
Authors: Yokoyama Olga T.
Published: June 2023

As a result of my earlier research on blood circulation and digestion, I have developed a strong conviction that clinical case studies—the endless series of all possible pathological variations and combinations of the organism’s functions—can be of great service to physiological thought. For this reason, having now been engaged for many years in the physiology of the cerebral hemispheres, I have thought many times that I should take advantage of the field of psychiatric phenomena as an auxiliary analytical material for the study of this physiology. Indeed, instead of our terribly crude—compared with the complexity and delicacy of the mechanism we study—method of destroying parts of the brain for the sake of analysis, we could have obtained in some cases a clearer, better defined and more refined decomposition of the brain’s work in its totality into elements, a delimitation of separate functions of the brain resulting from pathological causes, which sometimes reach an extremely high degree of differentiation of the effect.
On the so-called animal hypnosis
Authors: Yokoyama Olga T.
Published: June 2023

At the very end of the past century, biology witnessed the beginnings of an extremely important new direction—which by now have become fully established—to subject all the higher manifestations of animal life, all animal behavior, to a strictly objective analysis. This means limiting the analysis to juxtaposing the stimuli the animal is exposed to at any moment in a given environment with the visible responses to them—with the animal’s activities and reactions—and discovering the laws of this correlation. In this way, the research has acquired a natural-scientific deterministic foundation, completely tossing away all the attempts to make speculative and counterproductive guesses about the inner state of the animal as the putative cause of its actions, using analogies to our own subjective world.
The inhibitory type of the dog’s nervous system
Authors: Yokoyama Olga T.
Published: June 2023

I am highly honored to present to your kind attention a report on the latest results of my research, carried out jointly with my collaborators. I hope that the subject of the research has the potential of stimulating considerable interest. These studies were conducted on animals, specifically on the dog, this friend of man since prehistoric times. Moreover, it is 25 years now since we undertook the challenge to understand all the higher nervous activity of the animal, with no exceptions, in a purely physiological way, completely avoiding psychological concepts and terminology. Needless to say, the main organ of the higher nervous activity is the cerebral hemispheres.
A physiological theory of the types of nervous system, a.k.a. temperaments
Authors: Yokoyama Olga T.
Published: June 2023

A two-month summer break in our experiments using conditional reflexes on dogs presented us with an opportunity to observe special changes in the animals’ behavior. Dog ? 1. This animal, generally very active, once put on the stand after the break turned out to be much more excited than before the break. Its tail was constantly moving, and it reacted very quickly to the slightest movements of the experimenter. At the same time, all the conditional food reflexes had disappeared, and the dog wouldn’t even take the food offered to it after the conditional stimuli. After several fruitless attempts to evoke the conditional reactions, it was decided to apply a previously very well-developed differentiation, i.e., a very strong inhibitory process. After we did this, all the reflexes that had vanished were restored and the dog ate the food offered to it. A natural explanation for these facts is as follows. This dog had a very pronounced freedom reflex. Before the break, by systematically applying unconditional and conditional food stimuli, the freedom reflex was suppressed, inhibited. During the break, because of lack of reinforcement, the conditional food stimuli became weaker and the freedom reflex regained its strength and took the upper hand.
An attempt to interpret the symptomatology of hysteria physiologically
Authors: Yokoyama Olga T.
Published: June 2023

I report the results of my work done jointly with my colleagues, without making distinctions. The material we have at the present time is considerable, and today I can convey here, of course, only a small portion of it and only in a general way. What we mean by neuroses are chronic (lasting for weeks, months, or even years) deviations of the higher nervous activity from the norm. As far as we are concerned, the higher nervous activity is revealed primarily in the system of conditional positive and negative reflexes in response to all sorts of stimuli, and partly (to a minor degree) in the general behavior of our animals (dogs).
Physiology of the higher nervous activity
Authors: Yokoyama Olga T.
Published: June 2023

The objective study of the higher nervous activity using the method of conditional reflexes has advanced, expanded, and developed so much that it does not seem too audacious to attempt to physiologically interpret, analyze such a complex pathological picture as that presented by hysteria in all of its symptoms, even though hysteria is considered by all clinicians to be a mental disorder that is fully or primarily a psychogenic reaction to the surroundings. So this attempt will be at the same time a test of how well-equipped the theory of conditional reflexes is to pretend to explain physiologically the so-called psychic phenomena. And here again, unfortunately, it is impossible to dispense with a physiological introduction, however brief. Even in their country of birth conditional reflexes are still relatively unknown, and moreover, the theory is developing so quickly that many things, and important things, in this theory have not yet even been published and will be reported here for the first time.
Dynamic stereotypy of the higher part of the brain
Authors: Yokoyama Olga T.
Published: June 2023

Last year at the International Neurological Congress in Berne I reported on our experimental neuroses only in a most general way. Now I will describe in detail one example of a neurosis that has recently been studied substantively by one of my oldest and most appreciated collaborators, Petrova. When talking about purely experimental neuroses, we must begin from the question of the types of the animals’ (in our case, dogs’) nervous system. We distinguish three basic types: the strong, even very strong, but unbalanced one, whose inhibition is weak relative to its excitatory process; the strong and balanced one, with both opposite processes at the same level; and the weak one, with both processes weak, but sometimes one or the other of them especially weak.
Experimental pathology of the higher nervous activity
Authors: Yokoyama Olga T.
Published: June 2023

The images, pictures of our own behavior as well as the behavior of the familiar higher animals that participate in our daily lives (like dogs)—if we take behavior in its totality, in all of its minutest details of the kind we see especially in humans—present an enormous, really boundless variation. But since our and other higher animals’ behavior is determined and controlled by the nervous system, it should be possible to reduce this variation to a more or less limited number of basic properties of this system along with their combinations and gradations. In this way it should become possible to distinguish among the types of nervous activity, that is, among different bundles of the basic properties of the nervous system.
Speech Acts, Effects, and Responses
Authors: Sbisà Marina
Published: June 2023

Taking John Searle’s discussion of conversation as its point of departure, this paper examines the relationship between individual speech acts and conversational sequences. Instead of inquiring whether one can extend speech act theory to the study of conversation, it argues that the study of speech acts already presupposes some reference to conversational sequences. This is so because the hearer’s uptake, which is necessary for an illocutionary act to take effect, is indicated by the hearer’s response. This makes the success of illocutionary acts of any kind “conditional” on the hearer’s behavior (in a sense which should be kept distinct from the sense in which some illocutionary acts produce conditional obligations). The shift in illocutionary force that may occur when an utterance appears to be infelicitous under one interpretation but not under another, as well as the functioning of adjacency pairs, are both discussed in this light.
Illocutionary Force and Degrees of Strength in Language Use
Authors: Sbisà Marina
Published: June 2023

Some aspects of the received conception of a speech act do not allow illocutionary force to vary in degree, but a revised conception of the illocutionary act as bringing about a change in the interpersonal relation between the interlocutors is compatible with the results of pragmatic research on mitigation/reinforcement and can contribute to a better understanding of it. A speech-act theoretical framework is proposed in which mitigation and reinforcement are considered not as stylistic phenomena superficially affecting the speech act, but as the adjustment and tuning of its illocutionary effect. It is claimed that illocutionary effects and their adjustment and tuning can be described in deontic modal terms. In support of these claims, examples of mitigation or reinforcement taken from recorded conversations in Italian are analyzed. It is also pointed out that there are overlaps between their indicators and illocutionary force indicators.
Illocution and Silencing
Authors: Sbisà Marina
Published: June 2023

It has been claimed by various authors that pornography subordinates and silences women. This paper discusses the related problem of how to account for a person’s being “silenced.” Considering the case of the ineffective refusal of sexual advances, various ways of explaining what goes wrong are distinguished (perlocutionary failure, illocutionary disablement, misfire, lack of reciprocity and therefore of uptake, epistemic injustice). It is argued that none of them provides the complete picture of what is going on. Sexual refusal is then analyzed as an exercitive illocutionary act and its silencing as a denial of the woman’s authority over her own body and her entitlement to autonomous decision.
Varieties of Speech Act Norms
Authors: Sbisà Marina
Published: June 2023

This paper explores the field of speech act norms, shedding some light upon the different roles they play in the dynamics of illocution. A three-fold distinction is proposed: constitutive rules (upon which the performance of illocutionary acts depends), maxims (based on rational motivations, encoding regulative advice for optimal speech act performance in the perspective of the participants), and objective requirements for the overall correctness of the accomplished speech act. Some examples applying the proposed distinction to varieties of illocutionary act provide a very limited test of its potential as a descriptive framework. The proposal to consider rules of accommodation as a further kind of speech act norm is discussed and rejected. Since among the three kinds of norms, only constitutive rules can be said to be conventional, it is proposed that all speech acts may be considered as conventional for certain aspects and non-conventional for others.
Illocution and Power Imbalance
Authors: Sbisà Marina
Published: June 2023

This paper examines the role of speech as regards certain kinds of power imbalance. It introduces and illustrates exercitive illocutionary acts, consisting of the exercise of authority or influence and affecting the rights and obligations of the participants. After acknowledging that there are ways in which we bring about effects on the rights and obligations of the participants, other than the performance of Exercitives, it focuses attention on examples of Exercitives from informal speech situations, showing how the exercitive force of an utterance can be detected and what effects it may have on the degree of power or authority of the participants, either as its illocutionary effect or by accommodation. It also discusses a case in which the characteristic effects of Exercitives are achieved in a “backdoor” fashion and the strategies that may be employed to block them.
Luck and Metasemantics
Authors: King Jeffrey C.
Published: June 2023

In a series of works, Duncan Pritchard has defended a modal account of luck. On this account, events are the things that are lucky or not. For an event to be lucky is for it to occur in the actual world but, keeping the initial conditions for the event fixed, for there to be close possible worlds in which the event doesn’t occur. I intend to take on Pritchard’s modal account of luck here without argument. The question that concerns me here is whether the notion of luck has significant application in philosophy of language. I argue that it does. Specifically, in recent work I have defended an account of how contextually sensitive expression that are not pure indexicals, like deictic pronouns, tense, possessives, modals and so on, secure semantic values in context. I call such an account a metasemantics for the relevant expressions. In the present chapter, I argue that in a case where a hearer forms a true belief about the semantic value of a contextually sensitive expression, where my metasemantics assigns the semantic value in context to the expression, there are no nearby worlds that share the initial conditions of the actual world of utterance where that true belief is not formed. That is, the event of forming the true belief is not lucky. I claim that other metasemantic accounts do not have this property and that the fact that mine does is an argument in its favor.
Epistemicism without Metalinguistic Safety
Authors: Khoo Justin
Published: June 2023

Epistemicists claim that vague predicates have precise but unknowable cutoffs. But this leads to a problem. Suppose the cutoff for being tall is being more than N inches tall. This is a fact, so why can’t I know it? Williamson appeals to metalinguistic safety: we can know that p only if our belief that p is not metalinguistically lucky, meaning that it couldn’t have easily been the case that we continued to believe that the sentence ‘p’ expresses a truth even when it means something false. Claims about the precise cutoffs for vague predicates are not metalinguistically safe—even if “x is tall iff x is taller than N inches” is true, it could have easily meant something false, though we still to believed it. In this chapter, I argue against metalinguistic safety as a necessary condition on knowledge. This undermines the metalinguistic safety strategy for the epistemicist. I then offer the epistemicist an olive branch: they should opt for a slight variant of their view that I call diagonalized epistemicism. I show how this alternative version of epistemicism has a more satisfying response to why we cannot know the cutoffs of vague predicates. However, in an M. Night Shyamalan-style twist, I then argue we should not be diagonalized epistemicists either.
Introduction
Authors: Jankauskas Vytautas , Eckhard Steffen
Published: June 2023

This chapter summarizes the main findings of the book and introduces its conceptual framework, empirical strategy, and overall structure. It also discusses the implications of the book’s findings on evaluation research and practice as the book advances our knowledge about the evaluation’s role in international organizations’ (IOs’) policymaking. The book shows that evaluation is indeed used for political purposes in IOs, yet by changing the institutional architecture of evaluation systems, stakeholders can control the nature of such politics. Also, the chapter situates the book in the broader literature on IOs and global governance as its findings unveil how power dynamics between IO member states and their secretariats affect the functioning of IOs.
Stakeholder control of international organization evaluation systems
Authors: Jankauskas Vytautas , Eckhard Steffen
Published: June 2023

Chapter 4 examines the institutional design of international organizations’ (IOs) evaluation systems by conceptualizing, operationalizing, and measuring stakeholder control over IO evaluation units. Although formally independent, these units require resources that enable their work. IO member states and/or administrations have to approve their budgets, staff appointments, and evaluation agenda. As the findings show, the allocation of such control resources varies across 21 United Nations’ (UN) system IOs: while, in some organizations, evaluation units are controlled mainly by member states, in other IOs, it is the IO bureaucracy that decides upon the budget, staff, and evaluation agenda. As further chapters investigate, this variation creates tensions between the formal independence of the evaluation function and the concurrent dependency of evaluation units on necessary resources.