Retrosynthetic Simplicity.

Retrosynthetic simplicity is introduced as a metric by which methods can be evaluated. An argument in favor of reactions which are retrosynthetically simple is put forward, and recent examples in the context of skeletal editing from my own laboratory as well as contributions from others are analyzed critically through this lens.

[Evaluation of the Viral Hemorrhagic Fever Surveillance System in the Assaba region, Mauritania (2020-2022)]. / Évaluation du système de surveillance des fièvres hémorragiques virales dans la wilaya d'Assaba, Mauritanie (2020-2022).

Introduction: Several arboviral diseases have been known to be endemic (e.g., Crimean-Congo hemorrhagic fever, Rift Valley fever) or are emerging (dengue fever, chikungunya, O'nyong-nyong) in human populations in Mauritania, while others have become rare in recent years (e.g. yellow fever). Moreover, domestic animals, especially cattle, camels, goats, and sheep, are also known to be infected with some of these arboviruses (e.g. Crimean-Congo hemorrhagic fever, Rift Valley fever). For these reasons, viral hemorrhagic fever surveillance in Mauritania is part of the Integrated Disease Surveillance and Response (IDSR). However, limited information is available on the efficacy of the viral hemorrhagic fever surveillance system in the Assaba region of Mauritania. The aim of the present study was to assess the performance of the surveillance system, in particular its general utility, simplicity, flexibility, acceptability, and reactivity. Methods: A descriptive cross-sectional study was conducted from July to August 2022 in the Assaba region with the objective of evaluating the characteristics of the system by interviewing key actors involved in the surveillance of viral hemorrhagic fevers, with a focus on Rift Valley fever and Crimean-Congo hemorrhagic fever, using questionnaires developed following the guidelines of the Centers for Disease Control and Prevention (Atlanta, Georgia, USA). Data from 2020-2022 on viral hemorrhagic fevers from the National Institute of Public Health laboratory were analyzed. Medians, interquartile ranges, and proportions were calculated using Epi Info® 7.2.5.0 and Excel® 2021. Results: The questionnaire was answered by all twenty-six persons involved in the viral hemorrhagic fever surveillance system in Assaba region. The majority of survey respondents found the system to be useful (51%), simple (63%), acceptable (46%), responsive (64%), and flexible (46%). An analysis of the data revealed a positive predictive value of 28% for Rift Valley Fever. The weekly distribution of cases within the wilaya indicates that the moughataa of Kiffa recorded the highest number of cases in September, with a notable weekly peak during that month in 2020. According to the analysis of the National Institute of Public Health database, cases of viral hemorrhagic fevers were promptly handled. Survey responses and database analysis revealed issues related to data quality and data management mechanisms. These limitations in the surveillance system are likely to be due to insufficient resources and training of the personnel, in particular with regards to data collection and management, which in turn led to incomplete or missing data and invalid data entry. These weak points can be ascribed, at least in part, to financial constraints and inadequate attribution of priority to arboviral diseases. Despite these limitations, disease data generated by the surveillance system were generally reliable. Conclusion: The viral hemorrhagic fever surveillance system in the Assaba region adheres to the organization and functioning of the national viral hemorrhagic fever surveillance system, which is part of the IDSR. The characteristics of utility, simplicity, responsiveness, and flexibility of the viral hemorrhagic fever surveillance system are good, but acceptability and flexibility need further improvement. The earlier the first arboviral human or animal cases are detected, the more likely an active intervention can be organized in response to the emerging epidemic or epizootic and prevent the spread of the disease. An efficient viral surveillance system is the key to reducing the negative impact of arboviral diseases in Assaba region.

Inside Ockham's razor: A mechanism driving preferences for simpler explanations.

People often prefer simpler explanations, defined as those that posit the presence of fewer causes (e.g., positing the presence of a single cause, Cause A, rather than two causes, Causes B and C, to explain observed effects). Here, we test one hypothesis about the mechanisms underlying this preference: that people tend to reason as if they are using "agnostic" explanations, which remain neutral about the presence/absence of additional causes (e.g., comparing "A" vs. "B and C," while remaining neutral about the status of B and C when considering "A," or of A when considering "B and C"), even in cases where "atheist" explanations, which specify the absence of additional causes (e.g., "A and not B or C" vs. "B and C and not A"), are more appropriate. Three studies with US-based samples (total N = 982) tested this idea by using scenarios for which agnostic and atheist strategies produce diverging simplicity/complexity preferences, and asking participants to compare explanations provided in atheist form. Results suggest that people tend to ignore absent causes, thus overgeneralizing agnostic strategies, which can produce preferences for simpler explanations even when the complex explanation is objectively more probable. However, these unwarranted preferences were reduced by manipulations that encouraged participants to consider absent causes: making absences necessary to produce the effects (Study 2), or describing absences as causes that produce alternative effects (Study 3). These results shed light on the mechanisms driving preferences for simpler explanations, and on when these mechanisms are likely to lead people astray.

Managing Complexity in Socio-Technical Systems by Mimicking Emergent Simplicities in Nature: A Brief Communication.

In the context of socio-technical systems, traditional engineering approaches are inadequate, calling for a fundamental change in perspective. A different approach encourages viewing socio-technical systems as complex living entities rather than through a simplistic lens, which enhances our understanding of their dynamics. However, these systems are designed to facilitate human activities, and the goal is not only to comprehend how they operate but also to guide their function. Currently, we lack the appropriate terminology. Hence, we introduce two principal concepts, simplexity and complixity, drawing inspiration from how nature conceals intricate mechanisms beneath straightforward, user-friendly interfaces.

Mild Iron-Catalyzed Oxidative Cross-Coupling of Quinoxalinones with Indoles.

Utilizing iron chloride as a Lewis acid catalyst, we developed a straightforward and mild oxidative cross-coupling reaction between quinoxalinones and indoles, yielding a series of versatile 3-(indol-3-yl)quinoxalin-2-one derivatives. This approach allows for the incorporation of a wide array of functional groups into the final products, demonstrating its synthetic versatility. Notably, the method was successfully scaled up to gram-scale reactions while maintaining high yields. Our mechanistic investigation indicates that iron chloride serves as a catalyst to facilitate the formation of key intermediates which subsequently undergo oxidation to afford the desired products. The merits of this protocol include its cost effectiveness, operational simplicity, and the ease of product isolation via filtration.

Exploring Simplicity Bias in 1D Dynamical Systems.

Arguments inspired by algorithmic information theory predict an inverse relation between the probability and complexity of output patterns in a wide range of input-output maps. This phenomenon is known as simplicity bias. By viewing the parameters of dynamical systems as inputs, and the resulting (digitised) trajectories as outputs, we study simplicity bias in the logistic map, Gauss map, sine map, Bernoulli map, and tent map. We find that the logistic map, Gauss map, and sine map all exhibit simplicity bias upon sampling of map initial values and parameter values, but the Bernoulli map and tent map do not. The simplicity bias upper bound on the output pattern probability is used to make a priori predictions regarding the probability of output patterns. In some cases, the predictions are surprisingly accurate, given that almost no details of the underlying dynamical systems are assumed. More generally, we argue that studying probability-complexity relationships may be a useful tool when studying patterns in dynamical systems.

Recursive Numeral Systems Optimize the Trade-off Between Lexicon Size and Average Morphosyntactic Complexity.

Human languages vary in terms of which meanings they lexicalize, but this variation is constrained. It has been argued that languages are under two competing pressures: the pressure to be simple (e.g., to have a small lexicon) and to allow for informative (i.e., precise) communication, and that which meanings get lexicalized may be explained by languages finding a good way to trade off between these two pressures. However, in certain semantic domains, languages can reach very high levels of informativeness even if they lexicalize very few meanings in that domain. This is due to productive morphosyntax and compositional semantics, which may allow for construction of meanings which are not lexicalized. Consider the semantic domain of natural numbers: many languages lexicalize few natural number meanings as monomorphemic expressions, but can precisely convey very many natural number meanings using morphosyntactically complex numerals. In such semantic domains, lexicon size is not in direct competition with informativeness. What explains which meanings are lexicalized in such semantic domains? We will propose that in such cases, languages need to solve a different kind of trade-off problem: the trade-off between the pressure to lexicalize as few meanings as possible (i.e, to minimize lexicon size) and the pressure to produce as morphosyntactically simple utterances as possible (i.e, to minimize average morphosyntactic complexity of utterances). To support this claim, we will present a case study of 128 natural languages' numeral systems, and show computationally that they achieve a near-optimal trade-off between lexicon size and average morphosyntactic complexity of numerals. This study in conjunction with previous work on communicative efficiency suggests that languages' lexicons are shaped by a trade-off between not two but three pressures: be simple, be informative, and minimize average morphosyntactic complexity of utterances.

Posterior Lateral Arthrodesis as a Treatment Option for Lumbar Spinal Stenosis: Safety and Early Clinical Outcomes.

Introduction: Lumbar spinal stenosis (LSS) is a common condition caused by degenerative changes in the lumbar spine with age. LSS is caused by a variety of factors, including degenerative spondylosis and spondylolisthesis. People suffering with LSS experience neurogenic claudication, which causes severe physical limitations, discomfort, and a decrease in quality of life. Less invasive procedures are now being researched to improve the prognosis, success rate, and safety of LSS treatments. Posterior lateral spinal arthrodesis (PLSA) is a new surgical treatment for LSS. This study looks at the procedural and patient safety of PLSA. Materials and methods: This study is a multicenter retrospective analysis of the safety of PLSA who met the clinical indications for PLSA and underwent the procedure at eight interventional spine practices. Data was collected on demographical information, pre-procedural numeric rating scale score (NRS), post-procedural NRS, and complication reporting. Patients who were included had LSS with or without spondylolisthesis and had failed conservative treatments. A descriptive statistical analysis was performed to report the outcomes. Results were reported as mean and standard deviations for continuous outcomes, and frequency (%) for categorical outcomes. Results: This retrospective analysis involved 191 patients and 202 PLSA implants. The majority of patients were male Caucasians with a mean age of 69.2 years and a BMI of 31.1. A large majority of implants were placed at the L4-5 level, and the average pre-procedural NRS was 6.3 while the average post-procedural NRS was 3.1, indicating a 50.8% reduction in pain (p < 0.0001). Two patients reported complications, but they were unrelated to the device or surgical procedure; no infections, device malfunctions, or migrations were reported in the patient cohort. Conclusion: Preliminary results with PLSA implants indicate that it is a safe treatment option for patients with moderate LSS who do not respond to conservative management.

Research progress on dental materials for preventing root caries / 口腔疾病防治

@#The high incidence and untreated rate of root caries, a common and frequently occurring oral disease with challenging treatment in elderly individuals, is the main cause of tooth loss among elderly people, as rapid development results in pulpitis and periapical periodontitis or residual crown and root, which has been regarded as one of the common chronic oral diseases seriously affecting the quality of life of elderly people. Thus, early intervention and prevention are important. Traditional dental materials for preventing root caries have been widely used in clinical practice; however, they have the disadvantages of tooth coloring, remineralization and low sterilization efficiency. A series of new dental materials for preventing root caries have gradually become a research hotspot recently, which have the advantages of promoting the mineralization of deep dental tissue, prolonging the action time and enhancing adhesion. Future caries prevention materials should be designed according to the characteristics of root surface caries and the application population and should be developed toward simplicity, high efficiency and low toxicity. This review describes current research regarding anti-caries prevention material application, serving as a theoretical underpinning for the research of root caries prevention materials, which is important for both promotion in the effective prevention of root caries and improvement in the status of oral health and the quality of life among old people.

Prägnanz in visual perception.

How do we perceptually and cognitively organize incoming stimulation? A century ago, Gestalt psychologists posited the law of Prägnanz: psychological organization will always be as 'good' as possible given the prevailing conditions. To make the Prägnanz law a useful statement, it needs to be specified further (a) what a 'good' psychological organization entails, (b) how the Prägnanz tendency can be realized, and (c) which conditions need to be taken into account. Although the Gestalt school did provide answers to these questions, modern-day mentions of Prägnanz or good Gestalt often lack these clarifications. The concept of Prägnanz has been (mis)understood in many different ways, and by looking back on the rich history of the concept, we will attempt to present a more fine-grained view and promote a renewed understanding of the central role of Prägnanz in visual perception and beyond. We review Gestalt psychology's answers to the questions listed above, and also discuss the four main uses of the Prägnanz concept in more detail: (a) a Prägnanz tendency in each organizational process, (b) Prägnanz as a property of a Gestalt, (c) Prägnanz steps as internal reference points, and (d) Prägnanz in relation to aesthetic appreciation. As a key takeaway, Prägnanz is a multifaceted Gestalt psychological concept indicating the "goodness" of an experienced organization. Both the removal of unnecessary details and the emphasis on characteristic features of the overall organization compared to a reference organization can contribute to the emergence of a 'better' Gestalt. The stimulus constellation is not the only factor in determining the goodness of an organization, also the stimulus' interaction with an individual in a specific spatial and temporal context plays a role. Taking the ideas on Prägnanz as a generative framework and keeping the original Gestalt psychological context in mind, future research on perceptual organization can improve our understanding of the principles underlying psychological organization by further specifying how different organizational principles interact in concrete situations. Public significance statement: This paper reviews what a 'good' psychological organization entails, and how the incoming stimulation is clarified in human perception to achieve the best possible psychological organization. The review debunks common misconceptions on the meaning of "goodness" and synthesizes the most important perspectives and developments on "goodness" from its conception until now.

The Implementation of Renal Denervation in the Management of Resistant Hypertension Despite Use of Multitherapy Antihypertensives at Maximally Tolerated Doses: A Contemporary Literature Review.

Refractory hypertension is highly prevalent among the hypertensive population, and current clinical management has failed to provide optimal control for these individuals. This subtype of arterial hypertension is defined as a persistently elevated systolic blood pressure reading of 140 mmHg, or higher, despite multiple antihypertensive use at maximally tolerated dosing. These patients have an elevated risk of cardiovascular and renal complications, urging for the need of more effective therapeutic management. Renal sympathetic efferent nerves have been noted to play an important role in volume and blood pressure homeostasis. Before the implementation of oral antihypertensives, the use of surgical lumbar sympathectomy for the reduction of persistent hypertension was considered a life-saving approach. However, individuals were left with debilitating side effects, such as postural hypotension, syncope, and impotence. A new and minimally invasive technique has been proposed, where the kidneys undergo selective denervation in hopes of providing decreased cardiovascular morbidity and mortality for patients with resistant hypertension. Some studies demonstrated promising outcomes with a reduction in blood pressure, a decrease in medication reliance, and a potential long-lasting effect of the procedure with an overall improvement in cardiovascular health. Unfortunately, most of the available data was obtained from observational, uncontrolled studies with short-term follow-up, small sample sizes, and high variability in blood pressure measurement. Therefore, further evidence is needed to determine whether renal denervation provides long-term benefits for blood pressure control and improves outcomes for mortality and cardiovascular events in this patient population.

Not so simple! Causal mechanisms increase preference for complex explanations.

Mechanisms play a central role in how we think about causality, yet not all causal explanations describe mechanisms. Across five experiments, we find that people evaluate explanations differently depending on whether or not they include mechanisms. Despite common wisdom suggesting that explanations ought to be simple in the sense of appealing to as few causes as necessary to explain an effect, the literature is divided over whether people adhere to this principle. Our findings suggest that the presence of causal mechanisms in an explanation is one factor that reduces adherence. While competing explanations are often judged based on their probability of being correct, mechanisms afford a different way of evaluating explanations: They describe the underlying nature of causal relations. Complex explanations (appealing to multiple causes) contain more causal relations and thus allow for more mechanistic information, providing a fuller account of the causal network and promoting a greater sense of understanding.

Goodbye materialism: exploring antecedents of minimalism and its impact on millennials well-being.

The purpose of the study is to explore the antecedents of minimalism and, further, to study the impact of minimalism on millennials' well-being via a sense of fulfilment. To understand the origins of minimalism and its following effects on well-being, a theoretical framework is created. An online survey with a structured questionnaire was created to collect the necessary data from respondents. SMART PLS was used to analyse the suggested framework. This research establishes the mediating role of a sense of fulfilment in the interactions between minimalism and well-being and shows how environmental awareness, contemporary aesthetics, voluntary simplicity, normative influence, and resource sharing positively lead to minimalism. A minimalist lifestyle will help to preserve precious resources, reduce waste, and lower carbon emissions, all of which will have a significant positive influence on the environment. Additionally, clearing up clutter will give them more room and time, which will improve their well-being because they will have more time for their family and interests. The study suggests a thorough model to comprehend the origins of minimalism. Additionally, it established a connection between well-being and minimalism.

Evaluation of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020.

Introduction: Scrub typhus is one of the most underreported and fatal illnesses accounting for 23% of all febrile illness. Rajasthan reported cases during 2018-2019 in state reporting system but did not report any case to central Integrated Disease Surveillance Programme (IDSP) unit. We evaluated the Scrub typhus surveillance system in Alwar district, Rajasthan, with the objective of describing and evaluating the system and providing evidence-based recommendations to identify gaps. Material and Methods: In cross-sectional study, we reviewed records and conducted key informant interviews at district- and block-level health facilities. Using US Centers for Disease Control guidelines, we evaluated the system by framing indicators for selected attributes for a defined reference period. Overall performance was ranked as outstanding (90-100%), excellent (80-89%), very good (70-79%), good (60-69%), and poor (<60%). Results: Line list of confirmed cases was sent from district to block level for additional active case search (ACS) to implement control measures. We conducted 26 key informant interviews and reviewed records and calculated simplicity as 79%, flexibility 100%, data quality 46%, acceptability 92%, representativeness 48%, timeliness 43%, and stability 79%. Conclusions: Epidemiological surveillance (active and passive) is a core intervention under scrub typhus surveillance system. Lab reports were incompletely uploaded on IDSP portal. Surveillance reports should be updated after each ACS. Reporting format under IDSP should be uploaded timely, and lab reports from state should be sent within 48 hours of diagnosis so that case investigation is not delayed.

Comparison of simplicity, convenience, safety, and cost-effectiveness between use of insulin pen devices and disposable plastic syringes by patients with type 2 diabetes mellitus: a cross-sectional study from Bangladesh.

INTRODUCTION: Insulin pen devices and disposable plastic insulin syringes are two common tools for insulin administration. This study aims to compare the simplicity, convenience, safety, and cost-effectiveness of insulin pens versus syringe devices in patients with type 2 diabetes mellitus (T2DM). METHODS: A cross-sectional study was conducted at 14 diabetes clinics throughout Bangladesh from November 2021 to April 2022 among adults with T2DM injecting insulin by pen devices or disposable insulin syringes at least once a day for at least one year by purposive sampling. The simplicity, convenience, and safety of insulin devices were assessed using a structured questionnaire, and the study subjects were scored based on their answers; higher scores indicated a poorer response. Total scores for simplicity, convenience, and safety were obtained by adding the scores for relevant components. Their average monthly medical expense and cost of insulin therapy were recorded. The median values of the total scores and monthly expenses were compared between pen devices and disposable syringe users. RESULTS: 737 subjects were evaluated; 406 were pen users, and 331 were vial syringe users. The pen users had lower median scores for simplicity [6.0 (5.0-8.0) vs. 7.0 (5.0-9.0), p = 0.002], convenience [4.0 (3.0-6.0) vs. 5.0 (4.0-6.0), p < 0.001], and safety [7.0 (6.0-8.0) vs. 7.0 (6.0-9.0), p = 0.008] than vial syringe users. Pen devices were more expensive than vial syringes in terms of average medical expense per month [BDT 5000 (3500-7000) vs. 3000 (2000-5000), p < 0.001], the total cost of insulin therapy per month [BDT 2000 (1500-3000) vs. 1200 (800-1700), p < 0.001] and cost per unit of insulin used [BDT 2.08 (1.39-2.78) vs. 0.96 (0.64-1.39), p < 0.001]. Non-significant differences in favor of pens were observed in HbA1c levels [8.7 (7.8-10) vs. 8.9 (7.9-10)%, p = 0.607] and proportions of subjects having HbA1c < 7% (6.9 vs. 6.3%, p = 0.991). CONCLUSION: Insulin pens are simpler, more convenient, and safe but more expensive than vial syringes. Glycemic control is comparable between pen and syringe users. Long-term follow-up studies are needed to determine the clinical and economic impacts of such benefits of insulin pens.

Drawing conclusions: Representing and evaluating competing explanations.

Despite the increase in studies investigating people's explanatory preferences in the domains of psychology and philosophy, little is known about their preferences in more applied domains, such as the criminal justice system. We show that when people evaluate competing legal accounts of the same evidence, their explanatory preferences are affected by whether they are required to draw causal models of the evidence. In addition, we identify 'mechanism' as an explanatory feature that people value when evaluating explanations. Although previous research has shown that people can reason correctly about causality, ours is one of the first studies to show that generating and drawing causal models directly affects people's evaluations of explanations. Our findings have implications for the development of normative models of legal arguments, which have so far adopted a singularly 'unified' approach, as well as the development of modelling tools to support people's reasoning and decision-making in applied domains. Finally, they add to the literature on the cognitive basis of evaluating competing explanations in new domains.

Evolutionary insights from an anatomical network analysis of the hyolaryngeal apparatus in extant archosaurs (birds and crocodilians).

Adaptive radiation of archosaurs, represented by crocodilians, non-avian dinosaurs, and birds, since the Mesozoic has been studied mainly based on their major skeletal elements (skull, vertebrae, and limbs). However, little is known about the evolution of their hyolaryngeal apparatus, which is involved with feeding, respiration, and vocalization, because of poor fossil preservation and the difficulty in determining the musculoskeletal homology of the apparatus. Network analysis is a framework to quantitatively characterize the topological organization of anatomical structures for comparing structural integration and modularity regardless of ambiguous homology. Herein, we modeled the musculoskeletal system of hyolarynx in six species of extant archosaurs and its sister-taxon turtle, and conducted a network analysis using network parameters, modular partition, and bone centrality in a phylogenetic framework. The network parameters reveal that ancestral archosaurs have reduced the numbers of elements and links and acquired complex networks as a whole domain with strong modularity in the hyolarynx. Furthermore, the modular partition and centrality reveal that the hyoids are highly evolvable, while the larynx is constrained and less evolvable. The archosaur hyolarynx exhibits different evolutionary trends: crocodilians with the system integration, basihyal simplification, and ceratobranchial centralization; and birds with the simplicity, weak integration, and modularity of the hyolarynx, laryngeal integration with cricoid centrality, and tongue-module expansion with the acquisition of paraglossal. Four hyolaryngeal bones (ceratobranchial, basihyal, paraglossal, and cricoid) have played important roles in archosaur evolution, and their fossil records are keys to understanding the two major archosaur lineages toward crocodilians and birds.

Simplicity: Web-Based Visualization and Analysis of High-Throughput Cancer Cell Line Screens.

High-throughput drug screens are a powerful tool for cancer drug development. However, the results of such screens are often made available only as raw data, which is intractable for researchers without informatics skills, or as highly processed summary statistics, which can lack essential information for translating screening results into clinically meaningful discoveries. To improve the usability of these datasets, we developed Simplicity, a robust and user-friendly web interface for visualizing, exploring, and summarizing raw and processed data from high- throughput drug screens. Importantly, Simplicity allows for easy recalculation of summary statistics at user-defined drug concentrations. This allows Simplicity's outputs to be used with methods that rely on statistics being calculated at clinically relevant doses. Simplicity can be freely accessed at https://oncotherapyinformatics.org/simplicity/.

Evolution of the connectivity and indispensability of a transferable gene: the simplicity hypothesis.

BACKGROUND: The number of interactions between a transferable gene or its protein product and genes or gene products native to its microbial host is referred to as connectivity. Such interactions impact the tendency of the gene to be retained by evolution following horizontal gene transfer (HGT) into a microbial population. The complexity hypothesis posits that the protein product of a transferable gene with lower connectivity is more likely to function in a way that is beneficial to a new microbial host compared to the protein product of a transferable gene with higher connectivity. A gene with lower connectivity is consequently more likely to be fixed in any microbial population it enters by HGT. The more recently proposed simplicity hypothesis posits that the connectivity of a transferable gene might increase over time within any single microbial population due to gene-host coevolution, but that differential rates of colonization of microbial populations by HGT in accordance with differences in connectivity might act to counter this and even reduce connectivity over time, comprising an evolutionary trade-off. RESULTS: We present a theoretical model that can be used to predict the conditions under which gene-host coevolution might increase or decrease the connectivity of a transferable gene over time. We show that the opportunity to enter new microbial populations by HGT can cause the connectivity of a transferable gene to evolve toward lower values, particularly in an environment that is unstable with respect to the function of the gene's protein product. We also show that a lack of such opportunity in a stable environment can cause the connectivity of a transferable gene to evolve toward higher values. CONCLUSION: Our theoretical model suggests that the connectivity of a transferable gene can change over time toward higher values corresponding to a more sessile state of lower transferability or lower values corresponding to a more itinerant state of higher transferability, depending on the ecological milieu in which the gene exists. We note, however, that a better understanding of gene-host coevolutionary dynamics in natural microbial systems is required before any further conclusions about the veracity of the simplicity hypothesis can be drawn.

Integrin α3 negative podocytes: A gene expression study.

Integrin α3ß1 is a cell adhesion receptor widely expressed in epithelial cells. Pathogenic variants in the gene encoding the integrin α3 subunit ITGA3 lead to a syndrome including interstitial lung disease, nephrotic syndrome, and epidermolysis bullosa (ILNEB). Renal involvement mainly consists of glomerular disease caused by loss of adhesion between podocytes and the glomerular basement membrane. The aim of this study was to characterize the impact of loss of integrin α3 on human podocytes. ITGA3 was stably knocked-out in the human podocyte cell line AB8/13, designated as PodoA3-, and in human proximal tubule epithelial cell line HK2 using the targeted genome editing technique CRISPR/Cas9. Cell clones were characterized by Sanger sequencing, quantitative PCR, Western Blot and immunofluorescence staining. RNASeq of integrin α3 negative cells and controls was performed to identify differential gene expression patterns. Differentiated PodoA3- did not substantially change morphology and adhesion under standard culture conditions, but displayed significantly reduced spreading and adhesion when seed on laminin 511 in serum free medium. Gene expression studies demonstrated a distinct dysregulation of the adhesion network with downregulation of most integrin α3 interaction partners. In agreement with this, biological processes such as "extracellular matrix organization" and "cell differentiation" as well as KEGG pathways such as "ECM-receptor interaction", "focal adhesion" and the "PI3K-Akt signaling pathway" were significantly downregulated in human podocytes lacking the integrin α3 subunit.