Complex Hypothesis Research Articles

Memory Storage in Distributed Engram Cell Ensembles.

One of the most fascinating aspects of the brain is its ability to acquire new information from experience and retain it over time as memory. The search for physical correlates of memory, the memory engram, has been a longstanding priority in modern neurobiology. Advanced genetic approaches have led to the localization of engram cells in a few brain regions, including the hippocampus and cortex. Additionally, engram cells exhibit learning-induced, persistent modifications and have at least two states, active and silent. However, it has been hypothesized that engrams for a specific memory are distributed among multiple brain regions that are functionally connected, referred to as a unified engram complex. Recent tissue-clearing techniques have permitted high-throughput analyses of intact brain samples, which have been used to obtain a map of the engram complex for a contextual fear memory. Careful examination of these engram complex maps has revealed a potentially underappreciated contribution of subcortical regions, specifically thalamic nuclei, to memory function. These more holistic studies support the unified engram complex hypothesis for memory storage and have important implications for understanding dysfunctional engrams in the context of human disease.

Bayesian kinetic modeling for tracer-based metabolomic data

BackgroundStable Isotope Resolved Metabolomics (SIRM) is a new biological approach that uses stable isotope tracers such as uniformly 13C\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{13}C$$\\end{document}-enriched glucose (13C6\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{13}C_6$$\\end{document}-Glc) to trace metabolic pathways or networks at the atomic level in complex biological systems. Non-steady-state kinetic modeling based on SIRM data uses sets of simultaneous ordinary differential equations (ODEs) to quantitatively characterize the dynamic behavior of metabolic networks. It has been increasingly used to understand the regulation of normal metabolism and dysregulation in the development of diseases. However, fitting a kinetic model is challenging because there are usually multiple sets of parameter values that fit the data equally well, especially for large-scale kinetic models. In addition, there is a lack of statistically rigorous methods to compare kinetic model parameters between different experimental groups.ResultsWe propose a new Bayesian statistical framework to enhance parameter estimation and hypothesis testing for non-steady-state kinetic modeling of SIRM data. For estimating kinetic model parameters, we leverage the prior distribution not only to allow incorporation of experts’ knowledge but also to provide robust parameter estimation. We also introduce a shrinkage approach for borrowing information across the ensemble of metabolites to stably estimate the variance of an individual isotopomer. In addition, we use a component-wise adaptive Metropolis algorithm with delayed rejection to perform efficient Monte Carlo sampling of the posterior distribution over high-dimensional parameter space. For comparing kinetic model parameters between experimental groups, we propose a new reparameterization method that converts the complex hypothesis testing problem into a more tractable parameter estimation problem. We also propose an inference procedure based on credible interval and credible value. Our method is freely available for academic use at https://github.com/xuzhang0131/MCMCFlux.ConclusionsOur new Bayesian framework provides robust estimation of kinetic model parameters and enables rigorous comparison of model parameters between experimental groups. Simulation studies and application to a lung cancer study demonstrate that our framework performs well for non-steady-state kinetic modeling of SIRM data.

Oceanic Core Complex or not? When bathymetric structures challenge seafloor spreading models

We use regional magnetic and local multibeam bathymetric data to investigate the geological nature of a prominent high located off-axis near the junction between the Mohns and the Knipovich ridges, in the Norwegian-Greenland Sea. Given the location of this hill, near the bend marking the junction between these two ultraslow spreading centers and the bathymetric asymmetry on both sides of the ridge, an Oceanic Core Complex, corresponding to the outcropping part of an underlying detachment, was proposed as a possible interpretation. Nevertheless, the magnetization distribution over this hill is compatible with a basaltic environment and magnetic gradients are also identical to those existing in basaltic contexts, pointing towards a similar geology. Finally, a combined plate and magnetic reconstruction reveals that this hill has a conjugate structure and that regional magnetic anomalies are symmetric. These observations rule out the Oceanic Core Complex hypothesis, as detachment surfaces are often associated with a marked spreading asymmetry. We therefore propose that this protruding bathymetric feature should rather be seen as a basaltic hill and the depth asymmetry likely results from seafloor subsidence triggered by the massive accumulation of sediments from the Bear Island Fan, on the eastern flank of the ridge axis.

High-throughput sequencing application in the detection and discovery of viruses associated with the regulated citrus leprosis disease complex.

Citrus leprosis (CiL) is one of the destructive emerging viral diseases of citrus in the Americas. Leprosis syndrome is associated with two taxonomically distinct groups of Brevipalpus-transmitted viruses (BTVs), that consist of positive-sense Cilevirus, Higrevirus, and negative-sense Dichorhavirus. The localized CiL symptoms observed in multiple citrus species and other alternate hosts indicates that these viruses might have originated from the mites and eventually adopted citrus as a secondary host. Genetic diversity in the genomes of viruses associated with the CiL disease complex have complicated current detection and diagnostic measures that prompted the application of High-Throughput Sequencing (HTS) protocols for improved detection and diagnosis. Two cileviruses are known to infect citrus, and among them only citrus leprosis virus C2 (CiLV-C2) hibiscus strain (CiLV-C2H) has been reported in hibiscus and passion fruit in the US. Based on our current CiL disease complex hypothesis, there is a high probability that CiL disease is associated with more viruses/strains that have not yet been identified but exist in nature. To protect the citrus industry, a Ribo-Zero HTS protocol was utilized for detection of cileviruses infecting three different hosts: Citrus spp., Swinglea glutinosa, and Hibiscus rosa-sinensis. Real-time RT-PCR assays were used to identify plants infected with CiLV-C2 or CiLV-C2H or both in mixed infection in all the above-mentioned plant genera. These results were further confirmed by bioinformatic analysis using HTS generated data. In this study, we utilized HTS assay in confirmatory diagnostics to screen BTVs infecting Dieffenbachia sp. (family: Araceae), Passiflora edulis (Passifloraceae), and Smilax auriculata (Smilacaceae). Through the implementation of HTS and downstream data analysis, we detected not only the known cileviruses in the studied hosts but also discovered a new strain of CiLV-C2 in hibiscus from Colombia. Phylogenetically, the new hibiscus strain is more closely related to CiLV-C2 than the known hibiscus strain, CiLV-C2H. We propose this strain to be named as CiLV-C2 hibiscus strain 2 (CiLV-C2H2). The findings from the study are critical for citrus growers, industry, regulators, and researchers. The possible movement of CiLV-C2H2 from hibiscus to citrus by the Brevipalpus spp. warrants further investigation.

Pandemic and prejudice: Revisiting Bogardus’s social distance concept in a time of COVID-19

This study examined when the realistic threat of COVID-19 leads to prejudicial social distancing. American participants reported social distancing preferences from Chinese or Italian people (out-group target) after viewing increasing or decreasing COVID-19 case numbers (threat level) in China or Italy (threat relevance). On the Bogardus Social Distance Scale, there was support for a disease avoidance hypothesis: greater social distancing preferences were expressed under higher than under lower relevant threats. Responses on a bespoke COVID-19 Social Distance Scale, however, supported an a priori prejudice hypothesis: greater social distancing preferences were expressed toward a Chinese than toward an Italian out-group. Moreover, responses on a separate bespoke Modern Social Distance Scale supported a complex prejudice hypothesis: greater social distancing preferences were expressed toward Chinese than toward Italian out-groups under higher than under lower threat, regardless of threat relevance. These findings suggest that the threat of COVID-19 may enable prejudice expression accompanied by the rationale of disease avoidance.

Exploring the fractional Hirota Maccari system for its soliton solutions via impressive analytical strategies

In the field of marine engineering, the characteristics of wave propagation play an imperative character. In many geographical regions, the key source of environmental effects on artificial floating or stationary structures or seashores is waves. This article deals with the Hirota Maccari system (HMs) via a new fractional derivative operator known as the beta derivative. This aforesaid equation is a significant model which deals with a variety of nonlinear phenomenons in the fields of optical fibers, physics and other scientific fields. A complex wave hypothesis is applied to transform the aforesaid system with beta derivative into an ODE system. The modified Kudryashov’s (New version) and the Auxiliary equation methods are used to build a variety of soliton solutions of HMs with beta derivative. The singular, periodic, bright, dark solitons and mixed solitons are constructed with the above-mentioned approaches via soft computation in Mathematica. Some of them are numerically simulated for 2D and 3D representation. All the solutions of fractional HMs produced by the above two techniques are novel and have not been derived yet.

A Multidisciplinary Hypothesis about Serotonergic Psychedelics. Is it Possible that a Portion of Brain Serotonin Comes From the Gut?

Here we present a complex hypothesis about the psychosomatic mechanism of serotonergic psychedelics. Serotonergic psychedelics affect gut microbes that produce a temporary increase of 5-HT by their host enterochromaffin cells (ECs). This increased 5-HT production-which is taken up and distributed by platelets-may work as a hormone-like regulatory signal that could influence membrane permeability in the host organs and tissues and in the brain. Increased plasma 5-HT levels could enhance permeability of the blood-brain barrier (BBB). Transiently increased permeability of the BBB allows for plasma 5-HT to enter the central nervous system (CNS) and be distributed by the volume transmission. Next, this gut-derived 5-HT could modulate excitatory and inhibitory neurotransmission and produce special network disintegration in the CNS. This transient perturbation of the normal neural hierarchy allows patients access to suppressed fear information and perform an emotional reset, in which the amygdale may have a key role.

Непараметрические критерии согласия при проверке нормальности в условиях округления измерений

When analyzing measurement series in various applications, the verification of whether measurement errors belong to the normal law is considered as a mandatory procedure. For this purpose, various special tests for testing hypotheses about normality can be used; non-parametric tests of goodness or chi-square tests can be used. When using nonparametric goodness-of-fit tests to test normality, it must be taken into account that a complex hypothesis is being tested. When testing a complex hypothesis, the distributions of the statistics of the goodness-of-fit tests differ significantly from the classical ones that occur when testing simple hypotheses. It is known that the presence of rounding errors can significantly change the distribution of test statistics. In such situations, ignoring the fact of influence can lead to incorrect conclusions about the results of the normality test. In metrology, when carrying out high-precision measurements, as a rule, scientists do not even allow thoughts about the possible influence of D rounding errors on the results of statistical analysis. This allows the possibility of incorrect conclusions since there is no influence not only at small D, but at values of D much less than the standard deviation s of the measurement error distribution law and sample sizes n not exceeding some maximum values. For sample sizes larger than these maximum values, the real distributions of the test statistics deviate from the asymptotic ones towards larger statistics values. In this work, based on real and well-known data, using statistical modeling methods, we demonstrate the dependence of the distributions of statistics of nonparametric goodness-of-fit tests when testing normality on the ratio of D and s for specific n. The possibility of correct application of the tests under the influence of rounding errors on the conclusions is shown and implemented.

Do prepubertal hormones, 2D:4D index and psychosocial context jointly explain 11-year-old preadolescents’ involvement in bullying?

BackgroundBullying is a type of aggressive behavior that occurs repeatedly and intentionally in school environments and where there is a power imbalance. The main objective of this study was to analyze the association that hormones and the psychosocial context jointly have with bullying behavior. MethodParticipants were 302 11-year-old preadolescents from the Gipuzkoan cohort of the INMA Project. Bullying was assessed using the Olweus Bully/victim Questionnaire. Prenatal sexual hormones were assessed by calculating 2D:4D ratio and in order to measure prepubertal testosterone and cortisol levels saliva samples were collected within a week of each other. Additionally, various psychosocial factors were evaluated: executive function, family context, school environment and social context. To analyze our complex hypothesis, six metamodels were tested using structural equation modeling. ResultsIn relation to victims, results showed that victimization was related to worse school environment’ perception in boys, and higher stress and conflict in the family in girls. In the case of their involvement in bullying as a bully, lower salivary cortisol levels, worse school environment’ perception and lower peers and social support was related to being more frequently involved as a bully in boys, while having more family stress and conflict was related with being a bully in girls. ConclusionsThis approach makes it possible not only to explore the different biological and psychosocial factors affect bullying behavior, but also to explore associations between the predictor variables.

Severe Acute Hepatitis in Children: An Analysis from Philosophy of Science Using the Concept of Reduction

The present paper uses Carnap’s reduction concept to address the problem of new severe acute hepatitis in children. First, it tries to show how that concept can help understand why some previous hypotheses of causality on the new hepatitis in children should be rejected. Second, Carnap’s reduction concept is used to explain a complex hypothesis about the causes of that disease proposed in The Lancet in 2022. The latter hypothesis combines several factors: infection by SARS-CoV-2, a build-up of this virus in the bowel that comes in contact with blood circulation, and another infection by adenovirus. One of the points of the paper is to argue that a hypothesis can be described by means of a bilateral reduction sentence, which in turn would allow empirical comparison of the hypothesis in an easy way. Finally, the author considers a current cognitive framework, namely, the theory of mental models, to propose that bilateral reduction sentences should not be hard to handle for physicians or scientists.

Combining multiple fluorescence imaging techniques in biology: when one microscope is not enough.

While fluorescence microscopy has proven to be an exceedingly useful tool in bioscience, it is difficult to offer simultaneous high resolution, fast speed, large volume, and good biocompatibility in a single imaging technique. Thus, when determining the image data required to quantitatively test a complex biological hypothesis, it often becomes evident that multiple imaging techniques are necessary. Recent years have seen an explosion in development of novel fluorescence microscopy techniques, each of which features a unique suite of capabilities. In this Technical Perspective, we highlight recent studies to illustrate the benefits, and often the necessity, of combining multiple fluorescence microscopy modalities. We provide guidance in choosing optimal technique combinations to effectively address a biological question. Ultimately, we aim to promote a more well-rounded approach in designing fluorescence microscopy experiments, leading to more robust quantitative insight.

Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions

Neuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, or cortex. However, it has been hypothesized that engrams of a specific memory are distributed among multiple brain regions that are functionally connected, referred to as a unified engram complex. Here, we report a partial map of the engram complex for contextual fear conditioning memory by characterizing encoding activated neuronal ensembles in 247 regions using tissue phenotyping in mice. The mapping was aided by an engram index, which identified 117 cFos+ brain regions holding engrams with high probability, and brain-wide reactivation of these neuronal ensembles by recall. Optogenetic manipulation experiments revealed engram ensembles, many of which were functionally connected to hippocampal or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engram ensembles conferred a greater level of memory recall than reactivation of a single engram ensemble, reflecting the natural memory recall process. Overall, our study supports the unified engram complex hypothesis for memory storage.

Genetic and morphological polymorphisms of Aedes scapularis (Diptera: Culicidae), vector of filariae and arboviruses.

Aedes scapularis is a neotropical mosquito that is competent to vector viruses and filariae. It is reputed to be highly morphologically and genetically polymorphic, facts that have raised questions about whether it is a single taxonomic entity. In the last five decades, authors have posed the hypothesis that it could actually be a species complex under incipient speciation. Due to its epidemiological importance, its taxonomic status should be determined with confidence. Our objective was to investigate more deeply the polymorphism of Ae. scapularis to detect any evidence of incipient speciation of cryptic species. We then compared populational samples from the Southeastern, Northern and Northeastern regions of Brazil. The biological markers used in the comparison were: the complete mitochondrial DNA, the isolated mitochondrial gene cytochrome oxidase subunit I (COI) and wing geometry. As expected, high morphological/genetic polymorphism was observed in all Ae. scapularis populations, however it was not indicative of segregation or incipient speciation. There was no correlation between wing shape and the geographical origin of the populations analysed. A congruent observation resulted from the analysis of the COI gene, which revealed a high number of haplotypes (51) and no clusterization of populational samples according to the original biomes. In the phylogenetic analysis of the 13 mitochondrial protein-coding genes, the Ae. scapularis clade clustered with maximum support (100% bootstrap support and posterior probability of 1). No significant internal structure was observed in the Ae. scapularis clade, which was nearly a polytomy. Taken together, our results indicate that this species is not a species complex. We conclude that there was no indication, in the analysed regions, of the occurrence of more than one taxon in the species Ae. scapularis, despite it being highly polymorphic. By ruling out the former species complex hypothesis, our phylogenetic results reinforce that Ae. scapularis is a single taxonomic unit and should be monitored with standardized surveillance and control methods.

Prevention of Kidney and Bladder Failure Following Concomitant Valves Ablation and Bladder Neck Incision in Posterior Urethral Valves: The Bladder Valve Complex Hypothesis

Prevention of Kidney and Bladder Failure Following Concomitant Valves Ablation and Bladder Neck Incision in Posterior Urethral Valves: The Bladder Valve Complex Hypothesis

Distribution-free complex hypothesis testing for single-cell RNA-seq differential expression analysis

Distribution-free complex hypothesis testing for single-cell RNA-seq differential expression analysis

Distribution-free complex hypothesis testing for single-cell RNA-seq differential expression analysis

Distribution-free complex hypothesis testing for single-cell RNA-seq differential expression analysis

The largest hoplophonine and a complex new hypothesis of nimravid evolution

Nimravids were the first carnivorans to evolve saberteeth, but previously portrayed as having a narrow evolutionary trajectory of increasing degrees of sabertooth specialization. Here I present a novel hypothesis about the evolution of this group, including a description of Eusmilus adelos, the largest known hoplophonine, which forces a re-evaluation of not only their relationships, but perceived paleoecology. Using a tip-dated Bayesian analysis with sophisticated evolutionary models, nimravids can now be viewed as following two paths of evolution: one led to numerous early dirk-tooth forms, including E. adelos, while the other converged on living feline morphology, tens of millions of years before its appearance in felids.

Salted mullet: Protracted occurrence of Mugil cephalus under extreme hypersaline conditions

The fish faunas of eight estuaries along 130 km of the south coast of Western Australia were sampled seasonally for one year, during which Beaufort Inlet became markedly hypersaline (salinities up to 122 and > 100 for six months). These conditions were caused by a combination of low amounts of saline river flow, the bar of this shallow estuary remaining closed for 27 months and high rates of evaporation. Fish faunas in the nearshore, shallow and offshore, deeper waters of Beaufort Inlet were depauperate compared to nearby estuaries. The number of fish species declined as salinity increased, with the highly euryhaline, estuarine-resident atherinid Atherinosoma elongata being the only species to survive throughout the study. The cosmopolitan flathead mullet Mugil cephalus survived for the next longest period, living in salinities in excess of 100 for at least four months and in a maximum salinity of 122. This is the highest known salinity in which a marine-spawning fish species has been found globally. This finding provides support for the cryptic species complex hypothesis pertaining to M. cephalus and that individuals in south-western Australia may be a seperate species. The survival of these species for a relatively protracted time reflects the fact that they are euryhaline and have a suite of adaptations that allow them to occupy environments from freshwater to extreme hypersaline conditions. The longer occurrence of M. cephalus in the extreme salinities than Acanthopagrus butcheri and Aldrichetta forsteri, is likely also related to their primary diet of detritus, particulate organic matter and diatoms, all of which are abundant in Beaufort Inlet. In contrast, piscivorous and zoobenthivorous fish were depauperate and in low abundances, which may reflect limited food resources during hypersaline conditions, and/or more reduced euryhalinity by these species. Clearly, hypersalinity has a marked effect on the faunas and thus ecosystem functioning of estuaries, and with declines in rainfall and hotter temperatures projected in future climate change scenarios, more estuaries are likely to become increasingly hypersaline.

Addressing patient heterogeneity in disease predictive model development.

This paper addresses patient heterogeneity associated with prediction problems in biomedical applications. We propose a systematic hypothesis testing approach to determine the existence of patient subgroup structure and the number of subgroups in patient population if subgroups exist. A mixture of generalized linear models is considered to model the relationship between the disease outcome and patient characteristics and clinical factors, including targeted biomarker profiles. We construct a test statistic based on expectation maximization (EM) algorithm and derive its asymptotic distribution under the null hypothesis. An important computational advantage of the test is that the involved parameter estimates under the complex alternative hypothesis can be obtained through a small number of EM iterations, rather than optimizing the objective function. We demonstrate the finite sample performance of the proposed test in terms of type-I error rate and power, using extensive simulation studies. The applicability of the proposed method is illustrated through an application to a multicenter prostate cancerstudy.

Accounting for dissipation of the energy of the supple base

AnnotationWhen calculating the foundations and structures on a compliant basis for the action of dynamic effects, the mathematical model of the base should reflect the real conditions for deformation of the base, due to their lamination, limited by the distribution property, weight and others. This is more, in our opinion, the axisymmetric columnar model of a compliant base is responsible, which takes into account the important properties of the ground base at a dynamic effect, as the extremity of the oscillation distribution zone and its inertia. In this case, the model allows us to determine not only the movement of the boundary plane, but also the stress-strain state of the base. With resonant phenomena, the accounting of energy dissipation during oscillations of the base is essential. The paper discusses the adaptation of the axisymmetric columnar model on a dissipative base, in which the dispersion of energy is carried out according to the complex hypothesis by E.S. Sorokin. The model in question is a cylindrical body in the form of a rod height H and radius R, large enough to believe that the amplitudes of displacements on the cylindrical surface of the rod are zero, when the rod on the outer end is loading within the centrally located circular area with a radius r, much smaller R. The basis, obeying the three-axis linear physical law, is in the conditions of axial symmetry, therefore, only vertical u and radial w movements are observed, which are functions of variables x, r, t. The solution of the dynamic Liame equations described by the deformation of the cylindrical body was carried out by the discrete method of L.V. Vinokurov, according to which the solution was found in an analytical form in the variable x, and in the variable r - in the finite-difference. The use of a method of separation of variables by Fourier, a system of discrete differential equations in private derivatives was reduced to a system of differential equations in ordinary derivatives, the integration of which was carried out using Euler substitutions. Permanent integration was determined from the boundary conditions at the end of the cylindrical rod. The solutions obtained show that energy dissipation accounting causes a phase shift between the perturbing load and the movement of the base and to a significant decrease in the amplitudes of oscillations in the resonance zone.