Generation and timing of graded responses to morphogen gradients

Morphogen gradients are known to subdivide a naïve cell field into distinct zones of gene expression. Here we examine whether morphogens can also induce a graded response within such domains. To this end we explore the role of the Dorsal protein nuclear gradient along the dorso-ventral axis in defining the graded pattern of actomyosin constriction that initiates gastrulation in early Drosophila embryos. Two complementary mechanisms for graded accumulation of mRNAs of critical zygotic target genes were identified. First, activation of target-gene expression expands over time from the ventral-most region of high nuclear Dorsal to lateral regions where the levels are lower, due to a Dorsal-dependent priming probability of transcription sites. Thus, sites that are activated earlier will lead to more mRNA accumulation. Second, once the sites are primed, the rate of Pol II loading is also dependent on Dorsal levels. Morphological restrictions require that translation of the graded mRNA be delayed until completion of embryonic cell formation. Such timing is achieved by large introns, that provide a delay in production of the mature mRNAs.

A RANDOMIZED CONTROLLED TRIAL ON THE EFFICACY OF VACHADI CHOORNA IN SPEECH IMPAIRMENT IN CHILDREN UP TO 12 YEARS

Speech Impairment is the most common impairments presenting in early childhood (8-9%). It can make the children difficult to communicate with other people and often affects a childs quality of life. Objective: The aim of the study was to assess the efficacy of Vachadi Choorna in speech impairment in children up to 12 years. Experimental approach: The study was carried out as a Randomized Controlled Trial, with speech therapy as a control of which efficacy has been proved by earlier studies. Children with speech impairment satisfying the inclusion criteria were included in the study. The subjects were randomly distributed into the study and control groups using simple random sampling. Children in the study group received Vachadi Choorna in two divided doses for internal administration for 45 days while control group received speech therapy as per schedule fixed by Speech-Language pathologist for 45 days. Findings: The graded responses in both groups were assessed after the treatment and after follow up, clinically and also by using a scale based on Stuttering Severity Instrument for stuttering and Malayalam Articulation Test for Articulation. Discussion: Analysis of the data using the most appropriate statistical test showed that the trial drug and the speech therapy were effective in improving speech (p<0.001). Conclusion: The effect of the trial drug in improving speech was significantly greater than that of control group (p<0.05). Thus the efficacy of the drug combination applied in the trial group and its superiority over the control therapy was proved.

A Multidimensional Item Response Theory Model for Continuous and Graded Responses With Error in Persons and Items

Item response theory “dual” models (DMs) in which both items and individuals are viewed as sources of differential measurement error so far have been proposed only for unidimensional measures. This article proposes two multidimensional extensions of existing DMs: the M-DTCRM (dual Thurstonian continuous response model), intended for (approximately) continuous responses, and the M-DTGRM (dual Thurstonian graded response model), intended for ordered-categorical responses (including binary). A rationale for the extension to the multiple-content-dimensions case, which is based on the concept of the multidimensional location index, is first proposed and discussed. Then, the models are described using both the factor-analytic and the item response theory parameterizations. Procedures for (a) calibrating the items, (b) scoring individuals, (c) assessing model appropriateness, and (d) assessing measurement precision are finally discussed. The simulation results suggest that the proposal is quite feasible, and an illustrative example based on personality data is also provided. The proposals are submitted to be of particular interest for the case of multidimensional questionnaires in which the number of items per scale would not be enough for arriving at stable estimates if the existing unidimensional DMs were fitted on a separate-scale basis.

High Density Intramural Mapping of Post-Infarct Premature Ventricular Contractions.

Background: Spontaneous ventricular premature contractions (PVCs) in the post infarct milieu is assumed to be due to automaticity. However, the mechanism has not been studied with appropriate mapping tools. Objective: To study the mechanism of spontaneous PVCs with high density intramural mapping in a canine model, to test the hypothesis that post-infarct PVCs are due to re-entry rather than automaticity. Methods: In 15 anesthetized dogs, using 768 intramural unipolar electrograms, simultaneous recordings were made. After 30 mins of stabilization, recordings were made during the first 10 minutes of ischemia, and activation maps were constructed of individual beats. Acute ischemia was produced by clamping the left anterior descending coronary artery proximal to the first diagonal branch. The analysis was limited to the activation pattern of spontaneous ventricular beats. Results: In all experiments ST-T alternans occurred. In 8 of 15 dogs spontaneous ventricular beats occurred. In all 8 of these experiment earliest, ectopic activity occurred in the endocardium, well within the ischemic zone. From there, activity spread rapidly along the subendocardium, with endo-to epicardial spread along the non ischemic myocardium. Epicardial breakthrough always occurred at the border of the ischemic myocardium. In 3 dogs, delayed potentials were observed, which were earliest at the ischemic epicardium and extended transmurally with increasing delay towards the endocardium, where they culminated in a premature beat. Conclusion: Graded responses that occur with each sinus beat intramurally, when able to propagate from epicardium to endocardium is the mechanism by which PVCs are generated in post-infarct myocardium.

Ecdysone coordinates plastic growth with robust pattern in the developing wing

Animals develop in unpredictable, changing environments. To do this, they adjust their development according to environmental conditions to generate plastic variation in traits, while also buffering against environmental change to produce robust phenotypes. However, how organ development is coordinated to accommodate both plastic and robust developmental responses is poorly understood. Here, we propose that the steroid hormone ecdysone coordinates both plasticity in organ size and robustness of organ pattern in the developing wings of the fruit fly Drosophila melanogaster. Ablating the prothoracic glands (PGX), which synthesise and secrete ecdysone, resulted in wing discs that were reduced in size and delayed in the progression of Achaete and Senseless pattern. These effects were rescued by adding ecdysone to the food. Further, while wing growth was driven by both ecdysone and nutrition, ecdysone alone induced the progression of wing patterning. To further explore this difference in response, we quantified wing growth and patterning in PGX larvae that were either fed on standard diet or starved of yeast across a range of ecdysone concentrations. Disc growth rates increased in a graded, linear manner with ecdysone concentration in starved larvae. In contrast, Achaete and Senseless patterning rates showed threshold responses regardless of diet. This means that ecdysone confers robustness by turning on patterning once it exceeds threshold concentrations, while inducing graded responses for disc growth, tuning growth to environmental conditions. This potentially represents a generalizable mechanism through which hormones coordinate plastic growth with robust patterning in the face of environmental change.Significance StatementTo survive changes in their environment, organisms adjust processes like growth to match the environment while ensuring that development processes necessary for correct body function remain insensitive to perturbation. For instance, organ size changes with environmental conditions like food availability and temperature. However, the specification of cell types within an organ, known as patterning, remains constant. How do animals coordinate variable and invariant developmental programs within the same organ? In this study, we define how a single hormone, the steroid hormone ecdysone, controls both variable growth and constant patterning in the developing wing. This is important, as it reveals a key pathway that allows insects to cope with environmental change and also highlights potential limits to surviving these changes.

A multidimensional IRT model for continuous and graded responses with error in persons and items

This article proposes two multidimensional extensions of existing DMs: the M-DTCRM, intended for (approximately) continuous responses, and the M-DTGRM, intended for ordered-categorical responses (including binary). A rationale for the extension to the multiple-content-dimensions case, which is based on the concept of the multidimensional location index, is first proposed and discussed. Then, the models are described using both the factor-analytic and the IRT parameterizations. Procedures for (a) calibrating the items, (b) scoring individuals, (c) assessing model appropriateness, and (d) assessing measurement precision are finally discussed. The proposals are submitted to be of particular interest for the case of multidimensional questionnaires in which the number of items per scale would not be enough for arriving at stable estimates.

A multidimensional IRT model for continuous and graded responses with error in persons and items

This article proposes two multidimensional extensions of existing DMs: the M-DTCRM, intended for (approximately) continuous responses, and the M-DTGRM, intended for ordered-categorical responses (including binary). A rationale for the extension to the multiple-content-dimensions case, which is based on the concept of the multidimensional location index, is first proposed and discussed. Then, the models are described using both the factor-analytic and the IRT parameterizations. Procedures for (a) calibrating the items, (b) scoring individuals, (c) assessing model appropriateness, and (d) assessing measurement precision are finally discussed. The proposals are submitted to be of particular interest for the case of multidimensional questionnaires in which the number of items per scale would not be enough for arriving at stable estimates.

Bacterial quorum sensing allows graded responses to variations in density, on both individual and population scales

ABSTRACTQuorum sensing (QS) is a mechanism of cell-to-cell communication via diffusible signal molecules that controls multiple secreted factors including virulence factors in bacterial pathogens [1,2]. While the standard view is that QS functions as a density-sensing mechanism, the functional and evolutionary context of QS continues to be disputed [3–11]. A critical step in assessing the various adaptive hypotheses is establishing the functional capacities and limits of QS. Current functional studies largely focus on a dichotomy of QS on/off (or, quorate / sub-quorate) states, despite the increasing amount of heterogeneity on a cellular scale [4,12–16], overlooking the potential for intermediate, graded responses. In this paper we explore the functional capacity of QS to resolve finely graded environmental densities and introduce the use of reaction norms as a way to holistically characterize QS response. Here we show that Pseudomonas aeruginosa can deliver a graded response to variation in environmental population density on both the population and individual scales. We further resolve the linear population response to be the product of two component cellular reaction norms: the likelihood of being responsive and the intensity of response. Overall, this work reveals that there is no critical cell mass or ‘quorum’, at which QS is activated on either the individual cell or population scale.

ESTIMASI PARAMETER TES DENGAN PENSKORAN POLITOMUS MENGGUNAKAN GRADED RESPONSE MODEL PADA SAMPEL KECIL

Multiple choice tests with dichotomous scores are very often used by educators because it is easy to apply. Unfortunately, this scoring lacks an opportunity for educators to diagnose students' mistakes. This study aimed to analyze the items test using graded responses model (GRM). The data in this study was the response of the economics test that have been tested to 96 first-year students of economic education. The test form was multiple choice item using politomous scoring with ordinal scale 1-2-3-4-5. Test scoring use polytomous scores. Data was analyzed with descriptive quantitative techniques using PARSCALE application. The results showed that there are 50% items test that fit with the GRM model. Furthremore, the application of GRM model in this study seems less suitable because only 20% that have good quality. Big sample size is recommended when using the GRM model to obtain accurate estimation.

Response threshold variance as a basis of collective rationality

Determining the optimal choice among multiple options is necessary in various situations, and the collective rationality of groups has recently become a major topic of interest. Social insects are thought to make such optimal choices by collecting individuals' responses relating to an option's value (=a quality-graded response). However, this behaviour cannot explain the collective rationality of brains because neurons can make only ‘yes/no’ responses on the basis of the response threshold. Here, we elucidate the basic mechanism underlying the collective rationality of such simple units and show that an ant species uses this mechanism. A larger number of units respond ‘yes’ to the best option available to a collective decision-maker using only the yes/no mechanism; thus, the best option is always selected by majority decision. Colonies of the ant Myrmica kotokui preferred the better option in a binary choice experiment. The preference of a colony was demonstrated by the workers, which exhibited variable thresholds between two options' qualities. Our results demonstrate how a collective decision-maker comprising simple yes/no judgement units achieves collective rationality without using quality-graded responses. This mechanism has broad applicability to collective decision-making in brain neurons, swarm robotics and human societies.