Miracle-dz/UniFAR-FTUs huggingface dataset:
Evolutionary history of tuberculosis shaped by conserved mutations in the PhoPR virulence regulator

Significance In 1901, when Robert Koch proposed that the bacilli causing human and bovine tuberculosis were not identical, this view caused much controversy. Now, 113 y later, we know that the bovine tuberculosis agent, Mycobacterium bovis, together with other animal strains, forms a separate phylogenetic lineage apart from the human Mycobacterium tuberculosis lineages, but the molecular reasons why bovine and animal strains only play minor roles in human tuberculosis epidemiology remain unknown. Herein, we show by genetic transfer and virulence experiments that specific mutations in a virulence regulator contribute to lower fitness and virulence of M. bovis and related strains for the human host, likely obstructing the capacity of causing overt disease needed for efficient human-to-human transmission. Although the bovine tuberculosis (TB) agent, Mycobacterium bovis, may infect humans and cause disease, long-term epidemiological data indicate that humans represent a spill-over host in which infection with M. bovis is not self-maintaining. Indeed, human-to-human transmission of M. bovis strains and other members of the animal lineage of the tubercle bacilli is very rare. Here, we report on three mutations affecting the two-component virulence regulation system PhoP/PhoR (PhoPR) in M. bovis and in the closely linked Mycobacterium africanum lineage 6 (L6) that likely account for this discrepancy. Genetic transfer of these mutations into the human TB agent, Mycobacterium tuberculosis, resulted in down-regulation of the PhoP regulon, with loss of biologically active lipids, reduced secretion of the 6-kDa early antigenic target (ESAT-6), and lower virulence. Remarkably, the deleterious effects of the phoPR mutations were partly compensated by a deletion, specific to the animal-adapted and M. africanum L6 lineages, that restores ESAT-6 secretion by a PhoPR-independent mechanism. Similarly, we also observed that insertion of an IS6110 element upstream of the phoPR locus may completely revert the phoPR-bovis–associated fitness loss, which is the case for an exceptional M. bovis human outbreak strain from Spain. Our findings ultimately explain the long-term epidemiological data, suggesting that M. bovis and related phoPR-mutated strains pose a lower risk for progression to overt human TB, with major impact on the evolutionary history of TB.
Preference of RIG-I for short viral RNA molecules in infected cells revealed by next-generation sequencing

Intracellular detection of virus infections is a critical component of innate immunity carried out by molecules known as pathogen recognition receptors (PRRs). Activation of PRRs by their respective pathogen-associated molecular patterns (PAMPs) leads to production of proinflamatory cytokines, including type I IFN, and the establishment of an antiviral state in the host. Out of all PRRs found to date, retinoic acid inducible gene I (RIG-I) has been shown to play a key role in recognition of RNA viruses. On the basis of in vitro and transfection studies, 5′ppp RNA produced during virus replication is thought to bind and activate this important sensor. However, the nature of RNA molecules that interact with endogenous RIG-I during the course of viral infection has not been determined. In this work we use next-generation RNA sequencing to show that RIG-I preferentially associates with shorter, 5′ppp containing viral RNA molecules in infected cells. We found that during Sendai infection RIG-I specifically bound the genome of the defective interfering (DI) particle and did not bind the full-length virus genome or any other viral RNAs. In influenza-infected cells RIG-I preferentially associated with shorter genomic segments as well as subgenomic DI particles. Our analysis for the first time identifies RIG-I PAMPs under natural infection conditions and implies that full-length genomes of single segmented RNA virus families are not bound by RIG-I during infection.
Genetic differentiation and relationships of populations in the Cycas balansae complex (Cycadaceae) and its conservation implications.

BACKGROUND AND AIMS The Cycas balansae complex is arguably a controversial group with regard to species delineation. Some taxonomists recognize a single polymorphic species while others distinguish five narrowly defined ones. The unresolved taxonomy has the potential to bring about significant problems for species conservation. Thus, an investigation to examine the genetic diversity and differentiation in the C. balansae complex was performed to determine the relationship of populations and to test whether the morphologically defined segregations represent genetically distinct units. METHODS Inter-simple sequence repeat (ISSR) markers were employed to assess the genetic diversity in the C. balansae complex with a sample of 158 individuals from all extant populations in China. KEY RESULTS ISSR markers revealed low genetic diversity in all populations studied (H(E) and H(O) averaged 0.0639 and 0.0798 at the population level, respectively). Phenetic analysis showed that the C. balansae complex grouped into five clusters closely corresponding to the narrowly defined C. balansae, C. parvula, C. shiwandashanica, C. tanqingii and C. simplicipinna. CONCLUSIONS ISSR data suggest that the C. balansae complex has evolved into five genetically distinct units. These might be derived from a relatively widespread common ancestor through multiple vicariant events including geographical isolation resulting from the collision of the Indian plate with the Eurasian plate and from Pleistocene glaciations. In conservation, attention should be paid to each genetic unit.
Modelling gold futures: should the level of speculation inform our choice of variables?

ABSTRACT Prior literature provides conflicting evidence about the impact of speculation on gold futures returns, volatility, and the relationship between market fundamentals and prices. In this paper, we exploit trade volume information to determine the most appropriate family of factors to adopt when modelling gold futures. Using the Disaggregated Commitment of Traders report, we find that extreme levels of speculation are informative in that they signify a shift in the relative modelling accuracy of macroeconomic and latent factors. A simple composite prediction framework, incorporating the changing level of speculation, empirically demonstrates the uncovered phenomenon and offers improved predictive accuracy for gold futures prices. Furthermore, our findings are shown to be robust to alternative latent and macroeconomic model specifications.
Effects of Alcoholic Beverage Prices and Legal Drinking Ages on Youth Alcohol Use

Based on an analysis of the second National Health and Nutrition Examination Survey, conducted between 1976 and 1980, we find that the frequency of the consumption of beer, the most popular alcoholic beverage among youths, is inversely related to the real price of beer and to the minimum legal age for its purchase and consumption. The negative price and legal drinking age effects are by no means limited to reductions in the fraction of youths who consume beer infrequently (less than once a week). Instead, the fractions of youths who consume beer fairly frequently (1-3times a week) and frequently (4-7 times a week) fall more in absolute or percentage terms than the fraction of infrequent drinkers when price or the drinking age rises. These are striking findings because frequent and fairly frequent drinkers are likely to be responsible for a large percentage of youth motor vehicle accidents and deaths. Simulations suggest that, if reductions in youth alcohol use and abuse are desired, both a uniform drinking age of 21 and an increase in the Federal excise tax rate on beer are effective policies to accomplish this goal. They also suggest that the tax policy may be more potent than the drinking age policy. (This abstract was borrowed from another version of this item.)
Control design of client using mixed sensitivity problem for multilateral teleoperation system

This paper considers a control design of client side using mixed sensitivity problem for multilateral teleoperation system. For multilateral teleoperation system, only the client side is considered. The 1-DOF (degree of freedom) paddle system as a client side is used. The paddle system is modeled as linear system, the mixed sensitivity problem is applied. The weighting functions are designed to satisfy the control specification. The stability and control performance are verified by simulations and experiments. It can be shown that the position error between client side and teleoperator converges to zero, the teleoperation system is stable for time delays.
Volatile components of lemur scent secretions vary throughout the year

Olfactory signals can communicate a wide variety of information and are very important in many mammalian species. However, little is known about the olfactory communication of primates. This study used gas chromatography to examine the volatile components of the anogenital gland secretions of wild Milne‐Edward's sifaka, Propithecus edwardsi (Primates, Indriidae) (n = 17), captured in Ranomafana National Park, Madagascar. We compared scent swabs of animals and examined differences between social group, age class, sex, and season. The only identified differences in the volatiles were between swabs from the different seasons; all other categories were statistically indistinguishable. Am. J. Primatol. 68:1202–1207, 2006. © 2006 Wiley‐Liss, Inc.
On the Interaction of Growth, Trade and International Macroeconomics

Standard economic theories have severe difficulties in simultaneously explaining a number of key aggregate empirical facts: i) there are substantial differences in capital-labor ratios across time ii) despite continuously increasing capital-labor ratios, both factors still earn non-negligible shares in income iii) labor hours per capita are rather stable amid expanding consumption possibilities iv) price levels are higher in more developed countries v) there are no large gains from factor-proportions trade vi) the world trade-to-output ratio increases over time. I argue that standard economic theories ignore the vast improvements in goods quality and new products. I present an augmented standard model that incorporates these features and jointly rationalizes these six empirical facts.
Use of Citations within Manuscripts Published by the Journal of Agricultural Education.

Because publications serve as the institutional memory of a discipline, researchers have the responsibility of becoming familiar with and acknowledging previous literature. The use of citations in manuscripts is considered ethical best practice, and is a method of manuscript evaluation. In agricultural education, researchers have recommended that an evaluation of manuscript citations be conducted every ten years in order to ensure the integrity of the profession’s research repository. This study served as a descriptive evaluation of the use of citations in the Journal of Agricultural Education from 2003 to 2012. Findings indicated that the average number of citations used, the number of citations to support the conceptual framework, the number of citations from within and outside the profession, and the number of citations used to support findings increased over the 10-year time span.
Inspection Method for the Identification of TBT-containing Antifouling Paints

In order to ensure the effectiveness of the international convention which will prohibit the use of organotin compounds in antifouling paints applied to ships, it is essential to establish an inspection system to determine the presence of the prohibited compounds in the paint. In the present study, a method for the identification of organotin containing antifouling paints using a two-stage analysis process is investigated. Firstly, X-ray fluorescence analysis (XRF) is utilized, which could be used at the place of ship surveys or port state control. Using a portable XRF instrument customized for ship inspection, analysis is automatically executed and determines whether tin is present or not. If the presence of tin is confirmed by XRF, the sample is subsequently examined at an analytical laboratory using more rigorous analytical techniques, such as gas chromatograph mass spectrometry (GC-MS). A sampling device has been designed. It is a disc of approximately 10 mm diameter and has abrasive paper pasted to one of its flat surfaces. The device is pressed onto and then slid along a ship hull to lightly scrape off fragments of paint onto the abrasive paper. Preliminary field tests have revealed that sampling from a ship in dock yields successful collection of the paint for XRD analysis and that the resultant damage caused to the antifouling paint surface by the sampling technique was found to be negligible.
Resiliency in adolescents at high risk for substance abuse: flexible adaptation via subthalamic nucleus and linkage to drinking and drug use in early adulthood.

INTRODUCTION The personality trait resiliency is the ability to flexibly adapt impulse control relative to contextual demand. Low resiliency has been linked to later alcohol/drug problems. The underlying psychological and neural mechanisms are unknown, but neurocomputational models suggested relations between resiliency and working memory. Cortical-striatal connectivity has been proposed to underlie adaptive switches between cautious and risky behaviors. METHODS Working memory was probed in sixty-seven 18- to 22-year-olds from a larger community study of alcoholism, using the n-back task during functional magnetic resonance imaging. Functional connectivity between task-related regions was investigated with psychophysiological interaction analysis. Resiliency was measured in early teen years and related to early adulthood measures of drinking/drug use, task activation, and connectivity. Relationships with risk factors, including family history, age of drinking onset, and number of alcohol problems, were also investigated. RESULTS Higher resiliency was related to lower levels of substance use, fewer alcohol problems, and better working memory performance. Whole-brain regression revealed resiliency negatively correlated with activation of subthalamic nucleus (STN) and pallidum during the n-back. High and Low resiliency quartile groups (n = 17 each) differed in coupling strength between STN and median cingulate cortex, a region of reduced activation during working memory. The high resiliency group had later onset of drinking, fewer alcohol problems, had used fewer illicit drugs, and were less likely to smoke cigarettes than their low resiliency counterparts. CONCLUSIONS These findings suggest that resiliency in early adolescence may protect against alcohol problems and drug use, although the direction of this effect is currently unknown. This protective factor may relate to executive functioning as supported by the finding of a neural link shared between resiliency and working memory in basal ganglia structures. The STN, a key basal ganglia structure, may adaptively link flexible impulse control with cognitive processing, potentially modulating substance use outcomes.
Classification of Animals and People Ultrasonic Signatures

Personnel detection using inexpensive nonimaging sensors is becoming increasingly important for several applications, namely, border surveillance, perimeter protection, and urban operations. In this paper, we explore the utility of ultrasonic sensors to distinguish between people and animals walking. We explore the phenomenology associated with human and animal walking and identify model-based features in the spectrogram. In particular, we study the properties of micro-Doppler returns from various body parts (limbs) of the people and animals to identify the features. Finally, we develop two algorithms for classifying people and animals using the micro-Doppler signatures: one algorithm for the case when the signal-to-noise ratio (SNR) is high and another for low SNR. A support vector machine and a Bayesian classifier were used to classify the targets when the SNR is low. We present the results of the algorithms applied to actual data collected at a horse farm.
Approximate Bayesian Computation Without Summary Statistics: The Case of Admixture

In recent years approximate Bayesian computation (ABC) methods have become popular in population genetics as an alternative to full-likelihood methods to make inferences under complex demographic models. Most ABC methods rely on the choice of a set of summary statistics to extract information from the data. In this article we tested the use of the full allelic distribution directly in an ABC framework. Although the ABC techniques are becoming more widely used, there is still uncertainty over how they perform in comparison with full-likelihood methods. We thus conducted a simulation study and provide a detailed examination of ABC in comparison with full likelihood in the case of a model of admixture. This model assumes that two parental populations mixed at a certain time in the past, creating a hybrid population, and that the three populations then evolve under pure drift. Several aspects of ABC methodology were investigated, such as the effect of the distance metric chosen to measure the similarity between simulated and observed data sets. Results show that in general ABC provides good approximations to the posterior distributions obtained with the full-likelihood method. This suggests that it is possible to apply ABC using allele frequencies to make inferences in cases where it is difficult to select a set of suitable summary statistics and when the complexity of the model or the size of the data set makes it computationally prohibitive to use full-likelihood methods.
Business Cycle Uncertainty and Economic Welfare Revisited

Cho, Cooley, and Kim (RED, 2015) (CCK) consider the welfare effects of removing multiplicative productivity shocks from real business cycle models. In a model that admits an analytical solution they argue convincingly that the positive welfare effect of removing uncertainty can be dominated by a negative mean effect arising from the optimal response of household labor supply. While the presentation of this model is quite elaborate, the details of their subsequent quantitative analysis of several versions of the standard real business cycle model remain vague. We lay out the general procedure of computing second-order accurate approximations of welfare gains or losses in the canonical dynamic stochastic general equilibrium model. In order to be able to consider mean preserving increases in the size of shocks we extend the computation of second-order approximations of the policy functions pioneered by Schmitt-GrohA© and Uribe (JEDC, 2004). Our computations show that different from the results reported in CCK the mean effect never dominates the fluctuations effect. Welfare measures computed from weighted residuals methods confirm the logic behind our perturbation approach and verify the accuracy of our estimates.
Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints

The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought—involving ∼12% of the ancestral bilaterian genome—and that cis-regulatory constraints are crucial in determining metazoan genome architecture.
Continuous model reference adaptive control with sliding mode for a class of nonlinear plants with unknown state delay

In this paper, we develop a model reference adaptive control (MRAC) scheme with sliding mode for a class of nonlinear dynamic systems with state delay which is robust with respect to an unknown plant delay, to a nonlinear perturbation, and to an external disturbance with unknown bounds. A novel Lyapunov-Krasovskii type functional is introduced to design the adaptive controller with smooth control action, and the stability proof.
Evidence for Activity-Dependent Cortical Wiring: Formation of Interhemispheric Connections in Neonatal Mouse Visual Cortex Requires Projection Neuron Activity

Neuronal activity plays a pivotal role in shaping neuronal wiring. We investigated the role of neuronal activity in the formation of interhemispheric (callosal) axon projections in neonatal mouse visual cortex. Axonal labeling with enhanced green fluorescent protein (GFP) was used to demonstrate spatially organized pattern of callosal projections: GFP-labeled callosal axons from one hemisphere projected densely to a narrowly restricted region at the border between areas 17 and 18 in the contralateral hemisphere, in which they terminated in layers 1–3 and 5. This region- and layer-specific innervation pattern developed by postnatal day 15 (P15). To explore the role of neuronal activity of presynaptic and postsynaptic neurons in callosal connection development, an inwardly rectifying potassium channel, Kir2.1, was expressed in callosal projection neurons and their target postsynaptic neurons. Kir2.1 overexpression reduced the firing rate of cortical neurons. Kir2.1 overexpression in callosal projection neurons disturbed the growth of axons and their arbors that normally occurs between P7 and P13, whereas that in postsynaptic neurons had limited effect on the pattern of presynaptic callosal axon innervation. In addition, exogenous expression of a gain-of-function Kir2.1 mutant channel found in patients with a familial heart disease caused severe deficits in callosal axon projections. These results suggest that projection neuron activity plays a crucial role in interhemispheric connection development and that enhanced Kir2.1 activity can affect cortical wiring.