Evidence of Spatially Extensive Resistance to PCBs in an Anadromous Fish of the Hudson River

Populations of organisms that are chronically exposed to high levels of chemical contaminants may not suffer the same sublethal or lethal effects as naive populations, a phenomenon called resistance. Atlantic tomcod (Microgadus tomcod) from the Hudson River, New York, are exposed to high concentrations of polycyclic aromatic hydrocarbons (PAHs) and bioaccumulate polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). They have developed resistance to PCBs and PCDDs but not to PAHs. Resistance is largely heritable and manifests at early-life-stage toxic end points and in inducibility of cytochrome P4501A (CYP1A) mRNA expression. Because CYP1A induction is activated by the aryl hydrocarbon receptor (AHR) pathway, as are most toxic responses to these compounds, we sought to determine the geographic extent of resistance to CYP1A mRNA induction by PCBs in the Hudson River tomcod population. Samples of young-of-the-year tomcod were collected from seven locales in the Hudson River, extending from the Battery at river mile 1 (RM 1) to RM 90, and from the Miramichi River, New Brunswick, Canada. Laboratory-reared offspring of tomcod adults from Newark Bay, in the western portion of the Hudson River estuary, were also used in this study. Fish were partially depurated in clean water and intraperitoneally injected with 10 ppm coplanar PCB-77, 10 ppm benzo[a]pyrene (BaP), or corn oil vehicle, and levels of CYP1A mRNA were determined. CYP1A was significantly inducible by treatment with BaP in tomcod from the Miramichi River, from laboratory-spawned offspring of Newark Bay origin, and from all Hudson River sites spanning 90 miles of river. In contrast, only tomcod from the Miramichi River displayed significantly induced CYP1A mRNA expression when treated with PCB-77. Our results suggest that the population of tomcod from throughout the Hudson River estuary has developed resistance to CYP1A inducibility and probably other toxicities mediated by the AHR pathway. Tomcod from the Hudson River may represent the most geographically expansive population of vertebrates with resistance to chemical pollutants that has been characterized

Identification of disease-causing genes using microarray data mining and gene ontology

Background: One of the best and most accurate methods for identifying disease-causing genes is monitoring gene expression values in different samples using microarray technology. One of the shortcomings of microarray data is that they provide a small quantity of samples with respect to the number of genes. This problem reduces the classification accuracy of the methods, so gene selection is essential to improve the predictive accuracy and to identify potential marker genes for a disease. Among numerous existing methods for gene selection, support vector machine-based recursive feature elimination (SVMRFE) has become one of the leading methods, but its performance can be reduced because of the small sample size, noisy data and the fact that the method does not remove redundant genes. Methods: We propose a novel framework for gene selection which uses the advantageous features of conventional methods and addresses their weaknesses. In fact, we have combined the Fisher method and SVMRFE to utilize the advantages of a filtering method as well as an embedded method. Furthermore, we have added a redundancy reduction stage to address the weakness of the Fisher method and SVMRFE. In addition to gene expression values, the proposed method uses Gene Ontology which is a reliable source of information on genes. The use of Gene Ontology can compensate, in part, for the limitations of microarrays, such as having a small number of samples and erroneous measurement results. Results: The proposed method has been applied to colon, Diffuse Large B-Cell Lymphoma (DLBCL) and prostate cancer datasets. The empirical results show that our method has improved classification performance in terms of accuracy, sensitivity and specificity. In addition, the study of the molecular function of selected genes strengthened the hypothesis that these genes are involved in the process of cancer growth. Conclusions: The proposed method addresses the weakness of conventional methods by adding a redundancy reduction stage and utilizing Gene Ontology information. It predicts marker genes for colon, DLBCL and prostate cancer with a high accuracy. The predictions made in this study can serve as a list of candidates for subsequent wet-lab verification and might help in the search for a cure for cancers

A Neural Approach to Ordinal Regression for the Preventive Assessment of Developmental Dyslexia

Developmental Dyslexia (DD) is a learning disability related to the acquisition of reading skills that affects about 5% of the population. DD can have an enormous impact on the intellectual and personal development of affected children, so early detection is key to implementing preventive strategies for teaching language. Research has shown that there may be biological underpinnings to DD that affect phoneme processing, and hence these symptoms may be identifiable before reading ability is acquired, allowing for early intervention. In this paper we propose a new methodology to assess the risk of DD before students learn to read. For this purpose, we propose a mixed neural model that calculates risk levels of dyslexia from tests that can be completed at the age of 5 years. Our method first trains an auto-encoder, and then combines the trained encoder with an optimized ordinal regression neural network devised to ensure consistency of predictions. Our experiments show that the system is able to detect unaffected subjects two years before it can assess the risk of DD based mainly on phonological processing, giving a specificity of 0.969 and a correct rate of more than 0.92. In addition, the trained encoder can be used to transform test results into an interpretable subject spatial distribution that facilitates risk assessment and validates methodology.Comment: 12 pages, 4 figure

The operationalized psychodynamic diagnostics system. Clinical relevance, reliability and validity

In this paper, we present a multiaxial system for psychodynamic diagnosis, which has attained wide usage in Germany in the last 10 years. First we will discuss the 4 operationalized psychodynamic diagnostics (OPD) axes: illness experience and treatment assumptions, relationships, mental conflicts, and structure, then clinical applications will be outlined. Focus psychodynamic formulations can be employed both with inpatients and with outpatients. Studies show good reliability in a research context and acceptable reliability for clinical purposes. Validity will be separately summarized as content, criterion, and construct validity. Validity studies indicate good validity for the individual axes. Numerous studies on the OPD indicate areas of possible improvement, for example for clinical purposes the OPD should be more practically formulated

Atrial fibrillation in embolic stroke of undetermined source: role of advanced imaging of left atrial function

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. AIMS: Atrial fibrillation (AF) is detected in over 30% of patients following an embolic stroke of undetermined source (ESUS) when monitored with an implantable loop recorder (ILR). Identifying AF in ESUS survivors has significant therapeutic implications, and AF risk is essential to guide screening with long-term monitoring. The present study aimed to establish the role of left atrial (LA) function in subsequent AF identification and develop a risk model for AF in ESUS. METHODS AND RESULTS: We conducted a single-centre retrospective case-control study including all patients with ESUS referred to our institution for ILR implantation from December 2009 to September 2019. We recorded clinical variables at baseline and analysed transthoracic echocardiograms in sinus rhythm. Univariate and multivariable analyses were performed to inform variables associated with AF. Lasso regression analysis was used to develop a risk prediction model for AF. The risk model was internally validated using bootstrapping. Three hundred and twenty-three patients with ESUS underwent ILR implantation. In the ESUS population, 293 had a stroke, whereas 30 had suffered a transient ischaemic attack as adjudicated by a senior stroke physician. Atrial fibrillation of any duration was detected in 47.1%. The mean follow-up was 710 days. Following lasso regression with backwards elimination, we combined increasing lateral PA (the time interval from the beginning of the P wave on the surface electrocardiogram to the beginning of the A\u27 wave on pulsed wave tissue Doppler of the lateral mitral annulus) [odds ratio (OR) 1.011], increasing Age (OR 1.035), higher Diastolic blood pressure (OR 1.027), and abnormal LA reservoir Strain (OR 0.973) into a new PADS score. The probability of identifying AF can be estimated using the formula. Model discrimination was good [area under the curve (AUC) 0.72]. The PADS score was internally validated using bootstrapping with 1000 samples of 150 patients showing consistent results with an AUC of 0.73. CONCLUSION: The novel PADS score can identify the risk of AF on prolonged monitoring with ILR following ESUS and should be considered a dedicated risk stratification tool for decision-making regarding the screening strategy for AF in stroke.One-third of patients with a type of stroke called embolic stroke of undetermined source (ESUS) also have a heart condition called atrial fibrillation (AF), which increases their risk of having another stroke. However, we do not know why some patients with ESUS develop AF. To figure this out, we studied 323 patients with ESUS and used a special device to monitor their heart rhythm continuously for up to 3 years, an implantable loop recorder. We also looked at their medical history, performed a heart ultrasound, and identified some factors that increase the risk of identifying AF in the future. Factors associated with future AF include older age, higher diastolic blood pressure, and problems with the co-ordination and function of the upper left chamber of the heart called the left atrium.Based on these factors, we created a new scoring system that can identify patients who are at higher risk of developing AF better than the current scoring systems, the PADS score. This can potentially help doctors provide more targeted and effective treatment to these patients, ultimately aiming to reduce their risk of having another stroke

Coevolution in a One Predator–Two Prey System

Background: Our understanding of coevolution in a predator–prey system is based mostly on pair-wise interactions. Methodology and Principal Findings: Here I analyze a one-predator–two-prey system in which the predator’s attack ability and the defense abilities of the prey all evolve. The coevolutionary consequences can differ dramatically depending on the initial trait value and the timing of the alternative prey’s invasion into the original system. If the invading prey species has relatively low defense ability when it invades, its defense is likely to evolve to a lower level, stabilizing the population dynamics. In contrast, if when it invades its defense ability is close to that of the resident prey, its defense can evolve to a higher level and that of the resident prey may suddenly cease to evolve, destabilizing the population dynamics. Destabilization due to invasion is likely when the invading prey is adaptively superior (evolution of its defense is less constrained and fast), and it can also occur in a broad condition even when the invading prey is adaptively inferior. In addition, invasion into a resident system far from equilibrium characterized by population oscillations is likely to cause further destabilization

Decadal changes of the Western Arabian sea ecosystem

Historical data from oceanographic expeditions and remotely sensed data on outgoing longwave radiation, temperature, wind speed and ocean color in the western Arabian Sea (1950–2010) were used to investigate decadal trends in the physical and biochemical properties of the upper 300 m. 72 % of the 29,043 vertical profiles retrieved originated from USA and UK expeditions. Increasing outgoing longwave radiation, surface air temperatures and sea surface temperature were identified on decadal timescales. These were well correlated with decreasing wind speeds associated with a reduced Siberian High atmospheric anomaly. Shoaling of the oxycline and nitracline was observed as well as acidification of the upper 300 m. These physical and chemical changes were accompanied by declining chlorophyll-a concentrations, vertical macrofaunal habitat compression, declining sardine landings and an increase of fish kill incidents along the Omani coast

Early and Middle Holocene Hunter-Gatherer Occupations in Western Amazonia: The Hidden Shell Middens

We report on previously unknown early archaeological sites in the Bolivian lowlands, demonstrating for the first time early and middle Holocene human presence in western Amazonia. Multidisciplinary research in forest islands situated in seasonally-inundated savannahs has revealed stratified shell middens produced by human foragers as early as 10,000 years ago, making them the oldest archaeological sites in the region. The absence of stone resources and partial burial by recent alluvial sediments has meant that these kinds of deposits have, until now, remained unidentified. We conducted core sampling, archaeological excavations and an interdisciplinary study of the stratigraphy and recovered materials from three shell midden mounds. Based on multiple lines of evidence, including radiocarbon dating, sedimentary proxies (elements, steroids and black carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic origin and antiquity of these sites. In a tropical and geomorphologically active landscape often considered challenging both for early human occupation and for the preservation of hunter-gatherer sites, the newly discovered shell middens provide evidence for early to middle Holocene occupation and illustrate the potential for identifying and interpreting early open-air archaeological sites in western Amazonia. The existence of early hunter-gatherer sites in the Bolivian lowlands sheds new light on the region's past and offers a new context within which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. © 2013 Lombardo et al

Nanomaterial interactions with biomembranes: Bridging the gap between soft matter models and biological context

Synthetic polymers, nanoparticles, and carbon-based materials have great potential in applications including drug delivery, gene transfection, in vitro and in vivo imaging, and the alteration of biological function. Nature and humans use different design strategies to create nanomaterials: biological objects have emerged from billions of years of evolution and from adaptation to their environment resulting in high levels of structural complexity; in contrast, synthetic nanomaterials result from minimalistic but controlled design options limited by the authors' current understanding of the biological world. This conceptual mismatch makes it challenging to create synthetic nanomaterials that possess desired functions in biological media. In many biologically relevant applications, nanomaterials must enter the cell interior to perform their functions. An essential transport barrier is the cell-protecting plasma membrane and hence the understanding of its interaction with nanomaterials is a fundamental task in biotechnology. The authors present open questions in the field of nanomaterial interactions with biological membranes, including: how physical mechanisms and molecular forces acting at the nanoscale restrict or inspire design options; which levels of complexity to include next in computational and experimental models to describe how nanomaterials cross barriers via passive or active processes; and how the biological media and protein corona interfere with nanomaterial functionality. In this Perspective, the authors address these questions with the aim of offering guidelines for the development of next-generation nanomaterials that function in biological media