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Nanostructured materials have significantly influenced numerous scientific and technological areas, mainly due to the tuneability of their optical and electrical properties. When working with quantum dots (QDs)-based thin films, the high prevalence of trap states and low conductivity has been a remarkable challenge, which has been addressed by the fabrication of hybrid materials. However, on the road to improving their properties, fabrication of nanostructured hybrid materials, especially when involving 2D nanomaterials, still poses a challenging task, particularly when solution-processed approaches are considered. In the current work, the fabrication of a solution-processed QDs-2D nanomaterial hybrid, comprising PbS QDs and thermally reduced graphene oxide (rGO) is discussed. This study explores the nanostructured hybrid material's behavior when varying the weight percent ratio between the constituents, revealing a substantial impact of this parameter on the optoelectronic properties of the resulting hybrid material; particularly affecting the photogenerated charge carrier transfer, charge carrier mobility, charge carrier concentration and resistivity. Physical characterization of the hybrid material revealed a dramatic change in the interaction between the PbS QDs and the rGO as the weight percent of rGO increased in the hybrid material, showing a clear reduction of PbS QDs coverage on rGO's surface, which also produced an increment in the signals related to the oxidation of PbS QDs and rGO. The sample with 5% wt. of rGO showed optimal optoelectronic properties for possible applications in photodetector technologies or solar cells, displaying a high photogenerated current with a charge carrier mobility, charge carrier concentration, and resistivity of approximately 2.26 cm2/V-s, 1.27 × 1014 cm−3 and 2.18 × 104 Ω-cm, respectively. These findings serve as a foundational basis for the development of efficient optoelectronic devices based on this type of nanostructured hybrid material. [ABSTRACT FROM AUTHOR]

Several AutoML tools aim to facilitate the usability of machine learning algorithms, automatically recommending algorithms using techniques such as meta-learning, grid search, and genetic programming. However, the preprocessing step is usually not well handled by those tools. Thus, in this work, we present a systematic review of preprocessing algorithms selection with meta-learning, aiming to find the state of the art in this field. To perform this task, we acquired 450 references, of which we selected 37 to be evaluated and analyzed according to a set of questions earlier defined. Thus, we managed to identify information such as what was published on the subject; the topics more often presented in those works; the most frequently recommended preprocessing algorithms; the most used features selected to extract information for the meta-learning; the machine learning algorithms employed as meta-learners and base-learners in those works; and the performance metrics that are chosen as the target of the applications. [ABSTRACT FROM AUTHOR]

In hormone-responsive breast cancer cells, progesterone (P4) has been shown to act via its nuclear receptor (nPR), a ligand-activated transcription factor. A small fraction of progesterone receptor is palmitoylated and anchored to the cell membrane (mbPR) forming a complex with estrogen receptor alpha (ERα). Upon hormone exposure, either directly or via interaction with ERα, mbPR activates the SRC/RAS/ERK kinase pathway leading to phosphorylation of nPR by ERK. Kinase activation is essential for P4 gene regulation, as the ERK and MSK1 kinases are recruited by the nPR to its genomic binding sites and trigger chromatin remodeling. An interesting open question is whether activation of mbPR can result in gene regulation in the absence of ligand binding to intracellular progesterone receptor (iPR). This matter has been investigated in the past using P4 attached to serum albumin, but the attachment is leaky and albumin can be endocytosed and degraded, liberating P4. Here, we propose a more stringent approach to address this issue by ensuring attachment of P4 to the cell membrane via covalent binding to a stable phospholipid. This strategy identifies the actions of P4 independent from hormone binding to iPR. We found that a membrane-attached progestin can activate mbPR, the ERK signaling pathway leading to iPR phosphorylation, initial gene regulation and entry into the cell cycle, in the absence of detectable intracellular progestin. [ABSTRACT FROM AUTHOR]

Mitochondrial metabolism and function are modulated by changes in matrix Ca2+. Small increases in the matrix Ca2+ stimulate mitochondrial bioenergetics, whereas excessive Ca2+ leads to cell death by causing massive matrix swelling and impairing the structural and functional integrity of mitochondria. Sustained opening of the non-selective mitochondrial permeability transition pores (PTP) is the main mechanism responsible for mitochondrial Ca2+ overload that leads to mitochondrial dysfunction and cell death. Recent studies suggest the existence of two or more types of PTP, and adenine nucleotide translocator (ANT) and FOF1-ATP synthase were proposed to form the PTP independent of each other. Here, we elucidated the role of ANT in PTP opening by applying both experimental and computational approaches. We first developed and corroborated a detailed model of the ANT transport mechanism including the matrix (ANTM), cytosolic (ANTC), and pore (ANTP) states of the transporter. Then, the ANT model was incorporated into a simple, yet effective, empirical model of mitochondrial bioenergetics to ascertain the point when Ca2+ overload initiates PTP opening via an ANT switch-like mechanism activated by matrix Ca2+ and is inhibited by extra-mitochondrial ADP. We found that encoding a heterogeneous Ca2+ response of at least three types of PTPs, weakly, moderately, and strongly sensitive to Ca2+, enabled the model to simulate Ca2+ release dynamics observed after large boluses were administered to a population of energized cardiac mitochondria. Thus, this study demonstrates the potential role of ANT in PTP gating and proposes a novel mechanism governing the cryptic nature of the PTP phenomenon. [ABSTRACT FROM AUTHOR]

The human hematopoietic stem cell harbors remarkable regenerative potential that can be harnessed therapeutically. During early development, hematopoietic stem cells in the fetal liver undergo active expansion while simultaneously retaining robust engraftment capacity, yet the underlying molecular program responsible for their efficient engraftment remains unclear. Here, we profile 26,407 fetal liver cells at both the transcriptional and protein level including ~7,000 highly enriched and functional fetal liver hematopoietic stem cells to establish a detailed molecular signature of engraftment potential. Integration of transcript and linked cell surface marker expression reveals a generalizable signature defining functional fetal liver hematopoietic stem cells and allows for the stratification of enrichment strategies with high translational potential. More precisely, our integrated analysis identifies CD201 (endothelial protein C receptor (EPCR), encoded by PROCR) as a marker that can specifically enrich for engraftment potential. This comprehensive, multi-modal profiling of engraftment capacity connects a critical biological function at a key developmental timepoint with its underlying molecular drivers. As such, it serves as a useful resource for the field and forms the basis for further biological exploration of strategies to retain the engraftment potential of hematopoietic stem cells ex vivo or induce this potential during in vitro hematopoietic stem cell generation. During human embryonic development, haematopoietic stem cells of the foetal liver undergo expansion, while retaining engraftment capacity. Here the authors apply CITE-seq to profile single cells from a human foetal liver, identifying a molecular signature of engraftment potential [ABSTRACT FROM AUTHOR]

In spite of the high-density and strongly correlated nature of the atomic nucleus, experimental and theoretical evidence suggests that around particular ‘magic’ numbers of nucleons, nuclear properties are governed by a single unpaired nucleon1,2. A microscopic understanding of the extent of this behaviour and its evolution in neutron-rich nuclei remains an open question in nuclear physics3–5. The indium isotopes are considered a textbook example of this phenomenon6, in which the constancy of their electromagnetic properties indicated that a single unpaired proton hole can provide the identity of a complex many-nucleon system6,7. Here we present precision laser spectroscopy measurements performed to investigate the validity of this simple single-particle picture. Observation of an abrupt change in the dipole moment at N = 82 indicates that, whereas the single-particle picture indeed dominates at neutron magic number N = 82 (refs. 2,8), it does not for previously studied isotopes. To investigate the microscopic origin of these observations, our work provides a combined effort with developments in two complementary nuclear many-body methods: ab initio valence-space in-medium similarity renormalization group and density functional theory (DFT). We find that the inclusion of time-symmetry-breaking mean fields is essential for a correct description of nuclear magnetic properties, which were previously poorly constrained. These experimental and theoretical findings are key to understanding how seemingly simple single-particle phenomena naturally emerge from complex interactions among protons and neutrons.Precision laser spectroscopy measurements of neutron-rich indium isotopes were performed to investigate the validity and identify limitations of theoretical descriptions of nuclei based on simple single-particle approaches. [ABSTRACT FROM AUTHOR]

Key message: We propose using probability concepts from Bayesian models to leverage a more informed decision-making process toward cultivar recommendation in multi-environment trials. Statistical models that capture the phenotypic plasticity of a genotype across environments are crucial in plant breeding programs to potentially identify parents, generate offspring, and obtain highly productive genotypes for target environments. In this study, our aim is to leverage concepts of Bayesian models and probability methods of stability analysis to untangle genotype-by-environment interaction (GEI). The proposed method employs the posterior distribution obtained with the No-U-Turn sampler algorithm to get Hamiltonian Monte Carlo estimates of adaptation and stability probabilities. We applied the proposed models in two empirical tropical datasets. Our findings provide a basis to enhance our ability to consider the uncertainty of cultivar recommendation for global or specific adaptation. We further demonstrate that probability methods of stability analysis in a Bayesian framework are a powerful tool for unraveling GEI given a defined intensity of selection that results in a more informed decision-making process toward cultivar recommendation in multi-environment trials. [ABSTRACT FROM AUTHOR]

Understanding the evolution of the nuclear charge radius is one of the long-standing challenges for nuclear theory. Recently, density functional theory calculations utilizing Fayans functionals have successfully reproduced the charge radii of a variety of exotic isotopes. However, difficulties in the isotope production have hindered testing these models in the immediate region of the nuclear chart below the heaviest self-conjugate doubly-magic nucleus 100Sn, where the near-equal number of protons (Z) and neutrons (N) lead to enhanced neutron-proton pairing. Here, we present an optical excursion into this region by crossing the N = 50 magic neutron number in the silver isotopic chain with the measurement of the charge radius of 96Ag (N = 49). The results provide a challenge for nuclear theory: calculations are unable to reproduce the pronounced discontinuity in the charge radii as one moves below N = 50. The technical advancements in this work open the N = Z region below 100Sn for further optical studies, which will lead to more comprehensive input for nuclear theory development. Laser spectroscopic measurements of isotopes near the doubly-magic 100-Sn are challenging due to difficulties in their production. Here the authors measure the ground state charge radius of the proton-rich 96-Ag isotope and find a discontinuity in the nuclear size when crossing the neutron number N equal to 50. [ABSTRACT FROM AUTHOR]

Obesity is a global public health problem that results in chronic pathologies such as diabetes, cardiovascular diseases, and cancer. The treatment approach based on energy restriction and promotion of physical activity is ineffective in the long term. Due to the high prevalence of this pathology, complementary treatments such as brown adipose tissue activation (BAT) and white adipose tissue browning (WAT) have been proposed. Dietary polyphenols are plant secondary metabolites that can stimulate browning and thermogenesis of adipose tissue. They have also been shown to prevent body weight gain, and decrease systemic inflammation produced by high-fat diets. Ingested dietary polyphenols that reach the colon are metabolized by the gut microbiota (GM), regulating its composition and generating a great array of metabolites. GM is involved in the production of short chain fatty acids and secondary bile salts that regulate energetic metabolism. The alteration in the composition of GM observed in metabolic diseases such as obesity and type 2 diabetes can be attenuated by polyphenols. Recent studies support the hypothesis that GM would mediate WAT browning and BAT thermogenesis activation induced by polyphenol administration. Together, these results indicate that GM in the presence of polyphenols plays a fundamental role in the control of obesity possible through BAT activation. [ABSTRACT FROM AUTHOR]

An experimental study of the interaction between a Mylar® polymer film and a multimode fiber-optic is presented for the simultaneous fiber-optic detection of low-pressure and liquid levels. The junction between the polymer and optical fiber produces an interference spectrum with maximal visibility and free spectral range around 9 dB and 31 nm, respectively. Water pressure, which is controlled by the liquid level, stresses the polymer. As a result, the spectrum wavelength shifts to the blue region, achieving high sensitivities around 2.49 nm/kPa and 24.5 nm/m. The polymeric membrane was analyzed using a finite element model; according to the results, the polymer shows linear stress response. Furthermore, the membrane material is operated below the yielding point. Moreover, the finite analysis provides information about the stress effect over the thickness and the birefringence changes. This sensor exhibits a quadratic polynomial fitting with an adjusted R-squared of 0.9539. The proposed sensing setup offers a cost-effective alternative for liquid level and low-pressure detection. [ABSTRACT FROM AUTHOR]

Mitosis has been validated by numerous anti-cancer drugs as being a druggable process, and selective inhibition of parasite proliferation provides an obvious opportunity for therapeutic intervention against malaria. Mitosis is controlled through the interplay between several protein kinases and phosphatases. We show here that inhibitors of human mitotic kinases belonging to the Aurora family inhibit P. falciparum proliferation in vitro with various potencies, and that a genetic selection for mutant parasites resistant to one of the drugs, Hesperadin, identifies a resistance mechanism mediated by a member of a different kinase family, PfNek1 (PF3D7_1228300). Intriguingly, loss of PfNek1 catalytic activity provides protection against drug action. This points to an undescribed functional interaction between Ark and Nek kinases and shows that existing inhibitors can be used to validate additional essential and druggable kinase functions in the parasite. Morahan et al. investigate inhibitors of human mitotic kinases in P. falciparum and show a resistance mechanism to the drug Hesperadin through an epistatic interaction between the PfArk1 and PfNek1 kinases. This study demonstrates that existing inhibitors can be used to validate additional essential and druggable kinase functions in the parasite. [ABSTRACT FROM AUTHOR]

This work reports on the application of a novel electric field-ionization setup for high-resolution laser spectroscopy measurements on bunched fast atomic beams in a collinear geometry. In combination with multi-step resonant excitation to Rydberg states using pulsed lasers, the field ionization technique demonstrates increased sensitivity for isotope separation and measurement of atomic parameters over previous non-resonant laser ionization methods. The setup was tested at the Collinear Resonance Ionization Spectroscopy experiment at ISOLDE-CERN to perform high-resolution measurements of transitions in the indium atom from the 5s 2 5d 2 D 5 / 2 and 5s 2 5d 2 D 3 / 2 states to 5s 2 n p 2 P and 5s 2 n f 2 F Rydberg states, up to a principal quantum number of n = 72 . The extracted Rydberg level energies were used to re-evaluate the ionization potential of the indium atom to be 46 , 670.107 (4) cm - 1 . The nuclear magnetic dipole and nuclear electric quadrupole hyperfine structure constants and level isotope shifts of the 5s 2 5d 2 D 5 / 2 and 5s 2 5d 2 D 3 / 2 states were determined for 113 , 115 In. The results are compared to calculations using relativistic coupled-cluster theory. A good agreement is found with the ionization potential and isotope shifts, while disagreement of hyperfine structure constants indicates an increased importance of electron correlations in these excited atomic states. With the aim of further increasing the detection sensitivity for measurements on exotic isotopes, a systematic study of the field-ionization arrangement implemented in the work was performed at the same time and an improved design was simulated and is presented. The improved design offers increased background suppression independent of the distance from field ionization to ion detection. [ABSTRACT FROM AUTHOR]

Tin is the chemical element with the largest number of stable isotopes. Its complete proton shell, comparable with the closed electron shells in the chemically inert noble gases, is not a mere precursor to extended stability; since the protons carry the nuclear charge, their spatial arrangement also drives the nuclear electromagnetism. We report high-precision measurements of the electromagnetic moments and isomeric differences in charge radii between the lowest 1/2+, 3/2+, and 11/2− states in 117–131Sn, obtained by collinear laser spectroscopy. Supported by state-of-the-art atomic-structure calculations, the data accurately show a considerable attenuation of the quadrupole moments in the closed-shell tin isotopes relative to those of cadmium, with two protons less. Linear and quadratic mass-dependent trends are observed. While microscopic density functional theory explains the global behaviour of the measured quantities, interpretation of the local patterns demands higher-fidelity modelling. Measurements of the hyperfine structure of chemical elements isotopes provide unique insight into the atomic nucleus in a nuclear model-independent way. The authors present collinear laser spectroscopy data obtained at the CERN ISOLDE and measure hyperfine splitting along a long chain of odd-mass tin isotopes. [ABSTRACT FROM AUTHOR]

Molecular spectroscopy offers opportunities for the exploration of the fundamental laws of nature and the search for new particle physics beyond the standard model1–4. Radioactive molecules—in which one or more of the atoms possesses a radioactive nucleus—can contain heavy and deformed nuclei, offering high sensitivity for investigating parity- and time-reversal-violation effects5,6. Radium monofluoride, RaF, is of particular interest because it is predicted to have an electronic structure appropriate for laser cooling6, thus paving the way for its use in high-precision spectroscopic studies. Furthermore, the effects of symmetry-violating nuclear moments are strongly enhanced5,7–9 in molecules containing octupole-deformed radium isotopes10,11. However, the study of RaF has been impeded by the lack of stable isotopes of radium. Here we present an experimental approach to studying short-lived radioactive molecules, which allows us to measure molecules with lifetimes of just tens of milliseconds. Energetically low-lying electronic states were measured for different isotopically pure RaF molecules using collinear resonance ionisation at the ISOLDE ion-beam facility at CERN. Our results provide evidence of the existence of a suitable laser-cooling scheme for these molecules and represent a key step towards high-precision studies in these systems. Our findings will enable further studies of short-lived radioactive molecules for fundamental physics research. Measurements of low-energy electronic states of radium monofluoride validate predictions of the use of this short-lived radioactive molecule in exploring fundamental physics and provide evidence of its suitability for laser cooling. [ABSTRACT FROM AUTHOR]

Key message: Weighted outperformed unweighted genomic prediction using an unbalanced dataset representative of a commercial breeding program. Moreover, the use of the two cycles preceding predictions as training set achieved optimal prediction ability. Predicting the performance of untested single-cross hybrids through genomic prediction (GP) is highly desirable to increase genetic gain. Here, we evaluate the predictive ability (PA) of novel genomic strategies to predict single-cross maize hybrids using an unbalanced historical dataset of a tropical breeding program. Field data comprised 949 single-cross hybrids evaluated from 2006 to 2013, representing eight breeding cycles. Hybrid genotypes were inferred based on their parents' genotypes (inbred lines) using single-nucleotide polymorphism markers obtained via genotyping-by-sequencing. GP analyses were fitted using genomic best linear unbiased prediction via a stage-wise approach, considering two distinct cross-validation schemes. Results highlight the importance of taking into account the uncertainty regarding the adjusted means at each step of a stage-wise analysis, due to the highly unbalanced data structure and the expected heterogeneity of variances across years and locations of a commercial breeding program. Further, an increase in the size of the training set was not always advantageous even in the same breeding program. The use of the two cycles preceding predictions achieved optimal PA of untested single-cross hybrids in a forward prediction scenario, which could be used to replace the first step of field screening. Finally, in addition to the practical and theoretical results applied to maize hybrid breeding programs, the stage-wise analysis performed in this study may be applied to any crop historical unbalanced data. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) is a condition that alters different functions of the organism inducing high blood pressure (HBP). Although physical exercise is recommended for the treatment of HBP, it is not clear which exercise method is more efficient to reduce OS biomarkers in subjects with HBP and non-type 2 diabetes mellitus (T2DM). Therefore, this review aimed to determine the effect of physical exercise on the OS biomarkers of HBP animal models and non-T2DM prehypertensive/hypertensive human adults. Methodology: An online search was done in WoS, Scopus and PubMed (MeSH) databases with the following combination of keywords: "hypertension" AND "oxidative stress" AND "exercise". Results: A total of 1128 articles were identified, from which only six articles on animal research and six on human research fulfilled the inclusion and exclusion criteria. In animal models, exercise reduced OS biomarkers and decreased systolic blood pressure. In humans, five of these articles showed a significant decrease in OS biomarkers along with a decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and a single study found an increase in OS biomarkers co-occurring with a decrease in SBP/DBP. Conclusions: Based on the analyzed articles, it is concluded that physical exercise, in its different modalities, allows the reduction of OS biomarkers, together with a significant decrease in SBP/DBP. Moderate intensity aerobic exercise presents a higher body of evidence compared to resistance training and flexibility training. For this reason, it is recommended to conduct more randomized clinical trials with these last two methods. [ABSTRACT FROM AUTHOR]

Obesity is a major worldwide health threat. It is characterized by an abnormal adipose tissue overgrowth together with increased monocytes infiltration, causing inflammation and oxidative stress, events associated with several illnesses. Investigations have focused on the benefits of native fruit consumption, claiming these to be natural sources of bioactive compounds with antioxidant and anti-inflammatory characteristics. It has been widely stated that berries are a source of the most antioxidant compounds, and, thus, seem highly promising to endure research efforts on these vegetal matrices. The present article describes botanical, chemical and biomedical features of the Chilean native berries, Aristotelia chilensis, Ugni molinae, and Berberis microphylla. This work aims to potentiate incoming research focused on the search for novel treatments for first-order diseases with these particular plant sources. [ABSTRACT FROM AUTHOR]

The intensive production of polycyclic aromatic hydrocarbons by anthropogenic activities is a serious environmental problem. Therefore, new bioremediation methods are required to avoid widespread contamination. In this work, Serratia sp. AC-11 strain isolated from a tropical peat was selected for immobilization into chitosan beads, which were employed in the biodegradation of fluoranthene. The sizes of the produced beads were relatively uniform with an average diameter of 3 mm. The material was characterized by SEM and FT-IR, confirming the cells immobilization and the protective barrier formed by the chitosan surrounding the biomass. The immobilized bacteria were able to degrade 56% of fluoranthene (the initial concentration was 100 mg L−1) in just 1 day at twice the degradation rate achieved by free-living cells. Furthermore, the immobilized bacteria showed excellent removal during five reuse cycles, from 76% to 59% of biodegradation. These results showed the potential of this approach for remediation of contaminated sites. [ABSTRACT FROM AUTHOR]

Obesity is a public health problem present in both developed and developing countries. The white adipose tissue (WAT) is the main deposit of lipids when there is an excess of energy. Its pathological growth is directly linked to the development of obesity and to a wide number of comorbidities, such as insulin-resistance, cardiovascular disease, among others. In this scenario, it becomes imperative to develop new approaches to the treatment and prevention of obesity and its comorbidities. It has been documented that the browning of WAT could be a suitable strategy to tackle the obesity epidemic that is developing worldwide. Currently there is an intense search for bioactive compounds with anti-obesity properties, which present the particular ability to generate thermogenesis in the brown adipose tissue (BAT) or beige. The present study provide recent information of the bioactive nutritional compounds capable of inducing thermogenesis and therefore capable of generate positive effects on health. [ABSTRACT FROM AUTHOR]

Purpose: Barley is a low-glycemic index grain that can help diabetic and obese patients. The effect of barley intake depends on the host and the associated gut microbiota. This study investigated the effect of barley intake on the fecal microbiota, caecal biochemistry, and key biomarkers of obesity and inflammation.Methods: Obese db/db mice were fed diets with and without barley during 8 weeks; lean mice were used as lean controls. Fecal microbiota was evaluated using 16S marker gene sequencing in a MiSeq instrument; several markers of caecal biochemistry, obesity, and inflammation were also evaluated using standard techniques.Results: Bacterial richness (i.e., Operational Taxonomic Units) and Shannon diversity indexes were similar in all obese mice (with and without barley) and higher compared to lean controls. Barley intake was associated with increased abundances of Prevotella, Lactobacillus, and the fiber-degraders S24-7 (Candidatus Homeothermaceae) compared to both lean and obese controls. The analysis of unweighted UniFrac distances showed a separate clustering of samples for each experimental group, suggesting that consumption of barley contributed to a phylogenetically unique microbiota distinct from both obese and lean controls. Caecal butyrate concentrations were similar in all obese mice, while succinic acid was lower in the barley group compared to obese controls. Barley intake was also associated with lower plasma insulin and resistin levels compared to obese controls.Conclusions: This study shows that barley intake is associated with a different fecal microbiota, caecal biochemistry, and obesity biomarkers in db/db mice that tend to be more similar to lean controls. [ABSTRACT FROM AUTHOR]

Introduction Neonatal abstinence syndrome (NAS) is withdrawal syndrome in newborns following birth and is primarily caused by maternal drug use during pregnancy. This study examines trends, population correlates, and policy implications of NAS in two Southwest border states. Materials and Methods A cross-sectional analysis of Hospital Inpatient Discharge Data (HIDD) was utilized to examine the incidence of NAS in the Southwest border states of Arizona (AZ) and New Mexico (NM). All inpatient hospital births in AZ and NM from January 1, 2008 through December 31, 2013 with ICD9-CM codes for NAS (779.5), cocaine (760.72), or narcotics (760.75) were extracted. Results During 2008-2013 there were 1472 NAS cases in AZ and 888 in NM. The overall NAS rate during this period was 2.83 per 1000 births (95% CI 2.68-2.97) in AZ and 5.31 (95% CI 4.96-5.66) in NM. NAS rates increased 157% in AZ and 174% in NM. NAS newborns were more likely to have low birth weight, have respiratory distress, more likely to have feeding difficulties, and more likely to be on state Medicaid insurance. AZ border region (border with Mexico) had NAS rates significantly higher than the state rate (4.06 per 1000 births [95% CI 3.68-4.44] vs. 2.83 [95% CI 2.68-2.97], respectively). In NM, the border region rate (2.09 per 1000 births [95% CI 1.48-2.69]) was significantly lower than the state rate (5.31 [95% CI 4.96-5.66]). Conclusions Despite a dramatic increase in the incidence of NAS in the U.S. and, in particular, the Southwest border states of AZ and NM, there is still scant research on the overall incidence of NAS, its assessment in the southwest border, and associated long-term outcomes. The Healthy Border (HB) 2020 binational initiative of the U.S.-Mexico Border Health Commission is an initiative that addresses several public health priorities that not only include chronic and degenerative diseases, infectious diseases, injury prevention, maternal and child health but also mental health and addiction. The growing opioid epidemic and rise in NAS cases in the Southwest border, as partially shown in this study, provides another opportunity to track health illnesses and outcomes in the Southwest border, especially because there are targeted resources through High Intensity Drug Trafficking Areas (HIDTA) funding. [ABSTRACT FROM AUTHOR]

Breeding trials typically consist of phenotypic observations for various traits evaluated in multiple environments. For sugarcane in particular, repeated measures are obtained for plant crop and one or more ratoons, such that joint analysis through mixed models for modeling heterogeneous genetic (co)variances between traits, locations and harvests is appropriate. This modeling approach also enables us to include molecular marker information, aiding in understanding the genetic architecture of quantitative traits. Our work aims at detecting QTL and QTL by environment interactions by fitting mixed models with multiple QTLs, with appropriate modeling of multi-trait multi-environment data for outcrossing species. We evaluated 100 individuals from a biparental cross at two locations and three years for fiber content, sugar content (POL) and tonnes of cane per hectare (TCH). We detected 13 QTLs exhibiting QTL by location, QTL by harvest or the three-way interaction. Overall, 11 of the 13 effects presented some degree of pleiotropy, affecting at least two traits. Furthermore, these QTLs always affected fiber and TCH in the same direction, whereas POL was affected in the opposite way. There was no evidence in favor of the linked QTL over the pleiotropic QTL hypothesis for any detected genome position. These results provide valuable insights into the genetic basis of quantitative variation in sugarcane and the genetic relation between traits. [ABSTRACT FROM AUTHOR]

The spatial organization of membrane receptors at the nanoscale has major implications in cellular function and signaling. The advent of super-resolution techniques has greatly contributed to our understanding of the cellular membrane. Yet, despite the increased resolution, unbiased quantification of highly dense features, such as molecular aggregates, remains challenging. Here we describe an algorithm based on Bayesian inference of the marker intensity distribution that improves the determination of molecular positions inside dense nanometer-scale molecular aggregates. We tested the performance of the method on synthetic images representing a broad range of experimental conditions, demonstrating its wide applicability. We further applied this approach to STED images of GPI-anchored and model transmembrane proteins expressed in mammalian cells. The analysis revealed subtle differences in the organization of these receptors, emphasizing the role of cortical actin in the compartmentalization of the cell membrane. [ABSTRACT FROM AUTHOR]

Many plant species of great economic value (e.g., potato, wheat, cotton, and sugarcane) are polyploids. Despite the essential roles of autopolyploid plants in human activities, our genetic understanding of these species is still poor. Recent progress in instrumentation and biochemical manipulation has led to the accumulation of an incredible amount of genomic data. In this study, we demonstrate for the first time a successful genetic analysis in a highly polyploid genome (sugarcane) by the quantitative analysis of single-nucleotide polymorphism (SNP) allelic dosage and the application of a new data analysis framework. This study provides a better understanding of autopolyploid genomic structure and is a sound basis for genetic studies. The proposed methods can be employed to analyse the genome of any autopolyploid and will permit the future development of high-quality genetic maps to assist in the assembly of reference genome sequences for polyploid species. [ABSTRACT FROM AUTHOR]

Malaria is a devastating infection caused by protozoa of the genus Plasmodium. Drug resistance is widespread, no new chemical class of antimalarials has been introduced into clinical practice since 1996 and there is a recent rise of parasite strains with reduced sensitivity to the newest drugs. We screened nearly 2 million compounds in GlaxoSmithKline’s chemical library for inhibitors of P. falciparum, of which 13,533 were confirmed to inhibit parasite growth by at least 80% at 2 µM concentration. More than 8,000 also showed potent activity against the multidrug resistant strain Dd2. Most (82%) compounds originate from internal company projects and are new to the malaria community. Analyses using historic assay data suggest several novel mechanisms of antimalarial action, such as inhibition of protein kinases and host–pathogen interaction related targets. Chemical structures and associated data are hereby made public to encourage additional drug lead identification efforts and further research into this disease. [ABSTRACT FROM AUTHOR]

Mothers living with HIV (MLH) are at high risk for acute and chronic stress, given challenges related to their HIV status, ethnicity, economic and urban living conditions. Biomarkers combined into a composite index show promise in quantifying psychosocial stress in healthy people, but have not yet been examined among MLH. According, we examined potential biomarker correlates of stress [cortisol and catecholamines from home-collected urine and basic health indicators (blood pressure, height and weight, waist-to-hip ratio) measured during an interview] among 100 poor African American and Latina mothers MLH and demographic-matched control mothers without HIV ( n = 50). Participants had been enrolled in a randomized controlled trial about 18 months earlier and had either received (MLH-I) or were awaiting (MLH-W) the psychosocial intervention. Participation was high, biomarkers were correctly collected for 93% of cases, and a complete composite biomarker index (CBI) calculated for 133 mothers (mean age = 42). As predicted, MLH had a significantly higher CBI than controls, but there was no CBI difference across ethnicity or intervention group. CBI predicted CD4 counts independently after controlling for age, years since diagnosis, prior CD4 counts, medication adherence, and depression symptoms. The study demonstrates acceptability, feasibility and potential utility of community-based biomarker collections in evaluating individual differences in psychosocial stress. [ABSTRACT FROM AUTHOR]

When building genetic maps, it is necessary to choose from several marker ordering algorithms and criteria, and the choice is not always simple. In this study, we evaluate the efficiency of algorithms try (TRY), seriation (SER), rapid chain delineation (RCD), recombination counting and ordering (RECORD) and unidirectional growth (UG), as well as the criteria PARF (product of adjacent recombination fractions), SARF (sum of adjacent recombination fractions), SALOD (sum of adjacent LOD scores) and LHMC (likelihood through hidden Markov chains), used with the RIPPLE algorithm for error verification, in the construction of genetic linkage maps. A linkage map of a hypothetical diploid and monoecious plant species was simulated containing one linkage group and 21 markers with fixed distance of 3 cM between them. In all, 700 F2 populations were randomly simulated with 100 and 400 individuals with different combinations of dominant and co-dominant markers, as well as 10 and 20% of missing data. The simulations showed that, in the presence of co-dominant markers only, any combination of algorithm and criteria may be used, even for a reduced population size. In the case of a smaller proportion of dominant markers, any of the algorithms and criteria (except SALOD) investigated may be used. In the presence of high proportions of dominant markers and smaller samples (around 100), the probability of repulsion linkage increases between them and, in this case, use of the algorithms TRY and SER associated to RIPPLE with criterion LHMC would provide better results. [ABSTRACT FROM AUTHOR]

Sugarcane ( Saccharum spp.) is a clonally propagated outcrossing polyploid crop of great importance in tropical agriculture. Up to now, all sugarcane genetic maps had been developed using either full-sib progenies derived from interspecific crosses or from selfing, both approaches not directly adopted in conventional breeding. We have developed a single integrated genetic map using a population derived from a cross between two pre-commercial cultivars (‘SP80-180’ × ‘SP80-4966’) using a novel approach based on the simultaneous maximum-likelihood estimation of linkage and linkage phases method specially designed for outcrossing species. From a total of 1,118 single-dose markers (RFLP, SSR and AFLP) identified, 39% derived from a testcross configuration between the parents segregating in a 1:1 fashion, while 61% segregated 3:1, representing heterozygous markers in both parents with the same genotypes. The markers segregating 3:1 were used to establish linkage between the testcross markers. The final map comprised of 357 linked markers, including 57 RFLPs, 64 SSRs and 236 AFLPs that were assigned to 131 co-segregation groups, considering a LOD score of 5, and a recombination fraction of 37.5 cM with map distances estimated by Kosambi function. The co-segregation groups represented a total map length of 2,602.4 cM, with a marker density of 7.3 cM. When the same data were analyzed using JoinMap software, only 217 linked markers were assigned to 98 co-segregation groups, spanning 1,340 cM, with a marker density of 6.2 cM. The maximum-likelihood approach reduced the number of unlinked markers to 761 (68.0%), compared to 901 (80.5%) using JoinMap. All the co-segregation groups obtained using JoinMap were present in the map constructed based on the maximum-likelihood method. Differences on the marker order within the co-segregation groups were observed between the two maps. Based on RFLP and SSR markers, 42 of the 131 co-segregation groups were assembled into 12 putative homology groups. Overall, the simultaneous maximum-likelihood estimation of linkage and linkage phases was more efficient than the method used by JoinMap to generate an integrated genetic map of sugarcane. [ABSTRACT FROM AUTHOR]

Knowledge about genetic variability of a crop allows for more efficient and effective use of resources in plant improvement programs. The genetic variation within temperate maize has been studied extensively, but the levels and patterns of diversity in tropical maize are still not well understood. Brazilian maize germplasm represents a very important pool of genetic diversity due to many past introductions of exotic material. To improve our knowledge of the genetic diversity in tropical maize inbred lines, we fingerprinted 85 lines with 569 AFLP bands and 50 microsatellite loci. These markers revealed substantial variability among lines, with high rates of polymorphism. Cluster analysis was used to identify groups of related lines. Well-defined groups were not observed, indicating that the tropical maize studied is not as well organized as temperate maize. Three types of genetic distance measurements were applied (Jaccard’s coefficient, Modified Rogers’ distance and molecular coefficient of coancestry), and the values obtained with all of them indicated that the genetic similarities were small among the lines. The different coefficients did not substantially affect the results of cluster analysis, but marker types had a large effect on genetic similarity estimates. Regardless of genetic similarity coefficient used, estimates based on AFLPs were poorly correlated with those based on SSRs. Analyses using AFLP and SSR data together do not seem to be the most efficient manner of assessing variability in highly diverse materials because the result was similar to using AFLPs alone. It was seen that molecular markers can help to organize the genetic variability and expose useful diversity for breeding purposes. [ABSTRACT FROM AUTHOR]

Aplidin (APL) is a new antitumoral drug from marine origin currently in phase II clinical trials against a wide multiplicity of cancers. As resistance may be, as with other drugs, an important obstacle to the APL therapeutic efficacy, we have established an acquired resistance cellular model by continuous exposure of HeLa cells to the drug. The stably resistant subline generated (HeLa-APL), possessing more than 1000-fold relative resistance to APL than parental cells, did not show crossresistance to a subset of clinically relevant antitumoral agents. In addition, resistance was not related to overexpression of P-glycoprotein or differences in overall drug accumulation. Comparing to parental cells, HeLa-APL cells did not present either significant differences in the growth rate or apparent alterations in the cell cycle distribution. Aplidin induced rapid and persistent phosphorylation of both JNK and p38 MAPKs, resulting in activation of the mitochondrial apoptotic pathway in parental cells, but, notably, in HeLa-APL-resistant cells MAPKs activation only occurred in a slight and transiently manner, failing to activate the above-mentioned apoptotic machinery. These results suggest that sustained activation of JNK and p38 is essential for triggering the apoptotic programme induced by APL and that HeLa-APL cells bypass this apoptotic response by preventing the specific mechanisms that prime and sustain the long-term activation of these signalling cascades. Although far from human tumour physiology in vivo, HeLa-APL cells represent a potentially useful tool in gaining insights into the mode of action of APL, in selecting non-crossresistant APL structural analogues, as well as in investigating and developing methods to prevent resistance to this drug. [ABSTRACT FROM AUTHOR]

Examines the molecular events induced by Aplidin™ in human HeLa tumor cells, characterizing the apoptotic program which causes its cytotoxicity. Analysis of the time-dependent effects of Aplidin™ on the viability of HeLa cells; Description of the oxidative stress on Aplidin™-mediated apoptosis; Effect of Aplidin™ on mitogen-activated protein kinases family activity.

In studies of apical membrane current-voltage relationships, in order to avoid laborious intracellular microelectrode techniques, tight epithelia are commonly exposed to high serosal K concentrations. This approach depends on the assumptions that high serosal K reduces the basolateral membrane resistance and potential to insignificantly low levels, so that transepithelial values can be attributed to the apical membrane. We have here examined the validity of these assumptions in frog skins (Rana pipiens pipiens). The skins were equilibrated in NaCl Ringer's solutions, with transepithelial voltage Vt clamped (except for brief perturbations delta Vt) at zero. The skins were impaled from the outer surface with 1.5 M KCl-filled microelectrodes (Rel greater than 30 M omega). The transepithelial (short-circuit) current It and conductance gt = -delta It/delta Vt, the outer membrane voltage Vo (apical reference) and voltage-divider ratio (Fo = delta Vo/delta Vt), and the microelectrode resistance Rel were recorded continuously. Intermittent brief apical exposure to 20 microM amiloride permitted estimation of cellular (c) and paracellular (p) currents and conductances. The basolateral (inner) membrane conductance was estimated by two independent means: either from values of gt and Fo before and after amiloride or as the ratio of changes (-delta Ic/delta Vi) induced by amiloride. On serosal substitution of Na by K, within about 10 min, Ic declined and gt increased markedly, mainly as a consequence of increase in gp. The basolateral membrane voltage Vi (= -Vo) was depolarized from 75 +/- 4 to 2 +/- 1 mV [mean +/- SEM (n = 6)], and was partially repolarized following amiloride to 5 +/- 2 mV.(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

Intracellular Na+, K+, and Cl- activities (aiNa, aiK, aiCl) and transapical membrane potentials (V0) were measured with liquid ion-exchanger and open-tip microelectrodes in isolated short-circuited frog skins (R. pipiens) incubated at 23 degrees C in normal amphibian Ringer's solution. Under control conditions aiNa = 14 +/- 3 mM, aiK = 132 +/- 10 mM and aiCl = 18 +/- 3 mM (SD). The value of aiCl is 4.4 times the value corresponding to electrochemical equilibrium for this ion. Thus, Cl- is actively accumulated by epithelial cells of the frog skin. Shortly after addition of amiloride (2--5 microM) to the apical bathing medium, aiK, aiNa, and aiCl were essentially unchanged although V0 had hyperpolarized by about 30--40 mV. During long-term exposure to amiloride aiK and aiCl did not change significantly, V0 depolarized by about 16 mV from the maximal value and aiNa decreased to 8 +/- 3 mM. Immediately after exposure to amiloride the transmembrane driving force for Na+ increased from 124 to 154 mV. During further exposure to amiloride, despite changes in both V0 and aiNa, this driving force remained virtually constant. Since Isc during this period was close to zero, it is suggested that the observed driving force for Na+ under these condition approximates the maximal driving force generated by the Na+--K+ ATP-ase pump in the basolateral cell membrane. [ABSTRACT FROM AUTHOR]

The article offers the author's views on the emergence of optical antennas as tools for nanobioimaging by enhancing optical fields on a nanometre scale. It states that the main focus in nanophotonic research is to localize and enhance the optical radiation on the nanometre scale. The author opines that the reduction in detection volume enabled by optical antenna can make possible to investigate processes between individual molecules, but more research is needed before practical applications.

The cacao tree (Theobroma cacao L.) is a species of great importance because cacao beans are the raw material used in the production of chocolate. However, the economic success of cacao is largely limited by important diseases such as black pod, which is responsible for losses of up to 30-40% of the global cacao harvest. The discovery of resistance genes could extensively reduce these losses. Therefore, the aims of this study were to construct an integrated multipoint genetic map, align polymorphisms against the available cacao genome, and identify quantitative trait loci (QTLs) associated with resistance to black pod disease in cacao. The genetic map had a total length of 956.41 cM and included 186 simple sequence repeat (SSR) markers distributed among 10 linkage groups. The physical “in silico” map covered more than 200 Mb of the cacao genome. Based on the mixed model predicted means of Phytophthora evaluation, a total of 6 QTLs were detected for Phytophthora palmivora (1 QTL), Phytophthora citrophthora (1 QTL), and Phytophthora capsici (4 QTLs). Approximately 1.77-3.29% of the phenotypic variation could be explained by the mapped QTLs. Several SSR marker-flanking regions containing mapped QTLs were located in proximity to disease regions. The greatest number of resistance genes was detected in linkage group 6, which provides strong evidence for a QTL. This joint analysis involving multipoint and mixed-model approaches may provide a potentially promising technique for detecting genes resistant to black pod and could be very useful for future studies in cacao breeding. [ABSTRACT FROM AUTHOR]