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Withania somnifera, popularly known as Indian ginseng, is one of the most important medicinal plants. The plant is well studied in terms of its pharmaceutical activities and genes involved in biosynthetic pathways. However, not much is known about the regulatory mechanism of genes responsible for the production of secondary metabolites. The idea was to identify miRNA transcriptome responsible for the regulation of withanolide biosynthesis, specifically of root and leaf tissues individually. The transcriptome data of in vitro culture of root and leaf tissues of the plant was considered for miRNA identification. A total of 24 and 39 miRNA families were identified in root and leaf tissues, respectively. Out of these, 15 and 27 miRNA families have shown their involvement in different biological functions in root and leaf tissues, respectively. We report here, specific miRNAs and their corresponding target genes for corresponding root and leaf tissues. The target genes have also been analyzed for their role in withanolide metabolism. Endogenous root-miR5140, root-miR159, leaf-miR477, and leaf-miR530 were reported for regulation of withanolide biosynthesis. [ABSTRACT FROM AUTHOR]

The possibility that diet-derived miRNAs survive the gastrointestinal tract and exert biological effects in target cells is triggering considerable research in the potential abilities of alimentary preventive and therapeutic approaches. Many validation attempts have been carried out and investigators disagree on several issues. The barriers exogenous RNAs must surpass are harsh and adequate copies must reach target cells for biological actions to be carried out. This prospect opened a window for previously unlikely scenarios concerning exogenous non-coding RNAs, such as a potential role for breast milk microRNAs in infants’ development and maturation. This review is focused on the thorny path breast milk miRNAs face towards confirmation as relevant role players in infants’ development and maturation, taking into consideration the research carried out so far on the uptake, gastrointestinal barriers and potential biological effects of diet-derived miRNAs. We also discuss the future pharmacological and pharma-nutritional consequences of appropriate miRNAs research. [ABSTRACT FROM AUTHOR]

This article explores the perceptions of Ogoni people about the existence and causes of structural violence in their communities. It relies heavily on qualitative data collected from five oil-rich and three oil-poor Ogoni communities, between February and May 2014, during which 200 open-ended survey questionnaires were administered and 189 were returned. Three focus group discussions and 69 key informant interviews were also conducted. The findings of the article are that structural violence can be found in Ogoniland; it is manifested in both visible and invisible forms; it is blamed by elites on exogenous factors, but by the disadvantaged on both exogenous and endogenous factors; and it will only be eliminated by reducing inequality and increasing democratisation. [ABSTRACT FROM AUTHOR]

Alveolar macrophages are key contributors to both the promotion and resolution of inflammation in the lung and are categorized into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. The change in M1/M2 balance has been reported in various pulmonary diseases and is a target for therapeutic intervention. The aim of this study was to assess the modulation of M1/M2 phenotype in alveolar macrophages by water-soluble carbon monoxide-releasing molecule-3 (CORM-3). Rat alveolar macrophages (AM) (NR8383) in culture were stimulated with LPS (5 ng/ml)/IFN-γ (10 U/ml) or IL-4 (10 ng/ml)/IL-13 (10 ng/ml) to induce M1 and M2 phenotypes, respectively. Expression of M1 phenotype markers, iNOS and TNF-α, and M2 phenotype markers, CD206 and Ym-1, was assessed by western blotting after 1, 3, 6, or 24 h in the absence or presence of CORM-3 (0.15 mM) treatment. Inactive CORM-3 (iCORM-3) was used as a control. Treatment of naïve (unstimulated) AM with CORM-3 promoted progression of the M2 phenotype as evidenced by the increased expression of CD206 (at 1 h; 1.8-fold) and Ym-1 (at 3 h; 1.9-fold), respectively. Surprisingly, CORM-3 treatment also upregulated the expression of iNOS protein as assessed 6 h following stimulation of AM with CORM-3 (2.6-fold). On the contrary, CORM-3 effectively reduced LPS/IFN-γ-induced expression of iNOS protein (0.6-fold); however, it had no effect on TNF-α expression. Finally, CORM-3 acutely (1-3 h) upregulated CD206 (1.4-fold) and Ym-1 (1.6-fold) levels in IL-4-/IL-13-treated (M2-stimulus) macrophages. These findings indicate that CORM-3 modulates macrophage M1 and M2 phenotypes in vitro with respect to continuous suppression of iNOS expression in M1-polarized macrophages and transient (early-phase) upregulation of CD206 and Ym-1 proteins in M2-polarized macrophages. [ABSTRACT FROM AUTHOR]

This article presents an overview of the specific roles that business knowledge transfer, indigenization and human-development resource management (HDRM) play in the People’s Republic of China. By comparing American, Japanese and Soviet business and management theory and practice, the article analyzes exogenous and indigenous influences through time on China’s HDRM, in terms of their historical roots, as well as by presenting possible explanations for national adaptations to cultural, institutional and legal norms. The study views the impact of business-knowledge transfer on Chinese HDRM theory and practice as a dynamic process, leading to the evolution of a ‘hybrid’, indigenized national HDRM framework, still unfolding. Despite the study’s qualifications, the article offers recommendations for future research. [ABSTRACT FROM AUTHOR]

Summary: Multivariate polynomial regression (MPR) analysis was implemented to develop a nonlinear dynamic material flow model (DMFM) of tungsten in the United States for the years 1975–2000 without assumptions for lifetime distributions within reservoirs. Two external economic factors, the Consumer Price Index and the Industrial Production Index, were included as possible exogenous variables. Six types of vector time‐series models were developed using multilinear, simple interaction, and MPR models, each with and without the exogenous economic variables. The DMFMs developed in this work make one‐step‐ahead predictions. That is, the material flows in a given year were predicted using flows and exogenous variables from previous years. In contrast to approaches that utilize assumed lifetime distributions for material within reservoirs, such as the Weibull distribution, the approach used here is completely data driven. MPR models produced statistically better results than linear models for all 13 flows that were modeled. Four of these models used simple interaction terms (which we call linear interaction terms), and two of these incorporated exogenous variables. The other nine models utilized higher‐degree terms with interactions (called multivariate polynomial terms), and two of these incorporated exogenous variables. We conclude that nonlinear vector time series are capable of identifying complex relationships among material flows and exogenous variables. An understanding of these relationships has potential for managing, conserving, and/or forecasting the use of a resource. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the expression and effect of cytochrome c (Cytc) in patients with primary Sjogren's syndrome (pSS). In total, 35 newly diagnosed pSS patients and 35 healthy subjects were enrolled in the present study. The mRNA expression levels of Cytc were detected using reverse transcription.polymerase chain reaction and RT.quantitative PCR. The expression of the Cytc protein in labial salivary glands was detected by immunohistochemistry and was associated with the integral optical density (IOD) of clinical and laboratory variables. In addition, the content of Cytc in the cytoplasm and mitochondria were examined. The mRNA and protein expression levels of Cytc, and the content of Cytc in the cytoplasm of the pSS patients was increased significantly compared with the healthy controls (P<0.05). The content of Cytc in the mitochondria was significantly decreased compared with the healthy controls (P<0.05). The IOD of Cytc protein levels was positively correlated with immunoglobin G (r=0.8142, P<0.05) and erythrocyte sedimentation rate (r=0.7512, P<0.05). Cytc was upregulated in the pSS patients, indicating the potential role of Cytc in the pathogenesis and development of pSS. Further studies may facilitate the development of targeting this molecular pathway for the treatment of pSS. [ABSTRACT FROM AUTHOR]

Carbohydrate (CHO) ingestion during exercise lasting less than three hours improves endurance exercise performance but there is still debate about the optimal dose. We utilised stable isotopes and blood metabolite profiles to further examine metabolic responses to CHO (glucose only) ingestion in the 20-64 g⋅h-1 range, and to determine the association with performance outcome. In a double-blind, randomized cross-over design, male cyclists (n = 20, mean ± SD, age 34 ± 10 years, mass 75.8 ± 9 kg, peak power output 394 ± 36 W, VO2max 62 ± 9 mL⋅kg-1⋅min-1) completed four main experimental trials. Each trial involved a two-hour constant load ride (185 ± 25 W) followed by a time trial, where one of three CHO beverages, or a control (water), were administered every 15 min, providing 0, 20, 39 or 64 g CHO⋅h-1. Dual glucose tracer techniques, indirect calorimetry and blood analyses were used to determine glucose kinetics, exogenous CHO oxidation (EXO), endogenous CHO and fat oxidation; and metabolite responses. Regression analysis revealed that total exogenous CHO oxidised in the second hour of exercise, and suppression of serum NEFA concentration provided the best prediction model of performance outcome. However, the model could only explain ~19% of the variance in performance outcome. The present data demonstrate that consuming ~40 g⋅h-1 of CHO appears to be the minimum ingestion rate required to induce metabolic effects that are sufficient to impact upon performance outcome. These data highlight a lack of performance benefit and few changes in metabolic outcomes beyond an ingestion rate of 39 g⋅h-1. Further work is required to explore dose-response effects of CHO feeding and associations between multiple metabolic parameters and subsequent performance outcome. [ABSTRACT FROM AUTHOR]

Anthropoid primates arose during the Eocene approximately 55 million years ago (mya), and extant anthropoids share a most recent common ancestor ∼40 mya. Paleontology has been very successful at describing the morphological phenotypes of extinct anthropoids. Less well understood is the molecular biology of these extinct species as well as the phenotypic consequences of evolutionary variation in their genomes. Here we resurrect the most recent common ancestral anthropoid estrogen receptor β gene ( ESR2 ) and demonstrate that the function of this ancestral estrogen receptor has been maintained during human descent but was altered during early New World monkey (NWM) evolution by becoming a more potent transcriptional activator. We tested hypotheses of adaptive evolution in the protein coding sequences of ESR2 , and determined that ESR2 evolved via episodic positive selection on the NWM stem lineage. We separately co-transfected ESR2 constructs for human, NWM, and the anthropoid ancestor along with reporter gene vectors and performed hormone binding dose response experiments that measure transactivation activity. We found the transactivation potentials of the ancestral and human sequences to be significantly lower (p < 0.0001 in each comparison) than that of the NWM when treated with estradiol, the most prevalent estrogen. We conclude the difference in fold activation is due to positive selection in the NWM ERβ ligand binding domain. Our study validates inferential methods for detecting adaptive evolution that predict functional consequences of nucleotide substitutions and points a way toward examining the functional consequences of positive Darwinian selection. [ABSTRACT FROM AUTHOR]

Increasing susceptibility of broiler chickens to ascites syndrome has coincided with a continuing genetic and nutritional improvement in their feed efficiency and growth rate. Imbalance between oxygen supply and the oxygen required to sustain rapid growth rates and high food efficiencies is believed to be the primary cause of ascites. This imbalance is caused by exogenous and/or endogenous factors. Selection in fast growth broilers, have also resulted in the development of birds with changed anatomical, physiological, metabolic and hematological parameters including thyroid hormone activity, partial pressure of O2 and carbon dioxide in venous blood, cardiac β-adrenergic receptors and hematocrit levels that coincide with susceptibility to ascites in broiler chickens. Observations to date have indicated that the structural or endocrine changes are often linked with ascites susceptibility and may be influenced during the early stages of development, embryogenesis and incubation. In this review, particular attention is paid to the interactions between endogenous and exogenous factors as predisposing factors for development of ascites syndrome. Additionally, preventive management procedures like different lighting schedules, feed restriction protocols and supplementation of feed with antioxidants which reduce the incidence of ascites in broiler chickens are highlighted.

Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE) (1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE) (~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S) (~25 g/kg/day, KS), and βHB-S + medium chain triglyceride (MCT) (~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance travelled in open arms (chronic KS and KSMCT: SPD rats), and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a novel means of inducing nutritional ketosis.

Existing research has found that spatial attention alters how various stimulus properties are perceived (e.g., luminance, saturation), but few have explored whether it improves the accuracy of perception. To address this question, we performed two experiments using modified Posner cueing tasks, wherein participants made speeded detection responses to peripheral colour targets and then indicated their perceived colours on a colour wheel. In E1, cues were central and endogenous (i.e., prompted voluntary attention) and the interval between cues and targets (stimulus onset asynchrony, or SOA) was always 800 ms. In E2, cues were peripheral and exogenous (i.e., captured attention involuntarily) and the SOA varied between short (100 ms) and long (800 ms). A Bayesian mixed-model analysis was used to isolate the effects of attention on the probability and the fidelity of colour encoding. Both endogenous and short-SOA exogenous spatial cueing improved the probability of encoding the colour of targets. Improved fidelity of encoding was observed in the endogenous but not in the exogenous cueing paradigm. With exogenous cues, inhibition of return (IOR) was observed in both RT and probability at the long SOA. Overall, our findings reinforce the utility of continuous response variables in the research of attention.

The idea that covert mental processes such as spatial attention are fundamentally dependent on systems that control overt movements of the eyes has had a profound influence on theoretical models of spatial attention. However, theories such as Klein’s Oculomotor Readiness Hypothesis (OMRH) and Rizzolatti’s Premotor Theory have not gone unchallenged. We previously argued that although OMRH/Premotor theory is inadequate to explain pre-saccadic attention and endogenous covert orienting, it may still be tenable as a theory of exogenous covert orienting. In this article we briefly reiterate the key lines of argument for and against OMRH/Premotor theory, then evaluate the Oculomotor Readiness account of Exogenous Orienting (OREO) with respect to more recent empirical data. These studies broadly confirm the importance of oculomotor preparation for covert, exogenous attention. We explain this relationship in terms of reciprocal links between parietal ‘priority maps’ and the midbrain oculomotor centres that translate priority-related activation into potential saccade endpoints. We conclude that the OMRH/Premotor theory hypothesis is false for covert, endogenous orienting but remains tenable as an explanation for covert, exogenous orienting.

In this study, we reviewed state-of-the-art endogenous-based and exogenous-based stimuli-responsive drug delivery systems (DDS) for programmed site-specific release to overcome the drawbacks of conventional therapeutic modalities. This particular work focuses on the smart chemistry and mechanism of action aspects of several types of stimuli-responsive polymeric carriers that play a crucial role in extracellular and intracellular sections of diseased tissues or cells. With ever increasing scientific knowledge and awareness, research is underway around the globe to design new types of stimuli (external/internal) responsive polymeric carriers for biotechnological applications at large and biomedical and/or pharmaceutical applications, in particular. Both external/internal and even dual/multi-responsive behavior of polymeric carriers is considered an essential element of engineering so-called ‘smart’ DDS, which controls the effective and efficient dose loading, sustained release, individual variability, and targeted permeability in a sophisticated manner. So far, an array of DDS has been proposed, developed, and implemented. For instance, redox, pH, temperature, photo/light, magnetic, ultrasound, and electrical responsive DDS and/or all in all dual/dual/multi-responsive DDS (combination or two or more from any of the above). Despite the massive advancement in DDS arena, there are still many challenging concerns that remain to be addressed to cover the research gap. In this context, herein, an effort has been made to highlight those concerning issues to cover up the literature gap. Thus, the emphasis was given to the drug release mechanism and applications of endogenous and exogenous based stimuli-responsive DDS in the clinical settings.

A 93-year-old male presented with left eye pain, fever and loss of vision two days after complicated cataract surgery. A diagnosis of Serratia marcescens endophthalmitis and systemic bacteremia was made after the organism was identified on vitreous and peripheral blood cultures. This case demonstrates that an aggressive intraocular infection can lead to bacteremia [ABSTRACT FROM AUTHOR]

Quantitative predictions are ubiquitous in ecology, yet there is limited discussion on the nature of prediction in this field. Herein I derive a general quantitative framework for analyzing and partitioning the sources of uncertainty that control predictability. The implications of this framework are assessed conceptually and linked to classic questions in ecology, such as the relative importance of endogenous (density-dependent) vs. exogenous factors, stability vs. drift, and the spatial scaling of processes. The framework is used to make a number of novel predictions and reframe approaches to experimental design, model selection, and hypothesis testing. Next, the quantitative application of the framework to partitioning uncertainties is illustrated using a short-term forecast of net ecosystem exchange. Finally, I advocate for a new comparative approach to studying predictability across different ecological systems and processes and lay out a number of hypotheses about what limits predictability and how these limits should scale in space and time. [ABSTRACT FROM AUTHOR]

Retrovirus genes have become inserted into the human genome for more than one million years. These retroviruses are now inactivated due to mutation, such as deletions or nonsense mutations. After mutation, retroviruses eventually become fixed in the genome in the endogenous form and exist as traces of ancient viruses. These retroviruses are called human endogenous retroviruses (HERVs). HERVs cannot make fully active viruses, but a number of viral proteins (or even virus particles) are expressed under various conditions. By comparison with ERVs, some exogenous retroviruses are still infectious and cause serious diseases threatening human life. Recent studies have shown that some elements of HERVs are closely related to other exogenous retroviruses, including human immunodeficiency virus (HIV). This review will describe the regulation and interaction between HERVs and other active viral infections. In addition, we introduce the development of vaccines and therapeutic agents against these viral infections through the use of HERV elements. [ABSTRACT FROM AUTHOR]

It is generally-accepted that the presentation of an auditory cue will direct an observer's spatial attention to the region of space from where it originates and therefore facilitate responses to visual targets presented there rather than from a different position within the cued hemifield. However, to date, there has been surprisingly limited evidence published in support of such within-hemifield crossmodal exogenous spatial cuing effects. Here, we report two experiments designed to investigate within- and between-hemifield spatial cuing effects in the case of audiovisual exogenous covert orienting. Auditory cues were presented from one of four frontal loudspeakers (two on either side of central fixation). There were eight possible visual target locations (one above and another below each of the loudspeakers). The auditory cues were evenly separated laterally by 30° in Experiment 1, and by 10° in Experiment 2. The potential cue and target locations were separated vertically by approximately 19° in Experiment 1, and by 4° in Experiment 2. On each trial, the participants made a speeded elevation (i.e., up vs. down) discrimination response to the visual target following the presentation of a spatially-nonpredictive auditory cue. Within-hemifield spatial cuing effects were observed only when the auditory cues were presented from the inner locations. Between-hemifield spatial cuing effects were observed in both experiments. Taken together, these results demonstrate that crossmodal exogenous shifts of spatial attention depend on the eccentricity of both the cue and target in a way that has not been made explicit by previous research. [ABSTRACT FROM AUTHOR]

Bioleaching has been widely applied to recover sulfide minerals, however, little is known about the bioleaching behavior and mechanism of mixed oxide-sulfide copper ore with high-oxidative ratio. The leaching efficiency of artificial indigenous and exogenous microbial communities on a mixed oxide-sulfide copper ore with and without energy substrate was investigated. The results indicated that extra energy substrate was needed when bioleaching was applied to this kind of ore. The variation of leaching parameters caused by indigenous community was inferior to that caused by exogenous ones due to its lower activity. The leaching efficiency of sulfide part induced by indigenous strains was superior to that induced by exogenous ones, due to the stronger colonization ability of indigenous strains. It verified that both microbial activity and colonization ability were important properties affecting leaching efficiency. Sulfur oxidizers, which can oxidize sulfur or polysulfide formed on mineral surface and decrease leachate pH, played a more important role than ferrous oxidizers in bioleaching of high-oxidative oxide-sulfide ore. [ABSTRACT FROM AUTHOR]

The majority of commonly used anesthetic agents induce widespread neuronal degeneration in the developing mammalian brain. Downstream, the process appears to involve activation of the oxidative stress-associated mitochondrial apoptosis pathway. Targeting this pathway could result in prevention of anesthetic toxicity in the immature brain. Carbon monoxide (CO) is a gas that exerts biological activity in the developing brain and low dose exposures have the potential to provide neuroprotection. In recent work, low concentration CO exposures limited isoflurane-induced neuronal apoptosis in a dose-dependent manner in newborn mice and modulated oxidative stress within forebrain mitochondria. Because infants and children are routinely exposed to low levels of CO during low-flow general endotracheal anesthesia, such anti-oxidant and pro-survival cellular effects are clinically relevant. Here we provide an overview of anesthesia-related CO exposure, discuss the biological activity of low concentration CO, detail the effects of CO in the brain during development, and provide evidence for CO-mediated inhibition of anesthesia-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Recording electrodermal activity is a well-accepted physiological measurement for clinical approaches and research. Historically, applying a DC (direct current) signal to the skin to measure the conductance is the most common practice for exogenous recordings. However, this method can be subject to error due to electrode polarization even with 'nonpolarizing' electrodes-a problem that can be eliminated with alternating current (AC) methodology. For that reason, Boucsein et al. () called for research demonstrating an AC method that is validated by comparison to standard DC methodology. Additionally, the complex structure of human skin has electrical properties that include both resistance and capacitance, and AC recording enables the measurement of skin susceptance (associated with current flow through capacitors). Finally, AC recording permits the simultaneous recording of the endogenous skin potential. In this paper, the results from a direct comparison between both methods are presented, which has not been reported previously. The results demonstrated excellent agreement between a 20 Hz AC method and a standard DC method, supporting the validity of the AC recording methodology employed. The results also showed that an applied voltage of 0.2 V is sufficient for DC recordings. [ABSTRACT FROM AUTHOR]

Although essential for artificial insemination (AI) and MOET (multiple ovulation and embryo transfer), oestrus synchronisation and superovulation are associated with increased female reproductive tract mucus production and altered sperm transport. The effects of such breeding practices on the ovine cervicovaginal (CV) mucus proteome have not been detailed. The aim of this study was to qualitatively and quantitatively investigate the Merino CV mucus proteome in naturally cycling (NAT) ewes at oestrus and mid-luteal phase, and quantitatively compare CV oestrus mucus proteomes of NAT, progesterone synchronised (P4) and superovulated (SOV) ewes. Quantitative analysis revealed 60 proteins were more abundant during oestrus and 127 were more abundant during the luteal phase, with 27 oestrus specific and 40 luteal specific proteins identified. The oestrus proteins most disparate in abundance compared to mid-luteal phase were ceruloplasmin (CP), chitinase-3-like protein 1 (CHI3L1), clusterin (CLU), alkaline phosphatase (ALPL) and mucin-16 (MUC16). Exogenous hormones greatly altered the proteome with 51 and 32 proteins more abundant and 98 and 53 proteins less abundant, in P4 and SOV mucus, respectively when compared to NAT mucus. Investigation of the impact of these proteomic changes on sperm motility and longevity within mucus may help improve sperm transport and fertility following cervical AI. Significance This manuscript is the first to detail the proteome of ovine cervicovaginal mucus using qualitative and quantitative proteomic methods over the oestrous cycle in naturally cycling ewes, and also after application of common oestrus synchronisation and superovulation practices. The investigation of the mucus proteome throughout both the follicular and luteal periods of the oestrous cycle, and also after oestrous synchronisation and superovulation provides information about the endocrine control and the effects that exogenous hormones have on protein expression in the female reproductive tract. This information contributes to the field by providing important information on the changes that occur to the cervicovaginal mucus proteome after use of exogenous hormones in controlled breeding programs, which are commonly used on farm and also in a research setting. [ABSTRACT FROM AUTHOR]

Bone fracture healing is a complicated physiological regenerative process initiated in response to injury and is similar to bone development. To demonstratewhether an exogenous supply of parathyroid hormone-related protein (PTHrP) helps in bone fracture healing, closed mid-diaphyseal femur fractures were created and stabilized with intramedullary pins in eight-week-old wild-type (WT) PTHrP+/+ and PTHrP+/- mice. After administering PTHrP for two weeks, callus tissue properties were analyzed at one, two, and four weeks post-fracture (PF) by various methods. Bone formation-related genes and protein expression levels were evaluated by real-time reverse transcriptase-polymerase chain reaction and Western blots. At two weeks PF, mineral density of callus, bony callus areas, mRNA levels of alkaline phosphatase (ALP), type I collagen, Runt-related transcription factor 2 (Runx-2), and protein levels of Runx-2 and insulin-like growth factor-1 decreased in PTHrP+/- mice compared with WT mice. At four weeks PF, total collagen-positive bony callus areas, osteoblast number, ALP-positive areas, and type I collagen-positive areas all decreased in PTHrP+/- mice. At both two and four weeks PF, tartrate-resistant acid phosphatase-positive osteoclast number and surface decreased a little in PTHrP+/- mice. The study indicates that exogenous PTHrP provided by subcutaneous injection could redress impaired bone fracture healing, leading to mutation of activated PTHrP by influencing callus areas, endochondral bone formation, osteoblastic bone formation, and bone turnover. [ABSTRACT FROM AUTHOR]

Koala populations are in serious decline across many areas of mainland Australia, with infectious disease a contributing factor. Koala retrovirus (KoRV) is a gammaretrovirus present in most wild koala populations and captive colonies. Five subtypes of KoRV (A to E) have been identified based on amino acid sequence divergence in a hypervariable region of the receptor binding domain of the envelope protein. However, analysis of viral genetic diversity has been conducted primarily on KoRV in captive koalas housed in zoos in Japan, the United States, and Germany. Wild koalas within Australia have not been comparably assessed. Here we report a detailed analysis of KoRV genetic diversity in samples collected from 18 wild koalas from southeast Queensland. By employing deep sequencing we identified 108 novel KoRV envelope sequences and determined their phylogenetic diversity. Genetic diversity in KoRV was abundant and fell into three major groups; two comprised the previously identified subtypes A and B, while the third contained the remaining hypervariable region subtypes (C, D, and E) as well as four hypervariable region subtypes that we newly define here (F, G, H, and I). In addition to the ubiquitous presence of KoRV-A, which may represent an exclusively endogenous variant, subtypes B, D, and F were found to be at high prevalence, while subtypes G, H, and I were present in a smaller number of animals. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small regulatory RNAs that play important roles in animals, plants, and viruses. Deep-sequencing technology has been widely adopted in miRNA investigations. However, it is still a big mysterious why nearly all sequencing data contain miRNA sequences from exogenous species, called exo-miRNAs. In this study, we developed a novel platform, exo-miRExplorer, for mining and identifying exo-miRNAs from high-throughput small RNA sequencing experiments which originated from tissues and cell lines of multiple organisms. Thousands of exo-miRNAs are characterized with their expression abundance, the RNA families, original organisms and the sequencing platforms presented in exo-miRExplorer. Subsequently, we used exo-miRExplorer to perform further analysis. Comparative analysis of the exo-miRNAs between different sequencing datasets revealed significant correlation of exo-miRNAs between experiments in the same study. The plant-derived exo-miRNAs analysis provided robust evidence for non-diet source of exo-miRNAs. Virus-derived exo-miRNA analysis showed that pathogen RNAs could transfer to host cells and exist in deep-sequencing result at abundance level. In conclusion, exo-miRExplorer provides users with an integrative resource to facilitate detection and analysis of exo-miRNAs. exo-miRExplorer is available at the following URL:http://rna.sysu.edu.cn/exomiRDB/. [ABSTRACT FROM AUTHOR]

Multisensory integration (MSI) and exogenous spatial attention can both speedup responses to perceptual events. Recently, it has been shown that audiovisual integration at exogenously attended locations is reduced relative to unattended locations. This effect was observed at short cue-target intervals (200-250 ms). At longer intervals, however, the initial benefits of exogenous shifts of spatial attention at the cued location are often replaced by response time (RT) costs (also known as Inhibition of Return, IOR). Given these opposing cueing effects at shorter versus longer intervals, we decided to investigate whether MSI would also be affected by IOR. Uninformative exogenous visual spatial cues were presented between 350 and 450 ms prior to the onset of auditory, visual, and audiovisual targets. As expected, IOR was observed for visual targets (invalid cue RT

The paper proposes the analysis of a Basic New Keynesian model with imperfect competition in goods market and price adjustment mechanism for the macroeconomic context of Romania, as an emerging country. Given the vulnerabilities of the economy of Romania at the beginning and during the recent global economic and financial crisis, there is an increased interest to identify models that can explain the main features of Romania macroeconomic data and to put an eye on shocks that are really necessary to describe the stochastic dynamic of macroeconomic variables. [ABSTRACT FROM AUTHOR]

The endogenous metabolites excreted by organisms into their surrounding environment, termed the exometabolome, are important for many processes including chemical communication. In fish biology, such metabolites are also known to be informative markers of physiological status. While metabolomics is increasingly used to investigate the endogenous biochemistry of organisms, no non-targeted studies of the metabolic complexity of fish exometabolomes have been reported to date. In environmental chemistry, Chemcatcher® (Portsmouth, UK) passive samplers have been developed to sample for micro-pollutants in water. Given the importance of the fish exometabolome, we sought to evaluate the capability of Chemcatcher® samplers to capture a broad spectrum of endogenous metabolites excreted by fish and to measure these using non-targeted direct infusion mass spectrometry metabolomics. The capabilities of C18 and styrene divinylbenzene reversed-phase sulfonated (SDB-RPS) Empore™ disks for capturing non-polar and polar metabolites, respectively, were compared. Furthermore, we investigated real, complex metabolite mixtures excreted from two model fish species, rainbow trout (Oncorhynchus mykiss) and three-spined stickleback (Gasterosteus aculeatus). In total, 344 biological samples and 28 QC samples were analysed, revealing 646 and 215 m/z peaks from trout and stickleback, respectively. The measured exometabolomes were principally affected by the type of Empore™ (Hemel Hempstead, UK) disk and also by the sampling time. Many peaks were putatively annotated, including several bile acids (e.g., chenodeoxycholate, taurocholate, glycocholate, glycolithocholate, glycochenodeoxycholate, glycodeoxycholate). Collectively these observations show the ability of Chemcatcher® passive samplers to capture endogenous metabolites excreted from fish. [ABSTRACT FROM AUTHOR]

Clinical laboratory medicine is involved in the vast majority of patient care pathways. It has been estimated that pathology results inform 60–70% of critical patient care decisions. The primary goal of the laboratory is to produce precise and accurate results which reflect the true situation in vivo. It is not surprising that interference occurs in laboratory analysis given the complexity of some of the assays used to perform them. Interference is defined as “the effect of a substance upon any step in the determination of the concentration or catalytic activity of the metabolite”. Exogenous interferences are defined as those that derive from outside of the body and are therefore not normally found in a specimen and can cause either a positive or negative bias in analytical results. Interferences in analysis can come from various sources and can be classified as endogenous or exogenous. Exogenous substances could be introduced at any point in the sample journey. The laboratory must take responsibility for the quality of results produced. It has a responsibility to have processes in place to identify and minimise the occurrence and effect contamination and interference. To do this well the laboratory needs to work with clinicians and manufacturers. Failure to identify an erroneous result could have an impact on patient care, patient safety and also on hospital budgets. However it is not always easy to recognise interferences. This review summarises the types and sources of exogenous interference and some steps to minimise the impact they have. [ABSTRACT FROM AUTHOR]

Population fluctuations are driven by a combination of multiple factors, which can be classified into endogenous and exogenous. Endogenous factors are directly related to density-dependent forces, whereas exogenous factors are environmental drivers (e.g. climate). Several studies have reported the effects of endogenous and exogenous factors using exponential population models in mammals, birds or insects, but few works have explored the effects on reptiles, specifically in tortoises. In this study, we developed logistic population growth models to decipher the role of these factors on the population dynamics of the spur-thighed tortoise Testudo graeca. The role of environmental drivers in the distribution, movement, survival, reproduction or individual growth has been described for this species in previous works, but no studies have examined the effects of both endogenous and exogenous factors in population growth rates. Using long-term data of T. graeca in southeastern Iberian Peninsula (1999-2013), we fitted non-linear logistic models with endogenous and exogenous effects. The results showed that endogenous processes are important drivers of the population dynamics of this species, and that exogenous factors, such as freezing hours in winter, also directly affect the population growth rate. Intolerance of extreme winter temperatures may especially affect hatchlings and juvenile tortoises. Our models also showed that perturbations (i.e. a fire occurred during the monitoring period) have a lasting impact by reducing the carrying capacity of the population. This study shows that simple quantitative approaches based on population dynamic theory are useful for deciphering the ecological mechanisms underlying dynamics of tortoise populations. [ABSTRACT FROM AUTHOR]

We have developed a ratiometric fluorescent probe based on ICT mechanism for imaging intracellular sulfite (SO 3 2− ) in HeLa cells. The probe could selectively stain cells with scarce cytotoxicity and excellent photostability. The probe displayed a high selectivity for sulfite over other anions and active small biological molecules including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) at room temperature. The reaction could complete within 30 s and detection limit was as low as 76 nM, which is superior to some reported probes. The detecting mechanism was proved by MS, 1 H NMR and theoretical calculation. The probe can also detect endogenous sulfite in HepG2 cells. [ABSTRACT FROM AUTHOR]

Salient peripheral cues produce a transient shift of attention which is superseded by a sustained inhibitory effect. Cueing part of an object produces an inhibitory cueing effect (ICE) that spreads throughout the object. In dynamic scenes the ICE stays with objects as they move. We examined object-centred attentional facilitation and inhibition in a patient with visual form agnosia. There was no evidence of object-centred attentional facilitation. In contrast, object-centred ICE was observed in 3 out of 4 tasks. These inhibitory effects were strongest where cues to objecthood were highly salient. These data are evidence of a neuropsychological dissociation between the facilitatory and inhibitory effects of attentional cueing. From a theoretical perspective the findings suggest that ‘grouped arrays’ are sufficient for object-based inhibition, but insufficient to generate object-centred attentional facilitation. [ABSTRACT FROM AUTHOR]

Background: The rate of nosocomial infection appears to depend on whether it is calculated using the Center for Disease Control (CDC) or carrier state criteria. The objective of this study was to differentiate between primary endogenous (PE), secondary endogenous (SE) and exogenous (EX) infections, and to compare this classification with CDC criteria for nosocomial infections. Methods: Children hospitalized for more than 72 h at pediatric intensive care unit during 2004–2005 were enrolled. Children, who had the infection before the admission, and or did not develop an infection within the hospitalization were excluded. Surveillance samples were sampled on admission, and then twice a week. Diagnostic samples were obtained when infection was suspected based on the clinical condition and laboratory findings. Infections were evaluated as PE, SE and EX, and their incidences were compared with CDC criteria for nosocomial infections. Results: One hundred seventy eight patients were enrolled in the study. Forty-four patients (24.7%) develop infection. Twenty-seven patients (61.3%) had PE, 10 patients (22.7%) had SE, and 7 patients (15.9%) had EX infection. Secondary endogenous and EX infections are considered as nosocomial, thus 17 patients (38.6%) had a nosocomial infection. Thirty-one patients (70.5%) met CDC criteria for nosocomial infections. Seventeen patients (55%) were classified as PE, and 14 patients (45%) as SE or EX infections.Conclusion: Seventy percent of infections (31 out of 44 patients) met the CDC criteria for nosocomial infections, but only 39% of infections (17 out of 44 patients) were classified as nosocomial based on carrier state classification.

The main goal of the experiment was to test whether deployment ofattention could be strategically controlled. Subjects viewed five-letter arrays.Each array included a letter unique in shape (i.e. target). One of the letters ineach array (target or non-target) also differed from other letters in color orin position in relation to the array. That letter will be referred to as a featuresingleton. The probability ratio of the feature singleton being the target or anon-target letter was varied throughout three experiments. The ratios were (1)0.5 (target) : 0.5 (non-target); (2) 0.2 (target) : 0.8 (non-target); (3) 0.8 (target): 0.2 (non-target). Subjects in all three experimental conditions deployed serialprocesses, but failed to maintain complete intentional control during the courseof the search.

Stimuli-responsive drug delivery has attracted tremendous attention in the past decades. It provides a spatial- and temporal-controlled release in response to different triggers, thus enabling highly efficient drug delivery and minimizing drug side effects. Graphene-based nanomaterials have been broadly explored, and they show great potential in smart drug delivery due to their stimuli-responsive behavior and high loading capacity for an extended range of drug molecules. These characteristics are a result of high surface area, mechanical stability and chemical stability, and excellent optical, electrical, and thermal properties. Their great and infinite functionalization potential also allows them to be integrated into several types of polymers, macromolecules, or other nanoparticles, leading to the fabrication of novel nanocarriers with enhanced biocompatibility and trigger-sensitive properties. Thus, numerous studies have been dedicated to graphene modification and functionalization. In the current review, we introduce graphene derivatives and different graphene-based nanomaterials utilized in drug delivery and discuss the most important advances in their functionalization and modification. Also, their potential and progress in an intelligent drug release in response to different types of stimuli either endogenous (pH, redox conditions, and reactive oxygen species (ROS)) or exogenous (temperature, near-infrared (NIR) radiation, and electric field) will be debated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Khakpour, Salehi, Naghib, Ghorbanzadeh and Zhang.)

Visual attentional deficits are frequently reported in patients with mild traumatic brain injury (TBI). In the present study, the ability to orient visual attention (i.e., the use of endogenous and exogenous visual cues) was investigated using a modified Posner visual search task, in which the participant was required to search for a target shape (radial frequency patterns) amongst distractor shapes. Participants were required to determine whether a target radial frequency pattern was present or absent from an array of distractors. Attention to the target location was cued using central or peripheral cueing procedures to investigate endogenous or exogenous attention allocation. Predictability was not manipulated between central and peripheral cues. Search difficulty was varied by systematically changing the radial frequency difference between target and distractors (and thereby shape difference), and cues could be valid or invalid in that they correctly or incorrectly indicated the position of the target shape. Both target discriminability (i.e., identifying the presence or absence of the target) and reaction times were measured. Thirteen patients with chronic mild TBI and 21 age-, sex-, and IQ -matched healthy controls participated in the study. For control participants, both discrimination accuracy and reaction times improved with visual search efficiency, and they were sensitive to the type of cue, with performance worst for cue invalid conditions than valid conditions. However, the results for TBI patients were strikingly different; we find that discrimination accuracy slightly improved with visual search difficulty (compared to controls), but not reaction times, and TBI patients were largely insensitive to the type of visual cue, and did not show a selective deficit for central or peripheral cues, suggesting an impairment in both endogenous and exogenous visual attention. In conclusion, patients with mild TBI exhibit a poor ability to orient visual attention. • We investigated the ability to orient visual attention in patients with mild TBI. • The ability to orient visual attention is affected following TBI, with performance poorer than control participants. • Patients with mild TBI, were able to detect a visual cue, but did not benefit from valid cue, nor hindered by invalid cue. • Patients with mild TBI did not show a selective deficit in endogenous or exogenous visual attention. [ABSTRACT FROM AUTHOR]

• Semiconductor nanomaterials for cancer nanotheranostics. • Exogenous stimuli used for cancer imaging and therapy. • Endogenous tumor microenvironment (TME) to trigger cancer theranostics. • The challenges and perspective of semiconductor nanomateraials for tumor-specific theranostics. Nanotheranostics utilizing nanoparticles for diagnostics and treatment simultaneously, have attracted tremendous attention in anticancer therapy due to its excellent performance, such as distinct efficiency and specificity to tumor. Semiconductor nanomaterials, as a unique type of nanomaterials, have widely been harnessed for nanotheranostics because of the specific properties including the optical, magnetic and photoresponsive properties. Herein, this review firstly discussed serval types of semiconductor nanoparticles and the distinct properties for the potential biomedical applications. Metal chalcogenides, transition metal oxides and other inorganic semiconductors were overviewed for nanotheranostics application. Meanwhile, in order to improve the theranostics accuracy and efficiency, the exogenous and endogenous stimuli were comprehensively discussed. The exogenous stimuli, including light, magnetism, ultrasound, and radiation, which are commonly employed for imaging and therapy, were subsequently discussed according to the attributes. In addition, the tumor microenvironment (TME), which is well known as pH, reactive oxygen species (ROS), hypoxia, GSH, and enzymes, were tremendously utilized for TME-responsive sensor, therapy and drug release. In the end, the challenges and perspective of semiconductor nanomateraials for tumor-specific theranostics were also proposed. [ABSTRACT FROM AUTHOR]

Selective attention to a spatial location has shown enhance perception and facilitate behaviour for events at attended locations. However, selection relies not only on where but also when an event occurs. Recently, interest has turned to how intrinsic neural oscillations in the brain entrain to rhythms in our environment, and, stimuli appearing in or out of synch with a rhythm have shown to modulate perception and performance. Temporal expectations created by rhythms and spatial attention are two processes which have independently shown to affect stimulus processing but it remains largely unknown how, and if, they interact. In four separate tasks, this study investigated the effects of voluntary spatial attention and bottom-up temporal expectations created by rhythms in both unimodal and crossmodal conditions. In each task the participant used an informative cue, either colour or pitch, to direct their covert spatial attention to the left or right, and respond as quickly as possible to a target. The lateralized target (visual or auditory) was then presented at the attended or unattended side. Importantly, although not task relevant, the cue was a rhythm of either flashes or beeps. The target was presented in or out of sync (early or late) with the rhythmic cue. The results showed participants were faster responding to spatially attended compared to unattended targets in all tasks. Moreover, there was an effect of rhythmic cueing upon response times in both unimodal and crossmodal conditions. Responses were faster to targets presented in sync with the rhythm compared to when they appeared too early in both crossmodal tasks. That is, rhythmic stimuli in one modality influenced the temporal expectancy in the other modality, suggesting temporal expectancies created by rhythms are crossmodal. Interestingly, there was no interaction between top-down spatial attention and rhythmic cueing in any task suggesting these two processes largely influenced behaviour independently.