Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional dysregulation in developing trigeminal sensory neurons in the LgDel mouse model of DiGeorge 22q11.2 deletion syndrome

Abstract LgDel mice, which model the heterozygous deletion of genes at human chromosome 22q11.2 associated with DiGeorge/22q11.2 deletion syndrome (22q11DS), have cranial nerve and craniofacial dysfunction as well as disrupted suckling, feeding and swallowing, similar to key 22q11DS phenotypes. Divergent trigeminal nerve (CN V) differentiation and altered trigeminal ganglion (CNgV) cellular composition prefigure these disruptions in LgDel embryos. We therefore asked whether a distinct transcriptional state in a specific population of early differentiating LgDel cranial sensory neurons, those in CNgV, a major source of innervation for appropriate oropharyngeal function, underlies this departure from typical development. LgDel versus wild-type (WT) CNgV transcriptomes differ significantly at E10.5 just after the ganglion has coalesced. Some changes parallel altered proportions of cranial placode versus cranial neural crest-derived CNgV cells. Others are consistent with a shift in anterior–posterior patterning associated with divergent LgDel cranial nerve differentiation. The most robust quantitative distinction, however, is statistically verifiable increased variability of expression levels for most of the over 17 000 genes expressed in common in LgDel versus WT CNgV. Thus, quantitative expression changes of functionally relevant genes and increased stochastic variation across the entire CNgV transcriptome at the onset of CN V differentiation prefigure subsequent disruption of cranial nerve differentiation and oropharyngeal function in LgDel mice.
Cancer and older adult patient care

ABSTRACT Cancer occurs most frequently in patients aged 65 and older. With the increasing age of the world’s population, there will be a significant increase in cancer diagnoses in older adults. Aging imposes a wide variety of physiological responses, comorbidities, and ailments, but older patients are less represented in clinical studies. Specific needs of older patients with cancer often go under-recognized and consequently unmet. In this review, common diagnoses that can affect the outcomes of this population, including frailty, malnutrition, and delirium, are discussed. Areas that need further research to improve the care of geriatric cancer patients, particularly in the hospital settings, are also identified.
Galactose-functionalized GlycoAuNR as a photothermal conversion complex: Its binding to lectin RCA120 and hepatoma-targeting therapy

Glycopolymer-grafted gold nanorods (GlycoAuNRs) were designed and fabricated as a heptoma-targeting phototherapy nanoparticles. The block glycopolymer, poly (diethyleneglycol methacrylate)-block-poly(6-O-vinyladipoyl-α-D-galactose) (PDEGMA-b-POVNGA), was synthesized by RAFT polymerization and modified AuNRs with Au-S bonds via reducing the thioester at the end of glycopolymer to thiol (–SH). Galactose pendants of thermosensitive AuNRs@PDEGMA-b-POVNGA were exposed when the temperature of aqueous dispersion is above lower critical solution temperature, which was responsible for specific binding ability with ricinus communis agglutinin. In vitro experiment indicated that the synthesized glycopolymer could significantly improve cytocompatibility of AuNRs and target to hepatocellular carcinoma cells, owing to the galactose moiety that recognized the overexpressed asialoglycoprotein receptor on the hepatocellular carcinoma cells. Interestingly, the addition of ricinus communis agglutinin could inhibit the growth of the hepatocellular carcinoma cells in some extent. Furthermore, the photothermal therapy assay proved that glycoAuNRs-ricinus communis agglutinin could realize highly effective photothermal treatment for the tumor cells in vitro upon laser irradiation by cooperative effect.
The effect of postprandial glycaemia on cognitive function: a randomised crossover trial

Abstract The effect on cognitive test scores of generating differences in postprandial glycaemia using test foods or beverages has been inconsistent. Methodological issues may account for some of the variable results requiring further investigation using strong study designs into the relationship between glycaemia and cognitive functioning. The objective of this study was to determine the effects of postprandial glycaemia on cognitive function by examining cognition after consumption of foods that differ only by the rate of digestion of available carbohydrate in a population of young adults. In a double-blind, randomised, crossover trial, sixty-five participants received trifle sweetened either with a higher-glycaemic index (GI) sugar (sucrose; GI 65) or a lower-GI sugar (isomaltulose; GI 34). Cognitive tests were completed prior to trifle consumption, and 60 and 120 min after. There was no between-trifle difference at 60 min in performance on free word recall (0·0 (95 % CI –0·6, 0·5)), short delay word recall (0·0 (95 % CI –0·5, 0·5)), long delay word recall (0·0 (95 % CI –0·6, 0·6)), letter–number sequence recall (0·3 (95 % CI − 0·2, 0·7)) and visuo-spatial recall (–0·2 (95 % CI –0·6, 0·2)) tests. At 120 min, no difference was detected in any of these tests. The participants performed 7·7 (95 % CI 0·5,14·9) s faster in Reitan’s trail-making test B 60 min after the higher-GI trifle than the lower-GI trifle (P = 0·037). Our findings of a null effect on memory are generally consistent with other works in which blinding and robust control for confounding have been used.
Network between Cytokines, Cortisol and Occupational Stress in Gas and Oilfield Workers

To test whether gas and oil field work is accompanied by stress and altered immune function, the perception of workplace stress, levels of salivary cortisol, plasma levels, and mononuclear cell production of cytokines were examined in 80 healthy workers recruited among a population of operators on gas and oilfields. Specific questionnaires for determining the perception of anxiety, occupational stress, and subjective symptoms were administered. Salivary cortisol and cytokines plasma levels were evaluated by Elisa and to investigate immune function, both spontaneous and PHA- or LPS-induced expression and production of cytokines were assessed by qRT-PCR. Workers showed medium stress levels at work, with growth and increased motivation for work, and based on salivary cortisol concentrations, were divided into two groups of ≤10 ng/mL (n = 31) or >10 ng/mL (n = 49). Statistically significant higher plasma levels of IL-6, while lower TNFα, were detected in workers with cortisol >10 ng/mL. Also, BMI, DL, JD and Job strain were significantly higher in workers with cortisol >10 ng/mL. Thus, even modest variations of cortisol might have a role in the modulation of immune response and worker’s vulnerability to health imbalance.Thus, the evaluation of immune status, in addition to cortisol levels, could be useful to prevent illnesses; exacerbation of pre-existing conditions; morbidity; and consequent absences from work, with economic repercussions.
Characterization of Fungal Endophytes Isolated from the Metal Hyperaccumulator Plant Vachellia farnesiana Growing in Mine Tailings

Heavy metal pollution has become an environmental and health problem worldwide. With the aim of finding novel strategies for metal bioremediation, endophytic fungi from the heavy metal hyperaccumulator plant Vachellia farnesiana were isolated and characterized. The plants were growing in mine tailings, rich in Zn, Pb, and Cu. Morphological and phylogenetic analyses indicated that the fungal strains belonged to Neocosmospora and Aspergillus genera. The Neocosmospora isolate belongs to the Fusarium solani species complex (FSSC) that groups phytopathogen species. However, in this case the plants from which it was isolated did not show any signs of disease. Both fungal strains were able to remove significant amounts of heavy metals from liquid cultures, either in a mixture of the three metals or each metal in a single culture. In response to lead exposure, the Neocosmospora sp. strain secreted specific novel phenolic compounds other than anthraquinones or naphtoquinones, which have been described in similar situations. The Aspergillus sp. dropped the pH in the medium. High-performance liquid chromatography determinations indicated that this strain secreted mainly glutamic acid in response to lead, a novel mechanism, which has not been reported elsewhere. Malic and succinic acids were also produced in response to lead exposure. Possibly, glutamic and succinic acids (synthesized in the Krebs cycle) can be used to cope with metal toxicity due to the plant providing photosynthates to the fungus. These fungi showed the potential to be used for bioremediation or restoration of metal-polluted environments.
Effects of continuous positive airway pressure treatment on aortic stiffness in patients with resistant hypertension and obstructive sleep apnea: A randomized controlled trial

Resistant hypertension (RHT) is associated with obstructive sleep apnea (OSA) and increased aortic stiffness, measured by carotid‐femoral pulse wave velocity (cf‐PWV). We aimed to evaluate in a randomized controlled trial, the effect of Continuous positive airway pressure (CPAP) treatment on cf‐PWV in comparison with a control group in patients with RHT and moderate‐severe OSA. One‐hundred and sixteen patients were randomized to 6‐month CPAP treatment (56 patients) or no therapy (60 patients), while keeping their antihypertensive treatment unchanged. Carotid‐femoral pulse wave velocity was performed at the beginning and end of the 6‐month period. Intention‐to‐treat intergroup differences in cf‐PWV changes were assessed by a generalized mixed‐effects model with the allocation group as a fixed factor and adjusted for age, sex, changes in mean arterial pressure and the baseline cf‐PWV values. Subgroup sensitivity analyses were performed, excluding patients with low CPAP adherence and low cf‐PWV at baseline. CPAP and control groups had similar clinic‐laboratorial characteristics. Patients had a mean cf‐PWV of 9.4 ± 1.6 m/s and 33% presented cf‐PWV > 10 m/s. During treatment, the control group had a mean increase in cf‐PWV of +0.43 m/s (95% confidence interval [CI], +0.14 to +0.73 m/s; p = .005), whereas the CPAP group had a mean increase of +0.03 m/s (95% CI, −0.33 to +0.39 m/s; p = .87), resulting in a mean difference in changes between CPAP and control of −0.40 m/s (95% CI, −0.82 to +0.02 m/s; p = .059). Subgroup analyses did not change the results. In conclusion, a 6‐month CPAP treatment did not reduce aortic stiffness, measured by cf‐PWV, in patients with RHT and moderate/severe OSA, but treatment may prevent its progression, in contrast to no‐CPAP therapy.
Actuation Mechanism of Microvalves: A Review

The microvalve is one of the most important components in microfluidics. With decades of development, the microvalve has been widely used in many industries such as life science, chemical engineering, chip, and so forth. This paper presents a comprehensive review of the progress made over the past years about microvalves based on different actuation mechanisms. According to driving sources, plenty of actuation mechanisms are developed and adopted in microvalves, including electricity, magnetism, gas, material and creature, surface acoustic wave, and so on. Although there are currently a variety of microvalves, problems such as leakage, low precision, poor reliability, high energy consumption, and high cost still exist. Problems deserving to be further addressed are suggested, aimed at materials, fabrication methods, controlling performances, flow characteristics, and applications.
Regional differences in the ependyma of the optic tectal ventricle of adult zebrafish with structures referring to brain hydrodynamics

Classical electron microscopic morphological studies provide detailed ultrastructural information, which may lend insights into cellular functions. As a follow‐up to our morphological investigation of the adult zebrafish (Danio rerio) optic tectum, in this study, we have analyzed the ependymal structures lining the surfaces of the tectal ventricle: the torus, tegmental surface of the valvula cerebelli and the periventricular gray zone of the optic tectal cortex. We used toluidine blue stained plastic (semithin) sections for light microscopy and scanning electron microscopy. Our morphological findings of gated entrances and/or egresses indicate that, at least in the adult zebrafish brain, there may be a bidirectional direct flow communication between the ventricular cerebrospinal fluid and the parenchymal interstitial fluid.
Vasoinhibin generation and effect on neuronal apoptosis in the hippocampus of late mouse embryos.

Morphological and behavioral evidence suggests that vasoinhibin is present in the central nervous system, triggering neuroendocrine and behavioral responses to stress. Moreover, vasoinhibin reduces neuronal survival and differentiation of primary sensory neurons of the peripheral nervous system. In order to address the functional role played by vasoinhibin at the CNS, and to better understand the underlying mechanisms involved in its actions, we treated primary cultured hippocampal neurons obtained from E16 mice with a human recombinant vasoinhibin. We examined the resulting cellular changes focusing on neuronal cell death and explored the local generation of vasoinhibin within the hippocampus. Our results show that vasoinhibin significantly reduced neuronal cell density, increased immunoreactive activated caspase-3, and TUNEL-positive staining at 72, 16, and 24 h, respectively. Furthermore, vasoinhibin increased the expression of pro-apoptotic genes BAX, BAD, BIM and PUMA and decreased that of the anti-apoptotic gene BCL-2 at 24 h, as assessed by RT-qPCR. Vasoinhibin effects were blocked by co-incubation with a vasoinhibin antibody or with prolactin. Immunoreactive bands consistent with vasoinhibin were observed in hippocampal extracts by Western blot analysis, and a prolactin standard was cleaved to vasoinhibin by a hippocampal lysate in a heat- and cathepsin D inhibitor pepstatin A-dependent fashion. Taken together, these data support the notion that vasoinhibin is locally produced by cathepsin D within the embryonic mouse hippocampus, a brain region that plays a critical role in emotional regulation, resulting in decreased neuronal cell viability via the activation of the intrinsic apoptosis pathway.
How to Perform miRacles: A Step‐by‐Step microRNA Detection Protocol Using DNA Nanoswitches

MicroRNAs are short non‐coding RNAs involved in post‐transcriptional gene regulation, and are increasingly considered to be biomarkers for numerous biological processes and human diseases. Current techniques used for microRNA detection can be expensive and labor‐intensive, and typically require amplification, labeling, or radioactive probes. In this protocol, we describe a DNA nanoswitch–based microRNA detection assay termed “miRacles”: microRNA‐activated conditional looping of engineered switches. This method uses conformationally responsive DNA nanoswitches that detect the presence of specific microRNAs with a simple and unambiguous gel‐shift assay that can be performed on the benchtop. The assay is low cost, minimalistic, and capable of direct detection of specific microRNAs in unprocessed total RNA samples, with no enzymatic amplification, labeling, or special equipment. The protocol for detection of microRNAs in total RNA can be completed in as little as a few hours, making this assay a compelling alternative to qPCR and Northern blotting. © 2020 by John Wiley & Sons, Inc.
Communication of Hazards in Mixed-Reality Telerobotic Systems: The Usage of Naturalistic Avoidance Cues in Driving Tasks

Objective This study investigates the effect of naturalistic visual cues on human avoidance behavior for a potential use in telerobotic user interfaces incorporating mixed-reality environments (e.g., augmented reality). Background Telerobotic systems used in hazardous environments require interfaces that draw operators’ attention to potential dangers. Existing means of hazard notification can often distract or induce stress in operators. In the design and implementation of such interfaces, visual semiotics plays a critical role in creating more effective interfaces. Naturalistic visual cues such as Aposematism or Kindchenschema have proven effective to communicate danger or caution in nature, but the application of these cues in visual systems have yet to be thoroughly investigated. Method A study was conducted where 40 volunteering participants were asked to control a remote vehicle in a simulated environment. The environment contained a set of neutral and visually augmented obstacles that were designed to provoke avoidance behavior. Results The use of visual cues triggered greater avoidance behaviors in participants compared to neutral obstacles. The distance of avoidance was correlated with the type of cue present, with obstacles augmented by Aposematism (Cue A) having a greater participant–obstacle distance than Kindchenschema (Cue K). Conclusions This study shows the potential for the incorporation of naturalistic visual cues as a means to designate warning or caution in telerobotic environments. Applications The findings can offer practical guidelines for the design of visual cues in telerobotic interfaces. The further incorporation of such cues may reduce operator stress and the amount of human errors in telerobotic operations.
Sledgehammer to Scalpel: Broad Challenges to the Heart and Other Tissues Yield Specific Cellular Responses via Transcriptional Regulation of the ER-Stress Master Regulator ATF6α

There are more than 2000 transcription factors in eukaryotes, many of which are subject to complex mechanisms fine-tuning their activity and their transcriptional programs to meet the vast array of conditions under which cells must adapt to thrive and survive. For example, conditions that impair protein folding in the endoplasmic reticulum (ER), sometimes called ER stress, elicit the relocation of the ER-transmembrane protein, activating transcription factor 6α (ATF6α), to the Golgi, where it is proteolytically cleaved. This generates a fragment of ATF6α that translocates to the nucleus, where it regulates numerous genes that restore ER protein-folding capacity but is degraded soon after. Thus, upon ER stress, ATF6α is converted from a stable, transmembrane protein, to a rapidly degraded, nuclear protein that is a potent transcription factor. This review focuses on the molecular mechanisms governing ATF6α location, activity, and stability, as well as the transcriptional programs ATF6α regulates, whether canonical genes that restore ER protein-folding or unexpected, non-canonical genes affecting cellular functions beyond the ER. Moreover, we will review fascinating roles for an ATF6α isoform, ATF6β, which has a similar mode of activation but, unlike ATF6α, is a long-lived, weak transcription factor that may moderate the genetic effects of ATF6α.
Efficient removal of cytotoxic drugs from wastewater by single-stage combined photocatalysis–algae treatment process

ABSTRACT In this study, the efficiency of a single-stage combined photocatalysis–algae treatment process in the removal of the anticancer drug, flutamide (FLU), from aqueous solution has been evaluated. The removal abilities of the individual blue-green alga (Anabaena sp.), nano-sized MoS2 photocatalyst under visible light irradiation, and combined photocatalysis–algal treatment process were investigated. Using response surface optimization technique, 85.1% of the FLU removal was achieved at the optimum conditions of pH 7.0, nanophotocatalyst dose of 15.23 mg and 12.12 mL of the alga in 30 min. Compared to the individual biological and chemical treatment methods, a higher FLU removal efficiency was obtained at a shorter reaction time by using the combined treatment system. Kinetics study showed that FLU removal by the algal treatment, photocatalysis, and the combined processes followed the modified Freundlich, pseudo-first-order, and nonlinear sigmoidal kinetic models, respectively. The results indicate that a synergistic effect appears when algal treatment process and photocatalysis are performed simultaneously. The novel combined system is a low-cost and efficient microalgae-based technology for the removal of cytotoxic compounds from wastewaters. GRAPHICAL ABSTRACT
Feeding performance on a novel host: no adaptation over generations and differential patterns in two flea species

Abstract To model the colonization of a novel host by fleas, Synosternus cleopatrae and Xenopsylla ramesis, we established experimental lines maintained for 15 generations on a principal or a novel host (either co-occurring with a flea or not). We compared the blood meal size and the energy expended for digestion by fleas from the 15th generation of each line on these hosts between hosts within a line and between lines within a host asking (a) whether fleas adapt to a novel host (increased blood consumption/decreased energy expended for digestion); (b) if yes, whether this adaptation leads to the loss of ability to exploit an original host, and (c) whether the success of adaptation to a novel host depends on its ecological co-occurrence with a flea. The blood consumption and digestion energetics of fleas fed on the principal host differed from those on other hosts. The effect of the principal host on feeding performance differed between fleas, with S. cleopatrae consuming less blood and expending more energy for digestion on the principal than on any other host, whereas the opposite was true for X. ramesis. No changes in feeding performance on a novel host over generations were found. We propose several explanations for the lack of adaptation to a novel host over time. We explain the poor performance of S. cleopatrae on its principal host via its immune response mounting pattern. We argue that the principal host of a parasite is not necessarily the host on which the parasite demonstrates the best performance.
Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light–dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer’s and Parkinson’s disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.