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Nematode molting is a remarkable process where animals must repeatedly build a new apical extracellular matrix (aECM) beneath a previously built aECM that is subsequently shed. The nuclear hormone receptor NHR-23 (also known as NR1F1) is an important regulator of C. elegans molting. NHR-23 expression oscillates in the epidermal epithelium, and soma-specific NHR-23 depletion causes severe developmental delay and death. Tissue-specific RNAi suggests that nhr-23 acts primarily in seam and hypodermal cells. NHR-23 coordinates the expression of factors involved in molting, lipid transport/metabolism and remodeling of the aECM. NHR-23 depletion causes dampened expression of a nas-37 promoter reporter and a loss of reporter oscillation. The cuticle collagen ROL-6 and zona pellucida protein NOAH-1 display aberrant annular localization and severe disorganization over the seam cells after NHR-23 depletion, while the expression of the adult-specific cuticle collagen BLI-1 is diminished and frequently found in patches. Consistent with these localization defects, the cuticle barrier is severely compromised when NHR-23 is depleted. Together, this work provides insight into how NHR-23 acts in the seam and hypodermal cells to coordinate aECM regeneration during development. [ABSTRACT FROM AUTHOR]

Exposure to Pirimiphos-methyl (POM) has been reported to adversely affect sperm functions, leading to male infertility. This study seeks to investigate the effect of resveratrol on POM induced male reproductive dysfunction. Twenty-four male Sprague-Dawley rats weighing between 165g - 200g were randomly divided into four groups of control, the POM group (received 62.5mg/kg POM/b. w), POM + RES (received 62.5mg/kg POM and 20mg/kg body weight of resveratrol, and the RES group (received 20mg/kg body weight resveratrol) for 65 days. The results showed a significant decrease in body weight gain in the POM group, POM +RES group compared to the control. The relative liver weight of the POM group was also significantly increased compared with the control (p<0.05). RES + POM significantly increased the epididymal sperm count, motility, morphology, and testosterone level compared to the POM group. POM increased MDA and reduced SOD, GSH, and catalase activities, while POM + RES only reversed this trend in the MDA, catalase, and SOD levels. There was a significant increase in the cholesterol concentration of the POM group compared to the control while there were no significant differences in the HDL, LDL, and triglyceride levels across all the groups. There was distortion in the POM group's cytoarchitecture of the liver and testes compared to the control and RES groups. In conclusion, the results showed that POM disrupts sperm functions and caused hepatotoxicity in rats' livers. This study also shows that RES improves sperm parameters impaired by POM. [ABSTRACT FROM AUTHOR]

Introduction: Osmoprotectant supplementation can be used as a useful approach to enhance plant stress tolerance. However, the effect of silymarin and clove fruit extract (CFE) on wheat plants grown under cadmium (Cd) stress has not been studied. Methods: Wheat seeds were planted in plastic pots filled with ions-free sand. A ½-strength Hoagland's nutrient solution was used for irrigation. Pots were treated with eight treatments thirteen days after sowing: 1) Control, 2) 0.5 mM silymarin foliar application [silymarin], 3) 2% CFE foliar application [CFE], 4) CFE enriched with silymarin (0.24 g silymarin L-1 of CFE) [CFE-silymarin], 5)Watering wheat seedlings with a nutritious solution of 2 mMCd [Cd]. 6) Cadmium+ silymarin, 7) Cadmium+ CFE, and 8) Cadmium + CFE-silymarin. The experimental design was a completely randomized design with nine replicates. Results and discussion: The Cd stress decreased grain yield, shoot dry weight, leaf area, carotenoids, chlorophylls, stomatal conductance, net photosynthetic rate, transpiration rate, membrane stability index, nitrogen, phosphorus, and potassium content by 66.9, 60.6, 56.7, 23.8, 33.5, 48.1, 41.2, 48.7, 42.5, 24.1, 39.9, and 24.1%, respectively. On the other hand, Cd has an Application of CFE, silymarin, or CEF-silymarin for wheat plants grown under Cd stress, significantly improved all investigated biochemical, morphological, and physiological variables and enhanced the antioxidant enzyme activities. Applying CFE and/or silymarin enhanced plant tolerance to Cd stress more efficiently. Our findings suggest using CFE-silymarin as a meaningful biostimulator for wheat plants to increase wheat plants' tolerance to Cd stress via enhancing various metabolic and physiological processes. [ABSTRACT FROM AUTHOR]

The Microchannel X-ray Telescope (MXT) will be the first focusing X-ray telescope based on a narrow field "Lobster-Eye" optical design to be flown on a satellite, namely the Sino-French mission SVOM. SVOM will be dedicated to the study of Gamma-Ray Bursts and more generally time-domain astrophysics. The MXT telescope is a compact (focal length ∼ 1.15 m) and light (< 42 kg) instrument, sensitive in the 0.2–10 keV energy range. It is composed of an optical system, based on micro-pore optics (MPOs) of 40 μ m pore size, coupled to a low-noise pnCDD X-ray detector. In this paper we describe the expected scientific performance of the MXT telescope, based on the End-to-End calibration campaign performed in fall 2021, before the integration of the SVOM payload on the satellite. [ABSTRACT FROM AUTHOR]

The abundances of low first ionization potential (FIP) elements are three to four times higher in the closed loop active corona than in the photosphere, known as the FIP effect. Observations suggest that the abundances vary in different coronal structures. Here, we use the soft X-ray spectroscopic measurements from the Solar X-ray Monitor (XSM) onboard the Chandrayaan-2 orbiter to study the FIP effect in multiple A-class flares observed during the minimum of Solar Cycle 24. Using time-integrated spectral analysis, we derive the average temperature, emission measure, and the abundances of four elements – Mg, Al, Si, and S. We find that the temperature and emission measure scales with the sub-class of flares while the measured abundances show an intermediate FIP bias for the lower A-flares (e.g. A1), while for the higher A-flares, the FIP bias is near unity. To investigate it further, we perform a time-resolved spectral analysis for a sample of the A-class flares and examine the evolution of temperature, emission measure, and abundances. We find that the abundances drop from the coronal values towards their photospheric values in the impulsive phase of the flares and, after the impulsive phase, they quickly return to the usual coronal values. The transition of the abundances from the coronal to photospheric values in the impulsive phase of the flares indicates the injection of fresh unfractionated material from the lower solar atmosphere to the corona due to chromospheric evaporation. However, explaining the quick recovery of the abundances from the photospheric to coronal values in the decay phase of the flare is challenging. [ABSTRACT FROM AUTHOR]

Drug checking is increasingly being explored outside of festivals and events to be an ongoing service within communities, frequently integrated within responses to illicit drug overdose. The choice of instrumentation is a common question, and the demands on these chemical analytical instruments can be challenging as illicit substances may be more complex and include highly potent ingredients at trace levels. The answer remains nuanced as the instruments themselves are not directly comparable nor are the local demands on the service, meaning implementation factors heavily influence the assessment and effectiveness of instruments. In this perspective, we provide a technical but accessible introduction to the background of a few common drug checking methods aimed at current and potential drug checking service providers. We discuss the following tools that have been used as part of the Vancouver Island Drug Checking Project in Victoria, Canada: immunoassay test strips, attenuated total reflection IR-absorption spectroscopy, Raman spectroscopy from powder samples, surface-enhanced Raman scattering in a solution of colloidal gold nanoparticles, and gas chromatography–mass spectrometry. Using four different drug mixtures received and tested at the service, we illustrate the strengths, limitations, and capabilities of such instruments, and expose the scientific theory to give further insight into their analytical results. Each case study provides a walk-through-style analysis for a practical comparison between data from several different instruments acquired on the same sample. Ideally, a single instrument would be able to achieve all of the objectives of drug checking. However, there is no clear instrument that ticks every box; low cost, portable, rapid, easy-to-use and provides highly sensitive identification and accurate quantification. Multi-instrument approaches to drug checking may be required to effectively respond to increasingly complex and highly potent substances demanding trace level detection and the potential for quantification. [ABSTRACT FROM AUTHOR]

The FOXO transcription factor, DAF‐16, plays an integral role in insulin/IGF‐1 signaling (IIS) and stress response. In conditions of stress or decreased IIS, DAF‐16 moves to the nucleus where it activates genes that promote survival. To gain insight into the role of endosomal trafficking in resistance to stress, we disrupted tbc‐2, which encodes a GTPase activating protein that inhibits RAB‐5 and RAB‐7. We found that tbc‐2 mutants have decreased nuclear localization of DAF‐16 in response to heat stress, anoxia, and bacterial pathogen stress, but increased nuclear localization of DAF‐16 in response to chronic oxidative stress and osmotic stress. tbc‐2 mutants also exhibit decreased upregulation of DAF‐16 target genes in response to stress. To determine whether the rate of nuclear localization of DAF‐16 affected stress resistance in these animals, we examined survival after exposure to multiple exogenous stressors. Disruption of tbc‐2 decreased resistance to heat stress, anoxia, and bacterial pathogen stress in both wild‐type worms and stress‐resistant daf‐2 insulin/IGF‐1 receptor mutants. Similarly, deletion of tbc‐2 decreases lifespan in both wild‐type worms and daf‐2 mutants. When DAF‐16 is absent, the loss of tbc‐2 is still able to decrease lifespan but has little or no impact on resistance to most stresses. Combined, this suggests that disruption of tbc‐2 affects lifespan through both DAF‐16‐dependent and DAF‐16‐independent pathways, while the effect of tbc‐2 deletion on resistance to stress is primarily DAF‐16‐dependent. Overall, this work demonstrates the importance of endosomal trafficking for the proper nuclear localization of DAF‐16 during stress and that perturbation of normal endosomal trafficking is sufficient to decrease both stress resistance and lifespan. [ABSTRACT FROM AUTHOR]

Transcription factor EB (TFEB) is a conserved master transcriptional activator of autophagy and lysosomal genes that modulates organismal lifespan regulation and stress resistance. As neurons can coordinate organism‐wide processes, we investigated the role of neuronal TFEB in stress resistance and longevity. To this end, the Caenorhabditis elegans TFEB ortholog, hlh‐30, was rescued panneuronally in hlh‐30 loss of function mutants. While important in the long lifespan of daf‐2 animals, neuronal HLH‐30/TFEB was not sufficient to restore normal lifespan in short‐lived hlh‐30 mutants. However, neuronal HLH‐30/TFEB rescue mediated robust improvements in the heat stress resistance of wildtype but not daf‐2 animals. Notably, these mechanisms can be uncoupled, as neuronal HLH‐30/TFEB requires DAF‐16/FOXO to regulate longevity but not thermoresistance. Through further transcriptomics profiling and functional analysis, we discovered that neuronal HLH‐30/TFEB modulates neurotransmission through the hitherto uncharacterized protein W06A11.1 by inducing peripheral mitochondrial fragmentation and organismal heat stress resistance in a non‐cell autonomous manner. Taken together, this study uncovers a novel mechanism of heat stress protection mediated by neuronal HLH‐30/TFEB. [ABSTRACT FROM AUTHOR]

The aim of the present study was to correlate the antioxidant, antimicrobial, and cytotoxic activities of hydroalcoholic extracts obtained from the aerial parts of three Dracocephalum moldavica L. cultivars with their polyphenolic compositions. The polyphenols were identified and quantified using spectrophotometrical methods and LC–MS analysis. Their antioxidant capacities were assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. Their in vitro antimicrobial efficacies were assessed using the agar well diffusion and broth microdilution methods. Their cytotoxicity was investigated on normal diploid foreskin fibroblasts (BJ) and on colorectal adenocarcinoma (DLD-1) cell lines. The results pointed out significant amounts of polyphenolic compounds in the compositions of the tested cultivars, with rosmarinic acid as the main compound (amounts ranging between 5.337 ± 0.0411 and 6.320 ± 0.0535 mg/mL). All three cultivars displayed significant antioxidant (IC50 ranging between 35.542 ± 0.043 and 40.901 ± 0.161 µg/mL for the DPPH assay, and for the FRAP assay 293.194 ± 0.213 and 330.165 ± 0.754 µmol Trolox equivalent/mg dry vegetal material) and antimicrobial potential (especially towards the Gram-positive bacteria), as well as a selective toxicity towards the tumoral line. A significant positive correlation was found between antioxidant activity and the total phenolic acids (r2 = 0.987) and polyphenols (r2 = 0.951). These findings bring further arguments for strongly considering D. moldavica cultivars as promising vegetal products, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Impaired mitophagy is a primary pathogenic event underlying diverse aging-associated diseases such as Alzheimer and Parkinson diseases and sarcopenia. Therefore, augmentation of mitophagy, the process by which defective mitochondria are removed, then replaced by new ones, is an emerging strategy for preventing the evolvement of multiple morbidities in the elderly population. Based on the scaffold of spermidine (Spd), a known mitophagy-promoting agent, we designed and tested a family of structurally related compounds. A prototypic member, 1,8-diaminooctane (VL-004), exceeds Spd in its ability to induce mitophagy and protect against oxidative stress. VL-004 activity is mediated by canonical aging genes and promotes lifespan and healthspan in C. elegans. Moreover, it enhances mitophagy and protects against oxidative injury in rodent and human cells. Initial structural characterization suggests simple rules for the design of compounds with improved bioactivity, opening the way for a new generation of agents with a potential to promote healthy aging. [ABSTRACT FROM AUTHOR]

Galaxolide is one of the most frequently used synthetic polycyclic musks on the market and is commonly detected in aquatic waterways. Previous studies have mainly evaluated the toxicity of this emerging contaminant using water-only exposures; however, its high Log Kow (5.9) suggests that this compound is likely to partition to sediments. Three benthic invertebrates, Chironomus dilutus, Hyalella azteca, and Lumbriculus variegatus, were exposed to sediment-bound Galaxolide using both acute (10 d; survival) and chronic (28 d; survival and growth) bioassays. The acute and chronic LC50s for Galaxolide ranged from 238 to 736 mg/kg sediment (2400–7430 µg/g organic carbon [OC]) for all three species, which were above concentrations commonly detected in the environment (< 2.5 mg/kg). Growth effects (i.e., weight and/or length) were noted in two of the three organisms (with C. dilutus being the exception); however, these effects were also noted at concentrations above those that are environmentally relevant. Molecular level evaluations were conducted with surviving L. variegatus and C. dilutus collected from treatments near the LC50 value. Markers of oxidative stress (glutathione-s-transferase) and endocrine disruption (estrogen-related receptor) in C. dilutus were significantly decreased in the treatment group compared to controls by 0.7-fold and 1.9-fold, respectively. Although acute and chronic effects were largely absent at environmentally relevant concentrations, changes in endocrine response suggest that more sensitive endocrine-based endpoints, such as emergence (for C. dilutus) and molting (for H. azteca), are needed to ensure that the risk of this emerging contaminant is low at environmentally relevant concentrations. [ABSTRACT FROM AUTHOR]

We investigated the effects of B. thuringiensis-based biological insecticides, XenTari and Dipel, and deltamethrin on the reproductive development of pups of pregnant rats. Twenty 90-day-old pregnant rats were divided randomly onto four equal groups: control group (GC) administered only water; XenTari group (GX) administered 1 mg XenTari (containing Cry1Ac toxin of B. thuringiensis)/100 g body weight; Dipel group (GDi) administered 1 mg Dipel (containing Cry1Aa, Cry1Ab and Cry1Ac toxins of B. thuringiensis)/100 g body weight; and a deltamethrin group (GDe) administered 2 mg deltamethrin (0.08 ml Keshet 25EC)/kg body weight as a positive control. Insecticides were administered by gavage at doses of 1 mg/100 g/day (GX and GDi), and 2 mg/kg/day (GDe) during pregnancy and lactation. Treatment with both biologic and synthetic insecticides reduced the weight gain of the mothers. The biological insecticides reduced the number, weight and length, and increased malformation and mortality of the offspring. In female offspring for all three groups administered insecticides, opening of the vagina was delayed, metestrus was increased and estrogen and progesterone levels were reduced compared to proestrus, estrus and metestrus of the cycle. The ovaries of female offspring of all three groups administered insecticides contained numerous tertiary and atretic follicles, few corpora lutea, primary and secondary follicles, and reduced estrogen receptors compared to controls. In male offspring, all three groups exposed to insecticides exhibited reduced testosterone levels. Histopathological changes in the testes including vacuolation and desquamation of the seminiferous epithelium were observed only in the GX and GDi groups. The number of androgen receptors was reduced significantly in the testes and testicular morphometry revealed reduced tubule diameter, height of the seminiferous epithelium and total tubule length compared to the control. The biological insecticides, XenTari and Dipel, administered in sublethal doses to pregnant rats, caused reproductive changes in the offspring similar to those of the insecticide, deltamethrin. [ABSTRACT FROM AUTHOR]

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Objective Rosmarinic acid (RA), an anticancer, antiallergic, and antimicrobial agent, is a secondary metabolite in many plants of the family Lamiaceae including M. officinalis L. The application of nanoparticles (NPs) as a novel elicitor for the biosynthesis of bioactive compounds shown that the NPs could affect the secondary metabolites in plants by eliciting the expression of biosynthetic pathway genes. The present paper aimed to assess the effect of Magnetic Iron Oxide Nanoparticles (MIONPs) in comparison with their dissolved counterpart. Materials and methods Foliar application of different concentrations: including 5, 10, 25, and 50 mg/L Fe of ferric chloride and MIONPs on the plant leaves was performed. The relative mRNA levels of TAT, RAS, and HPPR were evaluated with quantitative real-time PCR (qRT-PCR) and compared between treated and untreated samples. Results This study showed the positive effects of ferric chloride and MIONPs on the expression of genes involved in the biosynthesis pathway of RA. The highest expression level of TAT, HPPR, and RAS genes was observed in plants treated with MIONPs at the concentration of 25 mg/L and the expression of genes decreased as the concentration increased to 50 mg/L. However, the genes expression was still higher compared to the control plant. Conclusions The results showed that the exposure of plants to ferric chloride and magnetic iron oxide nanoparticles led to an increase in the expression of the genes under study compared to control samples. However, the application of nano-scale iron particles had more effect than ferric chloride on the expression levels. An increase in the expression of genes involved in the biosynthesis pathway of RA through treatment with MIONPs provides an opportunity for induction of synthesis and accumulation of RA. Therefore, we hope to be able to enhance the production of RA in M. officinalis L. by using these NPs. [ABSTRACT FROM AUTHOR]

As a significant non-communicable disease, cardiovascular disease is the leading cause of death for both men and women, comprises almost twenty percent of deaths in most racial and ethnic groups, can affect greater than twentyfive million individuals worldwide over the age of twenty, and impacts global economies with far-reaching financial challenges. Multiple factors can affect the onset of cardiovascular disease that include high serum cholesterol levels, elevated blood pressure, tobacco consumption and secondhand smoke exposure, poor nutrition, physical inactivity, obesity, and concurrent diabetes mellitus. Yet, addressing any of these factors cannot completely eliminate the onset or progression of cardiovascular disorders. Novel strategies are necessary to target underlying cardiovascular disease mechanisms. The silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), a histone deacetylase, can limit cardiovascular injury, assist with stem cell development, oversee metabolic homeostasis through nicotinamide adenine dinucleotide (NAD+ ) pathways, foster trophic factor protection, and control cell senescence through the modulation of telomere function. Intimately tied to SIRT1 pathways are mammalian forkhead transcription factors (FoxOs) which can modulate cardiac disease to reduce oxidative stress, repair microcirculation disturbances, and reduce atherogenesis through pathways of autophagy, apoptosis, and ferroptosis. AMP activated protein kinase (AMPK) also is critical among these pathways for the oversight of cardiac cellular metabolism, insulin sensitivity, mitochondrial function, inflammation, and the susceptibility to viral infections such as severe acute respiratory syndrome coronavirus that can impact cardiovascular disease. Yet, the relationship among these pathways is both intricate and complex and requires detailed insight to successfully translate these pathways into clinical care for cardiovascular disorders. [ABSTRACT FROM AUTHOR]

In order to enhance natural products value, Melissa officinalis (lemon balm) aerial part (leaves) has been studied in this work. Hence, the objective of this study is to determine the chemical composition of the studied plant polyphenols extracts using HPLC/DAD, as well as evaluate their flavonoid extracts' antioxidant and antimicrobial activities using DPPH• and disk diffusion methods, respectively. The results of phenols chemical composition showed the existence of two phenolic acids, five flavonic aglycones and six heterosides, while the biologic results of the plant flavonoid extracts exhibited the existence of a good antioxidant and antimicrobial activities. [ABSTRACT FROM AUTHOR]

Military activities often involve high-intensity exercise that can disrupt antioxidant capacity. We investigated the effects of oregano supplementation on muscle damage, oxidative stress, and plasma antioxidant markers of soldiers performing the army combat readiness test (ACRT). Twenty-four healthy male soldiers (age: 24 ± 3 years, height: 167 ± 14 cm, mass: 66 ± 3 kg) were randomized into a placebo group (n = 12) or an oregano supplementation group (n = 12). The participants consumed a capsule containing 500 mg Origanum vulgare immediately after completing the ACRT. Blood sampling was taken before exercise, immediately after exercise, and 60 and 120 min after oregano consumption. Plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), and glutathione peroxidase (GPX) were measured at the four time points. The time × group interactions were found for CK (p < 0.0001, d = 3.64), LDH (p < 0.0001, d = 1.64), MDA (p < 0.0001, d = 9.94), SOD (p < 0.0001, d = 1.88), TAC (p < 0.0001, d = 5.68) and GPX (p < 0.0001, d = 2.38). In all variables, the difference between placebo and oregano groups were significant at 60 (p < 0.0001) and 120 (p < 0.0001) minutes after ACRT test. The main effect of time was also significant for all the variables (p < 0.0001). Our results suggest that oregano supplementation has the potential to reduce muscle damage and increase oxidative capacity following ACRT. Supplementation with oregano may serve as a dietary strategy to increase preparedness and promote recovery in military recruits. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the acceptance of Peer Physical Examination (PPE) in middle Eastern society with its associate factors, and PPE acceptance during Covid-19 pandemic. The acceptance of PPE is considered high in multiple studies carried out in the west, but there were nearly no studies investigating the acceptance of PPE in the middle east or low-income countries. Methods: A questionnaire was shared through social media with students with focus on clinical-year students. A total number of 657 medical students were collected with a 74.5% response rate. The questionnaire gathered demographic information and recorded previous experience of PPE. A 5-point-likert scale was used to assess acceptance of PPE, factors affecting it, and the influence of COVID-19 pandemic. It also considered body's areas students would accept to be examined. Associations between participants' demographic and other details were tested using independent-samples T Test and other tests, and a p-value of < 0.05 was considered significant. Results: Eighty percent of medical students accepted PPE, while 3% did not, and 17% were neutral. Males had statistically significantly higher acceptance rates of PPE (M = 3.94 out of 5). Also, females had lower acceptance of being examined by other gender than males but did not mind examining other gender. Furthermore, the groin area (thigh) was the most rejected area for examination (20% only accept it), followed by the breast (23%). There was no statistically significant difference between different Universities groups or between different academic performance groups, finally there was statistically significant effect of religion and society on acceptance of PPE and religion has affected females more than males (p- value = 0.002). 70.8% of students supported PPE during the COVID-19 pandemic, while 6.8% did not, and 22.4% were neutral. There was not a significant difference in acceptance and supporting of PPE during the COVID-19 pandemic between males and females. Conclusions: With an 80% acceptance rate, PPE represents an effective alternative to the absent life models in Syrian universities. The application of PPE is less likely to go without difficulties, but authors suggest the presence of a supervisor and single-gender groups with friends paired together if possible. [ABSTRACT FROM AUTHOR]

Forkhead box O (FOXO) transcription factors (TFs) are a subclass of the larger family of forkhead TFs. Mammalians express four members FOXO1, FOXO3, FOXO4, and FOXO6. The interest in FOXO function stems mostly from their observed role in determining lifespan, where in model organisms, increased FOXO activity results in extended lifespan. FOXOs act as downstream of several signaling pathway and are extensively regulated through post‐translational modifications. The transcriptional program activated by FOXOs in various cell types, organisms, and under various conditions has been described and has shed some light on what the critical transcriptional targets are in mediating FOXO function. At the cellular level, these studies have revealed a role for FOXOs in cell metabolism, cellular redox, cell proliferation, DNA repair, autophagy, and many more. The general picture that emerges hereof is that FOXOs act to preserve equilibrium, and they are important for cellular homeostasis. Here, we will first briefly summarize the general knowledge of FOXO regulation and possible functions. We will use genomic stability to illustrate how FOXOs ensure homeostasis. Genomic stability is critical for maintaining genetic integrity, and therefore preventing disease. However, genomic mutations need to occur during lifetime to enable evolution, yet their accumulation is believed to be causative to aging. Therefore, the role of FOXO in genomic stability may underlie its role in lifespan and aging. Finally, we will come up with questions on some of the unknowns in FOXO function, the answer(s) to which we believe will further our understanding of FOXO function and ultimately may help to understand lifespan and its consequences. [ABSTRACT FROM AUTHOR]

The human microbiota is believed to influence health. Microbiome dysbiosis may be linked to neurological conditions like Alzheimer’s disease, amyotrophic lateral sclerosis, and Huntington’s disease. We report the ability of a probiotic bacterial strain in halting neurodegeneration phenotypes. We show that Lacticaseibacillus rhamnosus HA-114 is neuroprotective in C. elegans models of amyotrophic lateral sclerosis and Huntington’s disease. Our results show that neuroprotection from L. rhamnosus HA-114 is unique from other L. rhamnosus strains and resides in its fatty acid content. Neuroprotection by L. rhamnosus HA-114 requires acdh-1/ACADSB, kat-1/ACAT1 and elo-6/ELOVL3/6, which are associated with fatty acid metabolism and mitochondrial β-oxidation. Our data suggest that disrupted lipid metabolism contributes to neurodegeneration and that dietary intervention with L. rhamnosus HA-114 restores lipid homeostasis and energy balance through mitochondrial β-oxidation. Our findings encourage the exploration of L. rhamnosus HA-114 derived interventions to modify the progression of neurodegenerative diseases.A probiotic bacterial strain (Lacticaseibacillus rhamnosus) delays neurodegeneration phenotypes in C. elegans models of amyotrophic lateral sclerosis and Huntington’s disease, with fatty acid extracts from the bacteria able to reproduce the protective effect. [ABSTRACT FROM AUTHOR]

The significance of the tracer testing technique is widely accepted in reservoir performance analysis in hydrology as well as in hydrocarbon exploration and production. The subsurface reservoir delineation for hydrocarbon exploration and optimum production is one of the most critical aspects of petroleum system analysis. The quality of the reservoir and its performance prediction require extensive knowledge of qualitative reservoir geology, its depositional environment, facies heterogeneity and engineering properties of subsurface formations. Tracer testing is amongst the few techniques available in the oil and gas (O&G) industry, which stands up to these expectations and is successfully used for quantitative determination and analysis of sub-seismic scale structural and stratigraphic heterogeneities. Tracer testing is also being utilized in determining residual oil saturation (Sor) and lateral correlation of reservoir properties in the subsurface. Apart from the O&G industry, the concentration-based applications of tracer testing have been proved in hydrology, geothermal and medical science. A comprehensive review is presented to explain the application of tracer testing technique to investigate porous media, mainly in O&G industry. The type of tracers used, their selection criteria, concentration, and natural versus gradient and qualitative to a quantitative application are discussed in the current review. Generally, two types of tracers (chemical and radioactive) are preferred in the petroleum industry for gas/fluid flow assessment, waterflood optimization and establishing connectivity between multiple wells. The current paper reviews both types of tracer tests, namely single well and inter well, in detail discussing the objectives, calculations, designing, injection, sampling, laboratory analysis and knowledge integration. The preliminary aim was to provide a review of the tracer testing technique used in reservoir evaluation and well-to-well connectivity analysis. [ABSTRACT FROM AUTHOR]

Due to its great medicinal value, the Moldavian dragonhead, belonging to Lamiaceae, is naturally distributed in Europe, Siberia, and Central Asia and planted in different Iranian provinces. This research studied the development of male/female reproductive organs. Flowers and buds in different stages of development were fixed and preserved in order to prepare microtome sections using appropriate solutions and embed them in paraffin. Hematoxylin-eosin was used to stain the slices. Based on the results, despite the relative simultaneity of the formation of stamen primordium and carpel, stamens develop faster than ovules. Nurses' cells in secretory and plasmodium types are rectangular, spindle-shaped, and often mononuclear or more. The microspore's tetrads had tetrahedral ornamentations, and mature pollen grains were hexacolpate with reticulate ornamentation of the exine. The ovules were anatropous, unitegmic, and tenuinucellate. The functional megaspore has a micropillar position, and the embryo sac development belongs to the Polygonum type. [ABSTRACT FROM AUTHOR]

Bioluminescence microscopy is an appealing alternative to fluorescence microscopy, because it does not depend on external illumination, and consequently does neither produce spurious background autofluorescence, nor perturb intrinsically photosensitive processes in living cells and animals. The low photon emission of known luciferases, however, demands long exposure times that are prohibitive for imaging fast biological dynamics. To increase the versatility of bioluminescence microscopy, we present an improved low-light microscope in combination with deep learning methods to image extremely photon-starved samples enabling subsecond exposures for timelapse and volumetric imaging. We apply our method to image subcellular dynamics in mouse embryonic stem cells, epithelial morphology during zebrafish development, and DAF-16 FoxO transcription factor shuttling from the cytoplasm to the nucleus under external stress. Finally, we concatenate neural networks for denoising and light-field deconvolution to resolve intracellular calcium dynamics in three dimensions of freely moving Caenorhabditis elegans. Bioluminescence microscopy with deep learning enables subsecond exposures for timelapse and volumetric imaging with denoising and yields high signal-to-noise ratio images of cells. [ABSTRACT FROM AUTHOR]

At the beginning of the testing phase and before the deployment phase of a project's development cycle, we need to predict files with a high chance of change. Software products are always prone to change due to several reasons, including fixing errors or improvements. In this work, we used the Eclipse (releases from 2.0 to 3.5) to investigate how prediction models can perform when learning from a release and predicting in the subsequent one, which contains new files that models have not seen. We compared the performance of these models with models that are trained and tested on the same release. We found no differences between predicting the same release or subsequent release on two pre Europa releases. Predicting change in newly created files helps improve maintenance planning for software project managers and reduce cost. It will also help to enhance the quality of software by improving the practices of developers. This study used the Adaptive Boost classifier with the decision tree J48 algorithm and combined it with the re‐sampling method. We find this to be better than using a meta classifier alone or combine the re‐sampling with the standard classification. We compared our results with related works and found that our results are outperforming. [ABSTRACT FROM AUTHOR]

Ageing is accompanied by alterations in several biochemical processes, highly influenced by its environment. It is controlled by the interactions at various levels of biological hierarchy. To maintain homeostasis, a number of nutrient sensors respond to the nutritional status of the cell and control its energy metabolism. Mitochondrial physiology is influenced by the energy status of the cell. The alterations in mitochondrial physiology and the network of nutrient sensors result in mitochondrial damage leading to age related metabolic degeneration and diseases. Calorie restriction (CR) has proved to be as the most successful intervention to achieve the goal of longevity and healthspan. CR elicits a hormetic response and regulates metabolism by modulating these networks. In this review, the authors summarize the interdependent relationship between mitochondrial physiology and nutrient sensors during the ageing process and their role in regulating metabolism. [ABSTRACT FROM AUTHOR]

Aim: We examined the novel role of NUCB1(Nucleobindin-1) associated with longevity in Drosophila melanogaster., Methods: We measured the lifespan, metabolic phenotypes, and mRNA levels of Drosophila insulin-like peptides (Dilps), the protein level of phosphorylated AKT, and the localization of FOXO and its target gene expressions in the NUCB1 knockdown condition., Results: NUCB1 knockdown flies show an extended lifespan and metabolic phenotypes such as increased circulating glucose level and starvation resistance. The mRNA expression levels of Dilps and the protein level of phosphorylated AKT, a downstream component of insulin signaling, were decreased in NUCB1 knockdown flies compared with the control flies. Also, the nuclear localization of FOXO and its target gene expressions, such as d4E-BP and InR, were elevated., Conclusions: The results show that NUCB1 knockdown flies exhibits an extended lifespan. These findings suggest that NUCB1 modulates longevity through insulin signaling in Drosophila. Geriatr Gerontol Int 2024; 24: 486-492., (© 2024 Japan Geriatrics Society.)

Many industrial chemicals have been reported as antiandrogenic substances. Exposure to these substances represents a potential risk to human health, particularly to the development of reproductive organs such as embryonic external genitalia (eExG). Currently, there is a need for more assay systems that can elucidate the toxicological actions and mechanisms of endocrine-disrupting chemicals. In this study, we show that the eExG slice culture assay is useful for the evaluation of the differing modes of action of endocrine-disrupting chemicals on urethra formation. We assessed the possible endocrine-disrupting activity of 3 chemicals with reported antiandrogenic function, diazinon, dibutyl phthalate, and fenitrothion (FNT) on eExG slices. Exposure to FNT, but not diazinon and dibutyl phthalate, induced defects of androgen-induced urethral masculinization and reduced expression of the androgen-target gene Mafb. Live imaging analyses showed that FNT treatment inhibited androgen-dependent MAFB induction within 12 h. Furthermore, FNT-treated tissue slices showed reduced expression of the androgen receptor. These results indicate that FNT disrupts androgen signaling by reduction of androgen receptor expression during androgen-induced eExG masculinization. This study thus highlights the importance of animal models, which allow for the effective assessment of tissue-specific endocrine-disrupting activity to further reveal the etiology of chemical-induced congenital anomalies. [ABSTRACT FROM AUTHOR]

Greenspaces provide several well-being (Dinnie et al., 2013) and psychosocial benefits (Addy et al., 2004). Community-engaged research affords community partners a voice in the project (Cushman et al., 2004). This study assessed Detroit community members’ perceived benefits of and suggestions for engaging with the community to support greenspaces. Through qualitative analysis, a three-step process for community-engaged planning was revealed. Findings highlight strategies that involve community members in this process to enhance community engagement and well-being. [ABSTRACT FROM AUTHOR]

Twenty-nine years following the breakthrough discovery that a single-gene mutation of daf-2 doubles Caenorhabditis elegans lifespan, it remains unclear where this insulin/IGF-1 receptor gene is expressed and where it acts to regulate ageing. Using knock-in fluorescent reporters, we determined that daf-2 and its downstream transcription factor daf-16 are expressed ubiquitously. Using tissue-specific targeted protein degradation, we determined that intracellular DAF-2-to-DAF-16 signaling in the intestine plays a major role in lifespan regulation, while that in the hypodermis, neurons, and germline plays a minor role. Notably, intestine-specific loss of DAF-2 activates DAF-16 in and outside the intestine, causes almost no adverse effects on development and reproduction, and extends lifespan by 94% in a way that partly requires non-intestinal DAF-16. Consistent with intestine supplying nutrients to the entire body, evidence from this and other studies suggests that altered metabolism, particularly down-regulation of protein and RNA synthesis, mediates longevity by reduction of insulin/IGF-1 signaling. The role of lifespan-regulating protein expression in specific tissues in C. elegans is murky. Here, the authors provide clarity by inducible degradation of longevity-related proteins, demonstrating that intestinal DAF-2 is a major determinant of lifespan in the worm. [ABSTRACT FROM AUTHOR]

Background: The diversity found in the chemical compounds of a single species in different regions results in different biologic characteristics which can be considered as a strong source for identifying new chemotypes. Hymenocrater incanus Bunge and Dracocephalum kotschyi Boiss. are exclusive species of the Lamiaceae family which grow in the western and central habitats of Iran. This study was designed and carried out to determine the yield, identify the chemical compounds, and evaluate the antimicrobial characteristics of the essential oil (EO) of these two species in Iran for the first time. Methods: The flowering twigs of the species D. kotschyi and H. incanus were collected from the villages of Totmach and Kamu in Isfahan province respectively, in May 2019. The EO of these plants was extracted and separated using the water distillation method, utilizing the Clevenger device. The EO compounds were analyzed using a gas chromatograph coupled with a mass spectrometer (GC-MS). The evaluation of antimicrobial characteristics was carried out by determining the growth inhibition zone implementing the Agar method, the minimum inhibition concentration (MIC), and the minimum bactericidal/fungicidal concentration (MFC/MBC) utilizing liquid dilution culture. Results: The results indicated that the highest yield belonged to the EO of D. kotschyi at %2.6 (w/w). In this EO there were citral (%25.44), neral (%20.87), α-pinene (%14.48), trans-geranic acid methyl ester (%9.74), and D-limonene (%6.87). Moreover, H. incanus had the dominant compounds (-)-Spathulenol (%12.61), caryophyllene (%10.00), linolenic acid (%8.54), 1,8-cineole (%5.95), palmitic acid (%5.35), and α-cadinol (%5.17). The largest diameter of growth inhibition zone belonged to the H. incanus EO against the Gram-positive bacteria S. pyogenes (~17.67mm). The strongest inhibition activities in the form of growth inhibition diameter exhibited by the D. kotschyi EO were against the Gram-negative bacteria S. paratyphi-A serotype (~ 12 mm), K. pneumoniae, and Sh. dysenteriae (~ 11 mm) which was significant compared to the Gram-positive rifampin (~ 8 mm). Conclusions: It can be seen that these species are new chemotypes with special and novel chemical compounds which can potentially be used to manufacture natural antibiotics against some bacterial strains. [ABSTRACT FROM AUTHOR]

Aging constitutes progressive physiological changes in an organism. These changes alter the normal biological functions, such as the ability to manage metabolic stress, and eventually lead to cellular senescence. The process itself is characterized by nine hallmarks: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These hallmarks are risk factors for pathologies, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Emerging evidence has been focused on examining the genetic pathways and biological processes in organisms surrounding these nine hallmarks. From here, the therapeutic approaches can be addressed in hopes of slowing the progression of aging. In this review, data have been collected on the hallmarks and their relative contributions to aging and supplemented with in vitro and in vivo antiaging research experiments. It is the intention of this article to highlight the most important antiaging strategies that researchers have proposed, including preventive measures, systemic therapeutic agents, and invasive procedures, that will promote healthy aging and increase human life expectancy with decreased side effects. [ABSTRACT FROM AUTHOR]

Teucrium polium L. is commonly used in folk medicine to treat hypertension and diabetes and to heal wounds. The present work aimed to evaluate the different biological activities of T. polium hydroalcoholic extract, its total phenol and flavonoid content, and its mineral elements. Results showed that T. polium extract showed significant antioxidant potential in 2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50 equal to 8.68 μg/mL but with moderate activity in galvinoxyl assay with IC50 of 21.82 μg/mL and mild activity in the β-carotene assay. It also showed a pronounced anti-hyperglycemic activity using α-amylase inhibitory assay (IC50 = 111.68 µg/mL) and exceeds that of acarbose. T. polium showed excellent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with IC50 values of 28.69 and 4.93 μg/mL, respectively, postulating its promising anti-Alzheimer potential. The plant extract exhibited a strong anti-inflammatory effect with Bovine Serum Albumin (BSA) denaturation inhibitory potential estimated by 97.53% at 2 mg/mL, which was further confirmed by the in vivo carrageen-induced edema model. The extract revealed its richness in flavonoids and phenols, evidenced by its polyphenols content (36.35 ± 0.294 μg GAE/mg) and flavonoids (24.30 ± 0.44 μg QE/mg). It is rich in minerals necessary for human health, such as calcium, potassium, iron, sodium, magnesium, manganese and zinc. Molecular docking performed for previously identified compounds on human α-amylase, 5-lipoxygenase (5-LOX) and acetylcholine esterase confirmed the results. Thus, it can be concluded that T. polium can be a good candidate for alleviating many health-debilitating problems and can be highly beneficial in the pharmaceutical industry and medical research. [ABSTRACT FROM AUTHOR]

The number density profiles of elements N and O in the altitude range of 120–250 km are retrieved by simulation based on X-ray occultation. Based on the parameters of the NICER telescope, the energy spectrum forward model of the Crab Nebula in the energy range of 0.25–8 keV during the occultation is constructed, and the energy spectrum simulation data are obtained by adding noise to the energy spectrum forward model at different tangent point altitudes. The NICER energy band includes the K-shell absorption edges (0.4 keV, 0.53 keV for N, O), and there are significant differences in X-ray cross sections at the K-shell absorption edges, which provides an opportunity to retrieve the atmospheric density of each element. The MCMC algorithm is used to fit the energy spectrum forward model and simulation data, and the density profiles of elements N and O are retrieved. It is found that the retrieved error of O element in the altitude range of 120–140 km is large, which may be related to the low proportion of O in the line of sight and the low signal-to-noise ratio of simulation data. In the altitude range of 140–200 km, the retrieved error of elements N and O is small, but in the altitude range of 200–250 km, the retrieved error of elements N and O becomes larger, and the inconsistency between the retrieved results and NRLMSISE-00 model values increases. This is because the number of absorbed photons is reduced due to the thin atmospheric density at higher altitude, which introduces great uncertainty into the retrieved results. This study lays a foundation for element density retrieval based on X-ray occultation measured data in the future. [ABSTRACT FROM AUTHOR]

X-ray Earth occultation sounding (XEOS) is an emerging method for measuring the neutral density in the lower thermosphere. In this paper, the X-ray Earth occultation (XEO) of the Crab Nebula is investigated using the Hard X-ray Modulation Telescope (Insight-HXMT). The pointing observation data on the 30 September 2018 recorded by the low-energy X-ray telescope (LE) of Insight-HXMT are selected and analysed. The extinction light curves and spectra during the X-ray Earth occultation process are extracted. A forward model for the XEO light curve is established, and the theoretical observational signal for light curve is predicted. The atmospheric density model is built with a scale factor to the commonly used Mass Spectrometer Incoherent Scatter Radar Extended model (MSIS) density profile within a certain altitude range. A Bayesian data analysis method is developed for the XEO light curve modelling and the atmospheric density retrieval. The posterior probability distribution of the model parameters is derived through the Markov chain–Monte Carlo (MCMC) algorithm with the NRLMSISE-00 model and the NRLMSIS 2.0 model as basis functions, and the respective best-fit density profiles are retrieved. It is found that in the altitude range of 105–200 km, the retrieved density profile is 88.8 % of the density of NRLMSISE-00 and 109.7 % of the density of NRLMSIS 2.0 by fitting the light curve in the energy range of 1.0–2.5 keV based on the XEOS method. In the altitude range of 95–125 km, the retrieved density profile is 81.0 % of the density of NRLMSISE-00 and 92.3 % of the density of NRLMSIS 2.0 by fitting the light curve in the energy range of 2.5–6.0 keV based on the XEOS method. In the altitude range of 85–110 km, the retrieved density profile is 87.7 % of the density of NRLMSISE-00 and 101.4 % of the density of NRLMSIS 2.0 by fitting the light curve in the energy range of 6.0–10.0 keV based on the XEOS method. Goodness-of-fit testing is carried out for the validation of the results. The measurements of density profiles are compared to the NRLMSISE-00 and NRLMSIS 2.0 model simulations and the previous retrieval results with NASA's Rossi X-ray Timing Explorer (RXTE) satellite. For further confirmation, we also compare the measured density profile to the ones by a standard spectrum retrieval method with an iterative inversion technique. Finally, we find that the retrieved density profile from Insight-HXMT based on the NRLMSISE-00 and NRLMSIS 2.0 models is qualitatively consistent with the previous retrieved results from RXTE. The results of light curve fitting and standard energy spectrum fitting are in good agreement. This research provides a method for the evaluation of the density profiles from MSIS model predictions. This study demonstrates that the XEOS from the X-ray astronomical satellite Insight-HXMT can provide an approach for the study of the upper atmosphere. The Insight-HXMT satellite can join the family of the XEOS. The Insight-HXMT satellite with other X-ray astronomical satellites in orbit can form a space observation network for XEOS in the future. [ABSTRACT FROM AUTHOR]

Background: Patient awareness of chronic kidney disease (CKD) is low in part due to suboptimal testing for CKD among those at risk and lack of discussions about kidney disease between patients and clinicians. To bridge these gaps, the National Kidney Foundation developed the Kidney Score Platform, which is a web-based series of tools that includes resources for health care professionals as well as an interactive, dynamic patient-facing component that includes a brief questionnaire about risk factors for kidney disease, individualized assessment of risk for developing CKD, and self-management tools to manage one’s kidney disease. Objective: The aim of this study is to perform usability testing of the patient component of the Kidney Score platform among veterans with and at risk for kidney disease and among clinicians working as primary care providers in Veterans Affairs administration. Methods: Think-aloud exercises were conducted, during which participants (veterans and clinicians) engaged with the platform while verbalizing their thoughts and making their perceptions, reasonings, and decision points explicit. A usability facilitator observed participants’ behaviors and probed selectively to clarify their comprehension of the tool’s instructions, content, and overall functionality. Thematic analysis on the audio-recording transcripts was performed, focusing on positive attributes, negative comments, and areas that required facilitator involvement. Results: Veterans (N=18) were 78% (14/18) male with a mean age of 58.1 years. Two-thirds (12/18) were of non-White race/ethnicity, 28% (5/18) had laboratory evidence of CKD without a formal diagnosis, and 50% (9/18) carried a diagnosis of hypertension or diabetes. Clinicians (N=19) were 29% (5/17) male, 30% (5/17) of non-White race/ethnicity, and had a mean of 17 (range 4-32) years of experience. Veterans and clinicians easily navigated the online tool and appreciated the personalized results page as well as the inclusion of infographics to deliver key educational messages. Three major themes related to content and communication about risk for CKD emerged from the think-aloud exercises: (1) tension between lay and medical terminology when discussing kidney disease and diagnostic tests, (2) importance of linking general information to concrete self-management actions, and (3) usefulness of the tool as an adjunct to the office visit to prepare for patient-clinician communication. Importantly, these themes were consistent among interviews involving both veterans and clinicians. Conclusions: Veterans and clinicians both thought that the Kidney Score Platform would successfully promote communication and discussion about kidney disease in primary care settings. Tension between using medical terminology that is used regularly by clinicians versus lay terminology to promote CKD awareness was a key challenge, and knowledge of this can inform the development of future CKD educational materials. [ABSTRACT FROM AUTHOR]

Glycosylphosphatidylinositol‐specific phospholipase D1 (GPLD1) hydrolyzes inositol phosphate linkages in proteins anchored to the cell membrane. Mice overexpressing GPLD1 show enhanced neurogenesis and cognition. Snell dwarf (DW) and growth hormone receptor knockout (GKO) mice show delays in age‐dependent cognitive decline. We hypothesized that augmented GPLD1 might contribute to retained cognitive function in these mice. We report that DW and GKO show higher GPLD1 levels in the liver and plasma. These mice also have elevated levels of hippocampal brain‐derived neurotrophic factor (BDNF) and of doublecortin (DCX), suggesting a mechanism for maintenance of cognitive function at older ages. GPLD1 was not increased in the hippocampus of DW or GKO mice, suggesting that plasma GPLD1 increases elevated these brain proteins. Alteration of the liver and plasma GPLD1 was unaltered in mice with liver‐specific GHR deletion, suggesting that the GH effect was not intrinsic to the liver. GPLD1 was also induced by caloric restriction and by each of four drugs that extend lifespan. The proteome of DW and GKO mice is molded by selective translation of mRNAs, involving cap‐independent translation (CIT) of mRNAs marked by N6 methyladenosine. Because GPLD1 protein increases were independent of the mRNA level, we tested the idea that GPLD1 might be regulated by CIT. 4EGI‐1, which enhances CIT, increased GPLD1 protein without changes in GPLD1 mRNA in cultured fibroblasts and mice. Furthermore, transgenic overexpression of YTHDF1, which promotes CIT by reading m6A signals, also led to increased GPLD1 protein, showing that elevation of GPLD1 reflects selective mRNA translation. [ABSTRACT FROM AUTHOR]

Sirtuin1 is a nutrient-sensitive class III histone deacetylase which is a well-known regulator of organismal lifespan. It has been extensively studied for its role in metabolic regulation as well. Along with its involvement in ageing and metabolism, Sirtuin1 directly deacetylates many critical proteins controlling cardiovascular pathophysiology. Studies using conditional expression and deletion of Sirtuin1 have revealed that it functions in a highly tissue/organ-specific manner. In the vasculature, Sirtuin1 controls endothelial homoeostasis by governing the expression of inflammatory mediators, oxidants and essential transcription factors. Adding to this complexity, Sirtuin1 expression and/or function is also governed by some of these target proteins. Therefore, the importance of better understanding the organ and tissue specificity of Sirtuin1 is highly desirable. Considering the huge volume of research done in this field, this review focuses on Sirtuin1 targets regulating vascular endothelial function. Here, we summarize the discovery of Sirtuin1 as a transcription controller and the further identification of direct target proteins involved in the vascular physiology. Overall, this review presents a holistic picture of the complex cross-talk involved in the molecular regulation of vascular physiology by Sirtuin1. [ABSTRACT FROM AUTHOR]

Telomeres are essential structures formed from satellite DNA repeats at the ends of chromosomes in most eukaryotes. Satellite DNA repeat sequences are useful markers for karyotyping, but have a more enigmatic role in the eukaryotic cell. Much work has been done to investigate the structure and arrangement of repetitive DNA elements in classical models with implications for species evolution. Still more is needed until there is a complete picture of the biological function of DNA satellite sequences, particularly when considering non-model organisms. Celebrating Gregor Mendel's anniversary by going to the roots, this review is designed to inspire and aid new research into telomeres and satellites with a particular focus on non-model organisms and accessible experimental and in silico methods that do not require specialized equipment or expensive materials. We describe how to identify telomere (and satellite) repeats giving many examples of published (and some unpublished) data from these techniques to illustrate the principles behind the experiments. We also present advice on how to perform and analyse such experiments, including details of common pitfalls. Our examples are a selection of recent developments and underexplored areas of research from the past. As a nod to Mendel's early work, we use many examples from plants and insects, especially as much recent work has expanded beyond the human and yeast models traditional in telomere research. We give a general introduction to the accepted knowledge of telomere and satellite systems and include references to specialized reviews for the interested reader. [ABSTRACT FROM AUTHOR]

In recent decades, the use of alpha; pure beta; or beta/gamma emitters in oncology, endocrinology, and interventional cardiology rheumatology, has proved to be an important alternative to the most common therapeutic regimens. Among radionuclides used for therapy in nuclear medicine, two rhenium radioisotopes are of particular relevance: rhenium-186 and rhenium-188. The first is routinely produced in nuclear reactors by direct neutron activation of rhenium-186 via 185Re(n,γ)186Re nuclear reaction. Rhenium-188 is produced by the decay of the parent tungsten-188. Separation of rhenium-188 is mainly performed using a chromatographic 188W/188Re generator in which tungsten-188 is adsorbed on the alumina column, similar to the 99Mo/99mTc generator system, and the radionuclide eluted in saline solution. The application of rhenium-186 and rhenium-188 depends on their specific activity. Rhenium-186 is produced in low specific activity and is mainly used for labeling particles or diphosphonates for bone pain palliation. Whereas, rhenium-188 of high specific activity can be used for labeling peptides or bioactive molecules. One of the advantages of rhenium is its chemical similarity with technetium. So, diagnostic technetium analogs labeled with radiorhenium can be developed for therapeutic applications. Clinical trials promoting the use of 186/188Re-radiopharmaceuticals is, in particular, are discussed. [ABSTRACT FROM AUTHOR]

Dracocephalum botryoides Steven and Dracocephalum austriacum L. are unexplored species of the Dracocephalum genus (Lamiaceae family) with a distribution in the Caucasus, where they are used in folk medicine and local cuisine. There are no data on the chemical composition of these Dracocephalum species. In this study, the application of a liquid chromatography-mass spectrometry technique for the metabolite profiling of methanol extracts from herbs and roots of D. austriacum and D. botryoides resulted in the identification of 50 compounds, including benzoic acid derivatives, phenylpropanoids, flavonoids and lignans. Water-soluble polysaccharides of the herbs and roots of D. austriacum and D. botryoides were isolated and characterized as mostly pectins with additive arabinogalactan-protein complexes and starch-like compounds. The antioxidant potential of the studied extracts of Dracocephalum and selected phenolics and water-soluble polysaccharides were investigated via radical-scavenging and ferrous (II) ion chelating assays. This paper demonstrates that herbs and roots of D. austriacum and D. botryoides are rich sources of metabolites and could be valuable plants for new biologically active products. To the best of our knowledge, this is the first study of whole plant metabolites and their antioxidant activity in D. austriacum and D. botryoides. [ABSTRACT FROM AUTHOR]

During aging, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In Caenorhabditis elegans, mutants of the insulin‐IGF‐1 receptor DAF2/IIRc represent a paradigm of healthy aging, as their increased lifespan is accompanied by a delay in age‐related loss of motility. Here, we investigated the DAF‐2/IIRc‐dependent relationship between longevity and motility using an auxin‐inducible degron to trigger tissue‐specific degradation of endogenous DAF‐2/IIRc. As previously reported, inactivation of DAF‐2/IIRc in neurons or intestine was sufficient to extend the lifespan of worms, whereas depletion in epidermis, germline, or muscle was not. However, neither intestinal nor neuronal depletion of DAF‐2/IIRc prevented the age‐related loss of motility. In 1‐day‐old adults, DAF‐2/IIRc depletion in neurons reduced motility in a DAF‐16/FOXO dependent manner, while muscle depletion had no effect. By contrast, DAF‐2 depletion in the muscle of middle‐age animals improved their motility independently of DAF‐16/FOXO but required UNC‐120/SRF. Yet, neuronal or muscle DAF‐2/IIRc depletion both preserved the mitochondria network in aging muscle. Overall, these results show that the motility pattern of daf‐2 mutants is determined by the sequential and opposing impact of neurons and muscle tissues and can be dissociated from the regulation of the lifespan. This work also provides the characterization of a versatile tool to analyze the tissue‐specific contribution of insulin‐like signaling in integrated phenotypes at the whole organism level. [ABSTRACT FROM AUTHOR]

High‐resolution bathymetry and three‐dimensional seismic data along the Cocos Ridge reveal a 245 km2 field of ∼1–4 km in diameter seafloor depressions. The seafloor depressions are part of a two‐tiered honeycomb pattern. The lower‐tier depressions have steep faults that truncate strata with chaotic internal reflections consistent with sediment collapse into the depression. These extend into a lens shaped interval just above igneous basement. Overlying these depressions is a second broader set with rough seafloor morphology with gently dipping boundaries defined by pinch‐out stratigraphic patterns. Drilling results indicate that the lens‐shaped zones that host the deeper depressions represent anomalous regions of high porosity, low velocity, and low density within calcareous rich sediment. Analysis of nannofossils from IODP Site U1414 suggests the collapse structures formed during the late Miocene, whereas the younger shallower depressions likely formed between the early Pliocene and the Pliocene‐Pleistocene boundary. Geochemical and petrological analysis at Site U1414 suggests that hydrothermal circulation during the late Miocene led to carbonate dissolution and collapse. Following collapse, focused fluid‐flow and bottom current scouring resulted in formation of the overlying set of depressions and a honeycomb seafloor morphology. Similar sets of depressions along the Carnegie Ridge to the south support the hypothesis that two‐tiered depressions formed in response to processes that occurred broadly across the Panama Basin between the late Miocene and the Pliocene‐Pleistocene transition. Geochemical results at Site U1414, combined with geophysical data, suggest this two‐tiered system of depressions currently guides ongoing fluid outflow. Plain Language Summary: We characterize a vast field of mega seafloor depressions along the Cocos Ridge using three‐dimensional geophysical data tied to drilling results. The mega depressions display distinct two‐tiered structures that form a honeycomb‐like pattern on the seafloor. By imaging faulting and sediment layers within the depressions, we reveal that the older, steeper‐walled depressions formed through collapse processes, whereas the younger, broader depressions likely formed through a combination of fluid‐flow and current scouring. Drilling results indicate that the older collapses formed during the late Miocene, and geochemical results suggest that hydrothermal circulation, likely along ridge‐parallel faults, dissolved carbonate‐rich sediments and led to collapse. In contrast, drilling results suggest the younger depressions formed sometime between the Pliocene and Pliocene‐Pleistocene boundary. Similar depressions imaged within the Panama Basin and along the Carnegie Ridge to the south suggest widespread Galapagos Hotspot volcanism and hydrothermal circulation led to dissolution and collapse of carbonate‐rich sediments across the eastern equatorial Pacific. Fluid‐flow through the existing collapses and water current activity following the closing of the Central American Seaway likely led to the formation of the younger depressions. Drilling results, seismic reflection indicators of fluid pathways, and indicators of seafloor seepage suggests these depressions are actively guiding fluid outflow. Key Points: The study provides three‐dimensional seismic tied to drilling results for understanding the development of mega‐depressions along the Cocos RidgeThe depressions formed initially through dissolution and collapse, driven by volcanism and hydrothermal circulationThe younger depressions likely formed through bottom current activity and fluid‐flow, the latter of which appears to be active today [ABSTRACT FROM AUTHOR]