Confirmation that Monochamol is a Male Produced Aggregation-Sex Pheromone for Monochamus maculosus Haldeman (Coleoptera: Cerambycidae).

The recognition of cerambycids as frequent and damaging invaders led to an increase in the interest in the chemical ecology of the group with the identification of pheromones and pheromone-like attractants for well over 100 species. Pheromone components of the Cerambycidae are often phylogenetically conserved, with a single compound serving as a pheromone component for several related species. In the subfamily Lamiinae, the compound 2-(undecyloxy)ethanol (monochamol) has been identified as an aggregation-sex pheromone for several species of the genus Monochamus. In other species, including Monochamus maculosus Haldeman, field trials have demonstrated that monochamol is a pheromone attractant, but at that point it was still unknown as to whether it was a pheromone for this species. Here we report the identification, and laboratory and field trials of a pheromone component produced by adult male M. maculosus. Chemical analyses of headspace volatile collections sampled from field collected beetles of both sexes revealed the presence of one male-specific compound that was identified as 2-(undecyloxy)ethanol. Electroantennography analyses showed that monochamol elicited responses from the antennae of female beetles. Traps baited with monochamol in the field captured M. maculosus adults of both sexes corroborating the identification of monochamol as the sex-aggregation pheromone of this species. The attractivity of monochamol to adult M. maculosus in our field trapping experiment was synergized by the addition of the host volatile α-pinene.

Can Pheromones Contribute to Phylogenetic Hypotheses? A Case Study of Chrysomelidae.

Pheromones mediate species-level communication in the search for mates, nesting, and feeding sites. Although the role of pheromones has long been discussed by various authors, their existence was not proven until the mid-twentieth century when the first sex pheromone was identified. From this finding, much has been speculated about whether this communication mechanism has acted as a regulatory agent in the process of speciation, competition, and sexual selection since it acts as an intraspecific barrier. Chrysomelidae is one of the major Phytophaga lineages, with approximately 40,000 species. Due to this immense diversity the internal relationships remain unstable when analyzed only with morphological data, consequently recent efforts have been directed to molecular analyses to establish clarity for the relationships and found their respective monophyly. Therefore, our goals are twofold 1) to synthesize the current literature on Chrysomelidae sex pheromones and 2) to test whether Chrysomelidae sex pheromones and their chemical structures could be used in phylogenetic analysis for the group. The results show that, although this is the first analysis in Chrysomelidae to use pheromones as a phylogenetic character, much can be observed in agreement with previous analyses, thus confirming that pheromones, when known in their entirety within lineages, can be used as characters in phylogenetic analyses, bringing elucidation to the relationships and evolution of organisms.

Effect of a probiotic fermented milk supplementation on behavior and sleep.

This study attempted to analyze the effect of supplementing Wistar-Kyoto rats with fermented milk containing the probiotic Bifidobacterium animalis BB-12 and pomegranate juice on the microbiota-gut-brain axis of rats, with special focus on their behavior, sleep patterns, and response to stress. This study was divided into two experiments: (1) For the behavioral analysis the animals were divided into two groups: Fermented probiotic milk (BB + 1) and control (BB-). (2) For the sleep analysis the animals were divided into two groups: Fermented probiotic milk (BB + 2) and control (H2O). For the behavioral analysis, the open field method was used, which evaluates the behavior after ten, twenty, and thirty days of supplementation. For sleep analysis, the animals were submitted to implantation of electrodes and 24 h polysomnography, followed by 48 h sleep deprivation (REM) and 48 h polysomnography, then euthanized 100 days after the beginning of the experiment. In addition, animal feces were collected before and after sleep deprivation to assess its effects on the microbiota. A decrease in anxiety-related behaviors was observed in the supplemented animals and an increase in sleep efficiency and a reduction in the number of awakenings of the animals before deprivation. It has also been observed that sleep deprivation decreased the amount of total bacterial DNA. The number of copies of genomes of the genus Bifidobacterium did not differ in both groups.

First Genotype-Phenotype Study in TBX4 Syndrome: Gain-of-Function Mutations Causative for Lung Disease.

Rationale: Despite the increased recognition of TBX4 (T-BOX transcription factor 4)-associated pulmonary arterial hypertension (PAH), genotype-phenotype associations are lacking and may provide important insights. Objectives: To compile and functionally characterize all TBX4 variants reported to date and undertake a comprehensive genotype-phenotype analysis. Methods: We assembled a multicenter cohort of 137 patients harboring monoallelic TBX4 variants and assessed the pathogenicity of missense variation (n = 42) using a novel luciferase reporter assay containing T-BOX binding motifs. We sought genotype-phenotype correlations and undertook a comparative analysis with patients with PAH with BMPR2 (Bone Morphogenetic Protein Receptor type 2) causal variants (n = 162) or no identified variants in PAH-associated genes (n = 741) genotyped via the National Institute for Health Research BioResource-Rare Diseases. Measurements and Main Results: Functional assessment of TBX4 missense variants led to the novel finding of gain-of-function effects associated with older age at diagnosis of lung disease compared with loss-of-function effects (P = 0.038). Variants located in the T-BOX and nuclear localization domains were associated with earlier presentation (P = 0.005) and increased incidence of interstitial lung disease (P = 0.003). Event-free survival (death or transplantation) was shorter in the T-BOX group (P = 0.022), although age had a significant effect in the hazard model (P = 0.0461). Carriers of TBX4 variants were diagnosed at a younger age (P < 0.001) and had worse baseline lung function (FEV1, FVC) (P = 0.009) than the BMPR2 and no identified causal variant groups. Conclusions: We demonstrated that TBX4 syndrome is not strictly the result of haploinsufficiency but can also be caused by gain of function. The pleiotropic effects of TBX4 in lung disease may be in part explained by the differential effect of pathogenic mutations located in critical protein domains.

Stimulation action of mefenpyr-diethyl on soybean, wheat, and signal grass plants.

Mefenpyr-diethyl is a safener used for protection of cereal plants under applications of ACCase and ALS inhibitor herbicides. Current studies are describing safeners using a new approach, relating these products to stimulation action on plants. The objective of this work was to evaluate the stimulation action of mefenpyr-diethyl on soybean, wheat, and signal grass plants. The experiment was conducted in a greenhouse, under a completely randomized design, with four replications, in two seasons. Mefenpyr-diethyl (50 g a.i. ha-1) was applied on soybean plants (at V4 stage), and wheat and signal grass plants (both with 15 cm height). The variables evaluated were plant height, dry matter, and lipid content of the three species, and number of tillers of wheat and signal grass plants. The application of mefenpyr-diethyl in the first season increased the number of tillers of wheat and height of soybean plants. The soybean presented 24 and 14% more dry matter than the control in the first and second season, respectively, and 0.5% more lipid content in plants treated with mefenpyr-diethyl. These results show the stimulation action of mefenpyr-diethyl on wheat and soybean plants, denoting its potential for growth promotion and indicating the need for studies with this approach. No effect was found for the signal grass plants.

Efficacy, acceptability, and tolerability of all available treatments for insomnia in the elderly: a systematic review and network meta-analysis.

OBJECTIVES: Symptoms of insomnia are highly prevalent in the elderly. A significant number of pharmacological and non-pharmacological interventions exist, but, up-to-date, their comparative efficacy and safety has not been sufficiently assessed. METHODS: We integrated the randomized evidence from every available treatment for insomnia in the elderly (>65 years) by performing a network meta-analysis. Several electronic databases were searched up to May 25, 2019. The two primary outcomes were total sleep time and sleep quality. Data for other 6 efficacy and 8 safety outcomes were also analyzed. RESULTS: Fifty-three RCTs with 6832 participants (75 years old on average) were included, 43 of which examined the efficacy of one or more drugs. Ten RCTs examined the efficacy of non-pharmacological interventions and were evaluated only with pairwise meta-analyses because they were disconnected from the network. The overall confidence in the evidence was very low primarily due to the small amount of data per comparison and their sparse connectedness. Several benzodiazepines, antidepressants, and z-drugs performed better in both primary outcomes, but few comparisons had data from more than one trial. The limited evidence on non-pharmacological interventions suggested that acupressure, auricular acupuncture, mindfulness-based stress reduction program, and tart cherry juice were better than their control interventions. Regarding safety, no clear differences were detected among interventions due to large uncertainty. CONCLUSIONS: Insufficient evidence exists on which intervention is more efficacious for elderly patients with insomnia. More RCTs, with longer duration, making more direct interventions among active treatments and presenting more outcomes are urgently needed.

Synthesis of novel 3,5,6-trisubstituted 2-pyridone derivatives and evaluation for their anti-inflammatory activity.

The inflammatory response is the reaction of living tissue to an injury of a foreign nature, such as infection and irritants, and occurs as part of the body's natural defence response. Compounds capable of inhibiting cyclooxygenase (COX) enzymes, especially COX-2, have great potential as anti-inflammatory agents. Herein we present the regioselective synthesis of 49 novel compounds based on the 2-pyridone nucleus. The topical anti-inflammatory activity of seventeen compounds was evaluated in mice by croton oil (CO) induced ear edema assay. Most of the compounds exhibited a high level of in vivo anti-inflammatory activity, reducing ear edema and myeloperoxidase (MPO) activity. The most active compounds (2a and 7a) were inhibitors of COX enzymes. Compound 2a selectively inhibited the COX-2, while 7a was nonselective. Further, the compound 2a showed effective binding at the active site of COX-2 co-crystal by docking molecular study.

Seasonal trends and primary contributors to the low-frequency soundscape of the Cordell Bank National Marine Sanctuary.

Passive acoustic monitoring of ocean soundscapes can provide information on ecosystem status for those tasked with protecting marine resources. In 2015, the National Oceanic and Atmospheric Administration (NOAA) established a long-term, continuous, low-frequency (10 Hz-2 kHz) passive acoustic monitoring site in the Cordell Bank National Marine Sanctuary (CBNMS), located offshore of the central United States of America (U.S.) west coast, near San Francisco, CA. The California Current flows southward along the coast in this area, supporting a diverse community of marine animals, including several baleen whale species. Acoustic data analysis revealed that both large vessels and vocalizing baleen whales contribute to the ambient soundscape of the CBNMS. Sound levels fluctuated by month with the highest levels in the fall and lowest levels in the summer. Throughout the year, very low-frequency (10-100 Hz) sound levels were most variable. Vessels and whales overlap in their contributions to ambient sound levels within this range, although vessel contributions were more omnipresent, while seasonal peaks were associated with vocalizing whales. This characterization of low-frequency ambient sound levels in the CBNMS establishes initial baselines for an important component of this site's underwater soundscape. Standardized monitoring of soundscapes directly supports NOAA's ability to evaluate and report on conditions within national marine sanctuaries.

Alterations in Xenobiotic-Metabolizing Enzyme Activities across Menstrual Cycle in Healthy Volunteers.

The purpose of the study was to determine whether the in vivo activities of drug-metabolizing enzymes CYP1A2 and CYP2A6, xanthine oxidase (XO), and N-acetyltransferase-2 (NAT2) vary across the menstrual cycle. Forty-two healthy women were studied at early follicular phase (EFP: 2nd to 4th days), late follicular phase (LFP: 10th to 12th days), and luteal phase (LP: 19th to 25th days) of a single menstrual cycle, and blood and urine samples were collected at each phase. Spot urine samples obtained 6 hours following 200-mg caffeine administration were used to determine caffeine metabolite ratios (CMRs); blood samples were used to determine CYP1A2*1F (rs762551) and CYP1A2*1C (rs2069514) polymorphisms and the hormonal profile (estradiol, progesterone, and luteinizing and follicle-stimulating hormones) at EFP, LFP, and LP. CMR and hormone variations were analyzed at three levels (EFP, LFP, LP) using one-way repeated-measures analysis of variance. CYP1A2 activity was lower and that of CYP2A6 and NAT2 were higher at LFP compared with EFP and LP. Enzyme alterations were significant in volunteers (n = 21) whose hormonal profiles at EFP, LFP, and LP corresponded to expected levels, but not in volunteers (n = 15) with presumed early or late sampling around LFP. No significant difference was detected in any enzyme activity in presumed anovulatory volunteers (n = 6). The reduction of CYP1A2 activity at LFP was not associated with smoking or CYP1A2*1F polymorphism. XO and NAT2 (fast acetylators) activities remained unaltered. It is suggested that drug-metabolizing enzyme activities are altered across the menstrual cycle. Selection of appropriate sampling periods verified by hormonal assessment and identification of anovulatory cycles are decisive factors in disclosing altered enzyme activity across the menstrual cycle.

Unconventional Method for Synthesis of 3-Carboxyethyl-4-formyl(hydroxy)-5-aryl-N-arylpyrazoles.

An alternative highly regioselective synthetic method for the preparation of 3,5-disubstituted 4-formyl-N-arylpyrazoles in a one-pot procedure is reported. The methodology developed was based on the regiochemical control of the cyclocondensation reaction of ß-enamino diketones with arylhydrazines. Structural modifications in the ß-enamino diketone system allied to the Lewis acid carbonyl activator BF3 were strategically employed for this control. Also a one-pot method for the preparation of 3,5-disubstituted 4-hydroxymethyl-N-arylpyrazole derivatives from the ß-enamino diketone and arylhydrazine substrates is described.

Expression profile of the GA733 gene family in colorectal cancer: correlation with clinicopathological parameters.

GA733-1/-2/-3 genes have been detected in various types of cancer, although their role has not been fully clarified. GA733-2 and GA733-1 have been correlated with lymph node metastases in laryngeal cancer and liver metastases, respectively. Only a few studies have elucidated the mechanisms regulating GA733-1/-2 expression and their effect on colorectal cancer. Therefore, the expression pattern and the role of the aforementioned molecules in colorectal carcinogenesis were evaluated in this study. Tissue samples were obtained from 40 patients with colorectal cancer with no liver metastases. GA733-1/-2 mRNA levels were evaluated by quantitative real-time polymerase chain reaction. GA733-1/-2 gene expression in noncancerous/cancerous tissues was also correlated with clinicopathological parameters. The GA733-1 mRNA levels were very low; however, the GA733-1 mRNA transcripts were higher in cancerous tissues than in normal tissues (median ratio, 0.004391/0.00093; range, 0.000001- 0.025139/0.000001-0.007761), respectively (P = 0.012). GA733-2 gene expression was higher in noncancerous tissues than in cancerous tissues (median ratio 273.31/115.64; range, 65.24-1,486.41/11.58-1,189.14; P = 0.0000195). Lower GA733-2 expression in cancer tissues appeared to correlate with lymph node metastases (P < 0.05). GA733-1 gene expression was significantly higher in cancerous samples; conversely, the GA733-2 mRNA levels were higher in noncancerous tissues, and were significantly correlated with lymph node perforation in colorectal cancer (P < 0.05). Therefore, GA733-1/-2 mRNA expression levels appear to be a potential predictive marker of tumorigenesis.

Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: association with morphological and prognostic criteria.

KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P < 0.05). Tumors with G>T codon 12 transversions and G>C transitions showed more frequent lymph node metastasis (P < 0.05, P < 0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P < 0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005). Additionally, we found that the histological features of preexisting adenoma were associated with the absence of BRAF mutations, in contrast to KRAS (P < 0.05). Our data suggested that there seems to be a correlation between morphological criteria and discrete genetic pathways in colorectal carcinogenesis. Moreover, ethnic or geographic factors may have an impact on genetic background of colorectal carcinomas, and specific types of KRAS mutations may influence the metastatic potential of colorectal tumors.

OsCYP706C2 diverts rice strigolactone biosynthesis to a noncanonical pathway branch.

Strigolactones exhibit dual functionality as regulators of plant architecture and signaling molecules in the rhizosphere. The important model crop rice exudes a blend of different strigolactones from its roots. Here, we identify the inaugural noncanonical strigolactone, 4-oxo-methyl carlactonoate (4-oxo-MeCLA), in rice root exudate. Comprehensive, cross-species coexpression analysis allowed us to identify a cytochrome P450, OsCYP706C2, and two methyl transferases as candidate enzymes for this noncanonical rice strigolactone biosynthetic pathway. Heterologous expression in yeast and Nicotiana benthamiana indeed demonstrated the role of these enzymes in the biosynthesis of 4-oxo-MeCLA, which, expectedly, is derived from carlactone as substrate. The oscyp706c2 mutants do not exhibit a tillering phenotype but do have delayed mycorrhizal colonization and altered root phenotype. This work sheds light onto the intricate complexity of strigolactone biosynthesis in rice and delineates its role in symbiosis and development.

Navigating the Transition to Adulthood: Insights from Caregivers of Autistic Individuals.

With many teens having to transition from a mainly educational system of support to a set of health and social service systems (Shattuck et al. in Autism Res Treat https://doi.org/10.1155/2014/924182 , 2017), there is a critical need to advance research and support services in the area of autism and transition to aid autistic* individuals and their families. This study aims to learn more about the experiences of caregivers of autistic young adults, their experiences navigating the transition process post-graduation, and what realistic steps could be undertaken by high schools, vocational schools, colleges, Regional Centers, and places of employment to ease this transition. Ten semi-structured interviews were conducted with caregivers of autistic young adults over the age of 18 focused on their experiences helping their children navigate the transition to adulthood. Using an iterative and inductive coding approach, three overarching themes were uncovered with twelve subthemes. The three major themes recurring in caregiver interviews were their experiences with navigating service receipt, exploring the landscape of opportunities available for their children, and the parent experiences specific to their role in their child's transition into adulthood. Findings from this study provide a chance for stakeholders to learn from the lived experiences of caregivers navigating the frustration and confusion pertaining to transition for their autistic adult child due to the highly prohibitive access to service receipt, experiencing significant financial burdens, finding a niche for their children that fits their needs, desires, and talents, and managing their well-being.

The variable influence of anthropogenic noise on summer season coastal underwater soundscapes near a port and marine reserve.

Monitoring soundscapes is essential for assessing environmental conditions for soniferous species, yet little is known about sound levels and contributors in Oregon coastal regions. From 2017 to 2021, during June-September, two hydrophones were deployed near Newport, Oregon to sample 10-13,000 Hz underwater sound. One hydrophone was deployed near the Port of Newport in a high vessel activity area, and another 17 km north within a protected Marine Reserve. Vessel noise and whale vocalizations were detected at both sites, but whales were recorded on more days at the Marine Reserve. Median sound levels in frequencies related to noise from various vessel types and sizes (50 - 4,000 Hz) were up to 6 dB higher at the Port of Newport, with greater diel variability compared to the Marine Reserve. In addition to documenting summer season conditions in Oregon waters, these results exemplify how underwater soundscapes can differ over short distances depending on anthropogenic activity.

Assessing variation in faecal glucocorticoid concentrations in gray whales exposed to anthropogenic stressors.

Understanding how individual animals respond to stressors behaviourally and physiologically is a critical step towards quantifying long-term population consequences and informing management efforts. Glucocorticoid (GC) metabolite accumulation in various matrices provides an integrated measure of adrenal activation in baleen whales and could thus be used to investigate physiological changes following exposure to stressors. In this study, we measured GC concentrations in faecal samples of Pacific Coast Feeding Group (PCFG) gray whales (Eschrichtius robustus) collected over seven consecutive years to assess the association between GC content and metrics of exposure to sound levels and vessel traffic at different temporal scales, while controlling for contextual variables such as sex, reproductive status, age, body condition, year, time of year and location. We develop a Bayesian Generalized Additive Modelling approach that accommodates the many complexities of these data, including non-linear variation in hormone concentrations, missing covariate values, repeated samples, sampling variability and some hormone concentrations below the limit of detection. Estimated relationships showed large variability, but emerging patterns indicate a strong context-dependency of physiological variation, depending on sex, body condition and proximity to a port. Our results highlight the need to control for baseline hormone variation related to context, which otherwise can obscure the functional relationship between faecal GCs and stressor exposure. Therefore, extensive data collection to determine sources of baseline variation in well-studied populations, such as PCFG gray whales, could shed light on cetacean stress physiology and be used to extend applicability to less-well-studied taxa. GC analyses may offer greatest utility when employed as part of a suite of markers that, in aggregate, provide a multivariate measure of physiological status, better informing estimates of individuals' health and ultimately the consequences of anthropogenic stressors on populations.

Patient Experience of Systemic Sclerosis-Related Calcinosis: An International Study Informing Clinical Trials, Practice, and the Development of the Mawdsley Calcinosis Questionnaire.

Systemic sclerosis (SSc) -related calcinosis can be a debilitating, constantly painful, poorly understood vascular complication of calcium hydroxyapatite deposition in soft tissue structures that affects approximately 40% of both limited and diffuse cutaneous SSc subtypes. This publication describes the iterative and multitiered international qualitative investigations that yielded remarkable insights into natural history, daily experience, and complications of SSc-calcinosis providing pivotal information for health management. Patient-driven question development and field testing, according to Food and Drug Administration guidance, propelled the development of a patient-reported outcome measure for SSc-calcinosis, the Mawdsley Calcinosis Questionnaire.