Cardiac psychophysiological tuning to socioaffective content is disrupted in aged rhesus monkeys (Macaca mulatta).

Aging ushers in numerous disruptions to autonomic nervous system (ANS) function. Although the effects of aging on ANS function at rest are well characterized, there is surprising variation in reports of age-related differences in ANS reactivity to psychosocial stressors, with some reports of decreases and other reports of increases in reactivity with age. The sources of variation in age-related differences are largely unknown. Nonhuman primate models of socioaffective aging may help to uncover sources of this variation as nonhuman primates share key features of human ANS structure and function and researchers have precise control over the environments in which they age. In this report, we assess how response patterns to dynamic socioaffective stimuli in the parasympathetic and sympathetic branches of rhesus monkeys (Macaca mulatta) ANS differ in aged compared to middle-aged monkeys. We find that respiratory sinus arrhythmia, a cardiac indicator of activity in the parasympathetic branch of the ANS, exhibits age-related disruptions in responding while monkeys view videos of conspecifics. This suggests that there are evolutionarily conserved mechanisms responsible for the patterns of affective aging observed in humans and that aged rhesus monkeys are a robust translational model for human affective aging.

Estimates of life history parameters in a high latitude, arid-country vervet monkey population.

We present data on life history parameters from a long-term study of vervet monkeys in the Eastern Cape, South Africa. Estimates are presented of age at first conception for females and age at natal dispersal for males, along with the probability of survival to adulthood for infants born during the study, female reproductive life-span, reproductive output (including lifetime reproductive success for a subset of females), and inter-birth interval (IBI) duration. We also assess the effect of maternal age and infant survival on length of IBI. We then go on to compare life history parameters for our population with those from two East African populations in Kenya (Amboseli and Laikipia). We find there is broad consensus across the three populations, although mean infant survival was considerably lower for the two East African sites. Such comparisons must be made cautiously, however, as local ecology across the duration of the studies obviously has an impact on the estimates obtained. With this caveat in place, we consider that the concordance between values is sufficient to enable the values reported here to be used in comparative studies of primate life history, although data from habitats with higher rainfall and lower levels of seasonality are needed, and the results presented here should not be seen as canonical.

Well-being of professional older adults' caregivers in Alberta's assisted living and long-term care facilities: a cross-sectional study.

BACKGROUND: For the care need of older adults, long-term care (LTC) and assisted living (AL) facilities are expanding in Alberta, but little is known about the caregivers' well-being. The purpose of the study was to investigate the physical health conditions, mental and emotional health (MEH), health behaviour, stress levels, quality of life (QOL), and turnover and absenteeism (TAA) among professional caregivers in Alberta's LTC and AL facilities. METHODS: This cross-sectional survey involved 933 conveniently selected caregivers working in Alberta's LTC and AL facilities. Standardised questions were selected from the Canadian Community Health Survey, Patient Health Questionnaire-9, and Short Form-36 QOL survey revalidated and administered to the participants. The new questionnaire was used to assess the caregivers' general health condition (GHC), physical health, health behaviour, stress level, QOL, and TAA. Data were analysed using descriptive statistics, Cronbach alpha, Pearson's correlation, one-way analysis of variance, and multiple linear regression. RESULTS: Of 1385 surveys sent to 39 facilities, 933 valid responses were received (response rate = 67.4%). The majority of the caregivers were females (90.8%) who were ≥ 35 years (73.6%), worked between 20 to 40 h weekly (67.3%), and were satisfied with their GHC (68.1%). The Registered Nurses had better GHC (mean difference [MD] = 0.18, p = 0.004) and higher TAA than the Health Care Aides (MD = 0.24, p = 0.005). There were correlations between caregivers' TAA and each of MEH (r = 0.398), QOL (r = 0.308), and stress (r = 0.251); p < 0.001. The most significant predictors of TAA were the propensity to quit a workplace or the profession, illness, job stress, and work-related injury, F (5, 551) = 76.62, p < 0.001, adjusted R2 = 0.998. CONCLUSION: Reducing the caregivers' job stressors such as work overload, inflexible schedule, and poor remuneration, and improving their quality of life, health behaviour, and mental, emotional, and physical health conditions may increase their job satisfaction and reduce turnover and absenteeism.

Perceived strategies for reducing staff-turnover and improving well-being and retention among professional caregivers in Alberta's continuing-care facilities: A qualitative study.

This qualitative study explored potential factors that lead to turnover and absenteeism and how to improve well-being and retention among professional older-adult-caregivers in Alberta's assisted living (AL) and long-term care (LTC) facilities. Four hundred and forty-seven participants aged 45-54 years were interviewed through a five-item, content-validated open-ended questionnaire. The questionnaire was self-administered in the English language and the soft copy of their responses was transferred into NVIVO version 12 software for coding. A thematic narrative analysis grounded in the "happy productive worker" theory was completed. The main themes were caregivers' perception of the factors affecting their well-being, absenteeism, and turnover, and caregivers' suggestions on ways to improve their well-being and retention. Participants reported that their professional well-being was suboptimal. They suggested that their employers should provide them with the needed social, psychological, and professional support, improve wages and hire more staff to ameliorate absenteeism and turnover rates.

Causal analysis as a bridge between qualitative and quantitative research.

Yarkoni argues that one solution is to abandon quantitative methods for qualitative ones. While we agree that qualitative methods are undervalued, we argue that both are necessary for thoroughgoing psychological research, complementing one another through the use of causal analysis. We illustrate how directed acyclic graphs can bridge qualitative and quantitative methods, thereby fostering understanding between different psychological methodologies.

Tetramic acid based alkaloids from Aspergillus amoenus Roberg strain UP197 - antibiotic properties and new pyranterreones.

The fungus Aspergillus amoenus Roberg strain UP197 was shown to produce antibacterial tetramic acid based alkaloids. Two new compounds, pyranterreone I and J (1 and 2), were isolated and characterized, in addition to the known compounds cordylactam, 7-hydroxycordylactam, pyranterreone C, D, F and G. Neither the pyranterreones nor the cordylacctams had previously been tested for antimicrobial activity. Thus, all isolated compounds were tested against a panel of clinically important bacteria and fungi. Pyranterreone C was active against Gram-positive and Gram-negative bacteria, with minimal inhibitory concentrations (MIC) between 1 and 8 µg/mL, whereas the MICs for all other compounds were >32 µg/mL. Pyranoterreone C was cytotoxic towards HepG2 cells, and since pyranterreone C reacted rapidly with the nucleophile cysteine, it is likely that the observed antibacterial activity is due to the chemical reactivity rather than enzymatic affinity, making it unsuitable for development as an antibacterial drug.

Selective Isolation of Multidrug-Resistant Pedobacter spp., Producers of Novel Antibacterial Peptides.

Twenty-eight multidrug-resistant bacterial strains closely related or identical to Pedobacter cryoconitis, Pedobacter lusitanus and Pedobacter steynii were isolated from soil samples by selection for multidrug-resistance. Approximately 3-30% of the selected isolates were identified as Pedobacter, whereas isolation without antibiotics did not yield any isolates of this genus. Next generation sequencing data showed Pedobacter to be on 69th place among the bacterial genera (0.32% of bacterial sequences). The Pedobacter isolates produced a wide array of novel compounds when screened by UHPLC-MS/MSMS, and hierarchical cluster analysis resulted in several distinct clusters of compounds produced by specific isolates of Pedobacter, and most of these compounds were found to be peptides. The Pedobacter strain UP508 produced isopedopeptins, whereas another set of strains produced pedopeptins, which both are known cyclic lipodepsipeptides produced by Pedobacter sp. Other Pedobacter strains produced analogous peptides with a sequence variation. Further strains of Pedobacter produced additional novel antibacterial cyclic lipopeptides (ca 800 or 1400 Da in size) and/or linear lipopeptides (ca 700-960 Da in size). A 16S rRNA phylogenetic tree for the Pedobacter isolates revealed several distinct clades and subclades of isolates. One of the subclades comprised isolates producing isopedopeptin analogs, but the isopedopeptin producing isolate UP508 was clearly placed on a separate branch. We suggest that the non-ribosomal peptide synthases producing pedopeptins, isopedopeptins, and the analogous peptides, may derive from a common ancestral non-ribosomal peptide synthase gene cluster, which may have been subjected to a mutation leading to changed specificity in one of the modules and then to a modular rearrangement leading to the changed sequence found in the isopedopeptins produced by isolate UP508.

In-peptide amino acid racemization via inter-residue oxazoline intermediates during acidic hydrolysis.

Isopedopeptins are antibiotic cyclic lipodepsipeptides containing the subsequence L-Thr-L-2,3-diaminopropanoic acid-D-Phe-L-Val/L-3-hydroxyvaline. Acidic hydrolysis of isopedopeptins in D2O showed the D-Phe residues to racemize extensively in peptides with L-3-hydroxyvaline but not in peptides with L-Val. Similarly, one Leu residue in pedopeptins, which are related peptides containing the subsequence Leu-2,3-diaminopropanoic acid-Leu-L-Val/L-3-hydroxyvaline, was found to racemize in peptides with L-3-hydroxyvaline. Model tetrapeptides, L-Ala-L-Phe-L-Val/3-hydroxyvaline-L-Ala, gave the corresponding results, i.e. racemization of L-Phe only when linked to a L-3-hydroxyvaline. We propose the racemization to proceed via an oxazoline intermediate involving Phe/Leu and the L-3-hydroxyvaline residues. The 3-hydroxyvaline residue may form a stable tertiary carbocation by loss of the sidechain hydroxyl group as water after protonation. Elimination of the Phe/Leu H-2 and ring-closure from the carbonyl oxygen onto the carbocation results in the suggested oxazoline intermediate. The reversed reaction leads to either retained or inversed configuration of Phe/Leu. Such racemization during acidic hydrolysis may occur whenever a 3-hydroxyvaline residue or any amino acid that can form a stable carbocation on the C-3, is present in a peptide. The proposed mechanism for racemization was supported by incorporation of 18O in the 3-hydroxyvaline sidechain when the acidic hydrolysis was performed in H2O/H218O (1:1). The 2,3-diaminopropanoic residues of isopedopeptins and pedopeptins were also found to racemize during acidic hydrolysis, as previously described. Based on the results, the configuration of the Leu and 2,3-diaminopropanoic acid residues of the pedopeptins were reassigned to be L-Leu and D-Leu, and 2 × L-2,3-diaminopropanoic acid.

Tolerance of muzzle contact underpins the acquisition of foraging information in vervet monkeys (Chlorocebus pygerythrus).

Muzzle contact, where one animal brings its muzzle into close proximity to that of another, has often been hypothesized as a straightforward means of socially mediated food investigation. Using 2,707 observations of muzzle contact occurring across 3 troops of wild vervet monkeys (Chlorocebus pygerythrus), we tested this social learning hypothesis. We first explored the social structuring of muzzle contact by analyzing the characteristics of initiators and receivers. Similar to previous research, juveniles initiated contact at higher rates than adults, particularly toward adult females and animals with lower dominance rankings. The highest number of contacts occurred between kin compared to contacts between nonkin. However, on the whole, contacts occurred at low rates, even among kin dyads. We next determined whether muzzle contact was used as a means to learn socially, specifically by animals seeking foraging information. We found that initiators did not overwhelmingly target foragers, meaning animals do not appear to directly seek information about food during muzzle contact. However, animals that contacted foragers were more likely forage themselves in comparison to those that contacted nonforagers, suggesting that foragers do provide food information. These findings indicate that both kin and low-ranking animals serve as discriminative stimuli for social tolerance and that foraging animals serve as discriminative stimuli for food availability. We conclude that broad social tolerance, rather than the recipient's knowledge, is the most likely antecedent to muzzle contact and that animals engage in this behavior as a low-cost means of maintaining a baseline level of information about their environment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Isopedopeptins A-H: Cationic Cyclic Lipodepsipeptides from Pedobacter cryoconitis UP508 Targeting WHO Top-Priority Carbapenem-Resistant Bacteria.

Pedobacter cryoconitis strain UP508 was isolated from a soil sample using a mixture of ampicillin, kanamycin, and nalidixic acid for selection. UP508 was found to produce >30 unknown antibacterial peptides, of which eight, isopedopeptins A-H (1-8), were isolated by bioassay-guided fractionation and characterized with respect to structures and biological properties. Compounds 1-8 were all composed of nine amino acid residues and one 3-hydroxy fatty acid residue, and the structures were ring-closed via an ester bond from the C-terminal aspartic acid to the 3-hydroxy fatty acid. The differences between the peptides were the size and branching of the 3-hydroxy fatty acid and the presence of a valine or a 3-hydroxyvaline residue. The isopedopeptins mainly had activity against Gram-negative bacteria, and isopedopeptin B (2), which had the best combination of antibacterial activity, in vitro cytotoxicity, and hemolytic properties, was selected for further studies against a larger panel of Gram-negative bacteria. Isopedopeptin B was found to have good activity against strains of WHO top-priority Gram-negative bacteria, i.e., carbapenem-resistant Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa, with minimal inhibitory concentrations (MIC) down to 1, 2, and 4 µg/mL, respectively. Furthermore, compound 2 had activity against colistin-resistant strains of A. baumannii, E. coli, and Klebsiella pneumoniae, with a MIC down to 8, 2, and 4 µg/mL, respectively. Compound 6 was tested in an E. coli liposome system where it induced significant leakage, indicating membrane disruption as one mechanism involved in isopedopeptin antibacterial activity. Isopedopeptin B stands out as a promising candidate for further studies with the goal to develop a new antibiotic drug.

Exploring the role of shift work in the self-reported health and wellbeing of long-term and assisted-living professional caregivers in Alberta, Canada.

BACKGROUND: Numerous studies have found negative outcomes between shift work and physical, emotional, and mental health. Many professional caregivers are required to work shifts outside of the typical 9 am to 5 pm workday. Here, we explore whether shift work affects the health and wellbeing of long-term care (LTC) and assisted-living (AL) professional caregivers. METHOD: The Caring for Professional Caregivers research study was conducted across 39 LTC and AL facilities in Alberta, Canada. Of the 1385 questionnaires distributed, 933 surveys (67.4%) were returned completed. After identifying 49 questions that significantly explained variances in the reported health status of caregivers, we examined whether there was a relationship between these questions and reported health status of caregivers working night shifts. RESULTS: We found significant differences between responses from those working different shifts across six of seven domains, including physical health, health conditions, mental/emotional health, quality of life, and health behaviors. In particular, we found that night shift caregivers were more likely to report incidents of poor heath (i.e., they lacked energy, had regular presences of neck and back pain, regular or infrequent incidents of fatigue or low energy, had difficulty falling asleep, and that they never do exercise) and less likely to report incidents of good health (i.e., did not expect their health to improve, were not satisfied with their health, do not have high self-esteem/were happy, were unhappy with their physical appearance, and do not get a good night's sleep), compared to caregivers working other shifts. CONCLUSIONS: Our study shows that professional caregivers working the night shift experience poor health status, providing further evidence that night shift workers' health is at risk. In particular, caregivers reported negative evaluations of their physical, mental/emotional health, lower ratings of their quality of life, and negative responses to questions concerning whether they engage in healthy behaviors. Our findings can support healthcare stakeholders outline future policies that ensure caregivers are adequately supported so that they provide quality care.

Antibacterial pyrrolidinyl and piperidinyl substituted 2,4-diacetylphloroglucinols from Pseudomonas protegens UP46.

In the search for new antibiotic compounds, fractionation of Pseudomonas protegens UP46 culture extracts afforded several known Pseudomonas compounds, including 2,4-diacetylphloroglucinol (DAPG), as well as two new antibacterial alkaloids, 6-(pyrrolidin-2-yl)DAPG (1) and 6-(piperidin-2-yl)DAPG (2). The structures of 1 and 2 were determined by nuclear magnetic resonance spectroscopy and mass spectrometry. Compounds 1 and 2 were found to have antibacterial activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus, with minimal inhibitory concentration (MIC) 2 and 4 µg ml-1, respectively, for 1, and 2 µg ml-1 for both pathogens for 2. The MICs for 1 and 2, against all tested Gram-negative bacteria, were >32 µg ml-1. The half maximal inhibitory concentrations against HepG2 cells for compounds 1 and 2 were 11 and 18 µg ml-1, respectively, which suggested 1 and 2 be too toxic for further evaluation as possible new antibacterial drugs. Stable isotope labelling experiments showed the pyrrolidinyl group of 1 to originate from ornithine and the piperidinyl group of 2 to originate from lysine. The P. protegens acetyl transferase (PpATase) is involved in the biosynthesis of monoacetylphloroglucinol and DAPG. No optical rotation was detected for 1 or 2, and a possible reason for this was investigated by studying if the PpATase may catalyse a stereo-non-specific introduction of the pyrrolidinyl/piperidinyl group in 1 and 2, but unless the PpATase can be subjected to major conformational changes, the enzyme cannot be involved in this reaction. The PpATase is, however, likely to catalyse the formation of 2,4,6-triacetylphloroglucinol from DAPG.

Antibacterial Isoquinoline Alkaloids from the Fungus Penicillium Spathulatum Em19.

In the search for new microbial antibacterial secondary metabolites, two new compounds (1 and 2) were isolated from culture broths of Penicillium spathulatum Em19. Structure determination by nuclear magnetic resonance and mass spectrometry identified the compounds as 6,7-dihydroxy-5,10-dihydropyrrolo[1,2-b]isoquinoline-3-carboxylic acid (1, spathullin A) and 5,10-dihydropyrrolo[1,2-b]isoquinoline-6,7-diol (2, spathullin B). The two compounds displayed activity against both Gram-negative and -positive bacteria, including Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, Klebsiella pneumonia, Pseudomonas aeruginosa, and Staphylococcus aureus. Compound 2 was more potent than 1 against all tested pathogens, with minimal inhibitory concentrations down to 1 µg/mL (5 µM) against S. aureus, but 2 was also more cytotoxic than 1 (50% inhibitory concentrations 112 and 11 µM for compounds 1 and 2, respectively, towards Huh7 cells). Based on stable isotope labelling experiments and a literature comparison, the biosynthesis of 1 was suggested to proceed from cysteine, tyrosine and methionine via a non-ribosomal peptides synthase like enzyme complex, whereas compound 2 was formed spontaneously from 1 by decarboxylation. Compound 1 was also easily oxidized to the 1,2-benzoquinone 3. Due to the instability of compound 1 and the toxicity of 2, the compounds are of low interest as possible future antibacterial drugs.

Antibacterial 3,6-Disubstituted 4-Hydroxy-5,6-dihydro-2H-pyran-2-ones from Serratia plymuthica MF371-2.

Bioassay-guided fractionation of culture extracts of Serratia plymuthica strain MF371-2 resulted in the isolation of two new antibacterial compounds with potent activity against Gram-positive bacteria, including Staphylococcus aureus LMG 15975 (MRSA). A spectroscopic investigation, in combination with synthesis, enabled the characterization of the compounds as 3-butyryl-4-hydroxy-6-heptyl-5,6-dihydro-2H-pyran-2-one (plymuthipyranone A, 1) and 3-butyryl-4-hydroxy-6-nonyl-5,6-dihydro-2H-pyran-2-one (plymuthipyranone B, 2). The MIC values for 1 and 2 against S. aureus LMG 15975 were determined to be 1-2 µg mL-1 and 0.8 µg mL-1, respectively. Compound 2 was found to have potent activity against many strains of S. aureus, including several mupirocin-resistant strains, other species of Staphylococcus, and vancomycin-resistant enterococci. Compound 2 was slightly cytotoxic for human cells, with CC50 values between 4.7 and 40 µg mL-1, but the CC50/MIC ratio was ≥10 for many tested combinations of human cells and bacteria, suggesting its possible use as an antibacterial agent. Several analogues were synthesized with different alkyl groups in the 3- and 6-positions (6-13), and their biological properties were evaluated. It was concluded that the activity of the compounds increased with the lengths of the alkyl and acyl substituents.

Cytotoxic Illudane Sesquiterpenes from the Fungus Granulobasidium vellereum (Ellis and Cragin) Jülich.

Eight illudane sesquiterpenes were obtained from the wood-decomposing fungus Granulobasidium vellereum (Ellis and Cragin) Jülich; among them were the enantiomers of the known compounds illudin M (1) and dihydroilludin M (4) and the diastereomers of illudin M (2) and illudin S (3), as well as two previously undescribed illudanes (5, 6). The cytotoxicity of compounds 1-4 and 6 was evaluated against two tumor cell lines (Huh7 and MT4), which showed that compounds 1-3 had potent cytotoxic activity, whereas compounds 4 and 6 had no or only moderate effects at concentrations up to 400 µM. Surprisingly, both compounds 2 and 3 were about 10 times more potent than 1. When the chemical reactivity of 1 and 2 was tested, compound 2 was shown to have a substantially higher reaction rate when reacted both with 2 M HCl and with cysteine, indicating that the difference in cytotoxicity is probably due to chemical reactivity and not to enzymatic affinity.

Cytotoxic illudalane sesquiterpenes from the wood-decay fungus Granulobasidium vellereum (Ellis & Cragin) Jülich.

Seven illudalane sesquiterpenes were obtained from the wood decomposing fungus Granulobasidium vellereum: granuloinden A, granuloinden B and dihydrogranuloinden, along with the previously known compounds radulactone, pterosin M, echinolactone A and D. Granuloinden B showed potent cytotoxic activity against the Huh7 and MT4 tumor cell lines (CC50 values of 6.7 and 0.15 µM, respectively), whereas granuloinden A and dihydrogranuloinden had no or moderate activity.

Sesquiterpenes from the saprotrophic fungus Granulobasidium vellereum (Ellis & Cragin) Jülich.

Twelve sesquiterpenes comprising either the protoilludane or the rare cerapicane carbon skeletons were obtained from the saprotrophic wood decomposing fungus Granulobasidium vellereum; 2a-hydroxycoprinolone (1), 3-hydroxycoprinolone (2), coprinolone diol B (3), granulodiene A (4), granulodiene B (5), granulone A (6), 8-deoxy-4a-hydroxytsugicoline B (7), granulone B (8), demethylgranulone (9), cerapicolene (10), as well as the known compounds radudiol and Δ(6)-coprinolone. The structures were determined using spectroscopic methods and biosynthetic considerations. Granulone A had growth stimulating effect on the total elongation of lettuce seedlings. None of the isolated compounds showed any antifungal effect.

Protoilludane sesquiterpenes from the wood decomposing fungus Granulobasidium vellereum (Ellis & Cragin) Jülich.

The secondary metabolites of the saprotrophic wood-decay basidiomycete fungus Granulobasidium vellereum were studied. Six sesquiterpenes were obtained; 2-hydroxycoprinolone (1), 8-deoxy-4a-hydroxytsugicoline (2), 8-deoxydihydrotsugicoline (3), which were previously not described, radulone A and B, and coprinolone ketodiol. Additionally, base-treatment of 1 yielded the diagnostic degradation products 1a and 1b, whereas radulone A was found to form 4 under mild acidic conditions. The structures were determined by NMR, MS, CD and polarimetry, along with biosynthetic considerations. Radulone A fully inhibited the spore germination of the potentially competing fungi Phlebiopsis gigantea, Coniophora puteana and Heterobasidion occidentale at 10µM, 500µM and 100µM, respectively. None of the other substances tested gave rise to any growth inhibition.