Feasibility and Effectiveness of Self-Management Education and Coaching on Patient Activation for Managing Cancer Treatment Toxicities.

BACKGROUND: Poorly managed cancer treatment toxicities negatively impact quality of life, but little research has examined patient activation in self-management (SM) early in cancer treatment. METHODS: We undertook a pilot randomized trial to evaluate the feasibility, acceptability, and preliminary effectiveness of the SMARTCare (Self-Management and Activation to Reduce Treatment Toxicities) intervention. This intervention included an online SM education program (I-Can Manage) plus 5 sessions of telephone cancer coaching in patients initiating systemic therapy for lymphoma or colorectal or lung cancer at 3 centers in Ontario, Canada, relative to a usual care control group. Patient-reported outcomes included patient activation (Patient Activation Measure [PAM]), symptom or emotional distress, self-efficacy, and quality of life. Descriptive statistics and Wilcoxon rank-sum tests were used to examine changes over time (baseline and at 2, 4, and 6 months) within and between groups. We used general estimating equations to compare outcomes between groups over time. The intervention group completed an acceptability survey and qualitative interviews. RESULTS: Of 90 patients approached, 62 (68.9%) were enrolled. Mean age of the sample was 60.5 years. Most patients were married (77.1%), were university educated (71%), had colorectal cancer (41.9%) or lymphoma (42.0%), and had stage III or IV disease (75.8%). Attrition was higher in the intervention group than among control subjects (36.7% vs 25%, respectively). Adherence to I-Can Manage was low; 30% of intervention patients completed all 5 coaching calls, but 87% completed ≥1. Both the continuous PAM total score (P<.001) and categorical PAM levels (3/4 vs 1/2) (P=.002) were significantly improved in the intervention group. CONCLUSIONS: SM education and coaching early during cancer treatment may improve patient activation, but a larger trial is needed. CLINICALTRIALS: gov Identifier: NCT03849950.

Maternal effects in mammals: Broadening our understanding of offspring programming.

The perinatal period is a sensitive time in mammalian development that can have long-lasting consequences on offspring phenotype via maternal effects. Maternal effects have been most intensively studied with respect to two major conditions: maternal diet and maternal stress. In this review, we shift the focus by discussing five major additional maternal cues and their influence on offspring phenotype: maternal androgen levels, photoperiod (melatonin), microbiome, immune regulation, and milk composition. We present the key findings for each of these topics in mammals, their mechanisms of action, and how they interact with each other and with the maternal influences of diet and stress. We explore their impacts in the contexts of both predictive adaptive responses and the developmental origins of disease, identify knowledge gaps and research opportunities in the field, and place a particular emphasis on the application and consideration of these effects in non-model species and natural ecological systems.

Combined exposure to maternal high-fat diet and neonatal lipopolysaccharide disrupts stress-related signaling but normalizes spatial memory in juvenile rats.

Both neonatal infections and exposure to maternal obesity are inflammatory stressors in early life linked to increased rates of psychopathologies related to mood and cognition. Epidemiological studies indicate that neonates born to mothers with obesity have a higher likelihood of developing neonatal infections, however effects on offspring physiology and behavior resulting from the combination of these stressors have yet to be investigated. The aim of this study was to explore immediate and persistent phenotypes resulting from neonatal lipopolysaccharide (nLPS) administration in rat offspring born to dams consuming a high-fat diet (HFD). Neural transcript abundance of genes involved with stress regulation and spatial memory were examined alongside related behaviors. At the juvenile age point, unlike offspring exposed to maternal HFD (mHFD) or nLPS alone, offspring with combined exposure to mHFD + nLPS displayed altered transcript abundances of stress-related genes in the ventral hippocampus (HPC) in a manner conducive to potentiating stress responses. For memory-related phenotypes, juveniles exposed to mHFD + nLPS exhibited normalized spatial memory and levels of memory-related gene expression in the dorsal HPC similar to control diet offspring, while control diet + nLPS, and mHFD offspring exhibited reduced levels of memory-related gene expression and impaired spatial memory. These findings suggest that dual exposure to unique inflammatory stressors in early life can disrupt neural stress regulation but normalize spatial memory processes.

DNA methylation profiles in adults born at extremely low birth weight.

Effects of stresses associated with extremely preterm birth may be biologically "recorded" in the genomes of individuals born preterm via changes in DNA methylation (DNAm) patterns. Genome-wide DNAm profiles were examined in buccal epithelial cells from 45 adults born at extremely low birth weight (ELBW; ≤1000 g) in the oldest known cohort of prospectively followed ELBW survivors (Mage = 32.35 years, 17 male), and 47 normal birth weight (NBW; ≥2500 g) control adults (Mage = 32.43 years, 20 male). Sex differences in DNAm profiles were found in both birth weight groups, but they were greatly enhanced in the ELBW group (77,895 loci) versus the NBW group (3,424 loci), suggesting synergistic effects of extreme prenatal adversity and sex on adult DNAm profiles. In men, DNAm profiles differed by birth weight group at 1,354 loci on 694 unique genes. Only two loci on two genes distinguished between ELBW and NBW women. Gene ontology (GO) and network analyses indicated that loci differentiating between ELBW and NBW men were abundant in genes within biological pathways related to neuronal development, synaptic transportation, metabolic regulation, and cellular regulation. Findings suggest increased sensitivity of males to long-term epigenetic effects of extremely preterm birth. Group differences are discussed in relation to particular gene functions.

Sex-specific maternal programming of corticosteroid-binding globulin by predator odour.

Predation is a key organizing force in ecosystems. The threat of predation may act to programme the endocrine hypothalamic-pituitary-adrenal axis during development to prepare offspring for the environment they are likely to encounter. Such effects are typically investigated through the measurement of corticosteroids (Cort). Corticosteroid-binding globulin (CBG) plays a key role in regulating the bioavailability of Cort, with only free unbound Cort being biologically active. We investigated the effects of prenatal predator odour exposure (POE) in mice on offspring CBG and its impact on Cort dynamics before, during and after restraint stress in adulthood. POE males, but not females, had significantly higher serum CBG at baseline and during restraint and lower circulating levels of Free Cort. Restraint stress was associated with reduced liver transcript abundance of SerpinA6 (CBG-encoding gene) only in control males. POE did not affect SerpinA6 promoter DNA methylation. Our results indicate that prenatal exposure to a natural stressor led to increased CBG levels, decreased per cent of Free Cort relative to total and inhibited restraint stress-induced downregulation of CBG transcription. These changes suggest an adaptive response to a high predator risk environment in males but not females that could buffer male offspring from chronic Cort exposure.

Bis(bipyridine)ruthenium(II) Ferrocenyl ß-Diketonate Complexes: Exhibiting Nanomolar Potency against Human Cancer Cell Lines.

The synthesis and characterization of new bis(bipyridine)ruthenium(II) ferrocenyl ß-diketonate complexes, [(bpy)2 Ru(Fc-acac)][PF6 ] (bpy=2,2'-bipyridine; Fc-acac=functionalized ferrocenyl ß-diketonate ligand) are reported. Alongside clinical platinum drugs, these bimetallic ruthenium-iron complexes have been screened for their cytotoxicity against MIA PaCa-2 (human pancreatic carcinoma), HCT116 p53+/+ (human colon carcinoma, p53-wild type) and ARPE-19 (human retinal pigment epithelial) cell lines. With the exception of one complex, the library exhibit nanomolar potency against cancerous cell lines, and their relative potencies are up to 40x, 400x and 72x more cytotoxic than cisplatin, carboplatin and oxaliplatin, respectively. Under hypoxic conditions, the complexes remain cytotoxic (sub-micromolar range), highlighting their potential in targeting hypoxic tumor regions. The Comet assay was used to determine their ability to damage DNA, and results show dose dependent damage which correlates well with the cytotoxicity results. Their potential to treat bacterial and fungal strains has been determined, and highlight complexes have selective growth inhibition of up to 87-100 % against Staphylococcus aureus and Candida albicans.

Rhodium(III) Dihalido Complexes: The Effect of Ligand Substitution and Halido Coordination on Increasing Cancer Cell Potency.

This work presents the synthesis of eight new rhodium(III) dihalido complexes, [RhX2(L)(LH)] (where X = Cl or I), which incorporate two bidentate N-(3-halidophenyl)picolinamide ligands. The ligands have different binding modes in the complexes, whereby one is neutral and bound via N,N (LH) coordination, while the other is anionic and bound via N,O (L) coordination. The solid state and solution studies confirm multiple isomers are present when X = Cl; however, after a halide exchange with potassium iodide (X = I) the complexes exist exclusively as single stable trans isomers. NMR studies reveal the Rh(III) trans diiodido complexes remain stable in aqueous solution with no ligand exchange reported over 96 h. Chemosensitivity data against a range of cancer cell lines show two cytotoxic complexes, where L = N-(3-bromophenyl)picolinamide ligand. The results have been compared to the analogous Ru(III) complexes and overall highlight the Rh(III) trans diiodido complex to be ∼78× more cytotoxic than the analogous Rh(III) dichlorido complex, unlike the Ru(III) complexes which are equitoxic against all cell lines. Additionally, the Rh(III) trans diiodido complex is more selective toward cancerous cells, with selectivity index (SI) values >25-fold higher than cisplatin against colorectal carcinoma.

Spin-States of Diastereomeric Iron(II) Complexes of 2,6-Bis(thiazolin-2-yl)pyridine (ThioPyBox) Ligands and a Comparison with the Corresponding PyBox Derivatives.

This report investigates homoleptic iron(II) complexes of thiazolinyl analogues of chiral PyBox tridentate ligands: 2,6-bis(4-phenyl-4,5-dihydrothiazol-2-yl)pyridine (L1Ph), 2,6-bis(4-isopropyl-4,5-dihydrothiazol-2-yl)pyridine (L1iPr), and 2,6-bis(4-tert-butyl-4,5-dihydrothiazol-2-yl)pyridine (L1t-Bu). Crystallographic data imply the larger and more flexible thiazolinyl rings reduce steric clashes between the R substituents in homochiral [Fe((R)-L1R)2]2+ or [Fe((S)-L1R)2]2+ (R = Ph, iPr, or t-Bu), compared to their PyBox (L2R) analogues. Conversely, the larger heterocyclic S atoms are in close contact with the R substituents in heterochiral [Fe((R)-L1Ph)((S)-L1Ph)]2+, giving it a more sterically hindered ligand environment than that in [Fe((R)-L2Ph)((S)-L2Ph)]2+ (L2Ph = 2,6-bis(4-phenyl-4,5-dihydrooxazol-2-yl)pyridine). Preformed [Fe((R)-L1Ph)((S)-L1Ph)]2+ and [Fe((R)-L1iPr)((S)-L1iPr)]2+ do not racemize by ligand redistribution in CD3CN solution, but homochiral [Fe(L1iPr)2]2+ and [Fe(L1t-Bu)2]2+ both undergo partial ligand displacement in that solvent. Homochiral [Fe(L1Ph)2]2+ and [Fe(L1iPr)2]2+ exhibit spin-crossover equilibria in CD3CN, centered at 344 ± 6 K and 277 ± 1 K respectively, while their heterochiral congeners are essentially low-spin within the liquid range of the solvent. These data imply that the diastereomers of [Fe(L1Ph)2]2+ and [Fe(L1iPr)2]2+ show a greater difference in their spin-state behaviors than was previous found for [Fe(L2Ph)2]2+. Gas-phase DFT calculations (B86PW91/def2-SVP) of the [Fe(L1R)2]2+ and [Fe(L2R)2]2+ complexes reproduce most of the observed trends, but they overstabilize the high-spin state of SCO-active [Fe(L1iPr)2]2+ by ca. 1.5 kcal mol-1. This might reflect the influence of intramolecular dispersion interactions on the spin states of these compounds. Attempts to model this with the dispersion-corrected functionals B97-D2 or PBE-D3 were less successful than our original protocol, confirming that the spin states of sterically hindered molecules are a challenging computational problem.

Cumulative risks predict epigenetic age in adult survivors of extremely low birth weight.

Long-term sequelae of extremely low birth weight (ELBW; ≤1000 g) may contribute to accelerated biological aging. This hypothesis was examined by analyzing a range of risk factors with a molecular age marker in adults born at ELBW or normal birth weight (NBW; ≥2500 g). DNAm age-the weighted average of DNA methylation at 353 cytosine-phosphate-guanine (CpG) sites from across the genome-was derived from a sample of 45 ELBW (Mage  = 32.35 years) and 47 NBW control (Mage  = 32.44 years) adults, using the Illumina 850k BeadChip Array. At two assessments undertaken 9 years apart (at 23 and 32 years), cumulative risks were summed from six domains with potential to affect physiological and psychological health: resting respiratory sinus arrhythmia, blood pressure, basal cortisol, grip strength, body mass index, and self-esteem. At age 32 years, cumulative risks were differentially associated with epigenetic age in ELBW survivors (interaction, p < 0.01). For each additional risk factor they possessed, ELBW survivors (B = 1.43) were biologically 2.16 years older than NBW adults (B = -0.73), by the fourth decade of life. Developmental change, epigenetic maintenance, and intervention targets are discussed.

Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring.

BACKGROUND: Maternal obesity as a result of high levels of saturated fat (HFD) consumption leads to significant negative health outcomes in both mother and exposed offspring. Offspring exposed to maternal HFD show sex-specific alterations in metabolic, behavioral, and endocrine function, as well as increased levels of basal neuroinflammation that persists into adulthood. There is evidence that psychosocial stress or exogenous administration of corticosterone (CORT) potentiate inflammatory gene expression; however, the response to acute CORT or immune challenge in adult offspring exposed to maternal HFD during perinatal life is unknown. We hypothesize that adult rat offspring exposed to maternal HFD would show enhanced pro-inflammatory gene expression in response to acute administration of CORT and lipopolysaccharide (LPS) compared to control animals, as a result of elevated basal pro-inflammatory gene expression. To test this, we examined the effects of acute CORT and/or LPS exposure on pro and anti-inflammatory neural gene expression in adult offspring (male and female) with perinatal exposure to a HFD or a control house-chow diet (CHD). METHODS: Rat dams consumed HFD or CHD for four weeks prior to mating, during gestation, and throughout lactation. All male and female offspring were weaned on to CHD. In adulthood, offspring were 'challenged' with administration of exogenous CORT and/or LPS, and quantitative PCR was used to measure transcript abundance of glucocorticoid receptors and downstream inflammatory markers in the amygdala, hippocampus, and prefrontal cortex. RESULTS: In response to CORT alone, male HFD offspring showed increased levels of anti-inflammatory transcripts, whereas in response to LPS alone, female HFD offspring showed increased levels of pro-inflammatory transcripts. In addition, male HFD offspring showed greater pro-inflammatory gene expression and female HFD offspring exhibited increased anti-inflammatory gene expression in response to simultaneous CORT and LPS administration. CONCLUSIONS: These findings suggest that exposure to maternal HFD leads to sex-specific changes that may alter inflammatory responses in the brain, possibly as an adaptive response to basal neuroinflammation.

Early life variations in temperature exposure affect the epigenetic regulation of the paraventricular nucleus in female rat pups.

Early life maternal care received has a profound effect on later-life behaviour in adult offspring, and previous studies have suggested epigenetic mechanisms are involved. Changes in thyroid hormone receptor signalling may be related to differences in maternal care received and DNA methylation modifications. We investigated the effects of variations in temperature exposure (a proxy of maternal contact) and licking-like tactile stimulation on these processes in week-old female rat pups. We assessed thyroid hormone receptor signalling by measuring circulating triiodothyronine and transcript abundance of thyroid hormone receptors and the thyroid hormone-responsive genes DNA methyltransferase 3a and oxytocin in the paraventricular nucleus of the hypothalamus. DNA methylation of the oxytocin promoter was assessed in relation to changes in thyroid hormone receptor binding. Repeated room temperature exposure was associated with a decrease in thyroid hormone receptor signalling measures relative to nest temperature exposure, while acute room temperature exposure was associated with an increase. Repeated room temperature exposure also increased thyroid hormone receptor binding and DNA methylation at the oxytocin promoter. These findings suggest that repeated room temperature exposure may affect DNA methylation levels as a consequence of alterations in thyroid hormone receptor signalling.

ß-Diketonate versus ß-Ketoiminate: The Importance of a Ferrocenyl Moiety in Improving the Anticancer Potency.

Herein we present a library of fully characterized ß-diketonate and ß-ketoiminate compounds that are functionalized with a ferrocenyl moiety. Their cytotoxic potential has been determined by screening against human breast adenocarcinomas (MCF-7 and MDA-MB-231), human colorectal carcinoma p53 wild type (HCT116 p53+/+ ) and normal human prostate (PNT2) cell lines. The ferrocenyl ß-diketonate compounds are more than 18 times more cytotoxic than the ferrocenyl ß-ketoiminate analogues. Against MCF-7, compounds functionalized at the meta position are up to nine times more cytotoxic than when functionalized at the para position. The ferrocenyl ß-diketonate compounds have increased selectivity towards MCF-7 and MDA-MB-231, with several complexes having selectivity index (SI) values that are more than nine times (MCF-7) and more than six times (MDA-MB-231) that of carboplatin. The stability of these compounds in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) has been assessed by NMR spectroscopy and mass spectrometry studies, and the compounds show no oxidation of the iron center from FeII to FeIII . Cytotoxicity screening was performed in both DMSO and DMF, with no significant differences observedin their potency.

Perinatal high-fat diet impairs pup retrieval and induces sex-specific changes in ultrasonic vocalization characteristics of rat pups.

Rodent pups emit ultrasonic vocalizations (USVs) to solicit maternal behavior, promoting their survival. Conversely, maternal behaviors affect the expression of pup USVs. We previously demonstrated that a maternal diet high in saturated fat (HFD) alters maternal behavior and is associated with early maturation of pups and their stress physiology. Here, we assessed the developmental profiles of pup USVs using quantitative and qualitative measures on postnatal days (PND)7 and 13. Quantitative measures included call counts, duration, and frequency, while qualitative measures examined calls' sonographic structures. HFD offspring lacked the typical decrease in USV numbers with age observed among control offspring. They also had shorter calls at PND7 compared to control and HFD offspring at PND13. HFD female offspring showed a greater number of one-frequency-sweep calls, while male pups showed a greater number of two-frequency-sweep calls compared to control offspring. Concomitantly, HFD dams showed impaired pup retrieval on PND7. The data suggest that fewer USVs of shorter duration in HFD offspring may alter dam solicitation and thus impair maternal pup retrieval. This study highlights the impacts of perinatal HFD exposure on the dyadic reciprocal interaction between dam and pups, which may set the stage for long-lasting effects on offspring physiology and behavior.

ß-Ketoiminato Iridium(III) Organometallic Complexes: Selective Cytotoxicity towards Colorectal Cancer Cells HCT116 p53-/.

This report presents a new library of organometallic iridium(III) compounds of the type [Cp*IrCl(L)] (Cp*=pentamethylcyclopentadienyl and L=a functionalized ß-ketoiminato ligand) showing moderate to high cytotoxicity against a range of cancer cell lines. All compounds show increased activity towards colorectal cancer, with preferential activity observed against the immortalized p53-null colorectal cell line, HCT116 p53-/-, with sensitivity factors (SF) up to 26.7. Additionally, the compounds have excellent selectivity for cancerous cells when tested against normal cell types, with selectivity ratios (SR) up to 35.6, contrary to that of cisplatin, which is neither selective nor specific for cancerous cells (SF=0.43 and SR=0.7-2.3). This work provides a preliminary understanding of the cytotoxicity of iridium compounds in the absence of p53 and has potential applications in treatment of cancers for which the p53 gene is absent or mutant.

Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness.

BACKGROUND: Gulf War illness (GWI) is an archetypal, medically unexplained, chronic condition characterised by persistent sickness behaviour and neuroimmune and neuroinflammatory components. An estimated 25-32% of the over 900,000 veterans of the 1991 Gulf War fulfil the requirements of a GWI diagnosis. It has been hypothesised that the high physical and psychological stress of combat may have increased vulnerability to irreversible acetylcholinesterase (AChE) inhibitors leading to a priming of the neuroimmune system. A number of studies have linked high levels of psychophysiological stress and toxicant exposures to epigenetic modifications that regulate gene expression. Recent research in a mouse model of GWI has shown that pre-exposure with the stress hormone corticosterone (CORT) causes an increase in expression of specific chemokines and cytokines in response to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. METHODS: C57BL/6J mice were exposed to CORT for 4 days, and exposed to DFP on day 5, before sacrifice 6 h later. The transcriptome was examined using RNA-seq, and the epigenome was examined using reduced representation bisulfite sequencing and H3K27ac ChIP-seq. RESULTS: We show transcriptional, histone modification (H3K27ac) and DNA methylation changes in genes related to the immune and neuronal system, potentially relevant to neuroinflammatory and cognitive symptoms of GWI. Further evidence suggests altered proportions of myelinating oligodendrocytes in the frontal cortex, perhaps connected to white matter deficits seen in GWI sufferers. CONCLUSIONS: Our findings may reflect the early changes which occurred in GWI veterans, and we observe alterations in several pathways altered in GWI sufferers. These close links to changes seen in veterans with GWI indicates that this model reflects the environmental exposures related to GWI and may provide a model for biomarker development and testing future treatments.

Both maternal care received and genotype influence stress-related phenotype in female rats.

Rat dams differ naturally in the level of maternal care they provide to their offspring within the same litter. We explored possible mechanisms of differential maternal care focused on genetic variation. We examined single nucleotide polymorphisms in the glucocorticoid receptor, FK506-binding protein, and serotonin transporter genes in two separate cohorts, and the relationship between differential maternal care received, genotype, and offspring phenotype. Allelic variation in all three genes was significantly associated with levels of maternal care received by offspring and behavioral and endocrine stress responses in adulthood. Differences in pup behavior were also associated with allelic variation in these genes. Together, these results indicate that the dam/pup interaction is dynamic and implicate the genotype of the offspring in influencing the level of maternal care received. They further suggest that some genotypes may have a dampening effect on the impact of maternal care on stress-related phenotypes in adulthood.

Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity.

A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX2 L2 ] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl2 L2 ] complexes but upon a halide exchange reaction to yield [RuI2 L2 ], only single trans isomers were detected. High cytotoxic activity against human cancer cell lines was observed, with the potencies of some complexes similar to or better than cisplatin. The conversion to [RuI2 L2 ] substantially increased the activity towards cancer cell lines by more than twelvefold. The [RuI2 L2 ] complexes displayed potent activity against the A2780cis (cisplatin-resistant human ovarian cancer) cell line, with a more than fourfold higher potency than cisplatin. Equitoxic activity was observed against normoxic and hypoxic cancer cells, which indicates the potential to eradicate both the hypoxic and aerobic fractions of solid tumours with similar efficiency. The activity of selected complexes against non-cancer ARPE-19 cells was also tested. The [RuI2 L2 ] complexes were found to be more potent than the [RuCl2 L2 ] analogues and also more selective towards cancer cells with a selectivity factor in excess of sevenfold.

Maternal programming of sex-specific responses to predator odor stress in adult rats.

Prenatal stress mediated through the mother can lead to long-term adaptations in stress-related phenotypes in offspring. This study tested the long-lasting effect of prenatal exposure to predator odor, an ethologically relevant and psychogenic stressor, in the second half of pregnancy. As adults, the offspring of predator odor-exposed mothers showed increased anxiety-like behaviors in commonly used laboratory tasks assessing novelty-induced anxiety, increased defensive behavior in males and increased ACTH stress reactivity in females in response to predator odor. Female offspring from predator odor-exposed dams showed increased transcript abundance of glucocorticoid receptor (NR3C1) on the day of birth and FK506 binding protein 5 (FKBP5) in adulthood in the amygdala. The increase in FKBP5 expression was associated with decreased DNA methylation in Fkbp5 intron V. These results indicate a sex-specific response to maternal programming by prenatal predator odor exposure and a potential epigenetic mechanism linking these responses with modifications of the stress axis in females. These results are in accordance with the mismatch hypothesis stating that an animal's response to cues within its life history reflects environmental conditions anticipated during important developmental periods and should be adaptive when these conditions are concurring.

Parent-offspring transaction: Mechanisms and the value of within family designs.

This article is part of a Special Issue "Parental Care". Parenting is best understood as a transactional process between parents and their offspring. Each responds to cues in the other, adapting their own behavior to that of their partner. One of the goals of parenting research in the past twenty years has been to untangle reciprocal processes between parents and children in order to specify what comes from the child (child effects) and what comes from the parent (parent effects). Child effects have been found to relate to genetic, pre and perinatal, family-wide, and child-specific environmental influences. Parent effects relate to stresses in the current context (e.g. financial strain, marital conflict), personality and ethnicity but also to adverse childhood experiences (e.g. parental mental health and substance abuse, poverty, divorce). Rodent models have allowed for the specification of biological mechanisms in parent and child effects, including neurobiological and genomic mechanisms, and of the causal role of environmental experience on outcomes for offspring through random assignment of offspring-mother groupings. One of the methods that have been developed in the human and animal models to differentiate between parent and child effects has been to study multiple offspring in the family. By holding the parent steady, and studying different offspring, we can examine the similarities and differences in how parents parent multiple offspring. Studies have distinguished between family average parenting, child-specific parenting and family-wide dispersion (the within family standard deviation). These different aspects of parenting have been differentially linked to offspring behavioral phenotypes.

Activation and deactivation of a robust immobilized Cp*Ir-transfer hydrogenation catalyst: a multielement in situ X-ray absorption spectroscopy study.

A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and "hot filtration" experiments ruled out leached Ir as the active catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand with an alkoxide to generate the active precatalyst. The exchange of the second chloride ligand, however, leads to a potassium alkoxide-iridate species as the deactivated form of this immobilized catalyst. These findings could be widely applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl substructure.