Polygenic risk scores for schizophrenia are associated with oculomotor endophenotypes.

BACKGROUND: Schizophrenia is a heterogeneous disorder with substantial heritability. The use of endophenotypes may help clarify its aetiology. Measures from the smooth pursuit and antisaccade eye movement tasks have been identified as endophenotypes for schizophrenia in twin and family studies. However, the genetic basis of the overlap between schizophrenia and these oculomotor markers is largely unknown. Here, we tested whether schizophrenia polygenic risk scores (PRS) were associated with oculomotor performance in the general population. METHODS: Analyses were based on the data of 2956 participants (aged 30-95) of the Rhineland Study, a community-based cohort study in Bonn, Germany. Genotyping was performed on Omni-2.5 exome arrays. Using summary statistics from a recent meta-analysis based on the two largest schizophrenia genome-wide association studies to date, we quantified genetic risk for schizophrenia by creating PRS at different p value thresholds for genetic markers. We examined associations between PRS and oculomotor performance using multivariable regression models. RESULTS: Higher PRS were associated with higher antisaccade error rate and latency, and lower antisaccade amplitude gain. PRS showed inconsistent patterns of association with smooth pursuit velocity gain and were not associated with saccade rate during smooth pursuit or performance on a prosaccade control task. CONCLUSIONS: There is an overlap between genetic determinants of schizophrenia and oculomotor endophenotypes. Our findings suggest that the mechanisms that underlie schizophrenia also affect oculomotor function in the general population.

Associations of genetic liability for Alzheimer's disease with cognition and eye movements in a large, population-based cohort study.

To identify cognitive measures that may be particularly sensitive to early cognitive decline in preclinical Alzheimer's disease (AD), we investigated the relation between genetic risk for AD and cognitive task performance in a large population-based cohort study. We measured performance on memory, processing speed, executive function, crystallized intelligence and eye movement tasks in 5182 participants of the Rhineland Study, aged 30 to 95 years. We quantified genetic risk for AD by creating three weighted polygenic risk scores (PRS) based on the genome-wide significant single-nucleotide polymorphisms coming from three different genetic association studies. We assessed the relation of AD PRS with cognitive performance using generalized linear models. Three PRS were associated with lower performance on the Corsi forward task, and two PRS were associated with a lower probability of correcting antisaccade errors, but none of these associations remained significant after correction for multiple testing. Associations between age and trail-making test A (TMT-A) performance were modified by AD genetic risk, with individuals at high genetic risk showing the strongest association. We conclude that no single measure of our cognitive test battery robustly captures genetic liability for AD as quantified by current PRS. However, Corsi forward performance and the probability of correcting antisaccade errors may represent promising candidates whose ability to capture genetic liability for AD should be investigated further. Additionally, our finding on TMT-A performance suggests that processing speed represents a sensitive marker of AD genetic risk in old age and supports the processing speed theory of age-related cognitive decline.

The Associations of Hearing Sensitivity and Different Cognitive Functions with Perception of Speech-in-Noise.

OBJECTIVES: Impaired speech-in-noise perception affects individuals' daily lives and is a frequent symptom of age-related hearing loss, which is a common disabling condition and a health concern in aging populations. The relative impact of hearing sensitivity loss and different cognitive functions on speech-in-noise perception is not well understood. We aimed to assess to what extent hearing sensitivity and different cognitive functions were associated with sentence-in-noise performance across the adult lifespan. DESIGN: This study is based on data of 2585 participants of the Rhineland Study, which is a German community-based cohort study of persons of age 30 years and older. We assessed speech-in-noise with a sentence-in-noise test (Göttinger Satztest), hearing sensitivity thresholds (air conduction pure-tone audiometry [PTA] average of 0.5, 1, 2, and 4 kHz), and the following cognitive domains: crystallized intelligence (German Mehrfachwahl-Wortschatz-Intelligenztest, MWT-B), executive functioning (Trail Making Test B, TMT), working memory (Digit Span forward, DS), and long-term memory (Verbal Learning and Memory Test delayed recall; VLMT). We examined the association between hearing sensitivity and cognitive functions with sentence-in-noise perception using a multivariable linear regression model adjusted for age, sex, and multiple potential confounders. RESULTS: Better hearing sensitivity was associated with better speech-in-noise perception (0.25 signal noise ratio [SNR] dB HL decrease per 5 dB HL decrease in PTA; 95% confidence interval [CI]: 0.20 to 0.25; p < 0.001). Better cognitive performance was also associated with better speech-in-noise perception, but to a lesser extent. Crystallized intelligence (MWT-B) showed an effect size of -0.10 SNR dB HL decrease per SD (95% CI: -0.14 to -0.06; p < 0.001), executive functioning (TMT) of -0.08 SNR dB HL decrease per SD (95% CI: -0.13 to -0.03; p = 0.002), working memory (DS) of -0.04 SNR dB HL decrease per SD (95% CI: -0.08 to -0.003; p = 0.03), and long-term memory (VLMT) of -0.03 SNR dB HL decrease per SD (95% CI: -0.07 to 0.01; p = 0.12). The standardized effect of hearing sensitivity (ß = 0.34) on speech-in-noise perception was four to five times larger than the effects of crystallized intelligence (ß = -0.08) and executive functioning (ß = -0.06). CONCLUSIONS: Hearing sensitivity was the strongest determinant of sentence-in-noise perception in adults above the age of 30. We determined the relative effect of different cognitive functions on sentence-in-noise perception. Crystallized intelligence and executive functions showed stronger associations while working and long-term memory functions had much smaller independent effects. Our results contribute to the understanding of determinants of speech-in-noise perception in aging adults.

Ten German versions of Rey's auditory verbal learning test: Age and sex effects in 4,000 adults of the Rhineland Study.

INTRODUCTION: Detecting early pathological cognitive decline is critical for dementia and aging-related research and clinical diagnostics. Rey's Auditory Verbal Learning Test (AVLT) is commonly used to measure episodic verbal memory. The test requires participants to learn a list of 15 words over several trials. Since multiple testing is often required to detect cognitive decline, but repeating the same test can bias results, we developed 10 German AVLT word lists. METHOD: We randomly assigned the lists to 4,000 participants (aged 30-94 years) from a population-based cohort to test their comparability, as well as aging effects and sex differences. RESULTS: Nine lists were highly comparable, with only one being slightly more difficult. Recall performance decreased on average by 0.6-1.1 words per trial per decade of age. Perseveration errors decreased with increasing age. Women remembered on average between 0.8 and 1.5 words per trial more than men, regardless of age. Women also outperformed men in the sum of Trials 1-5, learning over trials, retroactive inhibition, and false-positive and interference errors. Proactive inhibition remained stable across age and was unaffected by sex. CONCLUSION: This German AVLT version presents comparable lists including detailed age and sex references and therefore allows test repetition excluding training effects. These versions are a valuable resource for research and clinical application.

Perceived stress but not hair cortisol concentration is related to adult cognitive performance.

Chronic stress detrimentally affects cognition but evidence from population-based studies is scarce and largely based on one-dimensional stress assessments. In this study, we aimed to investigate associations of subjective and psychological chronic stress measures with cognition in a population-based sample of adults aged 30-95 years from the Rhineland Study. Participants completed the Perceived Stress Scale (subjective measure) and a cognitive test battery (N = 1766). Hair cortisol concentration (physiological measure) was assessed by liquid chromatography tandem mass spectrometry in 1098 participants. Cross-sectional associations between the two measures of chronic stress and cognition were investigated using multivariable linear regression models. Subjective and physiological measures of chronic stress were not associated with each other (B = 0.005 [95 %CI = -0.005 - 0.015]). Participants with higher perceived stress and specifically lower perceived self-efficacy performed worse in all cognitive domains (effect sizes ranged from ß = -0.129 [95 %CI = -0.177 - -0.080] to -0.054 [95 %CI = -0.099 - -0.009]; and from ß = 0.052 [95 %CI = 0.005 - 0.098] to 0.120 [95 %CI = 0.072 - 0.167], respectively). Relationships between subjective chronic stress measures and executive functioning were stronger in men compared to women (interaction ß = -0.144 [95 %CI = -0.221 - -0.067]). Relationships between perceived stress and working memory, and between perceived self-efficacy and executive functioning, processing speed, verbal episodic and working memory, increased with older age. Hair cortisol concentration was not associated with performance in any cognitive domain. Our results suggest that subjective and physiological measures capture different aspects of chronic stress in the general population.

Association of retinal layer measurements and adult cognitive function: A population-based study.

OBJECTIVE: To quantify the associations of peripapillary retinal nerve fiber layer (pRNFL) thickness and macular ganglion cell layer (mGCL) volume with cognitive functioning and to investigate how demographic and vascular health factors affect these associations in a population-based sample of adults. METHODS: The sample included the first 3,000 participants (age range 30-95 years) of the Rhineland Study (recruited from March 2016 to December 2018) who underwent spectral-domain optical coherence tomography and cognitive assessment at 1 of 2 identical study centers in Bonn, Germany. We used multiple linear regression models to examine the relationships between retinal layer measurements and cognitive functioning after adjustment for confounders, and we examined the moderating effects of demographic and vascular health factors. RESULTS: The analytical sample included 2,483 participants who were 54.3 years old (SD 13.8 years) on average. After full adjustment, each 1-SD decrease in mGCL volume was associated with a greater decrease in global function than that of pRNFL thickness (ß = -0.048 [95% confidence interval (CI) -0.077 to -0.018] vs ß = -0.021 [95% CI -0.049 to 0.007]). These relationships increased in strength with advancing age, were stronger in participants with hypertension, and were reversed in current smokers relative to nonsmokers. CONCLUSIONS: mGCL volume is more strongly related to adult cognitive functioning than pRNFL thickness, making it a better potential biomarker of neurodegeneration. Age and vascular health factors play important roles in determining the strength and direction of this association.

Inter- and Intraobserver Agreement in Measuring Urolithiasis Density on Nonenhanced Computed Tomography.

Introduction: Treatment choice for urolithiasis is partially based on measuring stone density in HU on nonenhanced computed tomography (NECT). Interobserver variability in these measurements could have treatment consequences. This study aims to assess the observer agreement of measuring HU and whether the use of a protocol leads to a better agreement. Materials and Methods: We retrospectively included 155 consecutive NECTs of patients with stones ≥4 mm. Five observers (two radiologists, one urologist, one urology resident, and one radiology resident) assessed all anonymized NECTs four times in randomized order. HU was measured without instruction (rounds 1 and 2) and subsequently using two protocols (A and B, rounds 3 and 4). Protocols comprised using bone setting, zoom, and measuring HU without the penumbra, in either three (A) or one (B) axial plane. The inter- and intraobserver agreement was evaluated using the intraclass correlation coefficient (ICC). Results: Interobserver agreement on HU measurement without protocol was as follows: ICC = 0.84 (confidence interval [CI]: 0.79-0.87). Agreement diminished with protocol A, ICC = 0.62 (CI: 0.37-0.76), and improved with protocol B, ICC = 0.90 (CI: 0.86-0.92). Intraobserver agreement without protocol was ICC = 0.87, with protocol A, ICC = 0.87, and with protocol B, ICC = 0.93. The biggest improvement was seen for urologists' agreement from no protocol to protocol B, where ICC improved from 0.81 (CI: 0.70-0.87) to 0.91 (CI: 0.84-0.94). Conclusions: Observer agreement of HU measurement of urolithiasis without protocol is already good but using zoom, bone setting, and measuring in a representative plane is recommended. This protocol results in higher agreement, especially among urologists. Measuring in three axial planes does not increase agreement.

A Functional MRI Paradigm for Efficient Mapping of Memory Encoding Across Sensory Conditions.

We introduce a new and time-efficient memory-encoding paradigm for functional magnetic resonance imaging (fMRI). This paradigm is optimized for mapping multiple contrasts using a mixed design, using auditory (environmental/vocal) and visual (scene/face) stimuli. We demonstrate that the paradigm evokes robust neuronal activity in typical sensory and memory networks. We were able to detect auditory and visual sensory-specific encoding activities in auditory and visual cortices. Also, we detected stimulus-selective activation in environmental-, voice-, scene-, and face-selective brain regions (parahippocampal place and fusiform face area). A subsequent recognition task allowed the detection of sensory-specific encoding success activity (ESA) in both auditory and visual cortices, as well as sensory-unspecific positive ESA in the hippocampus. Further, sensory-unspecific negative ESA was observed in the precuneus. Among others, the parallel mixed design enabled sustained and transient activity comparison in contrast to rest blocks. Sustained and transient activations showed great overlap in most sensory brain regions, whereas several regions, typically associated with the default-mode network, showed transient rather than sustained deactivation. We also show that the use of a parallel mixed model had relatively little influence on positive or negative ESA. Together, these results demonstrate a feasible, versatile, and brief memory-encoding task, which includes multiple sensory stimuli to guarantee a comprehensive measurement. This task is especially suitable for large-scale clinical or population studies, which aim to test task-evoked sensory-specific and sensory-unspecific memory-encoding performance as well as broad sensory activity across the life span within a very limited time frame.

Less head motion during MRI under task than resting-state conditions.

Head motion reduces data quality of neuroimaging data. In three functional magnetic resonance imaging (MRI) experiments we demonstrate that people make less head movements under task than resting-state conditions. In Experiment 1, we observed less head motion during a memory encoding task than during the resting-state condition. In Experiment 2, using publicly shared data from the UCLA Consortium for Neuropsychiatric Phenomics LA5c Study, we again found less head motion during several active task conditions than during a resting-state condition, although some task conditions also showed comparable motion. In the healthy controls, we found more head motion in men than in women and more motion with increasing age. When comparing clinical groups, we found that patients with a clinical diagnosis of bipolar disorder, or schizophrenia, move more compared to healthy controls or patients with ADHD. Both these experiments had a fixed acquisition order across participants, and we could not rule out that a first or last scan during a session might be particularly prone to more head motion. Therefore, we conducted Experiment 3, in which we collected several task and resting-state fMRI runs with an acquisition order counter-balanced. The results of Experiment 3 show again less head motion during several task conditions than during rest. Together these experiments demonstrate that small head motions occur during MRI even with careful instruction to remain still and fixation with foam pillows, but that head motion is lower when participants are engaged in a cognitive task. These finding may inform the choice of functional runs when studying difficult-to-scan populations, such as children or certain patient populations. Our findings also indicate that differences in head motion complicate direct comparisons of measures of functional neuronal networks between task and resting-state fMRI because of potential differences in data quality. In practice, a task to reduce head motion might be especially useful when acquiring structural MRI data such as T1/T2-weighted and diffusion MRI in research and clinical settings.

Breeding on the extreme edge: modulation of the adrenocortical response to acute stress in two High Arctic passerines.

Arctic weather in spring is unpredictable and can also be extreme, so Arctic-breeding birds must be flexible in their breeding to deal with such variability. Unpredictability in weather conditions will only intensify with climate change and this in turn could affect reproductive capability of migratory birds. Adjustments to coping strategies are therefore crucial, so here we examined the plasticity of the adrenocorticotropic stress response in two Arctic songbird species-the snow bunting (Plectrophenax nivalis) and Lapland longspur (Calcarius lapponicus)-breeding in northwest Greenland. Across the breeding season, the stress response was strongest at arrival and least robust during molt in male snow buntings. Snow bunting females had higher baseline but similar stress-induced corticosterone levels compared to males. Modification of the stress response was not due to adrenal insensitivity, but likely regulated at the anterior pituitary gland. Compared to independent nestlings and adult snow buntings, parental-dependent chicks had a more robust stress response. For Lapland longspurs, baseline corticosterone was highest at arrival in both male and females, and arriving males displayed a higher stress response compared to arriving females. Comparison of male corticosterone profiles collected at arrival in Greenland (76°N) and Alaska (67-71°N;) reveal that both species have higher stress responses at the more northern location. Flexibility in the stress response may be typical for birds nesting at the leading edges of their range and this ability will become more relevant as global climate change results in major shifts of breeding habitat and phenology for migratory birds.

Mineralization- and remodeling-unrelated improvement of the post-yield properties of rat cortical bone by high doses of olpadronate.

Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons. This study analyzes some effects of olpadronate on cortical bone modeling and post-yield properties in femurs diaphyses (virtually only-modeling bones) of young rats by mid-diaphyseal pQCT scans and bending tests. We studied 20/22 male/female animals traetad orally with olpadronate (45-90 mg/kg/d, 3 months) and 8/9 untreated controls. Both OPD doses enhanced diaphyseal cross-sectional moments of inertia (CSMI) with no change in cortical vBMD and elastic modulus. Yield stiffness and strength were mildly increased. Post-yield strength, deflection and energy absorption were strikingly enhanced. Ultimate strength was enhanced mainly because of effects on bone mass/geometry and post-yield properties. The large improvement of post-yield properties could be explained by improvements in bone geometry. Improvements in bone mass/geometry over weight-bearing needs suggest an enhanced modeling-related response to mechanical stimuli. Effects on tissue microstructural factors (not measured) could not be excluded. Results reveal novel olpadronate effects on bone strength and toughness unrelated to tissue mineralization and stiffness, even at high doses. Further studies could establish whether this could also occur in modeling-remodeling skeletons. If so, they could counteract the negative impact of anti-remodeling effects of bisphosphonates on bone strength.

Year-round territorial aggression is independent of plasma DHEA in the European nuthatch Sitta europaea.

Plasma testosterone can play an important role in promoting aggressive behaviors relating to territory defense in breeding male birds. Some birds defend territories also during the non-breeding phase, when testosterone circulates at basal levels. In such species, plasma levels of the pro-hormone dehydroepiandrosterone (DHEA) may support non-breeding territoriality by acting as a local substrate for sex steroids. To test this possible role of plasma DHEA, we examined the seasonal DHEA profile of male (and female) European nuthatches Sitta europaea: a male and female nuthatch pair will defend an all-purpose territory throughout the year. We hypothesized that plasma DHEA would be detectable in wintering nuthatches with a territory. However, only ca. half of the territorial wintering males (and females) displayed detectable DHEA levels, suggesting that plasma DHEA is not a major sex steroid precursor during non-breeding. Further, among hatching-year birds, plasma DHEA was significantly lower in territorial birds than in "floaters", i.e., subordinate birds without a territory. To experimentally examine the role of DHEA in non-breeding territoriality, we treated adult wintering males with DHEA and measured effects on aggressive responses to conspecific challenge. DHEA treatment elevated plasma levels of DHEA (and testosterone), but did not enhance territorial behaviors or their persistence. Taken together, our data suggest that DHEA (and, indeed, sex steroids per se) do not regulate non-breeding territoriality in the nuthatch. Given that territorial aggression in nuthatches is expressed year-round, a hormone for its activation may be redundant.

Irreducible lateral dislocation of patella with rotation.

Acute lateral patellar dislocation is relatively common in younger age group and most likely caused by indirect trauma. About 10% of acute patella dislocations are the result of a direct blow to the medial side. We report a case of irreducible lateral patellar dislocation which is of exceptional interest in that lateral patellar dislocation (extra-articular) occurred in comparatively older age group with arthritic knee, there was no direct trauma involved and it was associated with some rotation along long axis, impaction of patella on lateral femoral condyle and was locked underneath osteophytic ridge of lateral femoral condyle, which needed open reduction. This is a very rare injury, first of its kind being reported in Australia.

Thermoresponsive poly(2-oxazine)s.

The monomers 2-methyl-2-oxazine (MeOZI), 2-ethyl-2-oxazine (EtOZI), and 2-n-propyl-2-oxazine (nPropOZI) were synthesized and polymerized via the living cationic ring-opening polymerization (CROP) under microwave-assisted conditions. pEtOZI and pnPropOZI were found to be thermoresponsive, exhibiting LCST behavior in water and their cloud point temperatures (T(CP)) are lower than for poly(2-oxazoline)s with similar side chains. However, comparison of poly(2-oxazine) and poly(2-oxazoline)s isomers reveals that poly(2-oxazine)s are more water soluble, indicating that the side chain has a stronger impact on polymer solubility than the main chain. In conclusion, variations of both the side chains and the main chains of the poly(cyclic imino ether)s resulted in a series of distinct homopolymers with tunable T(CP).

Rearing conditions have long-term consequences for stress responsiveness in free-living great tits.

In captivity, the adrenocortical stress response can be permanently altered by events that occur during early life. Free-living animals have rarely been examined in this regard. To examine whether early-life events impact the hypothalamo-pituitary-adrenal (HPA) axis in the natural setting, we evaluated the stress response of free-living interspecifically cross-fostered great tits (Parus major). Cross-fostered birds may show a long-term potentiation of the adrenocortical stress response because species-specific nutritional requirements may not be met in the nest and/or cross-fostered birds may experience psychosocial stress while being raised by heterospecifics. Nevertheless, we hypothesized that in the natural setting, programmed changes in HPA function would be eclipsed by reactive responses to the immediate environment. Thus, we predicted that adult cross-fostered great tits and controls would show no differences in their adrenocortical stress response. Contrary to predictions, we found that stress responsiveness (i.e., the rate of the corticosterone increase associated with capture and handling) was significantly higher in cross-fostered great tits than in controls. Further, stress responsiveness was not significantly different between mature adults and first-year juveniles. Thus, data indicate significant effects of early rearing conditions on adrenocortical reactivity in the natural setting and also suggest that effects of rearing conditions in free-living animals can last into adulthood.

Poly(cyclic imino ether)s beyond 2-substituted-2-oxazolines.

2-Oxazolines (2-OZO) are 5-membered cyclic imino ethers whose cationic ring-opening polymerization (CROP) mechanism and resulting polymer properties are extensively studied. However, also 6- and 7-membered cyclic imino ethers can be polymerized via CROP. Together with the much less studied 4- and 5-substituted main-chain chiral poly(2-oxazoline)s (P-2-OZO), these compounds are interesting monomers to enhance the versatility of (co)poly(cyclic imino ether)s. To emphasize the potential of such alternative cyclic imino ether monomers, we provide an overview on the polymerizations of 2-oxazine (2-OZI) and chiral 4- and 5-substituted 2-OZO as well as of selected properties of the resulting polymers. In addition, the hydrolysis of these polymers into the corresponding poly(alkylene imine)s will be addressed.

Impact of season and social challenge on testosterone and corticosterone levels in a year-round territorial bird.

Plasma testosterone increases during breeding in many male vertebrates and has long been implicated in the promotion of aggressive behaviors relating to territory and mate defense. Males of some species also defend territories outside of the breeding period. For example, the European nuthatch (Sitta europaea) defends an all-purpose territory throughout the year. To contribute to the growing literature regarding the hormonal correlates of non-breeding territoriality, we investigated the seasonal testosterone and corticosterone profile of male (and female) nuthatches and determined how observed hormone patterns relate to expression of territorial aggression. Given that non-breeding territoriality in the nuthatch relates to the reproductive context (i.e., defense of a future breeding site), we predicted that males would exhibit surges in plasma testosterone throughout the year. However, we found that males showed elevated testosterone levels only during breeding. Thus, testosterone of gonadal origin does not appear to be involved in the expression of non-breeding territoriality. Interestingly, territorial behaviors of male nuthatches were stronger in spring than in autumn, suggesting that in year-round territorial species, breeding-related testosterone elevations may upregulate male-male aggression above non-breeding levels. In females, plasma testosterone was largely undetectable. We also examined effects of simulated territorial intrusions (STIs) on testosterone and corticosterone levels of breeding males. We found that STIs did not elicit a testosterone response, but caused a dramatic increase in plasma corticosterone. These data support the hypothesis that corticosterone rather than testosterone may play a role in the support of behavior and/or physiology during acute territorial encounters in single-brooded species.

The Effect of Hofmeister Salts on the LCST Transition of Poly(2-oxazoline)s with Varying Hydrophilicity.

The influence of Hofmeister salts was investigated on the cloud point of three poly(2-oxazoline)s, namely poly(2-ethyl-2-oxazoline) [PEtOx], poly(2-n-propyl-2-oxazoline) [PnPropOx], and poly(2-isopropyl-2-oxazoline) [PiPropOx]. In addition, a comb polymer based on oligo-2-ethyl-2-oxazoline side chains and a methacrylate backbone (POEtOxMA) was included in this investigation. It was found that the ionic response of the poly(2-oxazoline)s strongly depends on their hydrophilicity. The comb polymer POEtOxMA revealed a strikingly similar response to the salts as linear PEtOx even though the cloud points of the polymers in water differ. This indicates that the architecture does not significantly influence the effect of the Hofmeister ions, even though there is a difference in the absolute cloud point.

High-throughput, cell-free, liposome-based approach for assessing in vitro activity of lipid kinases.

Lipid kinases are central players in lipid signaling pathways involved in inflammation, tumorigenesis, and metabolic syndrome. A number of these kinase targets have proven difficult to investigate in higher throughput cell-free assay systems. This challenge is partially due to specific substrate interaction requirements for several of the lipid kinase family members and the resulting incompatibility of these substrates with most established, homogeneous assay formats. Traditional, cell-free in vitro investigational methods for members of the lipid kinase family typically involve substrate incorporation of [gamma-32P] and resolution of signal by thin-layer chromatography (TLC) and autoradiograph densitometry. This approach, although highly sensitive, does not lend itself to high-throughput testing of large numbers of small molecules (100 s to 1 MM+). The authors present the development and implementation of a fully synthetic, liposome-based assay for assessing in vitro activity of phosphatidylinositol-5-phosphate-4-kinase isoforms (PIP4KIIbeta and alpha) in 2 commonly used homogeneous technologies. They have validated these assays through compound testing in both traditional TLC and radioactive filterplate approaches as well as binding validation using isothermic calorimetry. A directed library representing known kinase pharmacophores was screened against type IIbeta phosphatidylinositol-phosphate kinase (PIPK) to identify small-molecule inhibitors. This assay system can be applied to other types and isoforms of PIPKs as well as a variety of other lipid kinase targets.

Composition of the body mass overshoot in European barn owl nestlings (Tyto alba): insurance against scarcity of energy or water?

European barn owl chicks (Tyto alba) show a body mass overshoot prior to fledging that has been predicted to serve as an energy reservoir during periods of stochastic food availability. However, the composition of the mass overshoot has heretofore not been directly examined in nestlings of this or any other species displaying a body mass overshoot during growth (e.g., raptors and seabirds). To experimentally determine whether the overshoot in body mass in juvenile European barn owls (Tyto alba) may act as an energy reservoir, we compared the body composition of owl chicks raised on an ad libitum diet to those fed a restricted diet designed to eliminate the overshoot. Chicks raised on the two diets were also compared for differences in maturation of diverse functions (e.g., locomotion) and tissues (e.g., skeletal development). Contrary to expectations, our results on body composition in juvenile barn owls indicate that the mass overshoot prior to fledging is primarily comprised of an increased water compartment. Thus, we suggest that the mass overshoot in owls (and possibly in other species) does not serve as an energy reservoir but, rather, may function as an insurance against dehydration when hot in-nest conditions force chicks to rely on evaporative cooling: temperatures in barn owl nests can reach up to 43 degrees C. We found no significant differences in maturation indexes between diet treatments at the time of fledging.