Late-onset Krabbe disease presenting as spastic paraplegia - implications of GCase and CTSB/D.

OBJECTIVE: Krabbe disease (KD) is a multisystem neurodegenerative disorder with severe disability and premature death, mostly with an infancy/childhood onset. In rare cases of late-onset phenotypes, symptoms are often milder and difficult to diagnose. We here present a translational approach combining diagnostic and biochemical analyses of a male patient with a progressive gait disorder starting at the age of 44 years, with a final diagnosis of late-onset KD (LOKD). METHODS: Additionally to cerebral MRI, protein structural analyses of the ß-galactocerebrosidase protein (GALC) were performed. Moreover, expression, lysosomal localization, and activities of ß-glucocerebrosidase (GCase), cathepsin B (CTSB), and cathepsin D (CTSD) were analyzed in leukocytes, fibroblasts, and lysosomes of fibroblasts. RESULTS: Exome sequencing revealed biallelic likely pathogenic variants: GALC exons 11-17: 33 kb deletion; exon 4: missense variant (c.334A>G, p.Thr112Ala). We detected a reduced GALC activity in leukocytes and fibroblasts. While histological KD phenotypes were absent in fibroblasts, they showed a significantly decreased activities of GCase, CTSB, and CTSD in lysosomal fractions, while expression levels were unaffected. INTERPRETATION: The presented LOKD case underlines the age-dependent appearance of a mildly pathogenic GALC variant and its interplay with other lysosomal proteins. As GALC malfunction results in reduced ceramide levels, we assume this to be causative for the here described decrease in CTSB and CTSD activity, potentially leading to diminished GCase activity. Hence, we emphasize the importance of a functional interplay between the lysosomal enzymes GALC, CTSB, CTSD, and GCase, as well as between their substrates, and propose their conjoined contribution in KD pathology.

Predicting physical activity by the personality styles of the five-factor model.

OBJECTIVE: Low neuroticism, high extraversion, and high conscientiousness are related to physical activity (PA). We tested whether the small size and heterogeneity of these relationships result because personality traits influence one another as well as because some narrow facets rather than the broad domains contain more specific variance relevant to PA. METHOD: Participants were men and women enrolled in the University of North Carolina Alumni Heart Study who completed the Revised NEO Personality Inventory (NEO-PI-R) and reported their past month's average activity on an 8-point scale. In Study 1, we examined prospective correlations between the five NEO-PI-R domains and PA. In Studies 2 and 3, we used multinomial logistic regression to examine associations between PA and trait pair combinations (personality styles) controlling for age, sex, educational achievement, relationship status, and depression. RESULTS: Study 1 revealed that lower neuroticism (N) and agreeableness (A) and higher conscientiousness (C) predicted more PA. Taken together, Studies 2 and 3 found that the combination of high Extraversion (E) and high openness (O) was related to higher PA and that combinations of low E and high A and low E and low C were related to lower PA. Study 3, which examined the activity facet of E (E4), found that E4 is an important driver of E-PA associations. CONCLUSIONS: Personality traits do not operate in isolation. They may influence how other traits are expressed and such nonadditive effects can impact PA. Assessment of personality styles could help to identify individuals at risk for PA avoidance and may be useful for developing personalized interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Detection of Trace Metal Contaminants in Organic Products Using Ion Current Rectifying Quartz Nanopipettes.

While ion current rectification (ICR) in aprotic solvent has been fundamentally studied, its application in sensing devices lacks exploration. The development of sensors operable in these solvents is highly beneficial to the chemical industry, where polar aprotic solvents, such as acetonitrile, are widely used. Currently, this industry relies on the use of inductively coupled plasma mass spectrometry (ICP-MS) and optical emission spectroscopy (OES) for the detection of metal contamination in organic products. Herein, we present the detection of trace amounts of Pd2+ and Co2+ using ion current rectification, in cyclam-functionalized quartz nanopipettes, with tetraethylammonium tetrafluoroborate (TEATFB) in MeCN as supporting electrolyte. This methodology is employed to determine the concentration of Pd in organic products, before and after purification by Celite filtration and column chromatography, obtaining comparable results to ICP-MS within minutes and without complex sample preparation. Finite element simulations are used to support our experimental findings, which reveal that the formation of double-junction diodes in the nanopore enables trace detection of these metals, with a significant response from baseline even at picomolar concentrations.

Mitochondrial enzyme FAHD1 reduces ROS in osteosarcoma.

This study investigated the impact of overexpressing the mitochondrial enzyme Fumarylacetoacetate hydrolase domain-containing protein 1 (FAHD1) in human osteosarcoma epithelial cells (U2OS) in vitro. While the downregulation or knockdown of FAHD1 has been extensively researched in various cell types, this study aimed to pioneer the exploration of how increased catalytic activity of human FAHD1 isoform 1 (hFAHD1.1) affects human cell metabolism. Our hypothesis posited that elevation in FAHD1 activity would lead to depletion of mitochondrial oxaloacetate levels. This depletion could potentially result in a decrease in the flux of the tricarboxylic acid (TCA) cycle, thereby accompanied by reduced ROS production. In addition to hFAHD1.1 overexpression, stable U2OS cell lines were established overexpressing a catalytically enhanced variant (T192S) and a loss-of-function variant (K123A) of hFAHD1. It is noteworthy that homologs of the T192S variant are present in animals exhibiting increased resistance to oxidative stress and cancer. Our findings demonstrate that heightened activity of the mitochondrial enzyme FAHD1 decreases cellular ROS levels in U2OS cells. However, these results also prompt a series of intriguing questions regarding the potential role of FAHD1 in mitochondrial metabolism and cellular development.

Associations Between a General Factor and Group Factor from the Spanish-Language Eysenck Personality Questionnaire-Revised Short Form's Neuroticism Scale and the Revised NEO Personality Inventory Domains and Facets.

Prior studies used exploratory bifactor analyses to examine the structure of the Neuroticism scale from the Short-scale Eysenck Personality Questionnaire-Revised (EPQ-RS). These studies revealed a general factor and two group factors-Anxious-Tense and Worried-Vulnerable. These factors were related to poorer mental health, but their associations with physical health differed, as did their genetic and neurobiological underpinnings. A later study found that their associations with the Big Five Inventory-2 Short Form's factors and facets differed. We reanalyzed data on 1,006 Spanish students who completed Spanish-language versions of the EPQ-RS and the Revised NEO Personality Inventory (NEO PI-R). Using confirmatory factor analysis, we showed that a model comprising the general factor and a group factor-Anxious-Tense-fit well. In later correlations, a joint factor analysis, and simultaneous multiple regressions, we showed that the EPQ-RS's general factor and the group factor had different patterns of associations with the NEO PI-R domains and facets. These associations were consistent with the definition of the EPQ-RS Neuroticism scale's general factor and that of the group factor. Further investigation into the EPQ-RS Neuroticism scale's structure can improve our understanding of neuroticism's relationship with health and other outcomes.

High Levels of Mutant Huntingtin Protein in Tear Fluid From Huntington's Disease Gene Expansion Carriers.

OBJECTIVE: Huntington's disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects middle-aged adults. HD is caused by a CAG repeat expansion in the HTT gene, resulting in the expression of mutant huntingtin (mHTT). Our aim was to detect and quantify mHTT in tear fluid, which, to our knowledge, has never been measured before. METHODS: We recruited 20 manifest and 13 premanifest HD gene expansion carriers, and 20 age-matched controls. All patients underwent detailed assessments, including the Unified Huntington's Disease Rating Scale (UHDRS) total motor score (TMS) and total functional capacity (TFC) score. Tear fluid was collected using paper Schirmer's strips. The level of tear mHTT was determined using single-molecule counting SMCxPRO technology. RESULTS: The average tear mHTT levels in manifest (67,223 ± 80,360 fM) and premanifest patients (55,561 ± 45,931 fM) were significantly higher than those in controls (1,622 ± 2,179 fM). We noted significant correlations between tear mHTT levels and CAG repeat length, "estimated years to diagnosis," disease burden score and UHDRS TMS and TFC. The receiver operating curve demonstrated an almost perfect score (area under the curve [AUC] = 0.9975) when comparing controls to manifest patients. Similarly, the AUC between controls and premanifest patients was 0.9846. The optimal cutoff value for distinguishing between controls and manifest patients was 4,544 fM, whereas it was 6,596 fM for distinguishing between controls and premanifest patients. CONCLUSION: Tear mHTT has potential for early and noninvasive detection of alterations in HD patients and could be integrated into both clinical trials and clinical diagnostics.

Stable Decoding from a Speech BCI Enables Control for an Individual with ALS without Recalibration for 3 Months.

Brain-computer interfaces (BCIs) can be used to control assistive devices by patients with neurological disorders like amyotrophic lateral sclerosis (ALS) that limit speech and movement. For assistive control, it is desirable for BCI systems to be accurate and reliable, preferably with minimal setup time. In this study, a participant with severe dysarthria due to ALS operates computer applications with six intuitive speech commands via a chronic electrocorticographic (ECoG) implant over the ventral sensorimotor cortex. Speech commands are accurately detected and decoded (median accuracy: 90.59%) throughout a 3-month study period without model retraining or recalibration. Use of the BCI does not require exogenous timing cues, enabling the participant to issue self-paced commands at will. These results demonstrate that a chronically implanted ECoG-based speech BCI can reliably control assistive devices over long time periods with only initial model training and calibration, supporting the feasibility of unassisted home use.

Accessing Position Space Wave Functions in Band Structure Calculations of Periodic Systems─A Generalized, Adapted Numerov Implementation for One-, Two-, and Three-Dimensional Quantum Problems.

In this work, a generalized, adapted Numerov implementation capable of determining band structures of periodic quantum systems is outlined. Based on the input potential, the presented approach numerically solves the Schrödinger equation in position space at each momentum space point. Thus, in addition to the band structure, the method inherently provides information about the state functions and probability densities in position space at each momentum space point considered. The generalized, adapted Numerov framework provided reliable estimates for a variety of increasingly complex test suites in one, two, and three dimensions. The accuracy of the proposed methodology was benchmarked against results obtained for the analytically solvable Kronig-Penney model. Furthermore, the presented numerical solver was applied to a model potential representing a 2D optical lattice being a challenging application relevant, for example, in the field of quantum computing.

Synthetic CTs for MRI-only brain RT treatment: integration of immobilization systems.

PURPOSE: Auxiliary devices such as immobilization systems should be considered in synthetic CT (sCT)-based treatment planning (TP) for MRI-only brain radiotherapy (RT). A method for auxiliary device definition in the sCT is introduced, and its dosimetric impact on the sCT-based TP is addressed. METHODS: T1-VIBE DIXON was acquired in an RT setup. Ten datasets were retrospectively used for sCT generation. Silicone markers were used to determine the auxiliary devices' relative position. An auxiliary structure template (AST) was created in the TP system and placed manually on the MRI. Various RT mask characteristics were simulated in the sCT and investigated by recalculating the CT-based clinical plan on the sCT. The influence of auxiliary devices was investigated by creating static fields aimed at artificial planning target volumes (PTVs) in the CT and recalculated in the sCT. The dose covering 50% of the PTV (D50) deviation percentage between CT-based/recalculated plan (∆D50[%]) was evaluated. RESULTS: Defining an optimal RT mask yielded a ∆D50[%] of 0.2 ± 1.03% for the PTV and between -1.6 ± 3.4% and 1.1 ± 2.0% for OARs. Evaluating each static field, the largest ∆D50[%] was delivered by AST positioning inaccuracy (max: 3.5 ± 2.4%), followed by the RT table (max: 3.6 ± 1.2%) and the RT mask (max: 3.0 ± 0.8% [anterior], 1.6 ± 0.4% [rest]). No correlation between ∆D50[%] and beam depth was found for the sum of opposing beams, except for (45°â€¯+ 315°). CONCLUSION: This study evaluated the integration of auxiliary devices and their dosimetric influence on sCT-based TP. The AST can be easily integrated into the sCT-based TP. Further, we found that the dosimetric impact was within an acceptable range for an MRI-only workflow.

Personality traits, rank attainment, and siring success throughout the lives of male chimpanzees of Gombe National Park.

Personality traits in many taxa correlate with fitness. Several models have been developed to try to explain how variation in these traits is maintained. One model proposes that variation persists because it is linked to trade-offs between current and future adaptive benefits. Tests of this model's predictions, however, are scant in long-lived species. To test this model, we studied male chimpanzees living in Gombe National Park, Tanzania. We operationalized six personality traits using ratings on 19 items. We used 37 years of behavioral and genetic data to assemble (1) daily rank scores generated from submissive vocalizations and (2) records of male siring success. We tested whether the association between two personality traits, Dominance and Conscientiousness, and either rank or reproductive success, varied over the life course. Higher Dominance and lower Conscientiousness were associated with higher rank, but the size and direction of these relationships did not vary over the life course. In addition, independent of rank at the time of siring, higher Dominance and lower Conscientiousness were related to higher siring success. Again, the size and direction of these relationships did not vary over the life course. The trade-off model, therefore, may not hold in long-lived and/or slowly reproducing species. These findings also demonstrate that ratings are a valid way to measure animal personality; they are related to rank and reproductive success. These traits could therefore be used to test alternative models, including one that posits that personality variation is maintained by environmental heterogeneity, in studies of multiple chimpanzee communities.

Lexicality-Modulated Influence of Auditory Cortex on Subthalamic Nucleus During Motor Planning for Speech.

Speech requires successful information transfer within cortical-basal ganglia loop circuits to produce the desired acoustic output. For this reason, up to 90% of Parkinson's disease patients experience impairments of speech articulation. Deep brain stimulation (DBS) is highly effective in controlling the symptoms of Parkinson's disease, sometimes alongside speech improvement, but subthalamic nucleus (STN) DBS can also lead to decreases in semantic and phonological fluency. This paradox demands better understanding of the interactions between the cortical speech network and the STN, which can be investigated with intracranial EEG recordings collected during DBS implantation surgery. We analyzed the propagation of high-gamma activity between STN, superior temporal gyrus (STG), and ventral sensorimotor cortices during reading aloud via event-related causality, a method that estimates strengths and directionalities of neural activity propagation. We employed a newly developed bivariate smoothing model based on a two-dimensional moving average, which is optimal for reducing random noise while retaining a sharp step response, to ensure precise embedding of statistical significance in the time-frequency space. Sustained and reciprocal neural interactions between STN and ventral sensorimotor cortex were observed. Moreover, high-gamma activity propagated from the STG to the STN prior to speech onset. The strength of this influence was affected by the lexical status of the utterance, with increased activity propagation during word versus pseudoword reading. These unique data suggest a potential role for the STN in the feedforward control of speech.

The contributions of mitochondrial and nuclear mitochondrial genetic variation to neuroticism.

Neuroticism is a heritable trait composed of separate facets, each conferring different levels of protection or risk, to health. By examining mitochondrial DNA in 269,506 individuals, we show mitochondrial haplogroups explain 0.07-0.01% of variance in neuroticism and identify five haplogroup and 15 mitochondria-marker associations across a general factor of neuroticism, and two special factors of anxiety/tension, and worry/vulnerability with effect sizes of the same magnitude as autosomal variants. Within-haplogroup genome-wide association studies identified H-haplogroup-specific autosomal effects explaining 1.4% variance of worry/vulnerability. These H-haplogroup-specific autosomal effects show a pleiotropic relationship with cognitive, physical and mental health that differs from that found when assessing autosomal effects across haplogroups. We identify interactions between chromosome 9 regions and mitochondrial haplogroups at P < 5 × 10-8, revealing associations between general neuroticism and anxiety/tension with brain-specific gene co-expression networks. These results indicate that the mitochondrial genome contributes toward neuroticism and the autosomal links between neuroticism and health.

Cortico-cortical feedback engages active dendrites in visual cortex.

Sensory processing in the neocortex requires both feedforward and feedback information flow between cortical areas1. In feedback processing, higher-level representations provide contextual information to lower levels, and facilitate perceptual functions such as contour integration and figure-ground segmentation2,3. However, we have limited understanding of the circuit and cellular mechanisms that mediate feedback influence. Here we use long-range all-optical connectivity mapping in mice to show that feedback influence from the lateromedial higher visual area (LM) to the primary visual cortex (V1) is spatially organized. When the source and target of feedback represent the same area of visual space, feedback is relatively suppressive. By contrast, when the source is offset from the target in visual space, feedback is relatively facilitating. Two-photon calcium imaging data show that this facilitating feedback is nonlinearly integrated in the apical tuft dendrites of V1 pyramidal neurons: retinotopically offset (surround) visual stimuli drive local dendritic calcium signals indicative of regenerative events, and two-photon optogenetic activation of LM neurons projecting to identified feedback-recipient spines in V1 can drive similar branch-specific local calcium signals. Our results show how neocortical feedback connectivity and nonlinear dendritic integration can together form a substrate to support both predictive and cooperative contextual interactions.

SARS-CoV-2 3CLpro mutations selected in a VSV-based system confer resistance to nirmatrelvir, ensitrelvir, and GC376.

Protease inhibitors are among the most powerful antiviral drugs. Nirmatrelvir is the first protease inhibitor specifically developed against the SARS-CoV-2 protease 3CLpro that has been licensed for clinical use. To identify mutations that confer resistance to this protease inhibitor, we engineered a chimeric vesicular stomatitis virus (VSV) that expressed a polyprotein composed of the VSV glycoprotein (G), the SARS-CoV-2 3CLpro, and the VSV polymerase (L). Viral replication was thus dependent on the autocatalytic processing of this precursor protein by 3CLpro and release of the functional viral proteins G and L, and replication of this chimeric VSV was effectively inhibited by nirmatrelvir. Using this system, we applied nirmatrelvir to select for resistance mutations. Resistance was confirmed by retesting nirmatrelvir against the selected mutations in additional VSV-based systems, in an independently developed cellular system, in a biochemical assay, and in a recombinant SARS-CoV-2 system. We demonstrate that some mutants are cross-resistant to ensitrelvir and GC376, whereas others are less resistant to these compounds. Furthermore, we found that most of these resistance mutations already existed in SARS-CoV-2 sequences that have been deposited in the NCBI and GISAID databases, indicating that these mutations were present in circulating SARS-CoV-2 strains.

Dominance in human (Homo sapiens) personality space and in hominoid phylogeny.

Unlike nonhuman primates, individual differences between humans in dominance do not appear as broad personality factors. This may be attributable to differences between the questionnaires used to study human and nonhuman primate personality. Alternatively, this may reflect differences in the organization of personality in humans and nonhuman primates. To determine which of these possibilities was most likely, 1,147 participants were recruited and asked to rate their personality and/or that of somebody else on the Hominoid Personality Questionnaire (HPQ), which has been used to study nonhuman primate personality. A large subset of these participants (~80%) also completed self- and/or rater reports of one of three questionnaires used to measure human personality. Exploratory factor analyses of HPQ rater report data yielded five factors. These factors correlated mostly in expected ways with scales from questionnaires used to study human personality. Exploratory factor analyses of HPQ self-report data yielded no clear number of factors and no consistent evidence with respect to the presence of a dominance factor. Subsequent analyses compared HPQ scales that represented dominance factors in chimpanzees, bonobos, mountain gorillas, and orangutans to scales derived from the Revised NEO Personality Inventory, including Fearless Dominance, which combined Neuroticism, Agreeableness, Conscientiousness, and Extraversion facets, Emotional Stability (the inverse of Neuroticism), and Extraversion's Assertiveness facet. Fearless Dominance and Assertiveness were most like the great ape dominance factors. The absence of human dominance factors, therefore, appears to reflect present or past social conditions of our species. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

End-to-end testing for stereotactic radiotherapy including the development of a Multi-Modality phantom.

PURPOSE: A new insert for a commercially available end-to-end test phantom was designed and in-house manufactured by 3D printing. Subsequently, the insert was tested for different stereotactic radiation therapy workflows (SRS, SBRT, FSRT, and Multimet) also in comparison to the original insert. MATERIAL AND METHODS: Workflows contained imaging (MR, CT), treatment planning, positioning, and irradiation. Positioning accuracy was evaluated for non-coplanar x-ray, kV- and MV-CBCT systems, as well as surface guided radiation therapy. Dosimetric accuracy of the irradiation was measured with an ionization chamber at four different linear accelerators including dynamic tumor tracking for SBRT. RESULTS: CT parameters of the insert were within the specification. For MR images, the new insert allowed quantitative analysis of the MR distortion. Positioning accuracy of the phantom with the new insert using the imaging systems of the different linacs was < 1 mm/degree also for MV-CBCT and a non-coplanar imaging system which caused > 3 mm deviation with the original insert. Deviation of point dose values was <3% for SRS, FSRT, and SBRT for both inserts. For the Multimet plans deviations exceeded 10% because the ionization chamber was not positioned in each metastasis, but in the center of phantom and treatment plan. CONCLUSION: The in-house manufactured insert performed well in all steps of four stereotactic treatment end-to-end tests. Advantages over the commercially available alternative were seen for quantitative analysis of deformation correction in MR images, applicability for non-coplanar x-ray imaging, and dynamic tumor tracking.

The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis.

Misalignment of physiological circadian rhythms promotes obesity which is characterized by white adipose tissue (WAT) expansion. Differentiation of Adipose stem/progenitor cells (ASCs) contributes to WAT increase but the importance of the cellular clock in this process is incompletely understood. In the present study, we reveal the role of the circadian transcription factor Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) in human ASCs, isolated from subcutaneous (s)WAT samples of patients undergoing routine elective plastic abdominal surgery. We show that circadian synchronization by serum-shock or stimulation with adipogenic stimuli leads to a different expression pattern of ARNTL2 relative to its well-studied paralogue ARNTL1. We demonstrate that ARNTL2 mRNA is downregulated in ASCs upon weight-loss (WL) whereas ARNTL2 protein is rapidly induced in the course of adipogenic differentiation and highly abundant in adipocytes. ARNTL2 protein is maintained in ASCs cooperatively by mechanistic Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPK) signalling pathways while ARNTL2 functions as an inhibitor on both circuits, leading to a feedback mechanism. Consistently, ectopic overexpression of ARNTL2 repressed adipogenesis by facilitating the degradation of ARNTL1, inhibition of Kruppel-Like Factor 15 (KLF15) gene expression and down-regulation of the MAPK-CCAAT/enhancer-binding protein ß (C/EBPß) axis. Western blot analysis of sWAT samples from normal-weight, obese and WL donors revealed that ARNTL2 protein was solely elevated by WL compared to ARNTL1 which underscores unique functions of both transcription factors. In conclusion, our study reveals ARNTL2 to be a WL-regulated inhibitor of adipogenesis which might provide opportunities to develop strategies to ameliorate obesity.

An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington's disease patient neurons.

Huntington's disease (HD) is a neurodegenerative disorder caused by poly-Q expansion in the Huntingtin (HTT) protein. Here, we delineate elevated mutant HTT (mHTT) levels in patient-derived cells including fibroblasts and iPSC derived cortical neurons using mesoscale discovery (MSD) HTT assays. HD patients' fibroblasts and cortical neurons recapitulate aberrant alternative splicing as a molecular fingerprint of HD. Branaplam is a splicing modulator currently tested in a phase II study in HD (NCT05111249). The drug lowers total HTT (tHTT) and mHTT levels in fibroblasts, iPSC, cortical progenitors, and neurons in a dose dependent manner at an IC50 consistently below 10 nM without inducing cellular toxicity. Branaplam promotes inclusion of non-annotated novel exons. Among these Branaplam-induced exons, there is a 115 bp frameshift-inducing exon in the HTT transcript. This exon is observed upon Branaplam treatment in Ctrl and HD patients leading to a profound reduction of HTT RNA and protein levels. Importantly, Branaplam ameliorates aberrant alternative splicing in HD patients' fibroblasts and cortical neurons. These findings highlight the applicability of splicing modulators in the treatment of CAG repeat disorders and decipher their molecular effects associated with the pharmacokinetic and -dynamic properties in patient-derived cellular models.

Laboratory-scale X-ray absorption spectroscopy of 3d transition metals in inorganic thin films.

In this paper we present laboratory-scale X-ray absorption spectroscopy applied to the research of nanometer-scale thin films. We demonstrate the Cu K edge X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) of CuI and CuO thin films grown with atomic layer deposition. Film thicknesses in the investigated samples ranged from 12 to 248 nm. Even from the thinnest films, XANES spectra can be obtained in 5-20 minutes and EXAFS in 1-4 days. In order to prove the capability of laboratory-based XAS for in situ measurements on thin films, we demonstrate an experiment on in situ oxidation of a 248 nm thick CuI film at a temperature of 240 °C. These methods have important implications for novel and enhanced possibilities for inorganic thin film research.