Muscle synergies are shared across fundamental subtasks in complex movements of skateboarding.

A common theory of motor control posits that movement is controlled by muscle synergies. However, the behavior of these synergies during highly complex movements remains largely unexplored. Skateboarding is a hardly researched sport that requires rapid motor control to perform tricks. The objectives of this study were to investigate three key areas: (i) whether motor complexity differs between skateboard tricks, (ii) the inter-participant variability in synergies, and (iii) whether synergies are shared between different tricks. Electromyography data from eight muscles per leg were collected from seven experienced skateboarders performing three different tricks (Ollie, Kickflip, 360°-flip). Synergies were extracted using non-negative matrix factorization. The number of synergies (NoS) was determined using two criteria based on the total variance accounted for (tVAF > 90% and adding an additional synergy does not increase tVAF > 1%). In summary: (i) NoS and tVAF did not significantly differ between tricks, indicating similar motor complexity. (ii) High inter-participant variability exists across participants, potentially caused by the low number of constraints given to perform the tricks. (iii) Shared synergies were observed in every comparison of two tricks. Furthermore, each participant exhibited at least one synergy vector, which corresponds to the fundamental 'jumping' task, that was shared through all three tricks.

Forensic neuropsychological assessment.

With its firm establishment as a neuropsychology subspecialty, forensic neuropsychological assessment is integral to many criminal and civil forensic evaluations. In addition to evaluating cognitive deficits, forensic neuropsychologists can provide reliable information regarding symptom magnification, malingering, and other neurocognitive and psychological issues that may impact the outcome of a particular legal case. This article is an overview and introduction to neuropsychological assessment in the forensic mental health context. Major issues impacting the current practice of forensic neuropsychology are summarized, and several examples from case law are highlighted.

Attorney demands for protected psychological test information: Is access necessary for cross examination or does it lead to misinformation? An interorganizational* position paper.

Objective: Some attorneys claim that to adequately cross examine neuropsychological experts, they require direct access to protected test information, rather than having test data analyzed by retained neuropsychological experts. The objective of this paper is to critically examine whether direct access to protected test materials by attorneys is indeed necessary, appropriate, and useful to the trier-of-fact. Method: Examples are provided of the types of nonscientific misinformation that occur when attorneys, who lack adequate training in testing, attempt to independently interpret neurocognitive/psychological test data. Results: Release of protected test information to attorneys introduces inaccurate information to the trier of fact, and jeopardizes future use of tests because non-psychologists are not ethically bound to protect test content. Conclusion: The public policy underlying the right of attorneys to seek possibly relevant documents should not outweigh the damage to tests and resultant misinformation that arise when protected test information is released directly to attorneys. The solution recommended by neuropsychological/psychological organizations and test publishers is to have protected psychological test information exchanged directly and only between clinical psychologist/neuropsychologist experts.

Peptidylglycine α-amidating monooxygenase and adrenomedullin measurement in patients with hepatic cirrhosis.

Background: Peptidylglycine α-amidating monooxygenase (PAM) is an enzyme involved in the maturation of regulatory peptides. Here we examined PAM activity and adrenomedullin (bio-ADM) concentrations in patients with hepatic cirrhosis and determined net changes across the liver, kidneys and leg. Materials & methods: A total of 48 patients with hepatic cirrhosis and 16 control subjects were included. All patients and controls underwent an invasive procedure with blood collected across organs. Results: PAM activity was increased in cirrhotic patients but without a net change across the liver, leg or kidney. In contrast, bio-ADM concentrations were associated with severity of disease and found to be higher in venous blood from the liver. Conclusion: Increased PAM activity in patients with hepatic cirrhosis may reflect other organs involved in cirrhotic disease.

Severe liver disease is a life-threatening condition that affects people all over the world. To improve doctors' ability to diagnose the disease and to follow the disease as it progresses, there is a need for new tools. Biomarkers are often used as such tools for measuring the presence and severity of a disease. In this study, we examined two potential biomarkers in blood from patients with severe liver disease: peptidylglycine α-amidating monooxygenase (PAM) activity and bioactive adrenomedullin (bio-ADM). We examined whether these biomarkers are present in blood and in amounts associated with disease severity. We also tested if the diseased liver releases the biomarkers. We found that bio-ADM is increased in blood from patients with severe liver disease and that the liver itself releases bio-ADM to the bloodstream. For PAM activity, we also detected increased activity in blood associated with disease severity. In contrast, however, this biomarker was not shown to be released by the liver. Taken together, the two biomarkers may help to improve severe liver disease diagnosis and maybe allow for biochemical follow-up as the disease progresses.

Psychophysiological stress response after a 6-week Mindful Self-Compassion training in psychiatric rehabilitation inpatients: a randomized post-test only study.

Objectives: Mindfulness-based interventions (including self-compassion interventions) are effective in improving stress management at psychological and physical levels. Mindful Self-Compassion (MSC) is a newly developed program particularly aimed at increasing self-compassion. The main objective of this study was to determine whether the psychophysiological stress response during a social-evaluative speaking task differs in inpatients participating in the MSC or the Progressive Muscle Relaxation (PMR) program at the end of their 6-week psychiatric rehabilitation stay (i.e., post-test only design). Method: Data from 50 inpatients (25 MSC, 25 PMR, 35 female) aged 19 to 76 years (M = 47.22, SD = 12.44) were analyzed in terms of psychophysiological stress response. For this purpose, heart rate variability, heart rate, and blood pressure were assessed together with several psychometric variables: positive and negative affect (PANAS), subjective stress perception (Visual Analog Scale), self-compassion (Self-Compassion Scale), cognitive reappraisal and suppression (Emotion Regulation Questionnaire), psychological distress (Brief Symptom Inventory-18), and appraisal and rumination (selected items). Results: After correction for alpha inflation no differences in the psychophysiological stress response and psychometric parameters between the MSC and PMR group were found. Discussion: In general, our results indicate that MSC is not superior to PMR training. However, more research with clinical randomized controlled trials investigating larger samples are needed to further affirm these initial findings.

Immunoassay-based quantification of full-length peptidylglycine alpha-amidating monooxygenase in human plasma.

A one-step sandwich chemiluminescence immunometric assay (LIA) was developed for the quantification of bifunctional peptidylglycine-α-amidating monooxygenase (PAM) in human plasma (PAM-LIA). PAM is responsible for the activation of more than half of known peptide hormones through C-terminal α-amidation. The assay employed antibodies targeting specific catalytic PAM-subunits, peptidylglycine alpha-hydroxylating monooxygenase (PHM) and peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PAL), to ensure detection of full-length PAM. The PAM-LIA assay was calibrated with a human recombinant PAM enzyme and achieved a detection limit of 189 pg/mL and a quantification limit of 250 pg/mL. The assay demonstrated good inter-assay (6.7%) and intra-assay (2.2%) variabilities. It exhibited linearity when accessed by gradual dilution or random mixing of plasma samples. The accuracy of the PAM-LIA was determined to be 94.7% through spiking recovery experiments, and the signal recovery after substance interference was 94-96%. The analyte showed 96% stability after six freeze-thaw cycles. The assay showed strong correlation with matched EDTA and serum samples, as well as matched EDTA and Li-Heparin samples. Additionally, a high correlation was observed between α-amidating activity and PAM-LIA. Finally, the PAM-LIA assay was successfully applied to a sub-cohort of a Swedish population-based study, comprising 4850 individuals, confirming its suitability for routine high throughput screening.

Layer- and cell-type-specific differences in neural activity in mouse barrel cortex during a whisker detection task.

To address the question which neocortical layers and cell types are important for the perception of a sensory stimulus, we performed multielectrode recordings in the barrel cortex of head-fixed mice performing a single-whisker go/no-go detection task with vibrotactile stimuli of differing intensities. We found that behavioral detection probability decreased gradually over the course of each session, which was well explained by a signal detection theory-based model that posits stable psychometric sensitivity and a variable decision criterion updated after each reinforcement, reflecting decreasing motivation. Analysis of multiunit activity demonstrated highest neurometric sensitivity in layer 4, which was achieved within only 30 ms after stimulus onset. At the level of single neurons, we observed substantial heterogeneity of neurometric sensitivity within and across layers, ranging from nonresponsiveness to approaching or even exceeding psychometric sensitivity. In all cortical layers, putative inhibitory interneurons on average proffered higher neurometric sensitivity than putative excitatory neurons. In infragranular layers, neurons increasing firing rate in response to stimulation featured higher sensitivities than neurons decreasing firing rate. Offline machine-learning-based analysis of videos of behavioral sessions showed that mice performed better when not moving, which at the neuronal level, was reflected by increased stimulus-evoked firing rates.

Mid-IR spectroscopy with NIR grating spectrometers.

Mid-infrared (mid-IR) spectroscopy is a crucial workhorse for a plethora of analytical applications and is suitable for diverse materials, including gases, polymers or biological tissue. However, this technologically significant wavelength regime between 2.5-10 µm suffers from technical limitations primarily related to the large noise in mid-IR detectors and the complexity and cost of bright, broadband mid-IR light sources. Here, using highly non-degenerate, broadband photon pairs from bright spontaneous parametric down-conversion (SPDC) in a nonlinear interferometer, we circumvent these limitations and realise spectroscopy in the mid-IR using only a visible (VIS) solid-state laser and an off-the-shelf, commercial near-infrared (NIR) grating spectrometer. With this proof-of-concept implementation, covering a broad range from 3.2 µm to 4.4 µm we demonstrate short integration times down to 1 s and signal-to-noise ratios above 200 at a spectral resolution from 12 cm-1 down to 1.5 cm-1 for longer integration times. Through the analysis of polymer samples and the ambient CO2 in our laboratory, we highlight the potential of this measurement technique for real-world applications.

Official position of the American Academy of Clinical Neuropsychology on test security.

To provide education regarding the critical importance of test security for neuropsychological and psychological tests, and to establish recommendations for best practices for maintaining test security in forensic, clinical, teaching, and research settings. Previous test security guidelines were not adequately specified. METHOD: Neuropsychologists practicing in a broad range of settings collaborated to develop detailed and specific guidance regarding test security to best ensure continued viability of neuropsychological and psychological tests. Implications of failing to maintain test security for both the practice of neuropsychology and for society at large were identified. Types of test data that can be safely disclosed to nonpsychologists are described.Specific procedures can be followed that will minimize risk of invalidating future use of neuropsychological and psychological measures.Clinical neuropsychologists must commit to protecting sensitive neuropsychological and psychological test information from exposure to nonpsychologists, and now have specific recommendations that will guide that endeavor.

Novel insights into peptide amidation and amidating activity in the human circulation.

C-terminal α-amidation is the final and essential step in the biosynthesis of several peptide hormones. Peptidylglycine α-amidating monooxygenase (PAM) is the only known enzyme to catalyse this reaction. PAM amidating activity (AMA) is known to be present in human circulation, but its physiological role and significance as a clinical biomarker remains unclear. We developed a PAM-specific amidation assay that utilizes the naturally occurring substrate Adrenomedullin-Gly (ADM-Gly, 1-53). Using our amidation assay we quantified serum amidating activities in a large population-based cohort of more than 4900 individuals. A correlation of serum amidating activity with several clinical parameters including high blood pressure was observed. Increasing PAM-AMA was an independent predictor of hard outcomes related to hemodynamic stress such as cardiovascular mortality, atrial fibrillation and heart failure during long-term follow-up (8.8 ± 2.5 years). Moreover, results from an animal study in rats utilizing recombinant human PAM provide novel insights into the physiological role of circulating PAM and show its potential significance in circulating peptide amidation.

Ultra-broadband SPDC for spectrally far separated photon pairs.

Photon pairs from spontaneous parametric down-conversion (SPDC) are important for a wide range of quantum optics experiments with spectral properties such as their bandwidths often being a crucial concern. Here we show the generic existence of particular phase-matching conditions in quasi-phase-matched KTP, MgO:LN, and SLT crystals that lead to ultra-broadband, widely nondegenerate photon pairs. It is based on the existence of group-velocity-matched, far apart wavelength pairs and, for 2 mm long crystals, results in SPDC bandwidths between 15 and 25 THz for photon pairs with the idler photon in the technologically relevant mid-IR range of 3-5 µm and the signal photon in the near-IR below 1100 nm. We experimentally demonstrate this type of broadband phase matching in ppKTP crystals for photon pairs centered at 800 and 3800 nm and measure a bandwidth of 15 THz. This novel method of generating broadband photon pairs will be highly beneficial for SPDC-based imaging, spectroscopy, refractometry, and optical coherence tomography with undetected mid-IR photons.

A novel and highly efficient purification procedure for native human dipeptidyl peptidase 3 from human blood cell lysate.

Dipeptidyl amino-peptidase 3 (DPP3) is an aminopeptidase involved in peptide degradation, including hormone peptides as angiotensin II and enkephalins. DPP3 plasma activity increases in septic patients and correlates with mortality risk. However, the exact physiological role of DPP3 remains unclear and animal studies are necessary to reveal the function of DPP3 in vivo. To this demand, we developed a two-step purification procedure for isolation of native human DPP3 from blood cell lysate (BCL) that is suitable for in vivo applications. With the use of monoclonal antibodies coupled to beads in combination with an ion-exchange chromatography, we recovered 68% of human DPP3 activity from BCL with a purity of ≥ 95%. Purified human DPP3 was assayed for activity and protein concentration using recently published DPP3-activity- and immunoassays. Additionally, protein stability and storage in relevant buffers were tested. Our results provide a promising strategy for fast and efficient isolation of human DPP3. The purified human DPP3 represents the native state of DPP3, suitable for future in vivo applications to investigate the physiological role of DPP3 and its involvement in pathophysiological conditions.

Reconstitution of Molybdoenzymes with Bis-Molybdopterin Guanine Dinucleotide Cofactors.

Molybdoenzymes are ubiquitous and play important roles in all kingdoms of life. The cofactors of these enzymes comprise the metal, molybdenum (Mo), which is bound to a special organic ligand system called molybdopterin (MPT). Additional small ligands are present at the Mo atom, including water, hydroxide, oxo-, sulfido-, or selenido-functionalities, and in some enzymes, amino acid ligand, such as serine, aspartate, cysteine, or selenocysteine that coordinate the cofactor to the peptide chain of the enzyme. The so-called molybdenum cofactor (Moco) is deeply buried within the protein at the end of a narrow funnel, giving access only to the substrate. In 1974, an assay was developed by Nason and coworkers using the pleiotropic Neurospora crassa mutant, nit-1, for the reconstitution of molybdoenzyme activities from crude extracts. These studies have led to the understanding that Moco is the common element in all molybdoenzymes from different organisms. The assay has been further developed since then by using specific molybdenum enzymes as the source of Moco for the reconstitution of diverse purified apo-molybdoenzymes. Alternatively, the molybdenum cofactor can be synthesized in vitro from stable intermediates and subsequently inserted into apo-molybdoenzymes with the assistance of specific Moco-binding chaperones. A general working protocol is described here for the insertion of the bis-molybdopterin guanine dinucleotide cofactor (bis-MGD) into its target molybdoenzyme using the example of Escherichia coli trimethylamine N-oxide (TMAO) reductase.

Functional Studies on Oligotropha carboxidovorans Molybdenum-Copper CO Dehydrogenase Produced in Escherichia coli.

The Mo/Cu-dependent CO dehydrogenase (CODH) from Oligotropha carboxidovorans is an enzyme that is able to catalyze both the oxidation of CO to CO2 and the oxidation of H2 to protons and electrons. Despite the close to atomic resolution structure (1.1 Å), significant uncertainties have remained with regard to the reaction mechanism of substrate oxidation at the unique Mo/Cu center, as well as the nature of intermediates formed during the catalytic cycle. So far, the investigation of the role of amino acids at the active site was hampered by the lack of a suitable expression system that allowed for detailed site-directed mutagenesis studies at the active site. Here, we report on the establishment of a functional heterologous expression system of O. carboxidovorans CODH in Escherichia coli. We characterize the purified enzyme in detail by a combination of kinetic and spectroscopic studies and show that it was purified in a form with characteristics comparable to those of the native enzyme purified from O. carboxidovorans. With this expression system in hand, we were for the first time able to generate active-site variants of this enzyme. Our work presents the basis for more detailed studies of the reaction mechanism for CO and H2 oxidation of Mo/Cu-dependent CODHs in the future.

Modulating the Molybdenum Coordination Sphere of Escherichia coli Trimethylamine N-Oxide Reductase.

The well-studied enterobacterium Escherichia coli present in the human gut can reduce trimethylamine N-oxide (TMAO) to trimethylamine during anaerobic respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor-containing enzyme that belongs to the dimethyl sulfoxide reductase family of molybdoenzymes. We report on a system for the in vitro reconstitution of TorA with molybdenum cofactors (Moco) from different sources. Higher TMAO reductase activities for TorA were obtained when using Moco sources containing a sulfido ligand at the molybdenum atom. For the first time, we were able to isolate functional bis-MGD from Rhodobacter capsulatus formate dehydrogenase (FDH), which remained intact in its isolated state and after insertion into apo-TorA yielded a highly active enzyme. Combined characterizations of the reconstituted TorA enzymes by electron paramagnetic resonance spectroscopy and direct electrochemistry emphasize that TorA activity can be modified by changes in the Mo coordination sphere. The combination of these results together with studies of amino acid exchanges at the active site led us to propose a novel model for binding of the substrate to the molybdenum atom of TorA.

Neuropsychologist Experts and Civil Capacity Evaluations: Representative Cases.

Clinical neuropsychologists accept more forensic referrals now and spend more time in forensic consulting than ever before. Recent surveys show weekly hours devoted to forensic consulting increased 97% in the past decade. During the same time period, the number of board certified neuropsychologists more than doubled. Under recently published Specialty Guidelines for Forensic Psychology, clinical neuropsychologists practice forensic psychology when applying scientific, technical, or specialized knowledge of neuropsychology to the law to assist in addressing legal, contractual, or administrative matters. Among those increasingly varied forensic referrals, clinical neuropsychologists are conducting more civil competency and capacity evaluations. Representative cases from three jurisdictions demonstrate how neuropsychologists provide expertize in matters involving testamentary capacity, contractual capacity, business judgments, and job capacity. Case presentations illustrate some of the strengths and weaknesses of neuropsychological evaluation of civil capacities. The article concludes with a "battle of experts" case involving five neuropsychologists with opposing opinions recently heard in a Federal Appellate court. Implications for neuropschology training and forensic competencies are considered. In offering quality services to the legal profession, neuropsychologists support the truth-seeking function of the judiciary, promote justice, protect the profession, and serve public policy.

[Religious/spiritual well-being in mentally ill persons III: first results of a body-centered awareness meditation for in-patient rehabilitation]. / Religiös/Spirituelles Befinden bei psychisch Kranken III: Erste Ergebnisse einer Körper-zentrierten Achtsamkeitsmeditation in der stationären Rehabilitation.

OBJECTIVE: In recent years, positive effects of religiosity and spirituality on mental health can be found as well documented in the literature. However, very few studies have examined the effects of a spiritually based therapeutic intervention among psychiatric patients. METHOD: For this reason, in this pilot study we examined the effectiveness of a morning body-centered meditation in comparison to a conventional morning walk in regards to subjective well-being and stress coping styles in 44 (26 females) randomly assigned psychiatric in-patients (according to ICD 10). The patients' amount of subjective well-being as well as their coping ability was assessed at the beginning and at the end of a 6 weeks therapy. RESULTS: Thereby we found a significant increase in Religious/Spiritual Well-Being, Awareness and more adequate Coping strategies. This was paralleled by a decrease of psychiatric symptoms. Overall the general assumption of a positive association between spirituality and mental health was affirmed. However, we did not find any differences between the two treatment methods (meditation vs. morning walk). CONCLUSIONS: Both interventions showed the same positive efficacy. Based on these initial results, possibilities and boundaries for the integration of religious/spiritual issues into the treatment of psychiatric patients are discussed.

Neuropsychologist experts and neurolaw: cases, controversies, and admissibility challenges.

Clinical neuropsychologists engage increasingly in forensic consulting activities because such expert opinions are generally relevant, reliable and helpful in resolving certain legal claims, especially those related to traumatic brain injury. Consequently, practitioners of law, medicine and psychology would benefit from understanding the nature of neuropsychological evidence, the standards for its admissibility, and its expanding role in neurolaw. This article reviews important evidentiary rules regulating relevance, preliminary questions, and expert testimony, while tracing federal key court decisions and progeny. Civil and criminal cases are detailed to illustrate the application of these rules and case law to neuropsychological evidence, with suggestions for overcoming motions to exclude such evidence. Expert neuropsychologists have a role in forensic consultation on brain trauma cases, even as the interdisciplinary dialog and understanding among law, medicine, and psychology continues to expand.

Identification of a bis-molybdopterin intermediate in molybdenum cofactor biosynthesis in Escherichia coli.

The molybdenum cofactor is an important cofactor, and its biosynthesis is essential for many organisms, including humans. Its basic form comprises a single molybdopterin (MPT) unit, which binds a molybdenum ion bearing three oxygen ligands via a dithiolene function, thus forming Mo-MPT. In bacteria, this form is modified to form the bis-MPT guanine dinucleotide cofactor with two MPT units coordinated at one molybdenum atom, which additionally contains GMPs bound to the terminal phosphate group of the MPTs (bis-MGD). The MobA protein catalyzes the nucleotide addition to MPT, but the mechanism of the biosynthesis of the bis-MGD cofactor has remained enigmatic. We have established an in vitro system for studying bis-MGD assembly using purified compounds. Quantification of the MPT/molybdenum and molybdenum/phosphorus ratios, time-dependent assays for MPT and MGD detection, and determination of the numbers and lengths of Mo-S and Mo-O bonds by X-ray absorption spectroscopy enabled identification of a novel bis-Mo-MPT intermediate on MobA prior to nucleotide attachment. The addition of Mg-GTP to MobA loaded with bis-Mo-MPT resulted in formation and release of the final bis-MGD product. This cofactor was fully functional and reconstituted the catalytic activity of apo-TMAO reductase (TorA). We propose a reaction sequence for bis-MGD formation, which involves 1) the formation of bis-Mo-MPT, 2) the addition of two GMP units to form bis-MGD on MobA, and 3) the release and transfer of the mature cofactor to the target protein TorA, in a reaction that is supported by the specific chaperone TorD, resulting in an active molybdoenzyme.

tRNA concentration fine tunes protein solubility.

Clusters of codons pairing to low-abundance tRNAs synchronize the translation with co-translational folding of single domains in multidomain proteins. Although proven with some examples, the impact of the ribosomal speed on the folding and solubility on a global, cell-wide level remains elusive. Here we show that upregulation of three low-abundance tRNAs in Escherichia coli increased the aggregation propensity of several cellular proteins as a result of an accelerated elongation rate. Intriguingly, alterations in the concentration of the natural tRNA pool compromised the solubility of various chaperones consequently rendering the solubility of some chaperone-dependent proteins.