Interactome Screening Identifies the ER Luminal Chaperone Hsp47 as a Regulator of the Unfolded Protein Response Transducer IRE1α.

Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cellular and biochemical analysis indicated that Hsp47 instigates IRE1α signaling through a physical interaction. Hsp47 directly binds to the ER luminal domain of IRE1α with high affinity, displacing the negative regulator BiP from the complex to facilitate IRE1α oligomerization. The regulation of IRE1α signaling by Hsp47 is evolutionarily conserved as validated using fly and mouse models of ER stress. Hsp47 deficiency sensitized cells and animals to experimental ER stress, revealing the significance of Hsp47 to global proteostasis maintenance. We conclude that Hsp47 adjusts IRE1α signaling by fine-tuning the threshold to engage an adaptive UPR.

Cardiac sympathetic-vagal activity initiates a functional brain-body response to emotional arousal.

A century-long debate on bodily states and emotions persists. While the involvement of bodily activity in emotion physiology is widely recognized, the specificity and causal role of such activity related to brain dynamics has not yet been demonstrated. We hypothesize that the peripheral neural control on cardiovascular activity prompts and sustains brain dynamics during an emotional experience, so these afferent inputs are processed by the brain by triggering a concurrent efferent information transfer to the body. To this end, we investigated the functional brain­heart interplay under emotion elicitation in publicly available data from 62 healthy subjects using a computational model based on synthetic data generation of electroencephalography and electrocardiography signals. Our findings show that sympathovagal activity plays a leading and causal role in initiating the emotional response, in which ascending modulations from vagal activity precede neural dynamics and correlate to the reported level of arousal. The subsequent dynamic interplay observed between the central and autonomic nervous systems sustains the processing of emotional arousal. These findings should be particularly revealing for the psychophysiology and neuroscience of emotions.

Intracortical brain-heart interplay: An EEG model source study of sympathovagal changes.

The interplay between cerebral and cardiovascular activity, known as the functional brain-heart interplay (BHI), and its temporal dynamics, have been linked to a plethora of physiological and pathological processes. Various computational models of the brain-heart axis have been proposed to estimate BHI non-invasively by taking advantage of the time resolution offered by electroencephalograph (EEG) signals. However, investigations into the specific intracortical sources responsible for this interplay have been limited, which significantly hampers existing BHI studies. This study proposes an analytical modeling framework for estimating the BHI at the source-brain level. This analysis relies on the low-resolution electromagnetic tomography sources localization from scalp electrophysiological recordings. BHI is then quantified as the functional correlation between the intracortical sources and cardiovascular dynamics. Using this approach, we aimed to evaluate the reliability of BHI estimates derived from source-localized EEG signals as compared with prior findings from neuroimaging methods. The proposed approach is validated using an experimental dataset gathered from 32 healthy individuals who underwent standard sympathovagal elicitation using a cold pressor test. Additional resting state data from 34 healthy individuals has been analysed to assess robustness and reproducibility of the methodology. Experimental results not only confirmed previous findings on activation of brain structures affecting cardiac dynamics (e.g., insula, amygdala, hippocampus, and anterior and mid-cingulate cortices) but also provided insights into the anatomical bases of brain-heart axis. In particular, we show that the bidirectional activity of electrophysiological pathways of functional brain-heart communication increases during cold pressure with respect to resting state, mainly targeting neural oscillations in the δ $$ \delta $$ , ß $$ \beta $$ , and γ $$ \gamma $$ bands. The proposed approach offers new perspectives for the investigation of functional BHI that could also shed light on various pathophysiological conditions.

A framework for quantifying the coupling between brain connectivity and heartbeat dynamics: Insights into the disrupted network physiology in Parkinson's disease.

Parkinson's disease (PD) often shows disrupted brain connectivity and autonomic dysfunctions, progressing alongside with motor and cognitive decline. Recently, PD has been linked to a reduced sensitivity to cardiac inputs, that is, cardiac interoception. Altogether, those signs suggest that PD causes an altered brain-heart connection whose mechanisms remain unclear. Our study aimed to explore the large-scale network disruptions and the neurophysiology of disrupted interoceptive mechanisms in PD. We focused on examining the alterations in brain-heart coupling in PD and their potential connection to motor symptoms. We developed a proof-of-concept method to quantify relationships between the co-fluctuations of brain connectivity and cardiac sympathetic and parasympathetic activities. We quantified the brain-heart couplings from electroencephalogram and electrocardiogram recordings from PD patients on and off dopaminergic medication, as well as in healthy individuals at rest. Our results show that the couplings of fluctuating alpha and gamma connectivity with cardiac sympathetic dynamics are reduced in PD patients, as compared to healthy individuals. Furthermore, we show that PD patients under dopamine medication recover part of the brain-heart coupling, in proportion with the reduced motor symptoms. Our proposal offers a promising approach to unveil the physiopathology of PD and promoting the development of new evaluation methods for the early stages of the disease.

Multidimensional assessment of heartbeat-evoked responses in disorders of consciousness.

Because consciousness does not necessarily translate into overt behaviour, detecting residual consciousness in noncommunicating patients remains a challenge. Bedside diagnostic methods based on EEG are promising and cost-effective alternatives to detect residual consciousness. Recent evidence showed that the cortical activations triggered by each heartbeat, namely, heartbeat-evoked responses (HERs), can detect through machine learning the presence of minimal consciousness and distinguish between overt and covert minimal consciousness. In this study, we explore different markers to characterize HERs to investigate whether different dimensions of the neural responses to heartbeats provide complementary information that is not typically found under standard event-related potential analyses. We evaluated HERs and EEG average non-locked to heartbeats in six types of participants: healthy state, locked-in syndrome, minimally conscious state, vegetative state/unresponsive wakefulness syndrome, comatose and brain-dead patients. We computed a series of markers from HERs that can generally separate the unconscious from the conscious. Our findings indicate that HER variance and HER frontal segregation tend to be higher in the presence of consciousness. These indices, when combined with heart rate variability, have the potential to enhance the differentiation between different levels of awareness. We propose that a multidimensional evaluation of brain-heart interactions could be included in a battery of tests to characterize disorders of consciousness. Our results may motivate further exploration of markers in brain-heart communication for the detection of consciousness at the bedside. The development of diagnostic methods based on brain-heart interactions may be translated into more feasible methods for clinical practice.

Dynamic fluctuations in ascending heart-to-brain communication under mental stress.

Dynamical information exchange between central and autonomic nervous systems, as referred to functional brain-heart interplay, occurs during emotional and physical arousal. It is well documented that physical and mental stress lead to sympathetic activation. Nevertheless, the role of autonomic inputs in nervous system-wise communication under mental stress is yet unknown. In this study, we estimated the causal and bidirectional neural modulations between electroencephalogram (EEG) oscillations and peripheral sympathetic and parasympathetic activities using a recently proposed computational framework for a functional brain-heart interplay assessment, namely the sympathovagal synthetic data generation model. Mental stress was elicited in 37 healthy volunteers by increasing their cognitive demands throughout three tasks associated with increased stress levels. Stress elicitation induced an increased variability in sympathovagal markers, as well as increased variability in the directional brain-heart interplay. The observed heart-to-brain interplay was primarily from sympathetic activity targeting a wide range of EEG oscillations, whereas variability in the efferent direction seemed mainly related to EEG oscillations in the γ band. These findings extend current knowledge on stress physiology, which mainly referred to top-down neural dynamics. Our results suggest that mental stress may not cause an increase in sympathetic activity exclusively as it initiates a dynamic fluctuation within brain-body networks including bidirectional interactions at a brain-heart level. We conclude that directional brain-heart interplay measurements may provide suitable biomarkers for a quantitative stress assessment and bodily feedback may modulate the perceived stress caused by increased cognitive demand.

Factor structure of the 10-item CES-D Scale among patients with persistent COVID-19.

The presence of persistent coronavirus disease 2019 (COVID-19) might be associated with significant levels of psychological distress that would meet the threshold for clinical relevance. The Center for Epidemiologic Studies Depression Scale (CES-D) version 10 has been widely used in assessing psychological distress among general and clinical populations from different cultural backgrounds. To our knowledge, however, researchers have not yet validated these findings among patients with persistent COVID-19. A cross-sectional validation study was conducted with 100 patients from the EXER-COVID project (69.8% women; mean (±standard deviation) ages: 47.4 ± 9.5 years). Confirmatory factor analyses (CFAs) were performed on the 10-item CES-D to test four model fits: (a) unidimensional model, (b) two-factor correlated model, (c) three-factor correlated model, and (d) second-order factor model. The diagonal-weighted least-squares estimator was used, as it is commonly applied to latent variable models with ordered categorical variables. The reliability indices of the 10-item CES-D in patients with persistent COVID-19 were as follows: depressive affect factor ( α Ord = 0 . 82 ${\alpha }_{\mathrm{Ord}}=0.82$ ; ω u - cat = 0 . 78 ${\omega }_{{\rm{u}}-\mathrm{cat}}=0.78$ ), somatic retardation factor ( α Ord = 0 . 78 ${\alpha }_{\mathrm{Ord}}=0.78$ ; ω u - cat = 0 . 56 ${\omega }_{{\rm{u}}-\mathrm{cat}}=0.56$ ), and positive affect factor ( α Ord = 0 . 56 ${\alpha }_{\mathrm{Ord}}=0.56$ ; ω u - cat = 0 . 55 ${\omega }_{{\rm{u}}-\mathrm{cat}}=0.55$ ). The second-order model fit showed good Omega reliability ( ω ho = 0 . 87 ${\omega }_{\mathrm{ho}}=0.87$ ). Regarding CFAs, the unidimensional-factor model shows poor goodness of fit, especially residuals analysis (root mean square error of approximation [RMSEA] = 0.081 [95% confidence interval, CI = 0.040-0.119]; standardized root mean square residual [SRMR] = 0.101). The two-factor correlated model, three-factor correlated model, and second-order factor model showed adequate goodness of fit, and the χ2 difference test ( ∆ X 2 $\unicode{x02206}{X}^{2}$ ) did not show significant differences between the goodness of fit for these models ( ∆ X 2 = 4.1128 $\unicode{x02206}{X}^{2}=4.1128$ ; p = 0.127). Several indices showed a good fit with the three-factor correlated model: goodness-of-fit index = 0.974, comparative fit index = 0.990, relative noncentrality index = 0.990, and incremental fit index = 0.990, which were all above 0.95, the traditional cut-off establishing adequate fit. On the other hand, RMSEA = 0.049 (95% CI = 0.000-0.095), where an RMSEA < 0.06-0.08 indicates an adequate fit. Item loadings on the factors were statistically significant ( λ j ≥ 0.449 ${\lambda }_{j}\ge 0.449$ ; p's < 0.001), indicating that the items loaded correctly on the corresponding factors and the relationship between factors ( ϕ ≥ 0.382 $\phi \ge 0.382$ ; p's ≤ 0.001. To our knowledge, this is the first study to provide validity and reliability to 10-item CES-D in a persistent COVID-19 Spanish patient sample. The validation and reliability of this short screening tool allow us to increase the chance of obtaining complete data in a particular patient profile with increased fatigue and brain fog that limit patients' capacity to complete questionnaires.

Putative intestinal permeability markers do not correlate with cardiometabolic health and gut microbiota in humans, except for peptides recognized by a widely used zonulin ELISA kit.

BACKGROUND AND AIMS: Cardiometabolic diseases refer to a group of interrelated conditions, sharing metabolic dysfunctions like insulin resistance, obesity, dyslipidemia, and hypertension. The gut microbiota has been associated with CMD and related conditions. Alterations in the intestinal epithelium permeability triggered by chronic stress and diet could bridge gut microbiota with inflammation and CMD development. Here, we assessed the relationship between intestinal permeability and circulating SCFAs with cardiometabolic health status (CMHS) and gut microbiota in a sample of 116 Colombian adults. METHODS AND RESULTS: Plasma levels of lipopolysaccharide-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP), claudin-3, and purported zonulin peptides (PZP) were measured by ELISA, whereas plasmatic levels of acetate, propionate, butyrate, isobutyrate, and valerate were measured by gas chromatography/mass spectrometry. In addition, for further statistical analysis, we took data previously published by us on this cohort, including gut microbiota and multiple CMD risk factors that served to categorize subjects as cardiometabolically healthy or cardiometabolically abnormal. From univariate and multivariate statistical analyses, we found the levels of I-FABP, LBP, and PZP increased in the plasma of cardiometabolically abnormal individuals, although only PZP reached statistical significance. CONCLUSIONS: Our results did not confirm the applicability of I-FABP, LBP, claudin-3, or SCFAs as biomarkers for associating intestinal permeability with the cardiometabolic health status in these subjects. On the other hand, the poorly characterized peptides detected with the ELISA kit branded as "zonulin" were inversely associated with cardiometabolic dysfunctions and gut microbiota. Further studies to confirm the true identity of these peptides are warranted.

Phonological and semantic verbal fluency test: Scoring criteria and normative data for clustering and switching strategies for Colombian children and adolescents.

BACKGROUND: Verbal fluency tests (VFT) are highly sensitive to cognitive deficits. Usually, the score on VFT is based on the number of correct words produced, yet it alone gives little information regarding underlying test performance. The implementation of different strategies (cluster and switching) to perform efficiently during the tasks provide more valuable information. However, normative data for clustering and switching strategies are scarce. Moreover, scoring criteria adapted to Colombian Spanish are missing. AIMS: (1) To describe the Colombian adaptation of the scoring system guidelines for clustering and switching strategies in VFT; (2) to determine its reliability; and (3) to provide normative data for Colombian children and adolescents aged 6-17 years. METHODS & PROCEDURES: A total of 691 children and adolescents from Colombia completed phonological (/f/, /a/, /s/, /m/, /r/ and /p/) and semantic (animals and fruits) VFT, and five scores were calculated: total score (TS), number of clusters (NC), cluster size (CS), mean cluster size (MCS) and number of switches (NS). The intraclass correlation coefficient was used for interrater reliability. Hierarchical multiple regressions were conducted to investigate which strategies were associated with VFT TS. Multiple regressions were conducted for each strategy, including as predictors age, age2 , sex, mean parents' education (MPE), MPE2 and type of school, to generate normative data. OUTCOMES & RESULTS: Reliability indexes were excellent. Age was associated with VFT TS, but weakly compared with strategies. For both VFT TS, NS was the strongest variable, followed by CS and NC. Regarding norms, age was the strongest predictor for all measures, while age2 was relevant for NC (/f/ phoneme) and NS (/m/ phoneme). Participants with higher MPE obtained more NC, and NS, and larger CS in several phonemes and categories. Children and adolescents from private school generated more NC, NS and larger CS in /s/ phoneme. CONCLUSIONS & IMPLICATIONS: This study provides new scoring guidelines and normative data for clustering and switching strategies for Colombian children and adolescents between 6 and 17 years old. Clinical neuropsychologists should include these measures as part of their everyday practice. WHAT THIS PAPER ADDS: What is already known on the subject VFT are widely used within the paediatric population due to its sensitivity to brain injury. Its score is based on the number of correct words produced; however, TS alone gives little information regarding underlying test performance. Several normative data for VFT TS in the paediatric population exist, but normative data for clustering and switching strategies are scarce. What this paper adds to existing knowledge The present study is the first to describe the Colombian adaptation of the scoring guidelines for clustering and switching strategies, and provided normative data for these strategies for children and adolescents between 6 and 17 years old. What are the potential or actual clinical implications of this work? Knowing VFT's performance, including strategy development and use in healthy children and adolescents, may be useful for clinical settings. We encourage clinicians to include not only TS, but also a careful analysis of strategies that may be more informative of the underlying cognitive processes failure than TS.

Neural Responses to Heartbeats Detect Residual Signs of Consciousness during Resting State in Postcomatose Patients.

The neural monitoring of visceral inputs might play a role in first-person perspective (i.e., the unified viewpoint of subjective experience). In healthy participants, how the brain responds to heartbeats, measured as the heartbeat-evoked response (HER), correlates with perceptual, bodily, and self-consciousness. Here we show that HERs in resting-state EEG data distinguishes between postcomatose male and female human patients (n = 68, split into training and validation samples) with the unresponsive wakefulness syndrome and in patients in a minimally conscious state with high accuracy (random forest classifier, 87% accuracy, 96% sensitivity, and 50% specificity in the validation sample). Random EEG segments not locked to heartbeats were useful to predict unconsciousness/consciousness, but HERs were more accurate, indicating that HERs provide specific information on consciousness. HERs also led to more accurate classification than heart rate variability. HER-based consciousness scores correlate with glucose metabolism in the default-mode network node located in the right superior temporal sulcus, as well as with the right ventral occipitotemporal cortex. These results were obtained when consciousness was inferred from brain glucose met`abolism measured with positron emission topography. HERs reflected the consciousness diagnosis based on brain metabolism better than the consciousness diagnosis based on behavior (Coma Recovery Scale-Revised, 77% validation accuracy). HERs thus seem to capture a capacity for consciousness that does not necessarily translate into intentional overt behavior. These results confirm the role of HERs in consciousness, offer new leads for future bedside testing, and highlight the importance of defining consciousness and its neural mechanisms independently from behavior.

Functional assessment of bidirectional cortical and peripheral neural control on heartbeat dynamics: A brain-heart study on thermal stress.

The study of functional Brain-Heart Interplay (BHI) from non-invasive recordings has gained much interest in recent years. Previous endeavors aimed at understanding how the two dynamical systems exchange information, providing novel holistic biomarkers and important insights on essential cognitive aspects and neural system functioning. However, the interplay between cardiac sympathovagal and cortical oscillations still has much room for further investigation. In this study, we introduce a new computational framework for a functional BHI assessment, namely the Sympatho-Vagal Synthetic Data Generation Model, combining cortical (electroencephalography, EEG) and peripheral (cardiac sympathovagal) neural dynamics. The causal, bidirectional neural control on heartbeat dynamics was quantified on data gathered from 26 human volunteers undergoing a cold-pressor test. Results show that thermal stress induces heart-to-brain functional interplay sustained by EEG oscillations in the delta and gamma bands, primarily originating from sympathetic activity, whereas brain-to-heart interplay originates over central brain regions through sympathovagal control. The proposed methodology provides a viable computational tool for the functional assessment of the causal interplay between cortical and cardiac neural control.

Targeting the vim by direct visualization of the cerebello-thalamo-cortical pathway in 3 T proton density MRI: correlation with focused ultrasound lesioning.

Surgical targeting of the ventral intermediate nucleus of the thalamus (VIM) has been historically done using indirect strategies. Here we depict the cerebello-thalamo-cortical tract (CTCT) through 3 T proton density (PD) in a cohort of patients who underwent high-intensity focus ultrasound (HIFUS) thalamotomy. Forty-seven patients treated in our institution with MR-guided HIFUS VIM thalamotomy were included in this study. PD weighted 3 T MRI used for presurgical planning was compared with postoperative MRI obtained 1 month after surgery. Images were processed with ISTX software (Brain lab, Munich, Germany). The coordinates of the VIM lesion concerning the inter-commissural line (ICL) were annotated. Deterministic tractographies using three ROIs were used to verify the different tracts. The triangle seen in the 3 T PD sequence at the level of the mesencephalic-diencephalic junction was systematically recognized. The posterior angle of this triangle at the junction of the CTCT and the ZI was denominated as "point P." The area of this triangle corresponds to the posterior subthalamic area (PSA) harboring the Raprl fibers. The CTCT was visible from 1 to 2.5 mm below the ICL. The average center of the final HIFUS lesion (point F) was 11 mm from the medial thalamic border of the thalamus (14.9 mm from the midline), 6.4 mm anterior to PC, and 0.6 mm above the ICL. The FUS point was consistently 1-2 mm directly above point P. The anterior border of the external angle of this triangle (point P) can be used as an intraparenchymal point for targeting the ventral border of the VIM. Three ROIs placed in a single slice around this triangle are a fast way to originate tractography of the CTCT, lemniscus medialis, and pyramidal tract.

AFOROS: A Low-Cost Wi-Fi-Based Monitoring System for Estimating Occupancy of Public Spaces.

Estimating the number of people present in a given venue in real-time is extremely useful from a security, management, and resource optimization perspective. This article presents the architecture of a system based on the use of Wi-Fi sensor devices that allows estimating, almost in real-time, the number of people attending an event that is taking place in a venue. The estimate is based on the analysis of the "probe request" messages periodically transmitted by smartphones to determine the existence of Wi-Fi access points in the vicinity. The method considers the MAC address randomization mechanisms introduced in recent years in smartphones, which prevents the estimation of the number of devices by simply counting different MAC addresses. To solve this difficulty, our Wi-Fi sensors analyze other fields present in the header of the IEEE 802.11 frames, the information elements, to extract a unique fingerprint from each smartphone. The designed system was tested in a set of real scenarios, obtaining an estimate of attendance at different public events with an accuracy close to 95%.

An IoT-Focused Intrusion Detection System Approach Based on Preprocessing Characterization for Cybersecurity Datasets.

Security in IoT networks is currently mandatory, due to the high amount of data that has to be handled. These systems are vulnerable to several cybersecurity attacks, which are increasing in number and sophistication. Due to this reason, new intrusion detection techniques have to be developed, being as accurate as possible for these scenarios. Intrusion detection systems based on machine learning algorithms have already shown a high performance in terms of accuracy. This research proposes the study and evaluation of several preprocessing techniques based on traffic categorization for a machine learning neural network algorithm. This research uses for its evaluation two benchmark datasets, namely UGR16 and the UNSW-NB15, and one of the most used datasets, KDD99. The preprocessing techniques were evaluated in accordance with scalar and normalization functions. All of these preprocessing models were applied through different sets of characteristics based on a categorization composed by four groups of features: basic connection features, content characteristics, statistical characteristics and finally, a group which is composed by traffic-based features and connection direction-based traffic characteristics. The objective of this research is to evaluate this categorization by using various data preprocessing techniques to obtain the most accurate model. Our proposal shows that, by applying the categorization of network traffic and several preprocessing techniques, the accuracy can be enhanced by up to 45%. The preprocessing of a specific group of characteristics allows for greater accuracy, allowing the machine learning algorithm to correctly classify these parameters related to possible attacks.

The Family Needs Questionnaire-Revised: a Rasch analysis of measurement properties in the chronic phase after traumatic brain injury.

PURPOSE: The main aim was to evaluate the measurement properties of the Family Needs Questionnaire-Revised (FNQ-R) in family members of individuals living with severe traumatic brain injury (TBI). METHODS: A total of 309 family members of individuals with severe TBI from Colombia, Denmark, Mexico, Norway and Spain participated. Rasch analysis of the FNQ-R and its 6 subscales was conducted. RESULTS: The Rasch analysis indicated a lack of fit of the 37-item FNQ-R to one single underlying construct of needs, and less than half of the items were invariant across the countries. Misfit of single items was revealed in the Need for Health Information, Need for Emotional Support, Need for Instrumental Support, Need for Professional Support and Need for Community Support Network subscales. Fit to the Rasch model was obtained after removal of misfitting items. The Involvement in Care subscale had too few items to be adequately assessed by the Rasch approach. CONCLUSION: The FNQ-R is a well-targeted instrument for assessing the unmet needs of caregivers regarding the need for health information, emotional support, professional support and a community support network after some scoring adjustment and the removal of misfitting items. Caution should be taken when comparing responses across countries.

At the crossroads: can desalination be a suitable public policy solution to address water scarcity in Chile's mining zones?

Water scarcity is a global issue that is threatening social and economic development. One approach to alleviating scarcity is the incorporation of new water sources into supply systems, including desalinated seawater for industrial and municipal use. In Chile, large volumes of water are used in water-scarce regions where mining takes place, alongside agriculture and small communities. This situation has driven a debate around policies to increase the use of seawater to satisfy the water demand of the mining industry. The economic, social and environmental implications of such a policy, however, are poorly understood and the current regulatory framework to address concerns and uncertainties is inadequate. This paper presents a technical, legal, economic and environmental appraisal of such a policy and considers options to improve outcomes. The appraisal suggests that clear regulations derived from economic, social and environmental analysis must be generated to provide legal certainty and reduce risks. Alternative or complementary water supply options should be allowed where mining operations can demonstrate negligible hydrological and social impacts or use innovative solutions such as stakeholder water rights swaps and water efficiency technologies. We provide insight that will help to drive a better policymaking process aimed at tackling water scarcity in Chile and in similar areas of the world.

Integrative genomic analysis by interoperation of bioinformatics tools in GenomeSpace.

Complex biomedical analyses require the use of multiple software tools in concert and remain challenging for much of the biomedical research community. We introduce GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative community resource that currently supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate integrative analysis by non-programmers, it offers a growing set of 'recipes', short workflows to guide investigators through high-utility analysis tasks.

Palladium-Catalyzed Direct α-C(sp3) Heteroarylation of Ketones under Microwave Irradiation.

Heteroaryl compounds are valuable building blocks in medicinal chemistry and chemical industry. A palladium-catalyzed direct α-C(sp3) heteroarylation of ketones under microwave irradiation is developed and reported in this study. Under optimized conditions, twenty-eight (28) heteroarylated ketones were prepared in this study to demonstrate the substrate scope of this reaction. The ground-state optimized structure of Pd(0) active catalyst with 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos) in toluene, and the products of its reaction with 3-bromopyridine and acetophenone were studied using all-atom density functional theory. This study provided insightful information for palladium catalytic system design to generate heteroaryl compounds.