Screening for novel protein-protein interactions in living human cells with the help of the split-ubiquitin system

Master'sMASTER OF SCIENC

Meeting the 24-h Movement Guidelines and Health-Related Outcomes Among Youth With Autism Spectrum Disorder: A Seven-Country Observational Study

Background: Meeting daily guidelines for physical activity, screen time, and sleep duration is associated with a host of health indicators for youth. In this cross-sectional observational study, we investigated the associations between adherence to the movement guidelines and health-related outcomes among youth with autism spectrum disorder (ASD). Methods: Parents of youth with ASD (10-17 years) from seven countries and regions were invited to provide online proxy-reports for child\u27s movement behaviors (i.e., physical activity, sleep and screen time), and health-related outcomes (i.e., body mass index [BMI], general health, and quality of life). A series of multiple linear regression analyses were used to examine the associations between meeting movement guidelines and health-related outcomes, adjusted for covariates. Results: The final sample consisted of 1165 youth with ASD. Compared with youth meeting all three guidelines, a higher BMI z-score was observed in those who met no guidelines (B = 0.62, P = 0.04), sedentary time only (B = 0.60, P = 0.047), and physical activity plus sleep only (B = 0.85, P = 0.04). Compared with meeting all three guidelines, meeting no guidelines was associated with poorer general health (B = - 0.46, P = 0.02). Further, compared with youth meeting all three guidelines, a lower quality of life score was observed in those who met no guidelines (B = - 0.47, P = 0.02) and physical activity only (B = - 0.62, P = 0.03). Lastly, there were dose-response associations between the number of guidelines met and all three health-related outcomes (all P(trend) \u3c 0.05). Conclusions: In conclusion, meeting more 24-h movement guidelines was generally associated with more favorable health-related outcomes in youth with ASD. The low level of adherence to all three guidelines (2.0%) suggests the urgent need to promote the adoption of all the guidelines in this group

Survey of laboratory practices for diagnosis of fungal infection in seven Asian countries: An Asia Fungal Working Group (AFWG) initiative

An online survey of mycology laboratories in seven Asian countries was conducted to assess the status, competence, and services available. Country representatives from the Asia Fungal Working Group (AFWG) contacted as many laboratories performing mycology diagnosis as possible in their respective countries, requesting that the laboratory heads complete the online survey. In total, 241 laboratories responded, including 71 in China, 104 in India, 11 in Indonesia, 26 in the Philippines, four in Singapore, 18 in Taiwan, and seven in Thailand. Overall, 129/241 (53.5%) surveyed mycology laboratories operate as separate designated mycology laboratories, 75/241 (31.1%) conduct regular formal staff training, 103/241 (42.7%) are accredited, and 88/157 (56.1%) participate in external quality assurance scheme (EQAS) programs. Microscopy and culture methods are available in nearly all laboratories, although few perform DNA sequencing (37/219; 16.9%) or use matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) (27/219; 12.3%) for isolate identification. Antifungal susceptibility testing is performed in 142/241 (58.9%) laboratories, mainly for yeasts. The most commonly performed nonculture diagnostic is cryptococcal antigen testing (66 laboratories), followed by galactomannan testing (55), polymerase chain reaction (PCR) diagnosis (37), and beta-D-glucan testing (24). Therapeutic drug monitoring is conducted in 21 laboratories. There is almost no access to advanced diagnostic tests, like galactomannan, β-D-glucan, and PCR, in the surveyed laboratories in Indonesia, the Philippines, and Thailand. These results highlight the need for development of quality laboratories, accreditation and training of manpower in existing laboratories, and access to advanced non–culture-based diagnostic tests to facilitate the diagnosis of fungal infections in Asia

Clinicians’ challenges in managing patients with invasive fungal diseases in seven Asian countries: An Asia Fungal Working Group(AFWG) Survey

Background: Invasive fungal diseases (IFD) are a serious threat, but physicians in Asia lack access to many advanced diagnostics in mycology. It is likely that they face other impediments in the management of IFD. A gap analysis was performed to understand the challenges Asian physicians faced in medical mycology. Methods: The Asia Fungal Working Group (AFWG) conducted a web-based survey on management practices for IFD among clinicians in China, India, Indonesia, Philippines, Singapore, Taiwan and Thailand. Findings: Among 292 respondents, 51.7% were infectious disease (ID) specialists. Only 37% of respondents had received formal training in medical mycology. They handled only around 2–4 proven cases of each fungal infection monthly, with invasive candidiasis the most common. For laboratory support, the majority had access to direct microscopy (96%) and histopathology (87%), but galactomannan and azole levels were available to 60% and 25% of respondents, respectively. The majority (84%) used clinical parameters for treatment response monitoring, and 77% followed the Infectious Diseases Society of America guidelines. The majority (84%) did not use the services of an ID physician. Where febrile neutropenia was concerned, 74% of respondents used the empirical approach. Only 30% had an antifungal stewardship program in their hospital. Eighty percent could not use preferred antifungals because of cost. Interpretation: The survey identified inadequacies in medical mycology training, non-culture diagnostics, access to antifungal drugs, and local guidelines as the major gaps in the management of IFDs in Asian countries. These gaps are targets for improvement

Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity

BACKGROUND Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. FINDINGS Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. INTERPRETATION IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs)

An Earth-mass planet in a time of COVID-19: KMT-2020-BLG-0414Lb

We report the discovery of KMT-2020-BLG-0414Lb, with a planet-to-host mass ratio q2 = 0:9- 1:2 × 10-5 = 3-4 q⊕ at 1σ, which is the lowest mass-ratio microlensing planet to date. Together with two other recent discoveries (4. q=q⊕. 6), it fills out the previous empty sector at the bottom of the triangular (log s; log q) diagram, where s is the planet-host separation in units of the angular Einstein radius θE. Hence, these discoveries call into question the existence, or at least the strength, of the break in the mass-ratio function that was previously suggested to account for the paucity of very low-q planets. Due to the extreme magnification of the event, Amax ∼ 1450 for the underlying single-lens event, its light curve revealed a second companion with q3 ∼ 0:05 and j log s3j ∼ 1, i.e., a factor ∼ 10 closer to or farther from the host in projection. The measurements of the microlens parallax ∼E and the angular Einstein radius ∼E allow estimates of the host, planet and second companion masses, (M1;M2;M3) ∼ (0:3M⊙; 1:0M⊙; 17MJ ), the planet and second companion projected separations, (a⊥;2; a⊥;3) ∼ (1:5; 0:15 or 15) au, and system distance DL ∼ 1 kpc. The lens could account for most or all of the blended light (I ∼ 19:3) and so can be studied immediately with high-resolution photometric and spectroscopic observations that can further clarify the nature of the system. The planet was found as part of a new program of high-cadence follow-up observations of high-magnification events. The detection of this planet, despite the considerable difficulties imposed by COVID-19 (two KMT sites and OGLE were shut down), illustrates the potential utility of this program

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Multiphoton Quantum Optics and Quantum State Engineering

We present a review of theoretical and experimental aspects of multiphoton quantum optics. Multiphoton processes occur and are important for many aspects of matter-radiation interactions that include the efficient ionization of atoms and molecules, and, more generally, atomic transition mechanisms; system-environment couplings and dissipative quantum dynamics; laser physics, optical parametric processes, and interferometry. A single review cannot account for all aspects of such an enormously vast subject. Here we choose to concentrate our attention on parametric processes in nonlinear media, with special emphasis on the engineering of nonclassical states of photons and atoms. We present a detailed analysis of the methods and techniques for the production of genuinely quantum multiphoton processes in nonlinear media, and the corresponding models of multiphoton effective interactions. We review existing proposals for the classification, engineering, and manipulation of nonclassical states, including Fock states, macroscopic superposition states, and multiphoton generalized coherent states. We introduce and discuss the structure of canonical multiphoton quantum optics and the associated one- and two-mode canonical multiphoton squeezed states. This framework provides a consistent multiphoton generalization of two-photon quantum optics and a consistent Hamiltonian description of multiphoton processes associated to higher-order nonlinearities. Finally, we discuss very recent advances that by combining linear and nonlinear optical devices allow to realize multiphoton entangled states of the electromnagnetic field, that are relevant for applications to efficient quantum computation, quantum teleportation, and related problems in quantum communication and information.Comment: 198 pages, 36 eps figure

Meeting the 24-hour movement guidelines and health-related outcomes among youth with autism spectrum disorder: a seven-country observational study

Background: Meeting daily guidelines for physical activity, screen time, and sleep duration is associated with a host of health indicators for youth. In this cross-sectional observational study, we investigated the associations between adherence to the movement guidelines and health-related outcomes among youth with autism spectrum disorder (ASD).Methods: Parents of youth with ASD (10–17 years) from seven countries and regions were invited to provide online proxy-reports for child’s movement behaviors (i.e., physical activity, sleep and screen time), and health-related outcomes (i.e., body mass index [BMI], general health, and quality of life). A series of multiple linear regression analyses were used to examine the associations between meeting movement guidelines and health-related outcomes, adjusted for covariates.Results: The final sample consisted of 1165 youth with ASD. Compared with youth meeting all three guidelines, a higher BMI z-score was observed in those who met no guidelines (B = 0.62, P = 0.04), “sedentary time only” (B = 0.60, P = 0.047), and “physical activity plus sleep only” (B = 0.85, P = 0.04). Compared with meeting all three guidelines, meeting no guidelines was associated with poorer general health (B = − 0.46, P = 0.02). Further, compared with youth meeting all three guidelines, a lower quality of life score was observed in those who met no guidelines (B = − 0.47, P = 0.02) and “physical activity only” (B = − 0.62, P = 0.03). Lastly, there were dose–response associations between the number of guidelines met and all three health-related outcomes (all Ptrend Conclusions: In conclusion, meeting more 24-h movement guidelines was generally associated with more favorable health-related outcomes in youth with ASD. The low level of adherence to all three guidelines (2.0%) suggests the urgent need to promote the adoption of all the guidelines in this group.</p

Epigenetic Analysis of KSHV Latent and Lytic Genomes

Epigenetic modifications of the herpesviral genome play a key role in the transcriptional control of latent and lytic genes during a productive viral lifecycle. In this study, we describe for the first time a comprehensive genome-wide ChIP-on-Chip analysis of the chromatin associated with the Kaposi's sarcoma-associated herpesvirus (KSHV) genome during latency and lytic reactivation. Depending on the gene expression class, different combinations of activating [acetylated H3 (AcH3) and H3K4me3] and repressive [H3K9me3 and H3K27me3] histone modifications are associated with the viral latent genome, which changes upon reactivation in a manner that is correlated with their expression. Specifically, both the activating marks co-localize on the KSHV latent genome, as do the repressive marks. However, the activating and repressive histone modifications are mutually exclusive of each other on the bulk of the latent KSHV genome. The genomic region encoding the IE genes ORF50 and ORF48 possesses the features of a bivalent chromatin structure characterized by the concomitant presence of the activating H3K4me3 and the repressive H3K27me3 marks during latency, which rapidly changes upon reactivation with increasing AcH3 and H3K4me3 marks and decreasing H3K27me3. Furthermore, EZH2, the H3K27me3 histone methyltransferase of the Polycomb group proteins (PcG), colocalizes with the H3K27me3 mark on the entire KSHV genome during latency, whereas RTA-mediated reactivation induces EZH2 dissociation from the genomic regions encoding IE and E genes concurrent with decreasing H3K27me3 level and increasing IE/E lytic gene expression. Moreover, either the inhibition of EZH2 expression by a small molecule inhibitor DZNep and RNAi knockdown, or the expression of H3K27me3-specific histone demethylases apparently induced the KSHV lytic gene expression cascade. These data indicate that histone modifications associated with the KSHV latent genome are involved in the regulation of latency and ultimately in the control of the temporal and sequential expression of the lytic gene cascade. In addition, the PcG proteins play a critical role in the control of KSHV latency by maintaining a reversible heterochromatin on the KSHV lytic genes. Thus, the regulation of the spatial and temporal association of the PcG proteins with the KSHV genome may be crucial for propagating the KSHV lifecycle