A novel combined scientific and artistic approach for the advanced characterization of interactomes: The akirin/subolesin model

The main objective of this study was to propose a novel methodology to approach challenges in molecular biology. Akirin/Subolesin (AKR/SUB) are vaccine protective antigens and are a model for the study of the interactome due to its conserved function in the regulation of different biological processes such as immunity and development throughout the metazoan. Herein, three visual artists and a music professor collaborated with scientists for the functional characterization of the AKR2 interactome in the regulation of the NF-¿B pathway in human placenta cells. The results served as a methodological proof-of-concept to advance this research area. The results showed new perspectives on unexplored characteristics of AKR2 with functional implications. These results included protein dimerization, the physical interactions with different proteins simultaneously to regulate various biological processes defined by cell type-specific AKR– protein interactions, and how these interactions positively or negatively regulate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-¿B) signaling pathway in a biological context-dependent manner. These results suggested that AKR2-interacting proteins might constitute suitable secondary transcription factors for cell-and stimulus-specific regulation of NF-¿B. Musical perspective supported AKR/SUB evolutionary conservation in different species and provided new mechanistic insights into the AKR2 interactome. The combined scientific and artistic perspectives resulted in a multidisciplinary approach, advancing our knowledge on AKR/SUB interactome, and provided new insights into the function of AKR2–protein interactions in the regulation of the NF-¿B pathway. Additionally, herein we proposed an algorithm for quantum vaccinomics by focusing on the model proteins AKR/SUB. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Relativistic Kramers-Pasternack Recurrence Relations

Recently we have evaluated the matrix elements $$,$where$O$$={1,\beta, i\mathbf{\alpha n}\beta} $are the standard Dirac matrix operators and the angular brackets denote the quantum-mechanical average for the relativistic Coulomb problem, in terms of generalized hypergeometric functions$_{3}F_{2}(1) $ for all suitable powers and established two sets of Pasternack-type matrix identities for these integrals. The corresponding Kramers--Pasternack three-term vector recurrence relations are derived here.Comment: 12 pages, no figures Will appear as it is in Journal of Physics B: Atomic, Molecular and Optical Physics, Special Issue on Hight Presicion Atomic Physic

Triggered crustal earthquake swarm across subduction segment boundary after the 2016 Pedernales, Ecuador megathrust earthquake

Megathrust ruptures and the ensuing postseismic deformation cause stress changes that may induce seismicity on upper plate crustal faults far from the coseismic rupture area. In this study, we analyze seismic swarms that occurred in the north Ecuador area of Esmeraldas, beginning two months after the 2016 M$_{w}$ 7.8 Pedernales, Ecuador megathrust earthquake. The Esmeraldas region is 70 km from the Pedernales rupture area in a separate segment of the subduction zone. We characterize the Esmeraldas sequence, relocating the events using manual arrival time picks and a local a-priori 3D velocity model. The earthquake locations from the Esmeraldas sequence outline an upper plate fault or shear zone. The sequence contains one major swarm and several smaller swarms. Moment tensor solutions of several events include normal and strike-slip motion and non-double-couple components. During the main swarm, earthquake hypocenters increase in distance from the first event over time, at a rate of a few hundred meters per day, consistent with fluid diffusion. Events with similar waveforms occur within the sequence, and a transient is seen in time series of nearby GPS stations concurrent with the seismicity. The events with similar waveforms and the transient in GPS time series suggest that slow aseismic slip took place along a crustal normal fault during the sequence. Coulomb stress calculations show a positive Coulomb stress change in the Esmeraldas region, consistent with seismicity being triggered by the Pedernales mainshock and large aftershocks. The characteristics of the seismicity indicate that postseismic deformation involving fluid flow and slow slip activated upper plate faults in the Esmeraldas area. These findings suggest the need for further investigation into the seismic hazard potential of shallow upper plate faults and the potential for megathrust earthquakes to trigger slow-slip and shallow seismicity across separate segments of subduction zones

Solution of the Cauchy Problem for a Time-Dependent Schoedinger Equation

We construct an explicit solution of the Cauchy initial value problem for the n-dimensional Schroedinger equation with certain time-dependent Hamiltonian operator of a modified oscillator. The dynamical SU(1,1) symmetry of the harmonic oscillator wave functions, Bargmann's functions for the discrete positive series of the irreducible representations of this group, the Fourier integral of a weighted product of the Meixner-Pollaczek polynomials, a Hankel-type integral transform and the hyperspherical harmonics are utilized in order to derive the corresponding Green function. It is then generalized to a case of the forced modified oscillator. The propagators for two models of the relativistic oscillator are also found. An expansion formula of a plane wave in terms of the hyperspherical harmonics and solution of certain infinite system of ordinary differential equations are derived as a by-product.Comment: 29 pages, 4 figure

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.</p

Essential Medicines at the National Level : The Global Asthma Network's Essential Asthma Medicines Survey 2014

Patients with asthma need uninterrupted supplies of affordable, quality-assured essential medicines. However, access in many low- and middle-income countries (LMICs) is limited. The World Health Organization (WHO) Non-Communicable Disease (NCD) Global Action Plan 2013-2020 sets an 80% target for essential NCD medicines' availability. Poor access is partly due to medicines not being included on the national Essential Medicines Lists (EML) and/or National Reimbursement Lists (NRL) which guide the provision of free/subsidised medicines. We aimed to determine how many countries have essential asthma medicines on their EML and NRL, which essential asthma medicines, and whether surveys might monitor progress. A cross-sectional survey in 2013-2015 of Global Asthma Network principal investigators generated 111/120 (93%) responses41 high-income countries and territories (HICs); 70 LMICs. Patients in HICs with NRL are best served (91% HICs included ICS (inhaled corticosteroids) and salbutamol). Patients in the 24 (34%) LMICs with no NRL and the 14 (30%) LMICs with an NRL, however no ICS are likely to have very poor access to affordable, quality-assured ICS. Many LMICs do not have essential asthma medicines on their EML or NRL. Technical guidance and advocacy for policy change is required. Improving access to these medicines will improve the health system's capacity to address NCDs.Peer reviewe

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Search for anisotropic gravitational-wave backgrounds using data from Advanced LIGO and Advanced Virgo's first three observing runs

We report results from searches for anisotropic stochastic gravitational-wave backgrounds using data from the first three observing runs of the Advanced LIGO and Advanced Virgo detectors. For the first time, we include Virgo data in our analysis and run our search with a new efficient pipeline called {\tt PyStoch} on data folded over one sidereal day. We use gravitational-wave radiometry (broadband and narrow band) to produce sky maps of stochastic gravitational-wave backgrounds and to search for gravitational waves from point sources. A spherical harmonic decomposition method is employed to look for gravitational-wave emission from spatially-extended sources. Neither technique found evidence of gravitational-wave signals. Hence we derive 95\% confidence-level upper limit sky maps on the gravitational-wave energy flux from broadband point sources, ranging from $F_{\alpha, \Theta} < {\rm (0.013 - 7.6)} \times 10^{-8} {\rm erg \, cm^{-2} \, s^{-1} \, Hz^{-1}},$ and on the (normalized) gravitational-wave energy density spectrum from extended sources, ranging from $\Omega_{\alpha, \Theta} < {\rm (0.57 - 9.3)} \times 10^{-9} \, {\rm sr^{-1}}$, depending on direction ($\Theta$) and spectral index ($\alpha$). These limits improve upon previous limits by factors of $2.9 - 3.5$. We also set 95\% confidence level upper limits on the frequency-dependent strain amplitudes of quasimonochromatic gravitational waves coming from three interesting targets, Scorpius X-1, SN 1987A and the Galactic Center, with best upper limits range from $h_0 < {\rm (1.7-2.1)} \times 10^{-25},$ a factor of $\geq 2.0$ improvement compared to previous stochastic radiometer searches.Comment: 23 Pages, 9 Figure