Zika virus (ZIKV) is a mosquito-borne flavivirus, and its infection may cause severe neurodegenerative diseases. The outbreak of ZIKV in 2015 in South American has caused severe human congenital and neurologic disorders. Thus, it is vitally important to figure out inner mechanism of ZIKV infection. Here, our data suggested that the ubiquitin-specific peptidase 38 (USP38) played an important role in host resistance to ZIKV infection, during which ZIKV infection did not affect USP38 expression. Mechanistically, USP38 bound to ZIKV envelope (E) protein through its C-terminal domain and attenuated its K48-linked and K63-linked polyubiquitination, thereby repressed the infection of ZIKV. In addition, we found that the deubiquitinase activity of USP38 was essential to inhibit ZIKV infection, and the mutant that lacked the deubiquitinase activity of USP38 lost ability to inhibit the infection. In conclusion, we found a novel host protein USP38 against ZIKV infection, and this may represent a potential therapeutic target for the treatment and prevention of ZIKV infection.

In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 0.414\% of these 3617 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.

Both in lung adenocarcinoma (LUAD) and severe acute respiratory syndromes (SARS) uncontrolled inflammation could be detected in lung tissue. Whether the similarity mechanism exists is still unknown. PDZ-binding motif (PBM) in SARS-CoV E protein has been demonstrated as virulence factor induce inflammation storm. Study function of PBM in LUAD is significant for mechanism exploration of carcinogenesis mediated by SARS-CoV. To identify gene expression fluctuation induced by PBM, a microarray sequencing data of lung tissue infected by wild type (SARS-CoV-E-wt) and recombinant virus (SARS-CoV-E-mutPBM) was analysis followed by functional enrichment analysis. To understand the role of screened specific genes in LUAD, overall survival and immune correlation were calculated. A total of 12 genes (MAPK1, PRKCA, FGFR4, KDR, PTPRD, BCL2L15, UBD, MAMDC2, LTBP4, PTPRB, LGI3 and ITGA8) might participate in initial and development stage of LUAD through expression variation and mutation. Meanwhile, a total of 12 genes (CARHSP1, EIF4E2, HMGA1, IL1R2, MAGOHB, PVR, ADCY9, ELF5, ESYT3, SCML4, SECL14L4 and THRA) could lead to poorer prognosis via dysregulation. In addition, MAMDC2 and ITGA8 down-regulated by PBM could also alter prognosis. Though the conservative PBM (-D-L-L-V-) could be found at the end of carboxyl terminal in multi E proteins of coronaviruses, the specific function of each one depend on the whole amino acid sequence simultaneously. In conclusion, PBM of SARS-CoV E protein could promote carcinogenesis of LUAD by dysregulating important gene expression profiles followed by influence immune response and overall prognosis. The results in present study also provided reference for the therapy of SARS-CoV-2 in LUAD patients.

Since the severe acute respiratory syndrome (SARS) outbreak in 2003, human coronaviruses (hCoVs) have been identified as causative agents of severe acute respiratory tract infections. Two more hCoV outbreaks have since occurred, the most recent being SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). The clinical presentation of SARS and MERS is remarkably similar to COVID-19, with hyperinflammation causing a severe form of the disease in some patients. Previous studies show that the expression of the SARS-CoV E protein is associated with the hyperinflammatory response that could culminate in acute respiratory distress syndrome (ARDS), a potentially fatal complication. This immune-mediated damage is largely caused by a cytokine storm, which is induced by significantly elevated levels of inflammatory cytokines interleukin (IL)-1beta and IL-6, which are partly mediated by the expression of the SARS-CoV E protein. The interaction between the SARS-CoV E protein and the host protein, syntenin, as well as the viroporin function of SARS-CoV E, are linked to this cytokine dysregulation. This review aims to compare the clinical presentation of virulent hCoVs with a specific focus on the cause of the immunopathology. The review also proposes that inhibition of IL-1beta and IL-6 in severe cases can improve patient outcome.

Laminopathies are causally associated with mutations on Lamin A gene (LMNA). To date, more than 400 mutations in LMNA have been reported in patients. These mutations are widely distributed throughout the entire gene and are associated with a wide range of phenotypes. Unfortunately, little is known about the mechanisms underlying the effect of the majority of these mutations. This is the case of more than 40 mutations that are located at exon 4. Using CRISPR/Cas9 technology, we have generated a collection of Lmna exon 4 mutants in mouse C2C12 myoblasts. These cell models include different types of exon 4 deletions and the presence of R249W mutation, one of the human variants associated with a severe type of laminopathy (LMNA-associated congenital muscular dystrophy). We have characterized these clones by measuring their nuclear circularity, myogenic differentiation capacity in 2D and 3D conditions, DNA damage, and p-ERK and p-AKT levels. Our results indicate that Lmna exon 4 mutants show abnormal nuclear morphology. In addition, levels and/or subcellular localization of different members of the lamin and LINC complex are altered in all these mutants. Whereas no significant differences were observed for ERK and AKT activities, the accumulation of DNA damage was associated to the Lmna p.R249W mutant myoblasts. Finally, significant myogenic differentiation defects were detected in the Lmna exon 4 mutants. These results have key implications in the development of future therapeutic strategies for the treatment of laminopathies.

In social & health sciences, many statistical procedures and estimation techniques rely on the underlying distributional assumption of normality of the data. Non-normality may lead to incorrect statistical inferences. This study evaluates the performance of selected normality tests on the stringency framework for the skewed alternative space. Stringency concept allows us to rank the tests uniquely. Bonett & Seier test (T_w) turns out to be the best statistics for slightly skewed alternatives and the Anderson-Darling (AD), Chen-Shapiro (CS), Shapiro-Wilk (W) and Bispo, Marques, & Pestana, (BCMR) statistics are the best choices for moderately skewed alternative distributions. Maximum loss of Jarque-Bera (JB) and its robust form (RJB), in terms of deviations from the power envelope, is greater than 50% even for large sample sizes which makes them less attractive in testing the hypothesis of normality against the moderately skewed alternatives. On balance, all selected normality tests except T_w and COIN performed exceptionally well against the highly skewed alternative space.

Nuclear lamins are type V intermediate filament proteins that form a filamentous meshwork beneath the inner nuclear membrane. Additionally, a sub-population of A-type and B-type lamins is localized in the nuclear interior. The nuclear lamina protects the nucleus from mechanical stress and mediates nucleo-cytoskeletal coupling. Lamins form a scaffold that partially tethers chromatin at the nuclear envelope. The nuclear lamina also stabilizes protein-protein interactions involved in gene regulation and DNA repair. The lamin-based protein sub-complexes are implicated in both nuclear and cytoskeletal organization, the mechanical stability of the nucleus, genome organization, transcriptional regulation, genome stability, and cellular differentiation. Here we review recent research in the field of nuclear lamins and their role in modulating various nuclear processes and their impact on cell function.

Insulation systems for the floor, roof and external walls play a prominent role in providing a thermal barrier for the building envelope. Design decisions made for the insulation material type and thickness can alleviate potential impacts on the embodied energy and improve the building thermal performance. This design problem is often addressed using a BIM-integrated optimisation approach. However, one major weakness lies in the current studies is that BIM is merely used as the source for design parameters input. This study proposes a BIM-based envelope insulation optimisation design framework using a common software Revit to find the trade-off between the total embodied energy of the insulation system and the thermal performance of the envelope by considering the material type and thickness. In addition, the framework also permits data visualisation in a BIM environment, and subsequent material library mapping together with instantiating the optimal insulation designs. The framework is tested on a case study based in Sydney, Australia. By analysing sample designs from the Pareto front, it is found that slight improvement in the thermal performance (1.3399 to 1.2112 GJ/m2) would cause the embodied energy to increase by more than 50 times.

In the Kingdom of Saudi Arabia (KSA), residential buildings’ energy consumption accounts for almost 50% of the building stock electricity consumption. The electricity generation consumes over one-third of the daily oil production. KSA was ranked as one of the highest countries in fossil fuel consumption per capita in 2014. Moreover, the KSA’s economy heavily relies on fossil fuel sources, namely oil reservoirs, whereby depletion will negatively affect the future development of the country. The total electricity consumption is annually growing by approximately 5-8%, which would lead to identical oil consumption to oil production in 2035. Currently, the KSA government is concerned to generate more renewable energy using large renewable energy plants. The government is investing in energy generation through renewable sources, by financing large scale photovoltaic farms to stop an economic crisis that may occur in 2035. The existing building stock consumes around 80% of the total current Saudi electricity that is generated. According to the Saudi energy efficiency report, the primary energy consumption per capita is over three times higher than the world average. Therefore, the residential buildings need further assessment as to their current energy consumption. This research used a survey to explore current user behaviour in residential buildings energy performance in the city of Jeddah, KSA. The findings of the survey showed: • The buildings thermal properties were found to be poorly designed • The majority of users within the buildings prefer a room temperature of below 24 °C, which requires a massive amount of cooling • Due to the climate conditions and the cultural aspects of KSA, housing units are occupied for more than 18 hours per day • An increase in user awareness has helped to slightly improve residential buildings energy efficiency Knowing the current high energy consumption sources and causes and being able to define available opportunities for further developments on building thermal properties enhancements and how to increase user awareness to reach self-sustaining buildings is essential.

The article presents a mathematical model to investigate the operability envelopes for subsea production tress (SPT) installation using drill pipe. The finite differential method was used to solve the established governing equations in which the ocean conditions were considered. Based on the evaluations of the ocean wave, ocean current, water depth, specification of drill pipe and SPT weight that might dominate the mechanical behaviors of the pipe, the operability envelopes with permissible ocean conditions for SPT installation were obtained. The results indicate that changes of depths in deep water and SPT weight have few effects on the operation conditions and it would be better to choose smaller pipe to obtain larger permissible ocean conditions during SPT installation.

While previous research has shown the use of attachable air-caps on windows to efficiently reduce a building’s energy consumption, the air-caps considered had to be attached to the entire window’s surface, thus limiting the occupants’ view and creating the inconvenience of needing to detach and attach the air-caps. In this study, a window-mounted air-cap roller module using Velcro tape that may be easily attached, detached, and rolled up or down was developed and performance tested in a full-scale test bed. It was found that as the area of the air-caps attached on a window increased, the required indoor lighting energy increased. However, the window insulation improved, thus reducing the cooling and heating energy needed. Attaching the air-caps to the entire window surface effectively reduced the building’s energy consumption, but views through the window may be disturbed. Thus, the developed window-mounted air-caps enable an occupant to reduce the building energy consumption and maintain their view according to their need. The findings of this study may contribute to a reduction in building energy consumption without sacrificing a pleasant indoor environment. Further studies may be needed to verify their efficacy under varying indoor and outdoor conditions.

Amorphous ferrite-type rare-earth (RE) substituted garnets and garnet-oxide nanocomposite layers are prepared on clear glass substrates by using RF magnetron sputter-deposition process. By using a combination approach employing custom-built spectrum-fitting software in conjunction with Swanepoel’s envelope method, the spectral dispersion function of optical constants and the layer thicknesses are derived accurately from the transmission spectra of the as-deposited samples. The effects of excess metal-oxides added to the base material systems during the co-deposition process are found to affect the refractive index and the optical absorption coefficients of garnet-oxide composites. A number of optical constant datasets are presented, enabling the experimentalists to design nanophotonic or integrated-optics devices employing these functional materials.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

Recent years have witnessed a breakthrough in identification of a trimer-of-hairpins motif within viral envelopes that triggers a broad range of virus-host fusion. Identifying a domain capable of controlling virus-host fusion remains a challenge due to sequence diversity, heavy glycan shielding and multiple conformations. Here, we report that HR2, a prevalent heptad repeat sequence comprising an alpha-helical coil anchored in viral membranes, is an accessible site to triterpenes, a class of widely distributed natural products. Triterpenes and their derivatives inhibit the entry of Ebola, HIV, and influenza A viruses with distinct structure-activity relationships. Specifically, triterpenoid probes, upon activation by ultraviolet light, capture the viral envelope via crosslinking the HR2 coil. Profiling the Ebola HR2 sequence using amino acid substitution, surface plasmon resonance (SPR) and nuclear magnetic resonance (NMR) spectroscopy disclosed six constitutive residues that are accessible to triterpenoids, leading to wrapping of the hydrophobic helix by triterpenoids and blocking of the HR1-HR2 interaction, which is critical in the trimer-of-hairpins formation. This finding was also observed in the envelopes of HIV and influenza A viruses and might potentially extend to a broader variety of viruses. Our findings might translate into a shared mechanism that host utilize natural product triterpenoids to antagonize membrane fusion of respective viruses, complementing the current repertoire of antiviral agents.

The monkeypox virus (MPXV) has become a major threat due to the increasing global caseload and the ongoing multi-country outbreak in non-endemic territories. Due to limited research in this avenue and the lack of intervention strategies, the present study was aimed to virtually screen bioactive phytochemicals against envelope proteins of MPXV via rigorous computational approaches. Molecular docking and molecular dynamic (MD) simulations were used to investigate the binding affinity of 12 phytochemicals against three envelope proteins of MPXV, viz., D13, A26, and H3. Silibinin, oleanolic acid, and ursolic acid were computationally identified as potential phytochemicals that showed strong binding affinity towards all the tested structural proteins of MPXV through molecular docking. The stability of the docked complexes was also confirmed by MD simulations. ADME analysis also computationally confirmed the drug-like properties of the phytochemicals, thereby asserting their suitability for consumption. Hence, this study envisions the candidature of bioactive phytochemicals as promising inhibitors against the MPXV, serving as template molecules that could further be experimentally evaluated for their efficacy against monkeypox.

Universal gravitation is investigated with principles of foundational classical (Newtonian) physics. The results reveal gravitation an atomic field action; hence, Newton’s law, although absolutely valid, unavoidably misleads in creating the impression of matter rather than waveform action. Six force constants fully define gravitation: (i) a waveform torque field ; (ii) an expansion force field ; (iii) a centripetal force field ; (iv) a matter-wave torque field (the force fields , and constitute gravitational inertial rest frame); (v) a Galilean acceleration field and (vi) nuclear inverse mass-squared centripetal force constant The inertial rest frame force constants sum up to give observational G = 2.266 + 2.61 + 2.61cos46^o) x 10^-11 = 6.689 x 10^-11 m³ kg^-1 s^-2. Notably, the procedure is able to account also for observational inclination of galaxies and their aligned conjunctions. An attempt is made to account for angular momentum quantization and rectilinear, parabolic or elliptic profile of objects in gravitational acceleration. Same quantitative expression, , defines the photon and gravitation thus uniquely unifying gravitation, electricity and magnetism; furthermore, the expression reveals the photon packed with tremendous energy amounting to some . It is argued that: (i) neither mass nor gravitation curves spacetime; (ii) the principles that sustain cosmic time-scale dynamic equilibrium, scale invariance and inertia are incompatible with quantum gravitation; and (iii) the cosmic vacuum field comprises gravitational (photonic) waves, hence the interferometer likely measures shock waves.

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilizing the membrane protein arrangement in the virion. The residues responsible for the M protein inter-actions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein, which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.

It is not easy to dynamically analyze thermal bridges that require multidimensional analysis in building energy simulations, which are mostly one-dimensional platforms. To solve this problem, many studies have been conducted and, recently, a study was conducted to model the thermal bridge based on the data by approaching this in a similar way to steady-state analysis, showing high accuracy. This was an early-stage study, which is only applicable when the indoor temperature is constant. By extending this study, a thermal bridge model that can be applied even when the indoor temperature changes over time is proposed and validated. Since the governing equation, the heat diffusion equation, is linear, the key idea is to create and apply two thermal bridge transfer function models by expressing the heat flow entering the room as a linear combination of the transfer function for indoor temperature and the transfer function for outdoor temperature. For the proposed thermal bridge model, the NRMSE of the model itself showed a high accuracy of 99.9%, and in the verification through annual simulation using the model, the NRMSE showed an accuracy of 88.8%.

We are witnessing the severe third outbreak mediated by coronaviruses affecting global public health with unprecedented economic consequences. A better understanding of its phylogenetics, exploration of sequence features and mutational changes could unveil its genealogy to gain insights into the mechanism of transmission and development of possible interventions. Our comparative genomic analyses of >160 isolates of SARS-CoV-2 reveal phylogenetic kinship with other coronaviruses and emergence of evolutionary divergence in clinical isolates. t-SNE-based clustering revealed different clades but no continent specific clusters. Amino acid substitutions at RBD of spike protein provide possible reasons for rapid transmission. Few proteins specific to SARS-CoV-2 were identified which could have implications as therapeutic targets and diagnostic biomarkers. Virtual screening identified repurposed drugs, known nutraceuticals, for specific interventions. These phylogenetic observations reveal the ancestry and computational studies reveal the emergency measures to interject this emerging pathogen that pose threat to whole of mankind.

Building envelope can play a crucial role in building improvement efficiency and the adoption of Phase Change Materials (PCMs) coupled with transparent elements may (i) allow a better control of the heat flows from/to the outdoor environment, (ii) increase the exploitation of solar energy at building scale and (iii) modulate the light transmission to avoid glare effects. Starting from a literature review of experimental works, this research identifies the main possible integration of PCM in transparent/translucent building envelope components (in glazing, in shutters and in multilayer façade system) drawing a global picture potentials and limitations of these technologies. Transparent envelopes with PCMs have been classified from the simplest “zero” technology, which integrates the PCM into the double glass unit (DGU), to more complex solutions – with different numbers of cavities of the glass (TGU), different position of PCM layer (internal/external shutter), and in combination with other materials (TIM, aerogel, prismatic solar reflector, PCM curtain controlled by an electric pump). The results of the analysis are resumed in a SWOT (strengths, weakness, opportunities and threats) analysis table to underline strengths and weaknesses of transparent building envelope components with PCMs, and to indicate opportunities and threats for future research and building application.

The less virulent human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 cause mild, self-limiting respiratory tract infections, while the more virulent SARS-CoV-1, MERS-CoV, and SARS-CoV-2 have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoVs infections, may provide insight into this disparate severity of the disease. We, therefore, generated full-length E protein models for SARS-CoV-1, -2, MERS-CoV, HCoV-229E, and HCoV-NL63 and docked C-terminal peptides of each model to the PDZ domain of the human PALS1 protein. The PDZ-binding motif (PBM) of the SARS-CoV-1, -2, and MERS-CoV models adopted a more flexible, extended coil while the HCoV-229E and HCoV-NL63 models adopted a less flexible alpha helix. All the E peptides docked to PALS1 occupied the same binding site and the more virulent hCoV E peptides generally interacted more stably with PALS1 than the less virulent ones. We propose that the increased flexibility of the PBM in more virulent hCoVs may permit more stable binding to various host proteins, thereby possibly contributing to more severe disease. This is the first paper to model full-length 3D structures for both more virulent and less virulent hCoVs E proteins, providing novel insights for possible drug and/or vaccine development.