New Sesterterpenes from the Antarctic Sponge sp.

Chemical investigation of the Antarctic sponge sp. has previously led to the identification of new suberitane derivatives, some of which show bioactivity toward respiratory syncytial virus (RSV). Our ongoing NMR-guided investigation of new specimens of the sponge resulted in the isolation of five new analogs (-), previously reported suberitenones A-D (-), and oxaspirosuberitenone ().

Effect of excluding fractured or abnormal vertebrae on the trabecular bone score measurement.

Unlabelled: Brief rationale: The use of L1-L4 vertebrae, without exclusions, has been recommended for trabecular bone score (TBS) measurements.

Main Result: Excluding abnormal and fractured vertebrae affected the TBS. Significance of the paper: Fracture or degenerative abnormality may not affect TBS.

Different contributions of fat and lean indices to bone strength by sex.

Bone strength depends on both bone density and quality. However, the differences in how body composition indices affect bone strength between men and women remains unclear. This study investigated the associations of various fat and lean indices with bone strength by sex.

Targeted degradation of the HPV oncoprotein E6 reduces tumor burden in cervical cancer.

Human Papilloma Virus (HPV)-related cancers are a global health burden, yet there are no targeted therapies available for chronically infected patients. The HPV protein E6 is essential for HPV-mediated tumorigenesis and immune evasion, making it an attractive target for antiviral drug development. In this study, we developed an E6-targeting Proteolysis Targeting Chimera (PROTAC) that inhibits the growth of HPV(+) tumors.

Anthoteibinenes A-E from the Irish Deep-Sea Coral : An Amination Puzzle.

Chemical investigation of extracts from the Irish deep-sea soft coral revealed cadinene-like sesquiterpenes, anthoteibinenes A-E, bearing unusual dimethylamine substitution. Structure elucidation was accomplished using 1D/2D NMR spectroscopy and high-resolution mass spectrometry, while NOESY NMR experiments, gauge invariant atomic orbital (GIAO) NMR calculations coupled with DP4+ probabilities measures, and ECD comparisons were incorporated to propose their relative and absolute configurations. Anthoteibinene B () exhibited 49% inhibition of respiratory syncytial virus (RSV) at 3.

Extracellular ISG15 triggers ISGylation via a type-I interferon independent non-canonical mechanism to regulate host response during virus infection.

Type-I interferons (IFN) induce cellular proteins with antiviral activity. One such protein is Interferon Stimulated Gene 15 (ISG15). ISG15 is conjugated to proteins during ISGylation to confer antiviral activity and regulate cellular activities associated with inflammatory and neurodegenerative diseases and cancer.

Consistency in Reporting of Loss of Righting Reflex for Assessment of General Anesthesia in Rats and Mice: A Systematic Review.

General anesthesia induces a reversible loss of consciousness (LOC), a state that is characterized by the inability to feel pain. Identifying LOC in animals poses unique challenges, because the method most commonly used in humans, responding to questions, cannot be used in animals. For over a century, loss of righting reflex (LORR) has been used to assess LOC in animals.

Analysis of the evolution of COVID-19 disease understanding through temporal knowledge graphs.

The COVID-19 pandemic highlighted two critical barriers hindering rapid response to novel pathogens. These include inefficient use of existing biological knowledge about treatments, compounds, gene interactions, proteins, etc. to fight new diseases, and the lack of assimilation and analysis of the fast-growing knowledge about new diseases to quickly develop new treatments, vaccines, and compounds.

The choice of region of interest after spinal procedures alters bone mineral density measurements.

Purpose: Vertebrae affected by artifacts, such as metallic implants or bone cement, should be excluded when measuring the spine bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Exclusion may be performed using two methods: first, the affected vertebrae are included in the region of interest (ROI) and subsequently excluded from the analysis; second, the affected vertebrae are completely excluded from the ROI. This study aimed to investigate the influence of metallic implants and bone cement on BMD with and without the inclusion of artifact-affected vertebrae in the ROI.

Bioengineered peptibodies as blockers of ion channels.

We engineered and produced an ion channel blocking peptibody, that targets the acetylcholine-activated inwardly rectifying potassium current (I). Peptibodies are chimeric proteins generated by fusing a biologically active peptide with the fragment crystallizable (Fc) region of the human immunoglobulin G (IgG). The I blocking peptibody was engineered as a fusion between the human IgG1 Fc fragment and the I inhibitor tertiapinQ (TP), a 21-amino acid synthetic peptidotoxin, originally isolated from the European honey bee venom.

Association of possible sarcopenic obesity with osteoporosis and fragility fractures in postmenopausal women.

Unlabelled: Possible sarcopenic obese women had a decreased likelihood of osteoporosis but an increased likelihood of fragility fractures compared with non-sarcopenic non-obese and sarcopenia-only women. Furthermore, possible sarcopenic obese women had lower values of trabecular bone score than non-sarcopenic non-obese and sarcopenia-only women.

Purpose: The coexistence of possible sarcopenia and obesity may have opposing effects on osteoporosis.

Human Respiratory Syncytial Virus NS2 Protein Induces Autophagy by Modulating Beclin1 Protein Stabilization and ISGylation.

Paramyxoviruses such as respiratory syncytial virus (RSV) are the leading cause of pneumonia in infants, the elderly, and immunocompromised individuals. Understanding host-virus interactions is essential for the development of effective interventions. RSV induces autophagy to modulate the immune response.

Respiratory Syncytial Virus Matrix Protein-Chromatin Association Is Key to Transcriptional Inhibition in Infected Cells.

The morbidity and mortality caused by the globally prevalent human respiratory pathogen respiratory syncytial virus (RSV) approaches that world-wide of influenza. We previously demonstrated that the RSV matrix (M) protein shuttles, in signal-dependent fashion, between host cell nucleus and cytoplasm, and that this trafficking is central to RSV replication and assembly. Here we analyze in detail the nuclear role of M for the first time using a range of novel approaches, including quantitative analysis of de novo cell transcription in situ in the presence or absence of RSV infection or M ectopic expression, as well as in situ DNA binding.

Respiratory Syncytial Virus Phosphoprotein Residue S156 Plays a Role in Regulating Genome Transcription and Replication.

Respiratory syncytial virus (RSV) is a single-stranded, negative-sense RNA virus in the family and genus that can cause severe disease in infants, immunocompromised adults, and the elderly. The RSV viral RNA-dependent RNA polymerase (vRdRp) complex is composed of the phosphoprotein (P) and the large polymerase protein (L). The P protein is constitutively phosphorylated by host kinases and has 41 serine (S) and threonine (T) residues as potential phosphorylation sites.

The Impact of the "Osteo" Component of Osteosarcopenia on Fragility Fractures in Post-Menopausal Women.

Osteosarcopenia, the coexistence of bone and muscle loss, is common in older adults, but its definition lacks international consensus. This cross-sectional study ( = 1199 post-menopausal women) aimed to determine the association between osteosarcopenia and fragility fractures and to investigate the impact of the definition of the "osteo" component. Bone mineral density and bone microarchitecture were measured by dual-energy X-ray absorptiometry and the trabecular bone score (TBS), respectively.

A Novel Live Attenuated Respiratory Syncytial Virus Vaccine Candidate with Mutations in the L Protein SAM Binding Site and the G Protein Cleavage Site Is Protective in Cotton Rats and a Rhesus Macaque.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in children of <5 years of age worldwide, infecting the majority of infants in their first year of life. Despite the widespread impact of this virus, no vaccine is currently available. For more than 50 years, live attenuated vaccines (LAVs) have been shown to protect against other childhood viral infections, offering the advantage of presenting all viral proteins to the immune system for stimulation of both B and T cell responses and memory.

3-Dimensional Printed Alternative to the Standard Synthetic Flocked Nasopharyngeal Swabs Used for Coronavirus Disease 2019 Testing.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be detected in respiratory samples by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs.

Methods: We developed a 3-dimensional printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab.

Hand grip strength in predicting the risk of osteoporosis in Asian adults.

Introduction: There is a need for a cost-effective method to identify individuals with a high risk of osteoporosis. This study aimed to investigate the suitability of hand grip strength in predicting the risk of osteoporosis in Asian adults.

Materials And Methods: In this cross-sectional, hospital-based study of 1007 participants, the bone mineral density of the spine and hips was evaluated using dual-energy X-ray absorptiometry according to the 2019 International Society for Clinical Densitometry official positions.

Comparing self-assessment, functional, and anthropometric techniques in predicting osteoporosis.

Unlabelled: The osteoporosis self-assessment tool was more accurate than hand grip strength, gait speed, and calf circumference in predicting osteoporosis in women. Hand grip strength was more accurate than the osteoporosis self-assessment tool, gait speed, and calf circumference in predicting osteoporosis in men.

Purpose: The osteoporosis self-assessment tool, functional assessment, and anthropometric measurement are different techniques to identify those at risk of osteoporosis.

Non-gradient and genotype-dependent patterns of RSV gene expression.

Respiratory syncytial virus (RSV) is a nonsegmented negative-strand RNA virus (NSV) and a leading cause of severe lower respiratory tract illness in infants and the elderly. Transcription of the ten RSV genes proceeds sequentially from the 3' promoter and requires conserved gene start (GS) and gene end (GE) signals. Previous studies using the prototypical GA1 genotype Long and A2 strains have indicated a gradient of gene transcription extending across the genome, with the highest level of mRNA coming from the most promoter-proximal gene, the first nonstructural (NS1) gene, and mRNA levels from subsequent genes dropping until reaching a minimum at the most promoter-distal gene, the polymerase (L) gene.

Poloxamer 188 decreases membrane toxicity of mutant SOD1 and ameliorates pathology observed in SOD1 mouse model for ALS.

Here we report a gain in function for mutant (mt) superoxide dismutase I (SOD1), a cause of familial amyotrophic lateral sclerosis (FALS), wherein small soluble oligomers of mtSOD1 acquire a membrane toxicity. Phosphatidylglycerol (PG) lipid domains are selectively targeted, which could result in membrane damage or "toxic channels" becoming active in the bilayer. This PG-selective SOD1-mediated membrane toxicity is largely reversible in vitro by a widely-available FDA-approved surfactant and membrane-stabilizer P188.