Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools.

Computational vaccinology includes epitope mapping, antigen selection, and immunogen design using computational tools. Tools that facilitate the prediction of immune response to biothreats, emerging infectious diseases, and cancers can accelerate the design of novel and next generation vaccines and their delivery to the clinic. Over the past 20 years, vaccinologists, bioinformatics experts, and advanced programmers based in Providence, Rhode Island, USA have advanced the development of an integrated toolkit for vaccine design called iVAX, that is secure and user-accessible by internet.

Do Levels of Stress Markers Influence the Retinal Nerve Fiber Layer Thickness in Young Adults?

Precis: Although mental or emotional stress may result raise in intraocular pressure (IOP) we found weak associations between endogenous stress markers concentrations and retinal nerve fiber layer (RNFL) thickness, thus limited evidence that stress affects retinal ganglion cells integrity.

Purpose: Increased exposure to glucocorticoids is linked to elevated IOP, which is a risk factor for glaucoma. We explored the RNFL thickness for changes that may mimic preclinical glaucomatous changes, in relation to the hormonal stress response.

T cell epitope content comparison (EpiCC) analysis demonstrates a bivalent PCV2 vaccine has greater T cell epitope overlap with field strains than monovalent PCV2 vaccines.

Porcine circovirus type 2 (PCV2) has one of the highest evolutionary rates among DNA viruses. Traditionally, PCV2 vaccines have been based on the 2a genotype as this was the first genotype discovered. Today, eight genotypes of PCV2 viruses have been identified, and, taken together with the rapid evolutionary rate, propensity to recombine, and high rate of vaccination, further variation in PCV2 is expected.

The Treatment of Acute Rheumatic Fever: Novel Use of Hydroxychloroquine.

Hydroxychloroquine (HCQ) suppresses an interleukin-1β-granulocyte-macrophage colony-stimulating factor cytokine axis, reported to be dysregulated in peripheral blood mononuclear cells of acute rheumatic fever patients ex vivo. We describe HCQ treatment for 2 patients with rheumatic carditis and a protracted inflammatory course. HCQ was associated with control of inflammatory markers, control of pericarditis in first patient and stabilization of progressive carditis in the second patient.

Mixed metal zero-mode guides (ZMWs) for tunable fluorescence enhancement.

Zero-mode waveguides (ZMWs) are capable of modifying fluorescence emission through interactions with surface plasmon modes leading to either plasmon-enhanced fluorescence or quenching. Enhancement requires spectral overlap of the plasmon modes with the absorption or emission of the fluorophore. Thus, enhancement is limited to fluorophores in resonance with metals ( Al, Au, Ag) used for ZMWs.

Network-based drug repurposing for novel coronavirus 2019-nCoV/SARS-CoV-2.

Human coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV) and 2019 novel coronavirus (2019-nCoV, also known as SARS-CoV-2), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV/SARS-CoV-2. Drug repurposing, representing as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery.

Autocatalytic chemical networks at the origin of metabolism.

Modern cells embody metabolic networks containing thousands of elements and form autocatalytic sets of molecules that produce copies of themselves. How the first self-sustaining metabolic networks arose at life's origin is a major open question. Autocatalytic sets smaller than metabolic networks were proposed as transitory intermediates at the origin of life, but evidence for their role in prebiotic evolution is lacking.

Bacterial Genes Outnumber Archaeal Genes in Eukaryotic Genomes.

Eukaryotes are typically depicted as descendants of archaea, but their genomes are evolutionary chimeras with genes stemming from archaea and bacteria. Which prokaryotic heritage predominates? Here, we have clustered 19,050,992 protein sequences from 5,443 bacteria and 212 archaea with 3,420,731 protein sequences from 150 eukaryotes spanning six eukaryotic supergroups. By downsampling, we obtain estimates for the bacterial and archaeal proportions.

A hydrogen-dependent geochemical analogue of primordial carbon and energy metabolism.

Hydrogen gas, H, is generated by alkaline hydrothermal vents through an ancient geochemical process called serpentinization, in which water reacts with iron-containing minerals deep within the Earth's crust. H is the electron donor for the most ancient and the only energy-releasing route of biological CO fixation, the acetyl-CoA pathway. At the origin of metabolism, CO fixation by hydrothermal H within serpentinizing systems could have preceded and patterned biotic pathways.

In Silico Insights into Protein-protein Interaction Disruptive Mutations in the PCSK9-LDLR complex.

Gain-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to reduced uptake of LDL (low density lipoprotein) cholesterol and, therefore, increased plasma LDL levels. However, the mechanism by which these mutants reduce LDL reuptake is not fully understood. Here, we have used molecular dynamics simulations, MM/PBSA (Molecular Mechanics/Poisson-Boltzmann Surface Area) binding affinity calculations, and residue interaction networks, to investigate the protein-protein interaction (PPI) disruptive effects of two of PCSK9's gain-of-function mutations, Ser127Arg and Asp374Tyr on the PCSK9 and LDL receptor complex.

Multi-Omic Analyses Provide Links between Low-Dose Antibiotic Treatment and Induction of Secondary Metabolism in Burkholderia thailandensis.

Low doses of antibiotics can trigger secondary metabolite biosynthesis in bacteria, but the underlying mechanisms are generally unknown. We sought to better understand this phenomenon by studying how the antibiotic trimethoprim activates the synthesis of the virulence factor malleilactone in Using transcriptomics, quantitative multiplexed proteomics, and primary metabolomics, we systematically mapped the changes induced by trimethoprim. Surprisingly, even subinhibitory doses of the antibiotic resulted in broad transcriptional and translational alterations, with ∼8.

Enhancing the Alternative Cellular Energy (ACE) Pathway with KELEA Activated Water as Therapy for Infectious Diseases.

Many infectious diseases have yet to be conquered by modern medicine. This is generally attributed to both a failure of the immune system and the lack of an effective anti-microbial pharmaceutical. Infections can be regarded as a competitive process between the microbe and the host for cellular energy-generated resources.

Physiological limits to life in anoxic subseafloor sediment.

In subseafloor sediment, microbial cell densities exponentially decrease with depth into the fermentation zone. Here, we address the classical question of 'why are cells dying faster than they are growing?' from the standpoint of physiology. The stoichiometries of fermentative ATP production and consumption in the fermentation zone place bounds on the conversion of old cell biomass into new.

Experimental and computational evidence for C=O π-bonding in [CHOH] and related oxonium ions.

The question of whether [CHOH] should be described as the hydroxymethyl cation, CHOH, or protonated formaldehyde, CH=OH, is reconsidered in the light of experimental information and new computational evidence. Previous arguments that the charge distribution in [CHOH] may be probed by considering the incremental stabilisation of [CHOH] induced by homologation on carbon (to give [CHCHOH]) or oxygen (to produce [CHOCH]) are critically examined. Cation stabilisation energies are shown to be better indicators of the nature of these oxonium ions.

Correction to: Co-Creation of a Lanreotide Autogel/Depot Syringe for the Treatment of Acromegaly and Neuroendocrine Tumours Through Collaborative Human Factor Studies.

In the Original Article, there is an error in the "participants" section of Results. The correct sentence is "A total of 213 participants took part in the studies, including 34 patients with acromegaly and 28 patients with NETs".

identification and modification of T cell epitopes in pertussis antigens associated with tolerance.

The resurgence of whooping cough since the introduction of acellular (protein) vaccines has led to a renewed interest in the development of improved pertussis vaccines; Outer Membrane Vesicles (OMVs) carrying pertussis antigens have emerged as viable candidates. An immunogenicity screen was carried out on 49 well-known proteins in order to better understand their potential role toward the efficacy of pertussis OMVs for vaccine design; seven proteins were identified as being good candidates for including in optimized cellular and acellular pertussis vaccines. We then screened these antigens for putative tolerance-inducing sequences, as proteins with reduced tolerogenicity have improved vaccine potency in preclinical models.

Extracellular Vesicles Mediate Neuroprotection and Functional Recovery after Traumatic Brain Injury.

The lack of effective therapies for moderate-to-severe traumatic brain injuries (TBIs) leaves patients with lifelong disabilities. Neural stem cells (NSCs) have demonstrated great promise for neural repair and regeneration. However, direct evidence to support their use as a cell replacement therapy for neural injuries is currently lacking.

Systems immunology reveals a linked IgG3-C4 response in patients with acute rheumatic fever.

Acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) are autoimmune sequelae of a Group A streptococcal infection with significant global mortality and poorly understood pathogenesis. Immunoglobulin and complement deposition were observed in ARF/RHD valve tissue over 50 years ago, yet contemporary investigations have been lacking. This study applied systems immunology to investigate the relationships between the complement system and immunoglobulin in ARF.

Methods of Cryoprotectant Preservation: Allogeneic Cellular Bone Grafts and Potential Effects.

Debridement of the bone surface during a surgical fusion procedure initiates an injury response promoting a healing cascade of molecular mediators released over time. Autologous grafts offer natural scaffolding to fill the bone void and to provide local bone cells. Commercial bone grafting products such as allografts, synthetic bone mineral products, etc.

Improvements in diabetic albuminuria and podocyte differentiation following Roux-en-Y gastric bypass surgery.

Background: Multiple studies demonstrate an albuminuria-lowering impact of Roux-en-Y gastric bypass surgery, but neither evaluation of its penetrance across different baseline levels of albuminuria nor its association with alterations in podocyte phenotype has previously been reported.

Methods: We profiled changes in body weight, glycaemic control and urinary albumin excretion following Roux-en-Y gastric bypass surgery in 105 patients with type 2 diabetes, albuminuria of varying degrees of severity and classified as being at moderate or high risk of chronic kidney disease progression according to the Kidney Disease: Improving Global Outcomes 2012 criteria. In parallel pre-clinical studies, the impact of Roux-en-Y gastric bypass surgery on markers of podocyte injury was assessed in the Zucker diabetic fatty rat model of diabetic kidney disease.

Therapeutic administration of Tregitope-Human Albumin Fusion with Insulin Peptides to promote Antigen-Specific Adaptive Tolerance Induction.

Type 1 Diabetes (T1D) is an autoimmune disease that is associated with effector T cell (Teff) destruction of insulin-producing pancreatic beta-islet cells. Among the therapies being evaluated for T1D is the restoration of regulatory T cell (Treg) activity, specifically directed toward down-modulation of beta-islet antigen-specific T effector cells. This is also known as antigen-specific adaptive tolerance induction for T1D (T1D ASATI).

Catalysts, autocatalysis and the origin of metabolism.

If life on Earth started out in geochemical environments like hydrothermal vents, then it started out from gasses like CO, N and H. Anaerobic autotrophs still live from these gasses today, and they still inhabit the Earth's crust. In the search for connections between abiotic processes in ancient geological systems and biotic processes in biological systems, it becomes evident that chemical activation (catalysis) of these gasses and a constant source of energy are key.

Differential functional patterns of memory CD4 and CD8 T-cells from volunteers immunized with Ty21a typhoid vaccine observed using a recombinant Escherichia coli system expressing S. Typhi proteins.

It is widely accepted that CD4 and CD8 T-cells play a significant role in protection against Salmonella enterica serovar Typhi (S. Typhi), the causative agent of the typhoid fever. However, the antigen specificity of these T-cells remains largely unknown.