Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination.

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

Structures of Vac8-containing protein complexes reveal the underlying mechanism by which Vac8 regulates multiple cellular processes.

Vac8, a yeast vacuolar protein with armadillo repeats, mediates various cellular processes by changing its binding partners; however, the mechanism by which Vac8 differentially regulates these processes remains poorly understood. Vac8 interacts with Nvj1 to form the nuclear-vacuole junction (NVJ) and with Atg13 to mediate cytoplasm-to-vacuole targeting (Cvt), a selective autophagy-like pathway that delivers cytoplasmic aminopeptidase I directly to the vacuole. In addition, Vac8 associates with Myo2, a yeast class V myosin, through its interaction with Vac17 for vacuolar inheritance from the mother cell to the emerging daughter cell during cell divisions. Here, we determined the X-ray crystal structure of the Vac8-Vac17 complex and found that its interaction interfaces are bipartite, unlike those of the Vac8-Nvj1 and Vac8-Atg13 complexes. When the key amino acids present in the interface between Vac8 and Vac17 were mutated, vacuole inheritance was severely impaired in vivo. Furthermore, binding of Vac17 to Vac8 prevented dimerization of Vac8, which is required for its interactions with Nvj1 and Atg13, by clamping the H1 helix to the ARM1 domain of Vac8 and thereby preventing exposure of the binding interface for Vac8 dimerization. Consistently, the binding affinity of Vac17-bound Vac8 for Nvj1 or Atg13 was markedly lower than that of free Vac8. Likewise, free Vac17 had no affinity for the Vac8-Nvj1 and Vac8-Atg13 complexes. These results provide insights into how vacuole inheritance and other Vac8-mediated processes, such as NVJ formation and Cvt, occur independently of one another.

Long-term changes in the phenotype and cytokine production of monocytes in COVID-19 recovered and vaccinated individuals.

Monocytes play a crucial role in the immune response against pathogens. Here, we sought to determine COVID-19 and the vaccine Gam-COVID-Vac induce long-term changes in the phenotype and cytokine production of circulating monocytes. Monocytes were purified from peripheral blood mononuclear cells of healthy donors who had not had COVID-19 or vaccination, who had received two doses of Gam-COVID-Vac, and who had mild/moderate COVID-19 in the last 6 months and evaluated by flow cytometry. To investigate the effect of SARS-CoV-2 proteins, monocytes were cultured for 2 days with or without stimulation with recombinant SARS-CoV-2 S1 and N peptides. Monocytes obtained from vaccinated and recovered individuals showed increased basal expression of HLA-DR, CD63, CXCR2, and TLR7. We also observed an increased frequency of CD63+ classical monocytes in both groups, as well as an increased frequency of HLA-DR+ non-classical monocytes in the COVID-19-recovered group compared to the control group. Monocytes from vaccinated and recovered donors produced higher basal levels of IL-6, IL-1ß, and TNF-α cytokines. Ex vivo stimulation with SARS-CoV-2 antigens induced increased expression of HLA-DR and TLR7 on monocytes obtained from the control group. The challenge with SARS-CoV-2 antigens had no effect on the production of IL-6, IL-1ß, and TNF-α cytokines by monocytes. The acquired data offer compelling evidence of enduring alterations in both the phenotype and functional status of circulating monocytes subsequent to vaccination with Gam-COVID-Vac and mild/moderate COVID-19 infection. At least some of these changes appear to be a consequence of exposure to SARS-CoV-2 S1 and N antigens.

Does Wound VAC Temporization Offer Patient-Reported Outcomes Similar to Single-Stage Excision Reconstruction After Myxofibrosarcoma Resection?

BACKGROUND: Vacuum-assisted closure (VAC) temporization is a promising technique to achieve local control in aggressive soft tissue sarcomas. Despite its previously reported efficacy, adoption of VAC temporization remains limited, primarily due to the scarce literature on patient-reported outcomes (PROs) supporting its efficacy. This study compared the postoperative PROs after VAC temporization or single-stage (SS) excision and reconstruction for patients undergoing surgical resection for myxofibrosarcoma management. METHODS: A retrospective analysis of myxofibrosarcoma patients who underwent surgical resections at our institution from 2016 to 2022 was performed. Postoperative PROs collected prospectively for those treated with VAC temporization or SS excision/reconstruction were compared using a visual analog scale (VAS) for pain and three Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires: Global Health Short-Form Mental (SF Mental), Global Health Short-Form Physical (SF Physical), and Physical Function Short-Form 10a (SF 10a). Absolute and differential (postoperative minus preoperative) scores at the 1-month, 3-month, 6-month, 1-year, and 2-year time points were compared. RESULTS: The analysis included 79 patients (47 treated with VAC temporization and 32 treated with SS excision/reconstruction). All outcomes were similar between the groups except for physical function 1 year after surgery, in which the differential PROMIS SF 10a scores were higher in the SS group (p = 0.001). All the remaining absolute and differential PROMIS and VAS pain scores were similar between the groups at all time points. Postoperative complications did not differ between the groups. CONCLUSION: The PROs for physical and mental health, physical function, and pain were similar between the myxofibrosarcoma patients who had VAC temporization and those who had SS excision/reconstruction after surgical resection.

Effect of concurrent infection of Helicobacter pylori with Toxoplasma gondii infection on gastric pathology.

BACKGROUND: Toxoplasma gondii (T. gondii) and Helicobacter pylori (H. pylori) are among the most prevalent foodborne parasitic and bacterial infections worldwide. However, the concurrent impact of coinfection on gastric pathology has yet to be studied in depth. The effect of coinfection generally either adds a synergetic or antagonistic impact; we aimed in the current work to assess the impact of T. gondii coinfection on the progression of H. pylori-associated gastric pathology and reporting H. pylori virulent strains. The study was conducted on 82 patients complaining of persistent gastrointestinal symptoms with failed treatment response and prone to endoscopy. They were subjected to stool examination to detect H. pylori antigen, serological screening for latent toxoplasmosis, endoscopy, histopathological examination, and molecular detection of H. pylori virulence strains in gastric biopsies. Out of the 82 patients, 62 patients were positive for H. pylori antigen in stool and 55 patients confirmed positivity by histopathology; out of them, 37 patients had isolated Vac As1 variants, 11 patients had combined Vac As1 and Cag A variants, and 7 patients had combined Vac As1, Cag A and VacAs2 variants. Patients with the combined two or three variances showed significantly deteriorated histopathological features than patients with a single Vac As1 variant (P < 0.05). Latent toxoplasmosis was positive among 35/82 patients. Combined H. pylori and Toxoplasma gondii infection had significantly marked inflammation than patients with isolated infection (P < 0.05). CONCLUSION: Screening for toxoplasmosis among H. pylori-infected patients is recommended as it is considered a potential risk factor for gastric inflammation severity. H. pylori gastric inflammation may be heightened by Toxoplasma coinfection.

Managing incisional wounds with Prevena VAC therapy in lower-extremity vascular surgery: A comparative study.

BACKGROUND: Vascular surgical site infections have been reported with an overall incidence of 5-10% for patients undergoing arterial interventions and as high as 10-20% for lower-limb bypass grafting procedures. Given that vascular surgery patients are known to be at a higher risk of postoperative wound infections and other complications, our objective was to evaluate a potential method to reduce such complications. This study compares the rate of wound healing complications between incisional negative pressure wound therapy (NPWT) and conventional dressings in vascular surgery patients with infra-inguinal incisions. The primary endpoint is complete closure of the wound at the 2-week follow-up appointment. Secondary endpoints include frequency infections requiring antibiotics, need for wound revision, and wound dehiscence. METHODS: A prospective cohort study with retrospective control group was performed following infra-inguinal vascular surgeries for peripheral arterial disease at the Mount Carmel Health System. The patients included in this study were those who underwent a lower-extremity vascular procedure with primary closure of an incision distal to the groin between January 2014 and July 2018. Patients that had received an infra-inguinal incision with primary closure were included. Patients in the experimental group who had a Prevena Wound VAC were compared with a retrospectively obtained control arm treated with conventional dressings. Data regarding wound healing and complications, specifically infections and wound dehiscence, were obtained. RESULTS: A total of 201 patients were recruited in our study: 64 in the Prevena group and 137 in the control group. There was a significant reduction in the number of open wounds in the Prevena group compared to the control group at the 2-week follow-up (10.9% Prevena vs 33.6% control; p = .0005). When evaluated in aggregate, there was a statistically significant reduction in the number of patients who succumbed to any complication in the Prevena arm compared with traditional dressings (13 (20.3%) Prevena vs 72 (52.6%) control; p < .0001). CONCLUSION: The results of our study suggest there should be a significant consideration for the use of NPWT as a prophylactic measure to reduce the risk of wound complications of primarily closed infra-inguinal incisions in vascular surgery patients following common vascular procedures. Its use is particularly effective for patients at enhanced risk of infection, especially those with poor vascularization from BMI, smoking, and diabetes. This leads to decreased trends in antibiotic use, ED visits, readmissions, and surgical revisions, which translates to decreased utilization of hospital resources and economic burden.

[Successful treatment of severe purulent peritonitis against the background of intraperitoneal hypertension syndrome (clinical case)]. / Uspeshnoe lechenie tyazhelogo gnoinogo peritonita na fone sindroma vnutribryushnoi gipertenzii (klinicheskii sluchai).

Traditional surgical treatment of widespread purulent peritonitis has some disadvantages that emphasizes the need for new approaches to postoperative care. The authors present successful treatment of diffuse purulent peritonitis using a combination of 'open abdomen' technology and VAC therapy. This approach reduces abdominal inflammation and intra-abdominal pressure. Combination of 'open abdomen' technology and VAC therapy provides effective control of inflammation and stabilization of patients with purulent peritonitis.

Does prophylactic negative pressure wound therapy prevent surgical site infection in abdominal surgery?

OBJECTIVE: To determine if prophylactic negative pressure wound therapy (pNPWT) allows for the prevention of surgical site infections (SSIs) in abdominal surgery. METHOD: A non-systematic review assessing the evidence was conducted in 2020. RESULTS: Retrospectve studies comparing patients with pNPWT with patients receiving standard wound dressing after abdominal surgery showed encouragning results in favour of pNPWT for reducing the incidence of SSIs, but randomised controlled trials have so far reported mixed results. CONCLUSION: New randomised controlled trials including a sufficient number of patients at risk of SSIs are needed for confirming the results of non-interventional studies.

Biodegradable temporising matrix: use of negative pressure wound therapy shows a significantly higher success rate.

OBJECTIVE: The purpose of this case series was to evaluate the efficacy of a synthetic biodegradable temporising matrix (BTM; PolyNovo Biomaterials Pty Ltd, Australia) and compare the outcome of BTM patients with and without negative pressure wound therapy (NPWT). METHOD: A retrospective chart review was conducted on patients admitted with deep full-thickness burns, traumatic or complex wound injuries treated with BTM. Electronic medical records and images were evaluated by a team of clinical professionals. Endpoints included: the measure of successful BTM integration; and comparison between patients treated with and without NPWT. Additional measures were BTM total surface area, BTM sites, timeliness of BTM application and any complications. RESULTS: A total of 28 patients were evaluated and 23 (82.1%) demonstrated overall successful BTM integration. Patients treated with BTM in conjunction with NPWT (n=16) demonstrated a significantly higher (p=0.046) integration rate compared to patients treated without NPWT (n=12) (93.8% versus 58.3%, respectively). Patients treated with BTM with NPWT continued to successfully integrate and sustain favourable outcomes despite the presence of severe infection or the development of haematomas. CONCLUSION: A significantly higher integration rate was demonstrated when BTM was used in conjunction with NPWT. The results of this study further support the efficacy of successful integration of BTM as a replacement for tissue loss in the treatment of deep, full-thickness burns, traumatic and complex wound injuries, and particularly favourable outcomes with the use of NPWT. To the best of our knowledge, this is the first reported case series comparing the clinical outcomes of BTM with and without the use of NPWT.

Is vacuum-assisted closure therapy the main culprit in right ventricular rupture after deep sternal wound infection?

Right ventricular rupture after deep sternal wound infection (DSWI) is a rare but fatal complication, and can occur with or without vacuum assisted closure (VAC) therapy. There is currently no strong evidence to suggest whether or not VAC therapy is a contributing factor to this complication. In total, 30 articles were retrieved and assessed through a systematic review strategy from 1953 to 2022. The keywords: 'vacuum assisted closure'; 'VAC'; 'negative pressure wound therapy'; 'deep sternal wound infection'; 'DSWI'; 'right ventricular rupture'; and 'cardiac rupture' were used in the search. Overall, 15 of the included articles satisfied the predefined eligibility criteria. Fatal right ventricular ruptures were reported in 18 (36%) out of 50 cases. In this article, the risk factors, mechanisms and management of right ventricular rupture are discussed. A novel view of the mechanism of VAC-associated right ventricular rupture is highlighted, with a focus on both pre- and intraoperative management.

Dissection of Antibody Responses of Gam-COVID-Vac-Vaccinated Subjects Suggests Involvement of Epitopes Outside RBD in SARS-CoV-2 Neutralization.

Millions of people have been vaccinated with Gam-COVID-Vac but fine specificities of induced antibodies have not been fully studied. Plasma from 12 naïve and 10 coronavirus disease 2019 (COVID-19) convalescent subjects was obtained before and after two immunizations with Gam-COVID-Vac. Antibody reactivity in the plasma samples (n = 44) was studied on a panel of micro-arrayed recombinant folded and unfolded severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins and 46 peptides spanning the spike protein (S) and by immunoglobulin G (IgG) subclass enzyme-linked immunosorbent assay (ELISA). The ability of Gam-COVID-Vac-induced antibodies to inhibit binding of the receptor-binding domain (RBD) to its receptor angiotensin converting enzyme 2 (ACE2) was investigated in a molecular interaction assay (MIA). The virus-neutralizing capacity of antibodies was studied by the pseudo-typed virus neutralization test (pVNT) for Wuhan-Hu-1 and Omicron. We found that Gam-COVID-Vac vaccination induced significant increases of IgG1 but not of other IgG subclasses against folded S, spike protein subunit 1 (S1), spike protein subunit 2 (S2), and RBD in a comparable manner in naïve and convalescent subjects. Virus neutralization was highly correlated with vaccination-induced antibodies specific for folded RBD and a novel peptide (i.e., peptide 12). Peptide 12 was located close to RBD in the N-terminal part of S1 and may potentially be involved in the transition of the pre- to post-fusion conformation of the spike protein. In summary, Gam-COVID-Vac vaccination induced S-specific IgG1 antibodies in naive and convalescent subjects in a comparable manner. Besides the antibodies specific for RBD, the antibodies induced against a peptide close to the N-terminus of RBD were also associated with virus-neutralization.

T-Cell Immunity in COVID-19-Recovered Individuals and Individuals Vaccinated with the Combined Vector Vaccine Gam-COVID-Vac.

The COVID-19 pandemic has required extensive research on the new coronavirus SARS-CoV-2 and the creation of new highly effective vaccines. The presence of T-cells in the body that respond to virus antigens suggests adequate antiviral immunity. We investigated T-cell immunity in individuals who recovered from mild and moderate COVID-19 and in individuals vaccinated with the Gam-COVID-Vac combined vector vaccine. The ELISPOT method was used to determine the number of T-cells responding with IFN-γ synthesis to stimulation by peptides containing epitopes of the S-protein or N-, M-, ORF3, and ORF7 proteins, using peripheral blood mononuclear cells (PBMCs). At the same time, the multiplex method was used to determine the accumulation of IFN-γ and other cytokines in the culture medium. According to the data obtained, the proportion of positive conclusions about the T-cell immune response to SARS-CoV-2 antigens in control, recovered, and vaccinated individuals was 12%, 70%, and 52%, respectively. At the same time, more than half of the vaccinated individuals with a T-cell response were sensitized to the antigens of N-, M-, ORF3, and ORF7 proteins not produced by Gam-COVID-Vac, indicating a high likelihood of asymptomatic SARS-CoV-2 infection. Increased IFN-γ release by single sensitized T-cells in response to specific stimulation in recovered and vaccinated individuals did not result in the accumulation of this and other cytokines in the culture medium. These findings suggest a balance between cytokine production and utilization by immunocompetent cells as a prerequisite for providing a controlled cytokine signal and avoiding a "cytokine storm".

TMEM106B in humans and Vac7 and Tag1 in yeast are predicted to be lipid transfer proteins.

TMEM106B is an integral membrane protein of late endosomes and lysosomes involved in neuronal function, its overexpression being associated with familial frontotemporal lobar degeneration, and point mutation linked to hypomyelination. It has also been identified in multiple screens for host proteins required for productive SARS-CoV-2 infection. Because standard approaches to understand TMEM106B at the sequence level find no homology to other proteins, it has remained a protein of unknown function. Here, the standard tool PSI-BLAST was used in a nonstandard way to show that the lumenal portion of TMEM106B is a member of the late embryogenesis abundant-2 (LEA-2) domain superfamily. More sensitive tools (HMMER, HHpred, and trRosetta) extended this to predict LEA-2 domains in two yeast proteins. One is Vac7, a regulator of PI(3,5)P2 production in the degradative vacuole, equivalent to the lysosome, which has a LEA-2 domain in its lumenal domain. The other is Tag1, another vacuolar protein, which signals to terminate autophagy and has three LEA-2 domains in its lumenal domain. Further analysis of LEA-2 structures indicated that LEA-2 domains have a long, conserved lipid-binding groove. This implies that TMEM106B, Vac7, and Tag1 may all be lipid transfer proteins in the lumen of late endocytic organelles.

The vacuolar morphology protein VAC14 plays an important role in sexual development in the filamentous ascomycete Sordaria macrospora.

The multiprotein Fab1p/PIKfyve-complex regulating the abundance of the phospholipid phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is highly conserved among eukaryotes. In yeast/mammals, it is composed of the phosphatidylinositol 3-phosphate 5-kinase Fab1p/PIKfyve, the PtdIns(3,5)P2 phosphatase Fig4p/Sac3 and the scaffolding subunit Vac14p/ArPIKfyve. The complex is located to vacuolar membranes in yeast and to endosomal membranes in mammals, where it controls the synthesis and turnover of PtdIns(3,5)P2. In this study, we analyzed the role and function of the Fab1p/PIKfyve-complex scaffold protein SmVAC14 in the filamentous ascomycete Sordaria macrospora (Sm). We generated the Smvac14 deletion strain ∆vac14 and performed phenotypic analysis of the mutant. Furthermore, we conducted fluorescence microscopic localization studies of fluorescently labeled SmVAC14 with vacuolar and late endosomal marker proteins. Our results revealed that SmVAC14 is important for maintaining vacuolar size and appearance as well as proper sexual development in S. macrospora. In addition, SmVAC14 plays an important role in starvation stress response. Accordingly, our results propose that the turnover of PtdIns(3,5)P2 is of great significance for developmental processes in filamentous fungi.

Preparation of colloidal nanoparticles PVA-PHEMA from hydrolysis of copolymers of PVAc-PHEMA as anticancer drug carriers.

The novel pH-responsive polymer nanoparticles have been widely used for drug delivery and cancer therapy. The pH-sensitive nanoparticles include chemical structures that can accept or donate protons in response to an environmental pH change. Polybases which mostly contain alkaline groups such as amines and hydroxy, accept protons at low pH and are neutral at higher pH values. This study aimed to prepare pH-sensitive colloidal amphiphilic poly(vinyl alcohol-2-hydroxyethyl methacrylate) (PVA-PHEMA) copolymers in cancer therapy applications. For this purpose, poly(vinyl acetate-2-hydroxyethyl methacrylate) (PVAc-PHEMA) copolymer nanoparticles were synthesized in different polymerization medium fractions from water and methanol and different monomer feed concentration. Then acetate groups were hydrolyzed, and the PHEMA-PVA nanoparticles were synthesized. The nanoparticles were further characterized using dynamic light scattering, Fourier transform infrared spectroscopy, scanning electron microscopy, and thermogravimetric analysis to identify the structural and morphological changes. The Methotrexate (MTX) was loaded into the nanoparticles, and drug release kinetics were evaluated. The results confirmed that PHEMA-PVA copolymeric nanoparticles could be favorably used in cancer therapy.

Modified application of vacuum-assisted closure in thoracic surgery patients.

OBJECTIVE: Surgical site infection (SSI), ranging from superficial, deep and to organ space, is one of the major predictors for morbidity and mortality in patients undergoing thoracic surgery. Care to accelerate SSI healing is taken to shorten hospital stay and reduce costs. The deep application of vacuum-assisted closure (VAC) in thoracic patients is not well established in the literature. In this study, the deep application and safety of VAC therapy in patients with various thoracic pathologies was evaluated. METHOD: A retrospective chart review of all patients who were admitted to the thoracic surgery service between July 2014 and July 2018 and who developed deep SSI was carried out. RESULTS: A total of 12 patients were included, and their demographic data analysed. There were various thoracic pathologies complicated with postoperative deep SSI treated with VAC. The duration of VAC application ranged from 4-40 days with an average hospital stay of 37.6 days. All patients showed clinical, radiological and microbiological improvement rather than developing complications except for one case of mortality due to septicaemia. CONCLUSION: In this study, partial intrapleural VAC therapy was safe for use in patients who underwent thoracic surgery, regardless of the underling pathology, with caution (i.e., with continued monitoring of the patient's tolerance to the treatment). The overall hospital stay may be reduced with the use of VAC. It also decreased perioperative morbidity, secondary to wound infection.

The effect of storage method on selected physicochemical and microbiological qualities of wild boar meat.

BACKGROUND: This study investigated the influence of the storage method on the physicochemical characteristics and microbial growth of m. longissimus thoracis et lumborum (LTL), m. biceps femoris (BF) and m. vastus lateralis (VL) of wild boar. Muscles were stored in a vacuum (VAC), in a modified high-oxygen atmosphere (MAP) or meat seasoning cabinet (DRY-AGED) for 21 days. RESULTS: Wild boar meat was characterised by a high protein and low fat content and a good amount of potassium, sodium, calcium, magnesium, zinc and iron. Significantly higher (P < 0.05) pH values were noted for DRY-AGED muscles stored for 21 days (up to 5.89 for VL). On day 21, a significant decrease in pH was noted for all MAP muscles (down to 5.23 for BF). Storage losses due to desiccation and water loss were significantly higher for DRY-AGED samples and ranged from 25.63% to 32.89% on day 21. MAP affected protein and lipid oxidation, which was also reflected in Warner-Bratzler shear force VAC and DRY-AGED had positive results regarding tenderness, whereas on day 21 the MAP-stored meat had toughened significantly (from 35.3 N to 50.7 N in LTL). Lipids were oxidised much faster than proteins during prolonged storage in MAP. Compared to the other methods, DRY-AGED had the best effect on microbial growth. CONCLUSION: These results indicate that the recommended methods for the storage of wild boar meat are either vacuum packing or dry ageing. The high oxygen content of MAP negatively affected the quality of wild boar meat and carried a risk of increased protein carbonylation. © 2022 Society of Chemical Industry.

Resource Recovery and the Sherwood Plot.

Our work analyzes the biophysical and economic foundations of the Sherwood Plot (SP). In general, the SP depicts the theoretical relationship between the cost of recovering a target material or an identified Value Added Compound (VAC) from a waste matrix and its dilution in the waste matrix; specifically suggesting that the recovery cost is reverse proportional to the VAC's dilution in it. We further utilize the SP as a scientifically consistent and economically coherent analytical framework for measuring resource recovery performance. Initially, we analyze the SP's fundamental physical properties, as well as its many potential economic extensions. Specifically, we substantiate the relation between a VAC's Entropy, Dilution and Recovery Cost. On these grounds we present the SP's remarkable and numerous economic properties that make it consistent to its physical foundations; thus integrating concisely its physical and economic aspects and postulate a generalized SP function. We further test econometrically the validity of an SP based on both deterministic and stochastic real data from a small-scale industrial unit of polyphenols' recovery from natural fruit juice production residual wastewater. In turn, based on the fusion of our theoretical argumentation and empirical findings we dive into the epistemological extensions of the SP. Specifically, we study how the recovery cost structure at the single industry level is revealed by the SP and can be useful for postulating cost structure ontologies. Cost ontologies are in turn useful as a diagnostic of the formation process of VAC recovery markets as well as their structure and concentration, defining the industrial shares when many industries operate in the recovery of the same VAC.

Features of the Humoral Response to Infection, Vaccination, and Revaccination during COVID-19.

IgM and IgG antibodies to the SARS-CoV-2 virus are detected in subjects who have recovered from COVID-19; IgM antibodies persist in a 1/3 of infected subjects up to 12 months from the moment of the disease, while IgG antibodies are present in the vast majority of cases (97%; medium and high levels antibodies were registered in 85% of cases). By the 12th month, 40% of those who recovered still have a very high level of IgG antibodies to the S-protein (>500 BAU/ml). In the feces, urine, and blood serum of patients with long-term persistent IgM antibodies, no coronavirus antigens were detected. After vaccination with the Gam-COVID-Vac vaccine, IgG antibodies to the S-protein are detected in 100% of cases and remain at a high level for 4 months, by the 5-6th month, the level of antibodies decreases. During revaccination, the level of IgG antibodies to S-protein reaches high values earlier than during primary vaccination, and remains high for 4 months (observation period). The blood sera of recovered and vaccinated patients have a high virus-neutralizing activity (at least 1:80), while its level is somewhat higher in recovered patients.

Proximity Interactome Map of the Vac14-Fig4 Complex Using BioID.

Conversion between phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate on endosomal membranes is critical for the maturation of early endosomes to late endosomes/lysosomes and is regulated by the PIKfyve-Vac14-Fig4 complex. Despite the importance of this complex for endosomal homeostasis and vesicular trafficking, there is little known about how its activity is regulated or how it interacts with other cellular proteins. Here, we screened for the cellular interactome of Vac14 and Fig4 using proximity-dependent biotin labeling (BioID). After independently screening the interactomes of Vac14 and Fig4, we identified 89 high-confidence protein hits shared by both proteins. Network analysis of these hits revealed pathways with known involvement of the PIKfyve-Vac14-Fig4 complex, including vesicular organization and PI3K/Akt signaling, as well as novel pathways including cell cycle and mitochondrial regulation. We also identified subunits of coatomer complex I (COPI), a Golgi-associated complex with an emerging role in endosomal dynamics. Using proximity ligation assays, we validated the interaction between Vac14 and COPI subunit COPB1 and between Vac14 and Arf1, a GTPase required for COPI assembly. In summary, this study used BioID to comprehensively map the Vac14-Fig4 interactome, revealing potential roles for these proteins in diverse cellular processes and pathways, including preliminary evidence of an interaction between Vac14 and COPI. Data are available via ProteomeXchange with the identifier PXD027917.