Given the continuing COVID-19 pandemic and much of the U.S. implementing social distancing owing to the lack of alternatives, there has been a push to develop a vaccine to eliminate the need for ...social distancing.
In 2020, the team developed a computational model of the U.S. simulating the spread of COVID-19 coronavirus and vaccination.
Simulation experiments revealed that to prevent an epidemic (reduce the peak by >99%), the vaccine efficacy has to be at least 60% when vaccination coverage is 100% (reproduction number=2.5–3.5). This vaccine efficacy threshold rises to 70% when coverage drops to 75% and up to 80% when coverage drops to 60% when reproduction number is 2.5, rising to 80% when coverage drops to 75% when the reproduction number is 3.5. To extinguish an ongoing epidemic, the vaccine efficacy has to be at least 60% when coverage is 100% and at least 80% when coverage drops to 75% to reduce the peak by 85%–86%, 61%–62%, and 32% when vaccination occurs after 5%, 15%, and 30% of the population, respectively, have already been exposed to COVID-19 coronavirus. A vaccine with an efficacy between 60% and 80% could still obviate the need for other measures under certain circumstances such as much higher, and in some cases, potentially unachievable, vaccination coverages.
This study found that the vaccine has to have an efficacy of at least 70% to prevent an epidemic and of at least 80% to largely extinguish an epidemic without any other measures (e.g., social distancing).
Cysteine can be specifically functionalized by a myriad of acid-base conjugation strategies for applications ranging from probing protein function to antibody-drug conjugates and proteomics. In ...contrast, selective ligation to the other sulfur-containing amino acid, methionine, has been precluded by its intrinsically weaker nucleophilicity. Here, we report a strategy for chemoselective methionine bioconjugation through redox reactivity, using oxaziridine-based reagents to achieve highly selective, rapid, and robust methionine labeling under a range of biocompatible reaction conditions. We highlight the broad utility of this conjugation method to enable precise addition of payloads to proteins, synthesis of antibody-drug conjugates, and identification of hyperreactive methionine residues in whole proteomes.
HIV-1 broadly neutralizing antibodies (bnAbs) develop in a subset of infected adults and exhibit high levels of somatic hypermutation (SHM) due to years of affinity maturation. There is no precedent ...for eliciting highly mutated antibodies by vaccination, nor is it practical to wait years for a desired response. Infants develop broad responses early, which may suggest a more direct path to generating bnAbs. Here, we isolated ten neutralizing antibodies (nAbs) contributing to plasma breadth of an infant at ∼1 year post-infection, including one with cross-clade breadth. The nAbs bind to envelope trimer from the transmitted virus, suggesting that this interaction may have initiated development of the infant nAbs. The infant cross-clade bnAb targets the N332 supersite on envelope but, unlike adult bnAbs targeting this site, lacks indels and has low SHM. The identification of this infant bnAb illustrates that HIV-1-specific neutralization breadth can develop without prolonged affinity maturation and extensive SHM.
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•Infant HIV-1 nAbs isolated at ∼1 year post-infection contribute to plasma breadth•An infant broadly neutralizing antibody targets a known Env supersite•Infant nAbs bind early transmitted Envs but do not neutralize corresponding virus•Infant HIV-1 neutralizing antibodies have low levels of somatic hypermutation
Potent and broad neutralizing antibody responses to HIV typically take years to develop in infected adults, but new data in infected infants reveal a different pathway for their rapid development.
Over the course of roughly a decade, the lasso peptide field has been transformed. Whereas new compounds were discovered infrequently via activity-driven approaches, now, the vast majority of lasso ...peptide discovery is driven by genome-mining approaches. This paper starts with a historical overview of the first genome-mining approaches for lasso peptide discovery, and then covers new tools that have emerged. Several examples of novel lasso peptides that have been discovered via genome mining are presented as are examples of new enzymes found associated with lasso peptide gene clusters. Finally, this paper concludes with future directions and unsolved challenges in lasso peptide genome mining.
Catalytic upgrading of bio-oils by esterification Ciddor, Lachlan; Bennett, James A; Hunns, James A ...
Journal of chemical technology and biotechnology (1986),
20/May , Letnik:
90, Številka:
5
Journal Article
While the positive relationship between avian diversity and habitat heterogeneity is widely accepted, it is primarily based on observed species richness without accounting for imperfect detection. ...Other facets of diversity such as functional diversity are also rarely explored. We investigated the avian diversity-landscape heterogeneity relationship in agricultural landscapes by considering two aspects of diversity: taxonomic diversity (species richness) estimated from a multi-species dynamic occupancy model, and functional diversity (functional evenness FEve and divergence FDiv) based on traits of occurring species. We also assessed how agricultural lands enrolled in a conservation program managed on behalf of declining early successional bird species (hereafter CP38 fields, an agri-environment scheme) influenced avian diversity. We analyzed breeding bird data collected at CP38 fields in Mississippi, USA, during 2010-2012, and two principal components of environmental variables: a gradient of heterogeneity (Shannon's landscape diversity index) and of the amount of CP38 fields (percent cover of CP38 fields; CP38). FEve did not show significant responses to environmental variables, whereas FDiv responded positively to heterogeneity and negatively to CP38. However, most FDiv values did not significantly differ from random expectations along an environmental gradient. When there was a significant difference, FDiv was lower than that expected. Unlike functional diversity, species richness showed a clear pattern. Species richness increased with increasing landscape heterogeneity but decreased with increasing amounts of CP38 fields. Only one species responded negatively to heterogeneity and positively to CP38. Our results suggest that the relationships between avian diversity and landscape heterogeneity may vary depending on the aspect of diversity considered: strong positive effects of heterogeneity on taxonomic diversity, but weakly positive or non-significant effects on functional diversity. Our results also indicate that effectiveness of CP38 in conserving avian diversity, particularly, taxonomic diversity, could be limited without the consideration of landscape heterogeneity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE: Primary hyperparathyroidism (pHPT) is a common clinical problem for which the only definitive management is surgery. Surgical management has evolved considerably during the last several ...decades. OBJECTIVE: To develop evidence-based guidelines to enhance the appropriate, safe, and effective practice of parathyroidectomy. EVIDENCE REVIEW: A multidisciplinary panel used PubMed to review the medical literature from January 1, 1985, to July 1, 2015. Levels of evidence were determined using the American College of Physicians grading system, and recommendations were discussed until consensus. FINDINGS: Initial evaluation should include 25-hydroxyvitamin D measurement, 24-hour urine calcium measurement, dual-energy x-ray absorptiometry, and supplementation for vitamin D deficiency. Parathyroidectomy is indicated for all symptomatic patients, should be considered for most asymptomatic patients, and is more cost-effective than observation or pharmacologic therapy. Cervical ultrasonography or other high-resolution imaging is recommended for operative planning. Patients with nonlocalizing imaging remain surgical candidates. Preoperative parathyroid biopsy should be avoided. Surgeons who perform a high volume of operations have better outcomes. The possibility of multigland disease should be routinely considered. Both focused, image-guided surgery (minimally invasive parathyroidectomy) and bilateral exploration are appropriate operations that achieve high cure rates. For minimally invasive parathyroidectomy, intraoperative parathyroid hormone monitoring via a reliable protocol is recommended. Minimally invasive parathyroidectomy is not routinely recommended for known or suspected multigland disease. Ex vivo aspiration of resected parathyroid tissue may be used to confirm parathyroid tissue intraoperatively. Clinically relevant thyroid disease should be assessed preoperatively and managed during parathyroidectomy. Devascularized normal parathyroid tissue should be autotransplanted. Patients should be observed postoperatively for hematoma, evaluated for hypocalcemia and symptoms of hypocalcemia, and followed up to assess for cure defined as eucalcemia at more than 6 months. Calcium supplementation may be indicated postoperatively. Familial pHPT, reoperative parathyroidectomy, and parathyroid carcinoma are challenging entities that require special consideration and expertise. CONCLUSIONS AND RELEVANCE: Evidence-based recommendations were created to assist clinicians in the optimal treatment of patients with pHPT.
The rise of antibiotic-resistant strains of bacterial pathogens has necessitated the development of new therapeutics. Antimicrobial peptides (AMPs) are a class of compounds with potentially ...attractive therapeutic properties, including the ability to target specific groups of bacteria. In nature, AMPs exhibit remarkable structural and functional diversity, which may be further enhanced through genetic engineering, high-throughput screening, and chemical modification strategies. In this review, we discuss the molecular mechanisms underlying AMP selectivity and highlight recent computational and experimental efforts to design selectively targeting AMPs. While there has been an extensive effort to find broadly active and highly potent AMPs, it remains challenging to design targeting peptides to discriminate between different bacteria on the basis of physicochemical properties. We also review approaches for measuring AMP activity, point out the challenges faced in assaying for selectivity, and discuss the potential for increasing AMP diversity through chemical modifications.
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