Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal.

We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.

Changes in growth and reproductive phenology of Allagoptera arenaria (Arecaceae) under climate change scenarios.

Climate change has led to shifts in phenology in many species distributed widely across taxonomic groups. It is, however, unclear how we should interpret these shifts without some sort of a yardstick. We assessed climate change effects on Allagoptera arenaria, a acaulescent palm, using open top chambers (OTCs) and rain gutters in the field to mimic expected temperature and rainfall changes in this area. In a coastal environment (restinga), using open top chambers (OTCs) and rain gutters in the field to mimic expected temperature and rainfall changes in this area, 40 A. arenaria individuals were selected and randomly allocated to four treatments: control (C), 25% rainfall increase (P), 2 °C temperature increase (T), and 2 °C temperature plus 25% rainfall increase (TP). For 2 years, every two weeks, we measured changes in growth and reproduction phenology to assess whether this species altered allocation patterns in response to new environmental conditions. Increases in aboveground biomass were higher in the TP than in the T treatment, which in turn had more reproductive cycles throughout the experimental period. We conclude that temperature increases may shorten the reproductive cycle of A. arenaria.

Tracking SARS-CoV-2 lineage B.1.1.7 dissemination: insights from nationwide spike gene target failure (SGTF) and spike gene late detection (SGTL) data, Portugal, week 49 2020 to week 3 2021.

We show that the SARS-CoV-2 B.1.1.7 lineage is highly disseminated in Portugal, with the odds of B.1.1.7 proportion increasing at an estimated 89% (95% confidence interval: 83-95%) per week until week 3 2021. RT-PCR spike gene target late detection (SGTL) can constitute a useful surrogate to track B.1.1.7 spread, besides the spike gene target failure (SGTF) proxy. SGTL/SGTF samples were associated with statistically significant higher viral loads, but not with substantial shift in age distribution compared to non-SGTF/SGTL cases.

Secondary forest fragments offer important carbon and biodiversity cobenefits.

Tropical forests store large amounts of carbon and high biodiversity, but are being degraded at alarming rates. The emerging global Forest and Landscape Restoration (FLR) agenda seeks to limit global climate change by removing carbon dioxide from the atmosphere through the growth of trees. In doing so, it may also protect biodiversity as a free cobenefit, which is vital given the massive shortfall in funding for biodiversity conservation. We investigated whether natural forest regeneration on abandoned pastureland offers such cobenefits, focusing for the first time on the recovery of taxonomic diversity (TD), phylogenetic diversity (PD) and functional diversity (FD) of trees, including the recovery of threatened and endemic species richness, within isolated secondary forest (SF) fragments. We focused on the globally threatened Brazilian Atlantic Forest, where commitments have been made to restore 1 million hectares under FLR. Three decades after land abandonment, regenerating forests had recovered ~20% (72 Mg/ha) of the above-ground carbon stocks of a primary forest (PF), with cattle pasture containing just 3% of stocks relative to PFs. Over this period, SF recovered ~76% of TD, 84% of PD and 96% of FD found within PFs. In addition, SFs had on average recovered 65% of threatened and ~30% of endemic species richness of primary Atlantic forest. Finally, we find positive relationships between carbon stock and tree diversity recovery. Our results emphasize that SF fragments offer cobenefits under FLR and other carbon-based payments for ecosystem service schemes (e.g. carbon enhancements under REDD+). They also indicate that even isolated patches of SF could help to mitigate climate change and the biodiversity extinction crisis by recovering species of high conservation concern and improving landscape connectivity.

Insulin Release Mechanism Modulated by Toxins Isolated from Animal Venoms: From Basic Research to Drug Development Prospects.

Venom from mammals, amphibians, snakes, arachnids, sea anemones and insects provides diverse sources of peptides with different potential medical applications. Several of these peptides have already been converted into drugs and some are still in the clinical phase. Diabetes type 2 is one of the diseases with the highest mortality rate worldwide, requiring specific attention. Diverse drugs are available (e.g., Sulfonylureas) for effective treatment, but with several adverse secondary effects, most of them related to the low specificity of these compounds to the target. In this context, the search for specific and high-affinity compounds for the management of this metabolic disease is growing. Toxins isolated from animal venom have high specificity and affinity for different molecular targets, of which the most important are ion channels. This review will present an overview about the electrical activity of the ion channels present in pancreatic ß cells that are involved in the insulin secretion process, in addition to the diversity of peptides that can interact and modulate the electrical activity of pancreatic ß cells. The importance of prospecting bioactive peptides for therapeutic use is also reinforced.

Performance and ingestive behavior of steers on integrated system using legume and/or energy supplementation.

This study aimed to evaluate the effect of a mixture of temperate and legume grasses with or without energy supplementation on the performance and feeding behavior of finishing beef steers. Eighteen Nellore-Zebu steers, average 23 months old and body weight (BW) of 380 kg, were used in a continuous grazing system, in a randomized block experimental design. Treatments were ORS: oat (Avena strigosa Schreb) + annual ryegrass (Lolium multiflorum Lam) + supplementation with corn bran; ORVS: oat + ryegrass + vetch (Vicia sativa L.) + supplementation with corn bran; and ORV: oat + ryegrass + vetch. Evaluations were conducted on pasture (forage mass, sward height, herbage accumulation, botanical composition, and chemical composition) and animal (performance and ingestive behavior). Stocking rate and forage mass were greater in treatments with energy supplementation (ORVS and ORS), thus presenting greater sward heights compared to the treatment without supplementation. There was greater participation of oats and ryegrass when vetch was absent (ORS). The presence of supplement (ORS and ORVS) increased the presence of oat stem. The presence of the supplement caused the contribution of the vetch to be lower, likely because of the higher animal load of these treatments. The higher presence of vetch increased crude protein content in the ORV treatment. The ORS exhibited greater gain per area compared to the ORV. Supplemented animals had lower grazing and greater idle time. The ORS treatment animals spent more time in other activities and consumed supplementation and less time grazing than the other treatments. The absence of supplement (ORV) caused the animals to spend more time grazing. Animals not supplemented showed a higher duration of daily chewing, number of chews per minute, number of daily chews, daily number of bites, and station numbers.

Backgrounding steers on temperate grasses mixed with vetch and/or using energy supplementation.

OBJECTIVE: The aim was to evaluate backgrounding beef steers on oat + ryegrass pastures mixed with vetch and/or using energy supplementation. METHODS: A randomized block design with three treatments and three replications was used. The treatments were: grass + supplement (oat + ryegrass + supplementation), legume + supplement (oat + ryegrass + vetch + supplementation) and grass + legume (oat + ryegrass + vetch). A continuous grazing system with a variable stocking rate was used. Twenty-seven intact crossbred steers (1/4 Marchigiana, 1/4 Aberdeen Angus and 2/4 Nellore) aged 7 months old and average weight of 190 kg were used. Steers were supplemented at 1% of the body weight of ground corn. The experiment lasted 84 days, between May and August 2014. Behavioral assessments were performed two times per experimental period, for 24 hours. RESULTS: The forage mass was different between treatments, being greater for steers fed without legume. The accumulation rate, forage allowance, and stocking rate did not differ between treatments due to the adequate adjustment of forage allowance. The final weight of animals, as well as the dry matter intake (kg/d), did not differ between treatments. However, forage intake was higher for non-supplemented animals in relation to supplemented steers. Supplement intake did not alter the total digestible nutrient intake due to pasture quality. Animals fed grass + supplement had higher live weight gain per area than those fed grass + legume. Animals without supplementation spent more time in grazing. CONCLUSION: Feeding behavior was not altered by mixing with vetch or supplementation. Non-supplemented animals started the grazing peak earlier and spent more time in grazing than those supplemented; however, the average daily gain was similar between treatments. The live weight gain per hectare was 47% higher in pastures in which the animals received supplementation compared with those mixed with vetch, a consequence of the substitutive effect.

A novel model of autosomal recessive polycystic kidney questions the role of the fibrocystin C-terminus in disease mechanism.

Autosomal recessive polycystic kidney disease (OMIM 263200) is a serious condition of the kidney and liver caused by mutations in a single gene, PKHD1. This gene encodes fibrocystin/polyductin (FPC, PD1), a large protein shown by in vitro studies to undergo Notch-like processing. Its cytoplasmic tail, reported to include a ciliary targeting sequence, a nuclear localization signal, and a polycystin-2 binding domain, is thought to traffic to the nucleus after cleavage. We now report a novel mouse line with a triple HA-epitope "knocked-in" to the C-terminus along with lox P sites flanking exon 67, which encodes most of the C-terminus (Pkhd1Flox67HA). The triple HA-epitope has no functional effect as assayed by phenotype and allows in vivo tracking of Fibrocystin. We used the HA tag to identify previously predicted Fibrocystin cleavage products in tissue. In addition, we found that Polycystin-2 fails to co-precipitate with Fibrocystin in kidney samples. Immunofluorescence studies with anti-HA antibodies demonstrate that Fibrocystin is primarily present in a sub-apical location the in kidney, biliary duct, and pancreatic ducts, partially overlapping with the Golgi. In contrast to previous studies, the endogenous protein in the primary cilia was not detectable in mouse tissues. After Cre-mediated deletion, homozygous Pkhd1Δ67 mice are completely normal. Thus, Pkhd1Flox67HA is a valid model to track Pkhd1-derived products containing the C-terminus. Significantly, exon 67 containing the nuclear localization signal and the polycystin-2 binding domain is not essential for Fibrocystin function in our model.

Post-fire regeneration in seasonally dry tropical forest fragments in southeastern Brazil.

Seasonally dry tropical forest is one of the highly threatened biome. However, studies on the effect of fire on these tree communities are still scarce. In this context, a floristic and structural survey in three forest areas in the southeast of Brazil that were affected by fire between 14 and 25 years ago was performed with the objective of evaluating post-fire regeneration. In each site, five systematically placed plots (25 m x 25 m each) were established. The more recently burnt site had significantly lower values of richness and diversity than the other two sites. However, the sites did not differ in density and basal area. Annona dolabripetala, Astronium concinnum, Joannesia princeps and Polyandrococos caudescens were within the 10 most important species for the three sites. Comparing these data with adjacent mature forests, the results indicated differences both in structural and floristic aspects, suggesting that the time after fire was not sufficient for recuperation of these areas. The recovery process indicate at least 190 years for areas return to basal area values close to those observed in mature forests nearby.

Productive performance of Holstein calves finished in feedlot or pasture.

The use of animals from dairy farms is an alternative to meat production since it provides an increment of total income for farmers. This study aims to evaluate the performance of Holstein calves finished in two feeding systems (feedlot or pasture). Forty-three animals with 58 days old and 57 kg were divided in two treatments: 23 animals finished in feedlot with corn silage plus concentrate based on corn and soybean meal (40:60); 20 animals kept in cultivated pastures according to the period of the year: Italian ryegrass (Lolium multiflorum) and pearl millet (Pennisetum americanum) with supplementation with the same feedlot-concentrate at 1% body weight. Animals were slaughtered with 200 kg. Dry matter and nutrient intake were determined, with the use of chromium oxide for estimating pasture intake. Feedlot animals had greater total intake and total digestible nutrients, resulting in higher average daily gain (0.949 vs 0.694 kg day-1). Crude protein intake, neutral detergent fiber and feed conversion did not show significant differences. Holstein calves have improved performance when finished in feedlot.

Influences of nitrogen fertilization and energy supplementation for growth perfomance of beef cattle on Alexander grass.

This study evaluated the influences of nitrogen fertilizer and energy supplementation cattle on the growth performance of beef cattle. This study was conducted at the Federal University of Technology of Paraná, Dois Vizinhos through continuous grazing on 6.3 ha, divided into nine paddocks. The treatments were: Alexander grass +100 kg ha-1 of N (N100); Alexander grass + 100 kg ha-1 of N + 0.5 kg per 100 kg of weight live supplementation of wheat bran (N100S); and Alexander grass +200 kg ha-1 of N (N200), with an average herbage allowance of 10% for all treatments. Crossbred and non-castrated steers with an average weight of 276 ± 41 kg were used for 107 days. The crude protein from entire plant differed (P < 0.05) between treatments, with the greater value (14.8%) occurring in the N200, and the lesser value (13.3%) occurring in the N100S. The herbage accumulation rate was greater (P < 0.05) in the N200 (55.7  DM ha-1 d-1) than that in the N100S and N100 (40.0 and 39.7 kg DM ha-1 d-1, respectively). The N100S produced greater (P < 0.05) average daily weight gains (0.815 kg animal day-1) than did the N200 (0.685 kg animal day-1) and N100 treatments (0.727 kg animal day-1).

Network analysis of a Pkd1-mouse model of autosomal dominant polycystic kidney disease identifies HNF4α as a disease modifier.

Autosomal Dominant Polycystic Kidney Disease (ADPKD; MIM ID's 173900, 601313, 613095) leads to end-stage kidney disease, caused by mutations in PKD1 or PKD2. Inactivation of Pkd1 before or after P13 in mice results in distinct early- or late-onset disease. Using a mouse model of ADPKD carrying floxed Pkd1 alleles and an inducible Cre recombinase, we intensively analyzed the relationship between renal maturation and cyst formation by applying transcriptomics and metabolomics to follow disease progression in a large number of animals induced before P10. Weighted gene co-expression network analysis suggests that Pkd1-cystogenesis does not cause developmental arrest and occurs in the context of gene networks similar to those that regulate/maintain normal kidney morphology/function. Knowledge-based Ingenuity Pathway Analysis (IPA) software identifies HNF4α as a likely network node. These results are further supported by a meta-analysis of 1,114 published gene expression arrays in Pkd1 wild-type tissues. These analyses also predict that metabolic pathways are key elements in postnatal kidney maturation and early steps of cyst formation. Consistent with these findings, urinary metabolomic studies show that Pkd1 cystic mutants have a distinct profile of excreted metabolites, with pathway analysis suggesting altered activity in several metabolic pathways. To evaluate their role in disease, metabolic networks were perturbed by inactivating Hnf4α and Pkd1. The Pkd1/Hnf4α double mutants have significantly more cystic kidneys, thus indicating that metabolic pathways could play a role in Pkd1-cystogenesis.

Unveiling Tst3, a Multi-Target Gating Modifier Scorpion α Toxin from Tityus stigmurus Venom of Northeast Brazil: Evaluation and Comparison with Well-Studied Ts3 Toxin of Tityus serrulatus.

Studies on the interaction sites of peptide toxins and ion channels typically involve site-directed mutations in toxins. However, natural mutant toxins exist among them, offering insights into how the evolutionary process has conserved crucial sequences for activities and molecular target selection. In this study, we present a comparative investigation using electrophysiological approaches and computational analysis between two alpha toxins from evolutionarily close scorpion species of the genus Tityus, namely, Tst3 and Ts3 from T. stigmurus and T. serrulatus, respectively. These toxins exhibit three natural substitutions near the C-terminal region, which is directly involved in the interaction between alpha toxins and Nav channels. Additionally, we characterized the activity of the Tst3 toxin on Nav1.1-Nav1.7 channels. The three natural changes between the toxins did not alter sensitivity to Nav1.4, maintaining similar intensities regarding their ability to alter opening probabilities, delay fast inactivation, and induce persistent currents. Computational analysis demonstrated a preference for the down conformation of VSD4 and a shift in the conformational equilibrium towards this state. This illustrates that the sequence of these toxins retained the necessary information, even with alterations in the interaction site region. Through electrophysiological and computational analyses, screening of the Tst3 toxin on sodium isoform revealed its classification as a classic α-NaTx with a broad spectrum of activity. It effectively delays fast inactivation across all tested isoforms. Structural analysis of molecular energetics at the interface of the VSD4-Tst3 complex further confirmed this effect.

Murine Models of Polycystic Kidney Disease.

Polycystic diseases affect approximately 1/1000 and are important causes of kidney failure. No therapies presently are in clinical practice that can prevent disease progression. Multiple mouse models have been produced for the genetic forms of the disease that most commonly affect humans. In this report, we review recent progress in the field and describe some of the outstanding challenges.

Mechanisms of Cyst Development in Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease is the most common inherited cause of end-stage kidney disease worldwide. Most cases result from mutation of either of 2 genes, PKD1 and PKD2, which encode proteins that form a probable receptor/channel complex. Studies suggest that a loss of function of the complex below an indeterminate threshold triggers cyst initiation, which ultimately results in dysregulation of multiple metabolic processes and downstream pathways and subsequent cyst growth. Noncell autonomous factors may also promote cyst growth. In this report, we focus primarily on the process of early cyst formation and factors that contribute to its variability with brief consideration of how new studies suggest this process may be reversible.

In vivo Polycystin-1 interactome using a novel Pkd1 knock-in mouse model.

PKD1 is the most commonly mutated gene causing autosomal dominant polycystic kidney disease (ADPKD). It encodes Polycystin-1 (PC1), a putative membrane protein that undergoes a set of incompletely characterized post-transcriptional cleavage steps and has been reported to localize in multiple subcellular locations, including the primary cilium and mitochondria. However, direct visualization of PC1 and detailed characterization of its binding partners remain challenging. We now report a new mouse model with HA epitopes and eGFP knocked-in frame into the endogenous mouse Pkd1 gene by CRISPR/Cas9. Using this model, we sought to visualize endogenous PC1-eGFP and performed affinity-purification mass spectrometry (AP-MS) and network analyses. We show that the modified Pkd1 allele is fully functional but the eGFP-tagged protein cannot be detected without signal amplification by secondary antibodies. Using nanobody-coupled beads and large quantities of tissue, AP-MS identified an in vivo PC1 interactome, which is enriched for mitochondrial proteins and components of metabolic pathways. These studies suggest this mouse model and interactome data will be useful to understand PC1 function, but that new methods and brighter tags will be required to track endogenous PC1.

Effect of the gain rate during growing phase on the performance and characteristics of carcass and meat of super precocious steers.

The aim was to evaluate the effect of different rates of weight gain during the backgrounding on animal performance and carcass and meat characteristics of steers finished in feedlots. Thirty-six Angus steers, 12 ± 2 months of age, were backgrounded during 91 days on Aruana grass pasture (Panicum maximum cv. Aruana) managed under different stocking rates to achieve three different weight gains: HIGH ADG (average daily gain)-no feed restriction (ADG = 0.846 kg); MEDIUM ADG-moderate feed restriction (ADG = 0.456 kg); and LOW ADG-high feed restriction (ADG = 0.154 kg). To ensure the difference in ADG, we offered 0.7% live weight of concentrate feed in the HIGH treatment and a better forage supply in the MEDIUM treatment. After the backgrounding, the animals were finished in feedlot. There was no effect of the previous performance on the animals' performance in the feedlot. The LOW presented higher weight (218.9 vs. 207.9 kg) and hot (54.0% vs. 51.3%) and cold (53.5% vs. 50.5%) carcass yield than the MEDIUM, besides presenting meat with less cooking losses (15.0% vs. 18.2%), marbling (7 vs. 4.0 points), palatability (7.1 vs. 6.3 points), juiciness (7.2 vs. 6.4 points), tenderness (7.1 vs. 6.3 points), and lower shear force (5.78 vs. 8.75 kg) than HIGH. LOW ADG steers stay longer in the finishing phase but presented in general better quality carcass and meat than those with MEDIUM or HIGH during the backgrounding.

Ts17, a Tityus serrulatus ß-toxin structurally related to α-scorpion toxins.

Ts17 was purified from the venom of the scorpion Tityus serrulatus, the most dangerous scorpion species in Brazil. The activity on Nav1.1-Nav1.7 channels was electrophysiologically characterized by patch-clamp technique. Ts17 amino acid sequence indicated high similarity to alpha-scorpion toxins; however, it presented beta-toxin activity, altering the kinetics of the Na+-channels. The most affected subtypes during activation (with and without prepulse) and inactivation phases were Nav1.2 and Nav1.5, respectively. For recovery from inactivation, the most affected voltage-gated sodium channel was Nav1.5. Circular dichroism spectra showed that Ts17 presents mainly ß-sheet and unordered structures at all analyzed pHs, and the maximum value of α-helix was found at pH 4.0 (13.3 %). Based on the results, Ts17 might be used as a template to develop a new cardiac drug. Key contribution Purification of Ts17 from Tityus serrulatus, electrophysiological characterization of Ts17 on voltage-gated sodium channel subtypes, ß-toxin classification.

Invasive alien acacias rapidly stock carbon, but threaten biodiversity recovery in young second-growth forests.

Under the UN-Decade of Ecosystem Restoration and Bonn Challenge, second-growth forest is promoted as a global solution to climate change, degradation and associated losses of biodiversity and ecosystem services. Second growth is often invaded by alien tree species and understanding how this impacts carbon stock and biodiversity recovery is key for restoration planning. We assessed carbon stock and tree diversity recovery in second growth invaded by two Acacia species and non-invaded second growth, with associated edge effects, in the Brazilian Atlantic Forest. Carbon stock recovery in non-invaded forests was threefold lower than in invaded forests. Increasingly isolated, fragmented and deforested areas had low carbon stocks when non-invaded, whereas the opposite was true when invaded. Non-invaded forests recovered threefold to sixfold higher taxonomic, phylogenetic and functional diversity than invaded forest. Higher species turnover and lower nestedness in non-invaded than invaded forests underpinned higher abundance of threatened and endemic species in non-invaded forest. Non-invaded forests presented positive relationships between carbon and biodiversity, whereas in the invaded forests we did not detect any relationship, indicating that more carbon does not equal more biodiversity in landscapes with high vulnerability to invasive acacias. To deliver on combined climate change and biodiversity goals, restoration planning and management must consider biological invasion risk. This article is part of the theme issue 'Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration'.