The monocled cobra (Naja kaouthia) is among the most feared snakes in Southeast Asia due to its toxicity, which is predominantly derived from long-chain α-neurotoxins. The only specific treatment for snakebite envenoming is antivenom based on animal-derived polyclonal antibodies. Despite the lifesaving importance of these medicines, major limitations in safety, supply consistency, and efficacy create a need for improved treatments. Here, we describe the discovery and subsequent optimization of a recombinant human monoclonal immunoglobulin G antibody against α-cobratoxin using phage display technology. Affinity maturation by light chain-shuffling resulted in a significant increase in in vitro neutralization potency and in vivo efficacy. The optimized antibody prevented lethality when incubated with N. kaouthia whole venom prior to intravenous injection. This study is the first to demonstrate neutralization of whole snake venom by a single recombinant monoclonal antibody, thus providing a tantalizing prospect of bringing recombinant antivenoms based on human monoclonal or oligoclonal antibodies to the clinic.
The rapid bio-sensing of the synthetic cannabinoids, AB-Fubinaca y AB-Pinaca, was developed and validated using six different electrode platforms. Screen-printed electrodes containing 3% tetrathiafulvalene (TTF) ink on the carbon electrode were modified with gold nanoparticles and carbon nanotubes. Then, acetylcholinesterase and glucuronyl transferase were immobilized on the surface of these carbon electrodes. A quantitative response was obtained by measuring the enzymatic inhibition caused by increasing concentrations of the target drugs. Acetylthiocholine iodide, serotonin, and β-D- phenolphthalein glucuronide were used as enzymatic substrates. Optimal pH, peak potential, and substrate concentration of each biosensor were studied. Analytical performance parameters and figures of merit, including LODs (< 1.5 × 10–4 mg/L), precision and reproducibility (< 10%), trueness (< 3%), demonstrate that the developed biosensors were able to interrogate low concentration of AB-Fubinaca y AB-Pinaca in a buffer environment. Michaelis Menten's apparent constants were estimated from inhibition calibration curves. They were lower than 2.0 × 10–3 M. Km inhibition values, and an interference study concluded which biosensor was the most selective for both drugs. AChE/AuNPs/SPCTTFEs with ATI, for AB-Fubinaca, pH = 7.00; ATI = 0.450 mM y Eap = +0.70 V; UDPGT/CNTNPs/SPCTTFEs with Serotonin substrate, AB-Pinaca, pH = 6.64; Cn Serotonin = 0.45 mM y Eap = +0.58 V. Performance parameters of the developed biosensors are acceptable as proof of concept, which opens an opportunity for their future application in forensic and chemical analysis.
Introduction: Arsenic, an element that can be harmful to human health, is abundant in the environment. It was among the first substances recognized as carcinogenic, and its presence in water is common in Latin America. Its levels in water sources are relevant for decision-making and sanitary control. This study is the first in Latin America with a mathematical model of the risk and burden of disease. Objective: To evaluate the exposure to low levels of arsenic in agricultural workers in a Costa Rican basin with this new technique. Methods: We sampled arsenic in three points along the Purires River, Cartago, between September 2011 and August 2012. We used “censored value” estimates; risk assessment with quadratic exponential models and Monte Carlo simulations to determine the risk of cancer, for agricultural workers, by type and route of exposure during irrigation. Results: Concentrations did not differ by site, but were higher in the dry season. The risk level and burden of disease were not acceptable. Disease burden is a more rigorous indicator than the individual calculation of probability of occurrence. Our estimated risk level is low compared to other studies outside the region, but not comparable to previous work in Latin America, which used a different method. Conclusion: A decade ago, in the Purires basin, arsenic concentrations were higher in the dry season and the risk level and burden of disease were not acceptable
Turrialba is a stratovolcano located at the easternmost part of the Costa Rican volcanic front. After remaining quiescent for more than a century, in 1996 it started to show signs of unrest, until a first phreatomagmatic explosion occurred on January, 2010. Since then, the activity evolved from phreatic to magmatic, in a series of distinct eruptive phases. In this paper, we investigate the seismic records that span the whole eruptive process (2010-present), in order to identify precursory signals and characterize the volcanic evolution. A long-term analysis was carried out based on the continuous records, as well as seismic catalogs (volcano-tectonic seismicity, harmonic tremor, etc.). In addition, the gradual character of the evolution of this eruption allowed for the analysis of independent precursory stages. Thus, we inspected in detail the most important of those periods, particularly, prior to the first 2010 phreatomagmatic eruption, and prior to the 2016 transition to an open vent system. Temporary tremor amplitude decreases were found to precede most of the eruptive phases. In total, 9 pre-eruptive tremor abatement periods were identified spanning several days (5–44), which often concurred with a decrease in the SO2 flux. The analysis of the volcano-tectonic seismicity highlights the migration of magma from a deep (6–10 km) reservoir beneath the neighboring Irazú volcano towards Turrialba volcano, especially between the years 2015 and 2016. This activity peaked on December 2016 when a Mw 5.5 earthquake took place between both volcanoes. Harmonic tremor episodes thrived in the later phase when the system finally opened (2017–2018). In the short-term, compounded tonal seismic signals were identified as precursor events, such as long-period events followed by harmonic tremor or by a multichromatic coda similar to tornillo-type events. The co-occurrence of tremor amplitude decreases and tonal seismic signals is interpreted to be caused by a sealing of the hydrothermal system, which blocked the circulation of fluids and permitted the resonances in the inner cavities. This process leaded to pressure accumulation and the consequent eruptions. Thus, trough a series of cycles of sealing and rupture the system of conduits gradually opened. The seismic characterization of this eruption constitutes insightful knowledge useful for monitoring and risk assessment purposes.
Recent lidar, survey, and excavation have facilitated the mapping of the Lomas Entierros archaeological site in Central Pacific Costa Rica, with a main occupation and construction dating from 800–1200 CE. The data document the architectural pattern of the site, which differs from other monumental sites known in the region in terms of the distribution of architectural features. The proposed regional architectural assemblage of a main mound, plaza and causeway as an epicenter of elite activity is not present at Lomas Entierros, where elites are located at the hilltop, on the northwestern sector of the site. Rather, the distribution at Lomas Entierros suggests factors such as elevation, visibility, and defensibility were more socially valued for the location of elite residences. Lay summary: The Lomas Entierros archaeological site flourished from 800–1200 CE in Central Pacific Costa Rica. However, heavy forest coverage has hindered traditional archaeological work for decades. Lidar technology now permits the mapping of the settlement’s architecture by deleting the vegetation layers collected in the data. Through the creation of digital models, survey, and excavation we have documented the architectural pattern of the site and compare it to other known settlements in the area. Lomas Entierros presents a different design that values elements of elevation, visibility, and defensibility. Understanding such differences permits us to register the variability of expressions in the use of space, construction patterns, power, and adaptation to the environment in past societies.
Background: Modern high-yielding crops, such as maize, are characterized by extensive yield stability across various environments and can cope with repetitive periods of moder- ate water shortage. However, there is conflicting evidence on how the nutritional status of the plants contributes to stress resilience and whether farmers have management options via nitrogen fertilization. Aims: We aimed at identifying factors relevant for improved growth recovery of maize after repeated water deficit stress (WDS). Methods: A pot experiment with maize and repeated WDS was conducted. Growth and recovery from stress and physiological parameters were measured. Results: The growth penalty of juvenile maize plants exposed to a moderate WDS was lost after additional exposure to a 2-week WDS. Primed plants transiently contained more osmolytes and performed superior in the second recovery phase when nitrogen fertil- ization was applied directly before the second WDS. Nitrogen fertilization did not affect the osmolyte quantity, and primed plants had transiently higher antioxidant levels, higher reactive oxygen species production and recovered more quickly with N addition. Conclusions: Pot experiments suggest that nitrogen fertilization may be an option to improve maize resilience to repeated WDS, a hypothesis that should be tested more rigorously in the field.
COVID-19 is a disease caused by the novel Coronavirus SARS-CoV-2 causing an acute respiratory disease that can eventually lead to severe acute respiratory syndrome (SARS). An exacerbated inflammatory response is characteristic of SARS-CoV-2 infection, which leads to a cytokine release syndrome also known as cytokine storm associated with the severity of the disease. Considering the importance of this event in the immunopathology of COVID-19, this study analyses cytokine levels of hospitalized patients to identify cytokine profiles associated with severity and mortality. Using a machine learning approach, 3 clusters of COVID-19 hospitalized patients were created based on their cytokine profile. Significant differences in the mortality rate were found among the clusters, associated to different CXCL10/IL-38 ratio. The balance of a CXCL10 induced inflammation with an appropriate immune regulation mediated by the anti-inflammatory cytokine IL-38 appears to generate the adequate immune context to overrule SARS-CoV-2 infection without creating a harmful inflammatory reaction. This study supports the concept that analyzing a single cytokine is insufficient to determine the outcome of a complex disease such as COVID-19, and different strategies incorporating bioinformatic analyses considering a broader immune profile represent a more robust alternative to predict the outcome of hospitalized patients with SARS-CoV-2 infection.
Tortilla is a staple food for several countries and a gluten-free alternative and can be enriched using other non-traditional flours to improve their nutritional value. Three different lime and moisture concentrations were tested, and 0.25 and 56.34 g/100 g were selected as the best parameters to formulate during the rest of the survey. Once these conditions were determined, three different flours of sweet potato, peach palm, and cassava, at levels of 10 and 25 g/100 g, were partially used to substitute nixtamalized corn during the tortilla preparation. Several nutritional parameters of the flours were determined, including amino acid, mineral, fatty acid, sugar profiling as well as dietary fiber (sweet potato ≈ corn > cassava > peach palm), and carotenoids (peach palm > sweet potato > cassava ≈ corn). Moisture behavior and capacity of rollability during tortillas storage were also monitored for 15 days at 4 °C. Of all substitutions, only with sweet potato substitutions and the cassava substitution at a 10 g/100 g level, the typical puffing for a traditional tortilla is observed. Meanwhile, substitutions using peach palm and cassava flour showed the most degradation in storage. Sweet potato and peach palm (60.0 and 58.8 g/100 g) are less starchy ingredients than corn and cassava (87.8 and 85.30 g/100 g). Also, resistant starch for the tortillas ranged from 0.945 to 1.336 (cassava > peach palm > sweet potato), values higher than those found in a corn tortilla. Sensory analysis was also performed; both sweet potato and peach palm substitutions at 25 g/100 g obtained the lowest values of approval, by a consumer panel, for color and taste, respectively. Rollability was diminished as refrigeration time progressed, but sweet potato tortilla seems to withstand degradation (4.67–5.00 rollability scale) more so than the control or other treatments (i.e., < 4). Overall, the partial substitution of corn flour improved the resistance to shear and deformation; this was especially true for the sweet potato substitution at day 0. Sweet potato substitutions generated a tortilla with a significantly higher induction period (ca. 45 hours, p < 0.05) and calculated shelf life (ca. 5 hours) than the other treatments. It can be demonstrated that using non-traditional flours can improve several tortilla parameters and be an additional vehicle for carotenoids in the diet.
This paper estimates the local effects of a Payment for Ecosystem Services (PES) program on income-based poverty rates in rural areas of Costa Rica between 2007–2009. Using household surveys and spatial geographic data, we are able to control for socioeconomic and geographic characteristics at the individual and census-tract level. Our results suggest that while payments did not affect poverty rates at the national level, poverty did increase in places where PES had the greatest effect on deforestation. This effect is stronger for uneducated males, who tend to work in agricultural activities. The trade-off between ecosystem services provision and poverty is not ubiquitous and, when present, could be addressed by targeting those groups that are most affected.
The effects of the COVID-19 pandemic have accentuated pleas worldwide for urgent action in social, political, and environmental matters. Many of these appeals portray the pandemic as a “wake-up call” to the many long-standing problems affecting societies worldwide, including social and economic inequality, political struggles, and climate change. Indeed, calls for urgent environmental action have predominated in the wake of the pandemic, on one hand by presenting contemporary human-environment interactions as a root cause, and on the other, by comparing the pandemic effects to what could possibly occur if effective remediating actions are not taken in the short term. In this chapter, we broadly examine some relevant perspectives on the pandemic-environment relationship in the Costa Rican institutional milieu with particular focus on those who envision the pandemic as a turning point towards a more environmentally-sound development model in a country commonly portrayed as “green” and highly dependent on nature-based tourism. In so doing, we seek to provoke discussions on how these perspectives that leverage on the pandemic crisis can lead to social and environmental change significant enough to effectively redirect development pathways toward sustainability.KeywordsPandemic-environment relationshipsSustainable developmentCosta RicaNature-based tourism
This study aimed to evaluate the expression of several differentiation markers in the apical papilla (AP) and dental pulp (DP) of human permanent teeth. Twenty young human teeth were extracted and classified according to three Moorrees tooth development stages: initial root formation (Ri), root length ½ (R1/2), and root length complete (Rc). Immunohistochemical assays were performed using STRO-1, VEGF Receptor-2, Neurofilament heavy (NFH), and Nestin antibodies and analyzed under light microscopy. Decalcified, formalin fixed paraffin embedded tooth sections stained with hematoxylin and eosin showed an apical cell rich zone between the DP and AP. The AP revealed fewer vascular and cellular components than the DP. STRO-1 was expressed on vascular and neuronal elements beneath the odontoblast (OB) and in the sub-odontoblastic (SOB) zone, and VEGFR-2 positive cells were observed in the endothelium, arterioles, and blood vessels. Neuroepithelial stem cell protein (Nestin) was highly expressed in differentiated odontoblasts in the predentin odontotoblast and odontoblast cell processes. Neurofilament heavy (NFH) was expressed in mature axons throughout the DP. STRO-1 and VEGFR-2 microvascular expression was higher at the stages Ri and R1/2 while STRO-1 and NFH expression showed strong spatial distribution of Rc neuronal elements as compared to Ri and R1/2. Differentiated OB and SOB cells showed Nestin expression, indicating a reservoir of newly differentiated odontoblast-like cells.
Identifying the source population of alien species is important to assess the distribution and potential effects in the invaded area. The araneid spider Cyrtophora citricola is widely distributed in Europe, Asia, and Africa; however, in the last 26 years, it has been reported in several countries across the Americas. To date, the geographic origin of the populations established in the Americas remains unclear, but considering the successful colonization after its recent arrival, assessing climatic similarities between the invaded and native geographic ranges could be useful to address this question. In this study, we used a combination of Species Distribution Models and Ordination Methods to assess the climatic match between the invaded region (the Americas) and two potential origins (southern Africa and the Mediterranean) aiming to determine the more likely origin for the populations established in the Americas. We found that the American populations of C. citricola occupy sites with climatic conditions more similar to those occupied by southern African populations, than to those occupied by the Mediterranean populations. Therefore, our results suggest a southern African rather than a Mediterranean origin for the populations established in America. In addition, our results also show that populations in America are spreading into sites that differ in climate conditions from those occupied by native populations. Further studies assessing intrinsic (e.g., physiological tolerances, plasticity, behavior, reproduction) and extrinsic (physical barriers, predator release) factors could provide further information to disentangle the mechanisms behind the geographic and climatic niche expansion of this species.
After establishing secondary contact, recently diverged populations may remain reproductively isolated or hybridize to a varying extent depending on factors such as hybrid fitness and the strength of assortative mating. Replicated contact zones between hybridizing taxa offer a unique opportunity to explore how different factors interact to shape patterns of hybridization. Here, we used genomic and phenotypic data from three independent contact zones between subspecies of the Variable Seedeater (Sporophila corvina), to examine how coloration and genetic divergence shape patterns of hybridization. We found that plumage coloration has limited introgression across contact zones, but the degree of plumage divergence does not explain overall patterns of introgression. Across two parallel contact zones between populations with divergent phenotypes (entirely black vs. pied plumage) populations hybridized extensively across one contact zone but not the other, suggesting that plumage divergence is not sufficient to maintain reproductive isolation. Where subspecies hybridized, hybrid zones were wide and formed by later-generation hybrids, suggesting that hybrids present similar or higher fitness than parental subspecies. Moreover, contemporary gene flow has played an important role in shaping patterns of genetic diversity between populations. Overall, our results demonstrate that divergence in plumage coloration is important in reducing gene flow but insufficient in maintaining reproductive isolation in this clade, and that other factors such as divergence in song and time since secondary contact may also play an important role in driving patterns of reduced hybridization and gene flow.
Myotonic dystrophy type 1 is a complex disease caused by a genetically unstable CTG repeat expansion in the 3'-untranslated region of the DMPK gene. Age-dependent, tissue-specific somatic instability has confounded genotype-phenotype associations, but growing evidence suggests that it also contributes directly toward disease progression. Using a well-characterized clinical cohort of DM1 patients from Costa Rica, we quantified somatic instability in blood, buccal cells, skin and skeletal muscle. Whilst skeletal muscle showed the largest expansions, modal allele lengths in skin were also very large and frequently exceeded 2000 CTG repeats. Similarly, the degree of somatic expansion in blood, muscle and skin were associated with each other. Notably, we found that the degree of somatic expansion in skin was highly predictive of that in skeletal muscle. More importantly, we established that individuals whose repeat expanded more rapidly than expected in one tissue (after correction for progenitor allele length and age), also expanded more rapidly than expected in other tissues. We also provide evidence suggesting that individuals in whom the repeat expanded more rapidly than expected in skeletal muscle, have an earlier age-at-onset than expected (after correction for the progenitor allele length). Pyrosequencing analyses of the genomic DNA flanking the CTG repeat revealed that the degree of methylation in muscle was well predicted by the muscle modal allele length and age, but that neither methylation of the flanking DNA, nor levels of DMPK sense and anti-sense transcripts, could obviously explain individual- or tissue-specific patterns of somatic instability.
The present work proposes a method to characterize, calibrate, and compare, any 2D SLAM algorithm, providing strong statistical evidence, based on descriptive and inferential statistics to bring confidence levels about overall behavior of the algorithms and their comparisons. This work focuses on characterize, calibrate, and compare Cartographer, Gmapping, HECTOR-SLAM, KARTO-SLAM, and RTAB-Map SLAM algorithms. There were four metrics in place: pose error, map accuracy, CPU usage, and memory usage; from these four metrics, to characterize them, Plackett–Burman and factorial experiments were performed, and enhancement after characterization and calibration was granted using hypothesis tests, in addition to the central limit theorem.
The article presents the results of a regional study analysing the factors that predict Latin American faculty adoption and use of geospatial technologies (GST) for teaching geography. The research involved an online survey with 337 participants from 17 countries, who answered a set of items adapted from the Unified Theory of Acceptance and Use of Technology on five GST – desktop GIS, web-based GIS, remote sensing, GPS, and digital globes. The data was analysed using a structural equation modelling. The results confirmed that faculty who identified pedagogical benefits of using GST considered technologies as easy to master, and valued the opinion of people influential to them about using technologies were more likely to be motivated to use GST for teaching. In addition, faculty willing to use the GST and report adequate institutional conditions were more likely to be using the technologies for teaching. Additional statistical testing found that human geography faculty expressed an infrequent use of these technologies compared to their physical geography and geospatial technologies colleagues, who did report a more consistent use of GST. These findings suggest a divide among Latin American faculty regarding the motivation and institutional conditions to implement technologies, based on their field of expertise.
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