Physiological evaluation of yeast strains under anaerobic conditions using glucose, fructose, or sucrose as the carbon source.

The aim of this study was to evaluate the physiology of 13 yeast strains by assessing their kinetic parameters under anaerobic conditions. They included Saccharomyces cerevisiae CAT-1 and 12 isolated yeasts from different regions in Brazil. The study aimed to enhance understanding of the metabolism of these strains for more effective applications. Measurements included quantification of sugars, ethanol, glycerol, and organic acids. Various kinetic parameters were analyzed, such as specific substrate utilization rate (qS), maximum specific growth rate (µmax), doubling time, biomass yield, product yield, maximum cell concentration, ethanol productivity (PEth), biomass productivity, and CO2 concentration. S. cerevisiae CAT-1 exhibited the highest values in glucose for µmax (0.35 h-1), qS (3.06 h-1), and PEth (0.69 gEth L-1 h-1). Candida parapsilosis Recol 37 did not fully consume the substrate. In fructose, S. cerevisiae CAT-1 stood out with higher values for µmax (0.25 h-1), qS (2.24 h-1), and PEth (0.60 gEth L-1 h-1). Meyerozyma guilliermondii Recol 09 and C. parapsilosis Recol 37 had prolonged fermentation times and residual substrate. In sucrose, only S. cerevisiae CAT-1, S. cerevisiae BB9, and Pichia kudriavzevii Recol 39 consumed all the substrate, displaying higher PEth (0.72, 0.51, and 0.44 gEth L-1 h-1, respectively) compared to other carbon sources.

Catalytic properties of amylases produced by Cunninghamella echinulata and Rhizopus microsporus.

The present work aimed to characterize and compare the catalytic properties of amylases from Cunninghamella echinulata and Rhizopus microsporus. The highest production of amylase by C. echinulata, 234.94 U g-1 of dry substrate (or 23.49 U mL-1), was obtained using wheat bran as a substrate, with 50-55% initial moisture and kept at 28 °C for 48 h. The highest production of amylases by R. microsporus, 224.85 U g-1 of dry substrate (or 22.48 U mL-1), was obtained cultivating wheat bran with 65% initial moisture at 45 °C for 24 h. The optimal activity of the amylases was observed at pH 5.0 at 60 °C for C. echinulata enzymes and at pH 4.5 at 65 °C for R. microsporus. The amylases produced by C. echinulata were stable at pH 4.0-8.0, while the R. microsporus enzymes were stable at pH 4.0-10.0. The amylases produced by C. echinulata remained stable for 1 h at 50 °C and the R. microsporus amylases maintained catalytic activity for 1 h at 55 °C. The enzymatic extracts of both fungi hydrolyzed starches from different plant sources and showed potential for liquefaction of starch, however the amylolytic complex of C. echinulata exhibited greater saccharifying potential.

Machine learning algorithms accurately identify free-living marine nematode species.

Background: Identifying species, particularly small metazoans, remains a daunting challenge and the phylum Nematoda is no exception. Typically, nematode species are differentiated based on morphometry and the presence or absence of certain characters. However, recent advances in artificial intelligence, particularly machine learning (ML) algorithms, offer promising solutions for automating species identification, mostly in taxonomically complex groups. By training ML models with extensive datasets of accurately identified specimens, the models can learn to recognize patterns in nematodes' morphological and morphometric features. This enables them to make precise identifications of newly encountered individuals. Implementing ML algorithms can improve the speed and accuracy of species identification and allow researchers to efficiently process vast amounts of data. Furthermore, it empowers non-taxonomists to make reliable identifications. The objective of this study is to evaluate the performance of ML algorithms in identifying species of free-living marine nematodes, focusing on two well-known genera: Acantholaimus Allgén, 1933 and Sabatieria Rouville, 1903. Methods: A total of 40 species of Acantholaimus and 60 species of Sabatieria were considered. The measurements and identifications were obtained from the original publications of species for both genera, this compilation included information regarding the presence or absence of specific characters, as well as morphometric data. To assess the performance of the species identification four ML algorithms were employed: Random Forest (RF), Stochastic Gradient Boosting (SGBoost), Support Vector Machine (SVM) with both linear and radial kernels, and K-nearest neighbor (KNN) algorithms. Results: For both genera, the random forest (RF) algorithm demonstrated the highest accuracy in correctly classifying specimens into their respective species, achieving an accuracy rate of 93% for Acantholaimus and 100% for Sabatieria, only a single individual from Acantholaimus of the test data was misclassified. Conclusion: These results highlight the overall effectiveness of ML algorithms in species identification. Moreover, it demonstrates that the identification of marine nematodes can be automated, optimizing biodiversity and ecological studies, as well as turning species identification more accessible, efficient, and scalable. Ultimately it will contribute to our understanding and conservation of biodiversity.

Two new species of Cyatholaimidae (Nematoda: Chromadorida) from the Southeastern Brazilian coast with emphasis on the pore complex and lateral pore-like structures.

Cyatholaimidae is a common and diverse family of mainly marine nematodes, potentially, with a large number of species to be discovered. The taxonomy of the group is marked by a lack of information about the evolutionary history of the characters and of detailed descriptions of morphological structures that may be taxonomically relevant. Two new species of the family are described from a sublittoral region in Southeastern Brazil, emphasizing the importance of the distribution and morphology of pore complex and pore-like structures present on the cuticle. The taxonomic importance of the cuticle ornamentation and spicule shape for the Biarmifer species, as well as the precloacal supplements structures of Pomponema species, are discussed. Biarmifer nesiotes sp. nov. differs from other species of the genus by the presence of eight longitudinal rows of pore complex on the cuticle and by the shape of the copulatory structure. Pomponema longispiculum sp. nov. differs from the most similar species, P. stomachor Wieser, 1954, by the smaller number of turns of the amphidial fovea, the shorter tail and the beginning of the cuticle lateral differentiation (3/4 of the pharynx length vs. end of the pharynx, respectively). We also obtained the SSU rDNA sequence from Pomponema longispiculum sp. nov., which is closely related to Pomponema sp. (MN250093) by about 91%. Updated tabular keys to species identification of each genus (Biarmifer and Pomponema) are included, containing morphometric data, characters related to cuticle ornamentation, and copulatory structures.

Characterization of fillets of Amazon and real hybrid sorubins / Caracterización de filetes de sorubinas híbridas amazónica y real

Background: Many fish hybrids (i.e., obtained by crossing two species) are produced rather than pure species because of their better growth rate and/or acceptance of formulated feed. However, few studies evaluate and compare their meats and acceptance, including, e.g., for the Amazon hybrid sorubim (Pseudoplatystoma reticulatum x Leiarius marmoratus) and the real hybrid sorubim (Pseudoplatystoma corruscans x L. marmoratus). Objective: Thus, this work aimed to evaluate the physical, chemical, microbiological, and sensory characteristics of fillets from the Amazon and real hybrid sorubins. Method:Proximate composition, instrumental color, water holding capacity, cooking losses, and shear force were measured.Microbiological analyses of the fillets were carried out for Salmonellasp. and Staphylococcusaureus to ensure food safety during sensory analysis. Results: Fillets presented excellent quality, classified in category A (lipids below 5% and proteins between 15 and 20%). There was no significant difference (p>0.05) between the evaluated fillets for several parameters: the average water holding capacities were 33.72 and 34.67%, the cooking losses were 14.93 and 13.41%, the shear forces were 2.21 and 1.74 kgf, and the luminosities were 49.61 and 45.04 for the fillets of Amazonian hybrid sorubim and real hybrid sorubim, respectively. Discussion: There was an evident relationship between water-holding capacities and shear forces. Amazonian hybrid sorubim fillets presented lower intensity of red. However, there was no sensory difference between the hybrids, and both had an acceptance rate above 80%. Conclusion: The hybridization does not alter the characteristics of the fish fillets

Antecedentes: Muchos híbridos de peces (i.e., obtenidos al cruzar dos especies) se producen en lugar de especies puras debido a su mejor tasa de crecimiento y/o aceptación de alimentos formulados. Sin embargo, pocos estudios evalúan y comparan sus carnes y aceptación, incluyendo, p. ej., para lo surubí híbrido amazónico (Pseudoplatystoma reticulatum x Leiarius marmoratus) y lo surubí híbrido real (Pseudoplatystoma corruscans x L. marmoratus). Objetivo: Así, el objetivo de este trabajo fue evaluar las características físicas, químicas, microbiológicas y sensoriales de filetes sorubines híbridos amazónico y real. Método: Se midió composición proximal, color instrumental, capacidad de retención de agua, pierdas por cocción y fuerza de corte. Se realizaron análisis microbiológicos de los filetes para Salmonella sp. y Staphylococcus aureus para garantizar la seguridad alimentaria durante el análisis sensorial. Resultados: Los filetes presentaron una excelente calidad, siendo clasificados en la categoría A (lípidos por debajo del 5% y proteínas entre 15 y 20%). No hubo diferencia significativa (p>0.05) entre los filetes evaluados para varios parámetros: las capacidades de retención de agua fueron 33.72 y 34.67%, las pierdas por cocción fueron 14.93 y 13.41%, las fuerzas de corte fueron 2.21 y 1.74 kgf y las luminosidades fueron 49.61 y 45.04 para los filetes de sorubim híbrido amazónico y sorubim híbrido real, respectivamente. Discusión: Hubo una relación evidente entre las capacidades de retención de agua y las fuerzas de corte. Los filetes de sorubim híbridos amazónicos presentaron menor intensidad de rojo. Sin embargo, no hubo diferencia sensorial entre los híbridos, y ambos tuvieron una tasa de aceptación superior al 80%. Conclusión: La hibridación no altera las características de los filetes de pescado

Metabolic engineering of Kluyveromyces marxianus for biomass-based applications.

Kluyveromyces marxianus ATCC 26,548 was cultivated in aerobic chemostats with [1-13C] and [U-13C] glucose as carbon source under three different growth conditions (0.10, 0.25, and 0.5 h-1) to evaluate metabolic fluxes. Carbon balances closed always within 97-102%. Growth was carbon limited, and the cell yield on glucose was the same. The extracellular side-product formation was very low, totaling 0.0008 C-mol C-mol-1 substrate at 0.5 h-1. The intracellular flux ratios did not show significant variation for metabolic flux analysis from labelling and biomass composition and metabolic flux ratio analysis from labelling. The observed strictly oxidative metabolism and the stability of the metabolism in terms of fluxes even at high growth rates, without triggering out the synthesis of by-products, is an extremely desired condition that underlines the potential of K. marxianus for biotechnological biomass-related applications and the comprehension of the metabolic pools and pathways is an important step to engineering this organism. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03324-x.

UV-B Irradiation Effect on Microalgae Performance in the Remediation of Effluent Derived from the Cigarette Butt Cleaning Process.

In this study, the potential of ultraviolet B (UV-B) radiation to alleviate the effects of pollutants in cigarette butt wastewater (CBW) was investigated using different Chlorella sorokiniana strains (F4, R1 and LG1). Microalgae were treated with UV-B (1.7 W m-2) for 3 days prior to their exposure to CBW and then incubated for 4 days in the absence or presence of UV-B. UV-B-untreated microalgae were used as the control. Comparative physiological responses, including photosynthetic pigments and non-enzymatic antioxidants, as well as nicotine and nicotyrine removal, were evaluated in 7-day cultures. UV-B treatments did not negatively impact algal chlorophyll or carotenoid production. UV-B acclimation was strain-dependent, correlating with native environment adaptations and genetic constitutions. UV-B as a pretreatment had long-term positive effects on non-enzymatic antioxidant capacity. However, LG1 needed more time to readjust the pro-oxidant/antioxidant balance, as it was the most UV-B-sensitive. Phenolic compounds played an important role in the antioxidant system response to UV-B, while flavonoids did not contribute to the total antioxidant capacity. Although cross-resistance between UV-B and CBW was observed in F4 and R1, only R1 showed nicotine/nicotyrine catabolism induction due to UV-B. Overall, the results suggest that UV-B activates defense pathways associated with resistance or tolerance to nicotine and nicotyrine.

Remediation Capacity of Different Microalgae in Effluents Derived from the Cigarette Butt Cleaning Process.

Microalgal-based remediation is an ecofriendly and cost-effective system for wastewater treatment. This study evaluated the capacity of microalgae in the remediation of wastewater from cleaning process of smoked cigarette butts (CB). At laboratory scale, six strains (one from the family Scenedesmaceae, two Chlamydomonas debaryana and three Chlorella sorokiniana) were exposed to different CB wastewater dilutions to identify toxicity levels reflected in the alteration of microalgal physiological status and to determine the optimal conditions for an effective removal of contaminants. CB wastewater could impact on microalgal chlorophyll and carotenoid production in a concentration-dependent manner. Moreover, the resistance and remediation capacity did not only depend on the microalgal strain, but also on the chemical characteristics of the organic pollutants. In detail, nicotine was the most resistant pollutant to removal by the microalgae tested and its low removal correlated with the inhibition of photosynthetic pigments affecting microalgal growth. Concerning the optimal conditions for an effective bioremediation, this study demonstrated that the Chlamydomonas strain named F2 showed the best removal capacity to organic pollutants at 5% CB wastewater (corresponding to 25 butts L−1 or 5 g CB L−1) maintaining its growth and photosynthetic pigments at control levels.

Pomalidomide, dexamethasone, and daratumumab immediately after lenalidomide-based treatment in patients with multiple myeloma: updated efficacy, safety, and health-related quality of life results from the phase 2 MM-014 trial.

Patients with relapsed/refractory multiple myeloma (RRMM) need proven subsequent therapies after early-line lenalidomide treatment failure. The phase 2 MM-014 trial (NCT01946477) investigated pomalidomide, dexamethasone, and daratumumab after 1 to 2 prior treatment lines (62.5%, 1 prior line) in patients with RRMM and prior lenalidomide (75.0%, lenalidomide refractory). With a median follow-up of 28.4 months, overall response rate was 77.7% (52.7% achieved very good partial response or better) and median progression-free survival was 30.8 months. For patients with lenalidomide-refractory disease, these outcomes were 76.2%, 47.6%, and 23.7 months, respectively. No new safety signals were observed; 64.3% experienced grade 3/4 neutropenia. Health-related quality of life was preserved or trended toward improvement through 12 treatment cycles. Pomalidomide, dexamethasone, and daratumumab given immediately after early-line lenalidomide-based treatment continues to demonstrate safety and efficacy, supporting pomalidomide-dexamethasone as a foundation of combination therapy in RRMM and providing evidence that the immunomodulatory agent class delivers benefit after lenalidomide treatment failure.

Integrated safety analysis of umbralisib, a dual PI3Kδ/CK1ε inhibitor, in relapsed/refractory lymphoid malignancies.

Phosphoinositide 3-kinase-δ (PI3Kδ) inhibitors are active in lymphoid malignancies, although associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kδ and casein kinase-1ε (CK1ε). This study analyzed integrated comprehensive toxicity data from 4 open-label, phase 1 and 2 studies that included 371 adult patients (median age, 67 years) with relapsed/refractory non-Hodgkin lymphoma (follicular lymphoma [n = 147]; marginal zone lymphoma [n = 82]; diffuse large B-cell lymphoma/mantle cell lymphoma [n = 74]; chronic lymphocytic leukemia [n = 43]; and other tumor types [n = 25]) who were treated with the recommended phase 2 dose of umbralisib 800 mg or higher once daily. At data cutoff, median duration of umbralisib treatment was 5.9 months (range, 0.1-75.1 months), and 107 patients (28.8%) received umbralisib for ≥12 months. Any-grade treatment-emergent adverse events (AEs) occurred in 366 (98.7%) of 371 patients, with the most frequent being diarrhea (52.3%), nausea (41.5%), and fatigue (31.8%). Grade 3 or higher treatment-emergent AEs occurred in 189 (50.9%) of 371 patients and included neutropenia (11.3%), diarrhea (7.3%), and increased aminotransferase levels (5.7%). Treatment-emergent serious AEs occurred in 95 (25.6%) of 371 patients. AEs of special interest were limited and included pneumonia (29 of 371 [7.8%]), noninfectious colitis (9 of 371 [2.4%]), and pneumonitis (4 of 371 [1.1%]). AEs led to discontinuation of umbralisib in 51 patients (13.7%). Four patients (1.1%) died of AEs, none of which was deemed related to umbralisib. No cumulative toxicities were reported. The favorable long-term tolerability profile and low rates of immune-mediated toxicities support the potential use of umbralisib for the benefit of a broad population of patients with lymphoid malignancies.

A metric for spatially explicit contributions to science-based species targets.

The Convention on Biological Diversity's post-2020 Global Biodiversity Framework will probably include a goal to stabilize and restore the status of species. Its delivery would be facilitated by making the actions required to halt and reverse species loss spatially explicit. Here, we develop a species threat abatement and restoration (STAR) metric that is scalable across species, threats and geographies. STAR quantifies the contributions that abating threats and restoring habitats in specific places offer towards reducing extinction risk. While every nation can contribute towards halting biodiversity loss, Indonesia, Colombia, Mexico, Madagascar and Brazil combined have stewardship over 31% of total STAR values for terrestrial amphibians, birds and mammals. Among actions, sustainable crop production and forestry dominate, contributing 41% of total STAR values for these taxonomic groups. Key Biodiversity Areas cover 9% of the terrestrial surface but capture 47% of STAR values. STAR could support governmental and non-state actors in quantifying their contributions to meeting science-based species targets within the framework.

Kinematic and Clinical Outcomes to Evaluate the Efficacy of a Multidisciplinary Intervention on Functional Mobility in Parkinson's Disease.

Introduction: Functional mobility (FM) is a concept that incorporates the capacity of a person to move independently and safely to accomplish tasks. It has been proposed as a Parkinson's disease (PD) functional and global health outcome. In this study, we aimed to identify which kinematic and clinical outcomes changes better predict FM changes when PD patients are submitted to a specialized multidisciplinary program. Methods: PD patients engaged in a pre-defined specialized multidisciplinary program were assessed at admission and discharge. Change from baseline was calculated for all kinematic and clinical outcomes, and Timed Up and Go (TUG) was defined as the primary outcome for FM. A stepwise multivariate linear regression was performed to identify which outcome measures better predict TUG changes. Results: Twenty-four patients were included in the study. The changes in TUG Cognitive test, supervised step length, and free-living (FL) step time asymmetry were identified as the best predictors of TUG changes. The supervised step length and FL step time asymmetry were able to detect a small to moderate effect of the intervention (d values ranging from -0.26 to 0.42). Conclusions: Our results support the use of kinematic outcome measures to evaluate the efficacy of multidisciplinary interventions on PD FM. The TUG Cognitive, step length, and FL step time asymmetry were identified as having the ability to predict TUG changes. More studies are needed to identify the minimal clinically important difference for step length and FL step time asymmetry in response to a multidisciplinary intervention for PD FM.

M-Triad: An improvement of the sediment quality triad.

The traditional sediment quality triad generally uses three lines of evidence (LOE) in the assessment, integrating environmental chemistry, ecology and ecotoxicology. However the assessment is performed without considering the multivariate structure within LOE. In order to improve the sediment quality assessment, the M-Triad is proposed. Instead of averaging the values within a LOE, the new approach is based on the Euclidean distance between each sampling station and the reference station (s) for each LOE. These distances are then plotted in a radar-chart to obtain the area of the triangle and the quality assessment is subsequently obtained from the difference between the triangle areas of the impacted and the reference station. Three studies were selected to test the applicability of the M-Triad. In two cases, the M-Triad returned a more realistic ranking of the stations as observed in the principal component analysis (PCA) from each LOE By including the Euclidean distance, the use of M-Triad is advantageous when multiple variables with negative or uncorrelated patterns within a LOE are analyzed simultaneously. The combination of the M-Triad and the results of the PCA allows one to identify multiple contamination gradients and how biota and bioassays respond to each of these gradients. In comparison to the traditional method, the M-Triad reduces the uncertainty of the final analysis, permitting a more comprehensive ecological assessment.

Umbralisib, a Dual PI3Kδ/CK1ε Inhibitor in Patients With Relapsed or Refractory Indolent Lymphoma.

PURPOSE: Phosphatidylinositol-3-kinase (PI3K) inhibitors have shown activity in relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). PI3K inhibitors have been hampered by poor long-term tolerability and toxicity, which interfere with continuous use. Umbralisib, a dual inhibitor of PI3Kδ/casein kinase-1ε, exhibits improved selectivity for PI3Kδ compared with other PI3K inhibitors. This phase IIb trial was designed to evaluate the efficacy and safety of umbralisib in patients with R/R iNHL. PATIENTS AND METHODS: In this multicohort, open-label, phase IIb study, 208 patients with R/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, or SLL) unresponsive to prior treatments (≥ 1 MZL; ≥ 2 FL/SLL), including ≥ 1 anti-CD20-based therapy, were administered umbralisib 800 mg orally once daily until disease progression, unacceptable toxicity, or study withdrawal. Primary end point is overall response rate; secondary end points include time to response, duration of response, progression-free survival, and safety. RESULTS: The median follow-up is 27.7 months (efficacy) and 21.4 months (safety). The overall response rate was 47.1%, and tumor reduction occurred in 86.4% of patients. The median time to response was 2.7-4.6 months. The median duration of response was not reached for MZL, 11.1 months for FL, and 18.3 months for SLL. Median progression-free survival was not reached for MZL, 10.6 months for FL, and 20.9 months for SLL. At least one grade ≥ 3 treatment-emergent adverse event (TEAE) was reported in 53.4% of patients. TEAEs led to umbralisib discontinuation in 32 patients (15.4%). A total of 31 patients (14.9%) discontinued because of a treatment-related adverse event. Grade ≥ 3 TEAEs reported in ≥ 10% of patients: neutropenia (11.5%) and diarrhea (10.1%). Increased ALT/AST (grade ≥ 3) occurred in 6.7%/7.2% of patients. CONCLUSION: Umbralisib achieved meaningful clinical activity in heavily pretreated patients with iNHL. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and adverse event-related discontinuations.

ß-glucosidase from thermophilic fungus Thermoascus crustaceus: production and industrial potential.

Microbial ß-glucosidases can be used in several industrial processes, including production of biofuels, functional foods, juices, and beverages. In the present work, production of ß-glucosidase by solid state cultivation of the fungus Thermoascus crustaceus in a low-cost cultivation medium (comprising agroindustrial residues) was evaluated. The highest production of ß-glucosidase, about 415.1 U/g substrate (or 41.51 U/mL), was obtained by cultivating the fungus in wheat bran with 70% humidity, during 96 h at 40°C. The enzymatic activity was optimum at pH 4.5 and 65°C. ß-Glucosidase maintained its catalytic activity when incubated at a pH range of 4.0-8.0 and temperature of 30-55°C. The enzyme was strongly inhibited by glucose; even when the substrate and glucose concentrations were equal, the inhibition was not reversed, suggesting a non-competitive inhibition. In the presence of up to 10% ethanol, ß-glucosidase maintained its catalytic activity. In addition to ß-glucosidase, the enzymatic extract showed activity of 36 U/g for endoglucanase, 256.2 U/g for xylanase, and 18.2 U/g for ß-xylosidase. The results allow to conclude that the fungus T. crustaceus has considerable potential for production of ß-glucosidase and xylanase when cultivated in agroindustrial residues, thereby reducing the cost of these biocatalysts.

Conservation resource allocation, small population resiliency, and the fallacy of conservation triage.

Some conservation prioritization methods are based on the assumption that conservation needs overwhelm current resources and not all species can be conserved; therefore, a conservation triage scheme (i.e., when the system is overwhelmed, species should be divided into three groups based on likelihood of survival, and efforts should be focused on those species in the group with the best survival prospects and reduced or denied to those in the group with no survival prospects and to those in the group not needing special efforts for their conservation) is necessary to guide resource allocation. We argue that this decision-making strategy is not appropriate because resources are not as limited as often assumed, and it is not evident that there are species that cannot be conserved. Small population size alone, for example, does not doom a species to extinction; plants, reptiles, birds, and mammals offer examples. Although resources dedicated to conserving all threatened species are insufficient at present, the world's economic resources are vast, and greater resources could be dedicated toward species conservation. The political framework for species conservation has improved, with initiatives such as the UN Sustainable Development Goals and other international agreements, funding mechanisms such as The Global Environment Facility, and the rise of many nongovernmental organizations with nimble, rapid-response small grants programs. For a prioritization system to allow no extinctions, zero extinctions must be an explicit goal of the system. Extinction is not inevitable, and should not be acceptable. A goal of no human-induced extinctions is imperative given the irreversibility of species loss.

Asignación de Recursos para la Conservación, Resiliencia de Poblaciones Pequeñas y la Falacia del Triaje de Conservación Resumen Algunos métodos de priorización de la conservación están basados en el supuesto de que las necesidades de la conservación superan a los actuales recursos y que no todas las especies pueden ser conservadas; por lo tanto, se necesita un esquema de triaje (esto es, cuando el sistema está abrumado, las especies deben dividirse en tres grupos con base en su probabilidad de supervivencia y los esfuerzos deben enfocarse en aquellas especies dentro del grupo con las mejores probabilidades de supervivencia y a aquellas en el grupo sin probabilidades de supervivencia o aquellas en el grupo que no necesita esfuerzos especializados para su conservación se les deben reducir o negar los esfuerzos de conservación) para dirigir la asignación de recursos. Discutimos que esta estrategia para la toma de decisiones no es apropiada porque los recursos no están tan limitados como se asume con frecuencia y tampoco es evidente que existan especies que no puedan ser conservadas. Por ejemplo, tan sólo un tamaño poblacional pequeño no es suficiente para condenar a una especie a la extinción; contamos con ejemplos en plantas, reptiles, aves y mamíferos. Aunque actualmente todos los recursos dedicados a la conservación de todas las especies amenazadas son insuficientes, los recursos económicos mundiales son vastos y se podrían dedicar mayores recursos a la conservación de especies. El marco de trabajo político para la conservación de especies ha mejorado, con iniciativas como los Objetivos de Desarrollo Sustentable de la ONU y otros acuerdos internacionales, el financiamiento de mecanismos como el Fondo para el Medio Ambiente Mundial, y el surgimiento de muchas organizaciones no gubernamentales mediante programas de subsidios pequeños hábiles y de respuesta rápida. Para que un sistema de priorización no permita las extinciones, las cero extinciones deben ser un objetivo explícito del sistema. La extinción no es inevitable y no debería ser aceptable. El objetivo de cero extinciones inducidas por humanos es imperativo dada la irreversibilidad de la pérdida de especies.

Phase 2 study of the safety and efficacy of umbralisib in patients with CLL who are intolerant to BTK or PI3Kδ inhibitor therapy.

Intolerance is the most common reason for kinase inhibitor (KI) discontinuation in chronic lymphocytic leukemia (CLL). Umbralisib, a novel highly selective phosphatidylinositol 3-kinase Î´ (PI3Kδ)/CK1ε inhibitor, is active and well tolerated in CLL patients. In this phase 2 trial (NCT02742090), umbralisib was initiated at 800 mg/d in CLL patients requiring therapy, who were intolerant to prior BTK inhibitor (BTKi) or PI3K inhibitor (PI3Ki) therapy, until progression or toxicity. Primary end point was progression-free survival (PFS). Secondary end points included time to treatment failure and safety. DNA was genotyped for CYP3A4, CYP3A5, and CYP2D6 polymorphisms. Fifty-one patients were enrolled (44 BTKi intolerant and 7 PI3Kδi intolerant); median age was 70 years (range, 48-96), with a median of 2 prior lines of therapy (range, 1-7), 24% had del17p and/or TP53 mutation, and 65% had unmutated IGHV. Most common adverse events (AEs) leading to prior KI discontinuation were rash (27%), arthralgia (18%), and atrial fibrillation (16%). Median PFS was 23.5 months (95% CI, 13.1-not estimable), with 58% of patients on umbralisib for a longer duration than prior KI. Most common (≥5%) grade ≥3 AEs on umbralisib (all causality) were neutropenia (18%), leukocytosis (14%), thrombocytopenia (12%), pneumonia (12%), and diarrhea (8%). Six patients (12%) discontinued umbralisib because of an AE. Eight patients (16%) had dose reductions and were successfully rechallenged. These are the first prospective data to confirm that switching from a BTKi or alternate PI3Ki to umbralisib in this BTKi- and PI3Ki-intolerant CLL population can result in durable well-tolerated responses.

Reproductive toxicity in male juvenile rats: Antagonistic effects between isolated agrochemicals and in binary or ternary combinations.

The management of agrochemicals in Brazilian agriculture impacts global environmental sustainability and food security, since this country is one of the major agro-food exporters in the world. Acephate, carbendazim, and dithiocarbamates (DTCs) such as mancozeb, are among the most detected agrochemicals in Brazilian agro-food products, occurring in combination in several crops, especially in fruit cultures. The present study evaluated the impact of the exposure to isolated agrochemicals and all the combined possible mixtures (binary and ternary forms) on the reproductive parameters of male juvenile rats, known to be a vulnerable biological system and developmental window. Data were analyzed using Generalized Linear Models (GzLM), considering each agrochemical as an independent factor. The study revealed higher reproductive toxicity exerted by isolated agrochemicals when compared to the combined treatments, which exhibited mostly an antagonistic effect. Results suggest endocrine disruptive effects of each one separately on the weight of reproductive organs and testicular histomorphometry, besides changes in testicular SOD activity. The full factorial experimental design employed here allowed us to conclude that it is not possible to scale-up the effects of the isolated treatments to the mixtures, showing how difficult it is to know beforehand the response and cross-talk among the multiple physiological mechanisms disturbed by complex mixtures. Considering that food products are shared on a global scale and that some of these three agrochemicals have already been prohibited in EU countries, the consumption of some Brazilian products puts global human health at risk, that of children.

The relative contribution of non-selection and selection processes in marine benthic assemblages.

We tested the hypothesis that the ubiquity of marine meiofaunal nematodes and their indiscriminate passive dispersal create assemblages that are less limited by its environment; whereas the relatively smaller population sizes of macrofauna, associated with their ability to track environmental conditions before settlement, renders their distribution more environmentally-restricted. We compared the empirical distribution of macrofauna and nematode species with that of communities simulated under different assumptions of selection (e.g. environmental filtering) and non-selection (e.g. dispersal limitation) processes. Selection processes were the prime driver of both meio- and macrofauna assemblages, with rare species strongly contributing to this component. The total number of species explained by non-selection processes was 27% higher in nematodes than in macrofauna. Our results underline the importance of a species-level approach to determine the contribution of selection and non-selection assembly processes. Moreover, they highlight the important yet overlooked role of dispersal and stochastic processes in determining species dynamics.