Receptor kinase signaling of BRI1 and SIRK1 is tightly balanced by their interactomes as revealed from domain-swap chimaera in AE-MS approaches.

At the plasma membrane, in response to biotic and abiotic cues, specific ligands initiate the formation of receptor kinase heterodimers, which regulate activities of plasma membrane proteins and initiate signaling cascades to the nucleus. In this study, we utilized affinity enrichment mass spectrometry (AE-MS) to investigate the stimulus-dependent interactomes of LRR receptor kinases in response to their respective ligands, with an emphasis on exploring structural influences and potential cross-talk events at the plasma membrane. BRI1 and SIRK1 were chosen as receptor kinases with distinct coreceptor preference. By using interactome characteristic of domain-swap chimera following a gradient boosting learning algorithm trained on SIRK1 and BRI1 interactomes, we attribute contributions of extracellular domain, transmembrane domain, juxtamembrane domain and kinase domain of respective ligand-binding receptors to their interaction with their coreceptors and substrates. Our results revealed juxtamembrane domain as major structural element defining the specific substrate recruitment for BRI1 and extracellular domain for SIRK1. Furthermore, the learning algrorithm enabled us to predict the phenotypic outcomes of chimeric receptors based on different domain combinations, which was verified by dedicated experiments. As a result, our work reveals a tightly controlled balance of signaling cascade activation dependent on ligand-binding receptors domains and the internal ligand status of the plant. Moreover, our study shows the robust utility of machine learning classification as a quantitative metric for studying dynamic interactomes, dissecting the contribution of specific domains and predicting their phenotypic outcome.

Role of HLA-B*58:01-restricted CD8+ T cells in HIV-1 subtype AE infection.

HLA-B*58:01 and HLA-B*57 are protective alleles against HIV-1 subtype B or C infection whereas these HLA alleles have not been reported as protective in HIV-1 subtype AE infection. Although HLA-B*58:01-restricted and HLA-B*57-restricted HIV-1-specific CD8+ T cells have been thoroughly analyzed in subtype B or C infection, they have only been partially analyzed in subtype AE infection. We identified six HLA-B*58:01-restricted subtype AE epitopes in Vietnamese individuals infected with subtype AE. HLA-B*58:01-restricted T-cell responses to Gag epitopes, which may control disease progression in HLA-B*58:01+ and HLA-B*57+ individuals infected with subtype B or C, were not protective in subtype AE infection. These findings suggest that the loss of HLA-B*58:01-restricted T cells specific for some Gag epitopes and/or their reduced ability may account for the lack of protective effects conferred by HLA-B*58:01 in subtype AE infection.

Selective inhibitors of the PSEN1-gamma-secretase complex.

Clinical development of γ-secretases, a family of intramembrane cleaving proteases, as therapeutic targets for a variety of disorders including cancer and Alzheimer's disease was aborted because of serious mechanism-based side effects in the phase III trials of unselective inhibitors. Selective inhibition of specific γ-secretase complexes, containing either PSEN1 or PSEN2 as the catalytic subunit and APH1A or APH1B as supporting subunits, does provide a feasible therapeutic window in preclinical models of these disorders. We explore here the pharmacophoric features required for PSEN1 versus PSEN2 selective inhibition. We synthesized a series of brain penetrant 2-azabicyclo[2,2,2]octane sulfonamides and identified a compound with low nanomolar potency and high selectivity (>250-fold) toward the PSEN1-APH1B subcomplex versus PSEN2 subcomplexes. We used modeling and site-directed mutagenesis to identify critical amino acids along the entry part of this inhibitor into the catalytic site of PSEN1. Specific targeting one of the different γ-secretase complexes might provide safer drugs in the future.

Novel functions of the anion exchanger AE4 (SLC4A9).

The kidney plays a crucial role in acid-base homeostasis. In the distal nephron, α-intercalated cells contribute to urinary acid (H+) secretion and ß-intercalated cells accomplish urinary base (HCO3-) secretion. ß-intercalated cells regulate the acid base status through modulation of the apical Cl-/HCO3- exchanger pendrin (SLC26A4) activity. In this review, we summarize and discuss our current knowledge of the physiological role of the renal transporter AE4 (SLC4A9). The AE4, as cation-dependent Cl-/HCO3- exchanger, is exclusively expressed in the basolateral membrane of ß-intercalated cells and is essential for the sensing of metabolic acid-base disturbances in mice, but not for renal sodium reabsorption and plasma volume control. Potential intracellular signaling pathways are discussed that might link basolateral acid-base sensing through the AE4 to apical pendrin activity.

Strong Positive Selection in Aedes aegypti and the Rapid Evolution of Insecticide Resistance.

Aedes aegypti vectors the pathogens that cause dengue, yellow fever, Zika virus, and chikungunya and is a serious threat to public health in tropical regions. Decades of work has illuminated many aspects of Ae. aegypti's biology and global population structure and has identified insecticide resistance genes; however, the size and repetitive nature of the Ae. aegypti genome have limited our ability to detect positive selection in this mosquito. Combining new whole genome sequences from Colombia with publicly available data from Africa and the Americas, we identify multiple strong candidate selective sweeps in Ae. aegypti, many of which overlap genes linked to or implicated in insecticide resistance. We examine the voltage-gated sodium channel gene in three American cohorts and find evidence for successive selective sweeps in Colombia. The most recent sweep encompasses an intermediate-frequency haplotype containing four candidate insecticide resistance mutations that are in near-perfect linkage disequilibrium with one another in the Colombian sample. We hypothesize that this haplotype may continue to rapidly increase in frequency and perhaps spread geographically in the coming years. These results extend our knowledge of how insecticide resistance has evolved in this species and add to a growing body of evidence suggesting that Ae. aegypti has an extensive genomic capacity to rapidly adapt to insecticide-based vector control.

Flexible Anionic Groups-Activated Structure Dissymmetry for Strong Nonlinearity in Ln2 Ae3 MIV 3 S12 Family.

Structural dissymmetry and strong second-harmonic generation (SHG) responses are key conditions for nonlinear optical (NLO) crystals, and targeted combinatorial screening of suitable anionic groups has become extremely effective. Herein, optimal combination of flexible SnSn (n = 5, 6) groups and highly electropositive cations (lanthanides (Ln3+ ) and alkaline earth (Ae2+ : Sr, Ca) metals) affords the successful synthesis of 12 NLO thiostannates including Ln2 Sr3 Sn3 S12 (Pmc21 ) and Ln2 Ca3 Sn3 S12 (P-62m); whereas 17 rigid GeS4 or SiS4 tetrahedra-constructed Ln2 Ae3 Ge3 S12 and Ln2 Ae3 Si3 S12 crystallize in the centrosymmetric (CS) Pnma. This unprecedented CS to noncentrosymmetric (NCS) structural transformation (Pnma to P-62m to Pmc21 ) in the Ln2 Ae3 MIV 3 S12 family indicates that chemical substitution of the tetrahedral GeS4 /SiS4 units with SnSn breaks the original symmetry to form the requisite NCS structures. Remarkably, strong polarization anisotropy and hyperpolarizability of the Sn(4+) S5 unit afford huge performance improvement from the nonphase-matching (NPM) SHG response (1.4 × AgGaS2 and Δn = 0.008) of La2 Ca3 Sn3 S12 to the strong phase-matching (PM) SHG effect (3.0 × AgGaS2 and Δn = 0.086) of La2 Sr3 Sn3 S12 . Therefore, Sn(4+) S5 is proven to be a promising "NLO-active unit." This study verifies that the coupling of flexible SnSn building blocks into structures opens a feasible path for designing targeted NCS crystals with strong nonlinearity and optical anisotropy.

Cobalamins Function as Allosteric Activators of an Angelman Syndrome-Associated UBE3A/E6AP Variant.

Genetic aberrations of the maternal UBE3A allele, which encodes the E3 ubiquitin ligase E6AP, are the cause of Angelman syndrome (AS), an imprinting disorder. In most cases, the maternal UBE3A allele is not expressed. Yet, approximately 10 percent of AS individuals harbor distinct point mutations in the maternal allele resulting in the expression of full-length E6AP variants that frequently display compromised ligase activity. In a high-throughput screen, we identified cyanocobalamin, a vitamin B12-derivative, and several alloxazine derivatives as activators of the AS-linked E6AP-F583S variant. Furthermore, we show by cross-linking coupled to mass spectrometry that cobalamins affect the structural dynamics of E6AP-F583S and apply limited proteolysis coupled to mass spectrometry to obtain information about the regions of E6AP that are involved in, or are affected by binding cobalamins and alloxazine derivatives. Our data suggest that dietary supplementation with vitamin B12 can be beneficial for AS individuals.

Archaeal Kink-Turn Binding Protein Mediates Inhibition of Orthomyxovirus Splicing Biology.

Despite lacking a DNA intermediate, orthomyxoviruses complete their replication cycle in the nucleus and generate multiple transcripts by usurping the host splicing machinery. This biology results in dynamic changes of relative viral transcripts over time and dictates the replicative phase of the infection. Here, we demonstrate that the family of archaeal L7Ae proteins uniquely inhibit the splicing biology of influenza A virus, influenza B virus, and Salmon isavirus, revealing a common strategy utilized by Orthomyxoviridae members to achieve this dynamic. L7Ae-mediated inhibition of virus biology was lost with the generation of a splicing-independent strain of influenza A virus and attempts to select for an escape mutant resulted in variants that conformed to host splicing biology at significant cost to their overall fitness. As L7Ae recognizes conventional kink turns in various RNAs, these data implicate the formation of a similar structure as a shared strategy adopted by this virus family to coordinate their replication cycle. IMPORTANCE Here, we demonstrate that a family of proteins from archaea specifically inhibit this splicing biology of all tested members of the Orthomyxoviridae family. We show that this inhibition extends to influenza A virus, influenza B virus, and isavirus genera, while having no significant impact on the mammalian transcriptome or proteome. Attempts to generate an escape mutant against L7Ae-mediated inhibition resulted in mutations surrounding the viral splice sites and a significant loss of viral fitness. Together, these findings reveal a unique biology shared among diverse members of the Orthomyxoviridae family that may serve as a means to generate future universal therapeutics.

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies.

Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = -0.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = -0.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection. IMPORTANCE Development of an effective HIV-1 vaccine will be facilitated by better understanding the dynamics between the founder virus and the early humoral responses. Variations between subtypes may influence the evolution of immune responses and should be considered as we strive to understand these dynamics. In this study, autologous founder envelope neutralization and heterologous functional humoral responses were evaluated after acute infection by HIV-1 CRF01_AE, a subtype that has not been thoroughly characterized. The evolution of these humoral responses was assessed in relation to envelope characteristics, magnitude of elicited immune responses, and viral load. Understanding immune parameters in natural infection will improve our understanding of protective responses and aid in the development of immunogens that elicit protective functional antibodies. Advancing our knowledge of correlates of positive clinical outcomes should lead to the design of more efficacious vaccines.

A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema.

BACKGROUND: Hereditary angioedema (HAE) is a potentially fatal disease characterized by unpredictable, recurrent, often disabling swelling attacks. In a randomized phase 2 study, donidalorsen reduced HAE attack frequency and improved patient quality-of-life (ISIS721744-CS2, NCT04030598). We report the 2-year interim analysis of the phase 2 open-label extension (OLE) study (ISIS 721744-CS3, NCT04307381). METHODS: In the OLE, the on-treatment study period consisted of fixed (weeks 1-13, donidalorsen 80 mg subcutaneously every 4 weeks [Q4W]) and flexible (weeks 17-105, donidalorsen 80 mg Q4W, 80 mg every 8 weeks [Q8W], or 100 mg Q4W) dosing periods. The primary outcome was incidence and severity of treatment-emergent adverse events (TEAEs). The secondary outcomes included efficacy, pharmacodynamic, and quality-of-life assessments. RESULTS: Seventeen patients continued in the OLE study. No serious TEAEs or TEAEs leading to treatment discontinuation were reported. Mean monthly HAE attack rate was 96% lower than the study run-in baseline rate (mean, 0.06/month; 95% confidence interval [CI], 0.02-0.10; median, 0.04 on-treatment vs. mean, 2.70/month; 95% CI, 1.94-3.46; median, 2.29 at baseline). Mean monthly attack rate for Q8W dosing (n = 8) was 0.29 (range, 0.0-1.7; 95% CI, -0.21 to 0.79; median, 0.00). Mean plasma prekallikrein and D-dimer concentrations decreased, and Angioedema Quality of Life Questionnaire total score improved from baseline to week 105 with donidalorsen. CONCLUSION: The 2-year interim results of this phase 2 OLE study of donidalorsen in patients with HAE demonstrated no new safety signals; donidalorsen was well tolerated. There was durable efficacy with a 96% reduction in HAE attacks.

Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Achieving conservation and restoration outcomes through ecologically beneficial aquaculture.

A range of conservation and restoration tools are needed to safeguard the structure and function of aquatic ecosystems. Aquaculture, the culturing of aquatic organisms, often contributes to the numerous stressors that aquatic ecosystems face, yet some aquaculture activities can also deliver ecological benefits. We reviewed the literature on aquaculture activities that may contribute to conservation and restoration outcomes, either by enhancing the persistence or recovery of one or more target species or by moving aquatic ecosystems toward a target state. We identified 12 ecologically beneficial outcomes achievable via aquaculture: species recovery, habitat restoration, habitat rehabilitation, habitat protection, bioremediation, assisted evolution, climate change mitigation, wild harvest replacement, coastal defense, removal of overabundant species, biological control, and ex situ conservation. This list may be expanded as new applications are discovered. Positive intentions do not guarantee positive ecological outcomes, so it is critical that potentially ecologically beneficial aquaculture activities be evaluated via clear and measurable indicators of success to reduce potential abuse by greenwashing. Unanimity on outcomes, indicators, and related terminology will bring the field of aquaculture-environment interactions into line with consensus standards in conservation and restoration ecology. Broad consensus will also aid the development of future certification schemes for ecologically beneficial aquaculture.

Se necesita una gama de herramientas de conservación y restauración para salvaguardar la estructura y función de los ecosistemas acuáticos. La acuacultura (el cultivo de organismos acuáticos) generalmente contribuye a los numerosos estresantes que soportan los ecosistemas acuáticos, aunque algunas actividades de la acuacultura también pueden proporcionar beneficios ecológicos. Revisamos la literatura sobre las actividades de acuacultura que pueden contribuir a los resultados de conservación y restauración, ya sea al incrementar la persistencia o recuperación de una o más especies objetivo o al llevar a los ecosistemas acuáticos hacia un estado objetivo. Identificamos doce resultados con beneficios ecológicos que pueden lograrse con la acuacultura: recuperación de la especie, recuperación del hábitat, restauración del hábitat, rehabilitación del hábitat, protección del hábitat, bioreparación, evolución asistida, mitigación del cambio climático, sustitución de la captura silvestre, defensa costera, eliminación de las especies sobreabundantes, control biológico y conservación ex situ. Esta lista puede expandirse conforme se descubren nuevas aplicaciones. Las intenciones positivas no garantizan resultados ecológicos positivos, así que es importante que se evalúen las actividades de acuacultura con un posible beneficio ecológico por medio de indicadores del éxito claros y medibles para reducir el abuso potencial por ecoblanqueo o greenwashing. La unanimidad en los resultados, indicadores y terminología relacionada armonizará las interacciones entre la acuacultura y el ambiente con los estándares de la conservación y la ecología de la restauración. Un consenso generalizado también ayudará con el desarrollo de futuros esquemas de certificación para la acuacultura con beneficios ecológicos. Obtención de resultados de conservación y restauración a través de la acuacultura con beneficios ecológicos.

Influence of microclimate and forest management on bat species faced with global change.

Climate refugia, areas where climate is expected to remain relatively stable, can offer a near-term safe haven for species sensitive to warming temperatures and drought. Understanding the influence of temperature, moisture, and disturbance on sensitive species is critical during this time of rapid climate change. Coastal habitats can serve as important refugia. Many of these areas consist of working forestlands, and there is a growing recognition that conservation efforts worldwide must consider the habitat value of working lands, in addition to protected areas, to effectively manage large landscapes that support biodiversity. The sensitivity of forest bats to climate and habitat disturbance makes them a useful indicator taxon. We tested how microclimate and forest management influence habitat use for 13 species of insectivorous bats in a large climate refugium in a global biodiversity hotspot. We examined whether bat activity during the summer dry season is greater in forests where coastal fog provides moisture and more stable temperatures across both protected mature stands and those regularly logged. Acoustic monitoring was conducted at a landscape scale with 20 study sites, and generalized linear mixed models were used to examine the influence of habitat variables. Six species were positively associated with warmer nighttime temperature, and 5 species had a negative relationship with humidity or a positive relationship with climatic moisture deficit. Our results suggest that these mammals may have greater climate adaptive capacity than expected, and, for now, that habitat use may be more related to optimal foraging conditions than to avoidance of warming temperatures and drought. We also determined that 12 of the 13 regionally present bat species were regularly detected in commercial timberland stands. Because forest bats are highly mobile, forage over long distances, and frequently change roosts, the stewardship of working forests must be addressed to protect these species.

Influencia del microclima y el manejo forestal sobre especies de murciélagos ante el cambio global Resumen Los refugios climáticos, áreas en donde se espera que el clima permanezca relativamente estable, pueden ofrecer un santuario a corto plazo para las especies sensibles al aumento de temperaturas y la sequía. Es muy importante entender la influencia de la temperatura, la humedad y las perturbaciones sobre las especies sensibles durante estos tiempos de cambio climático repentino. Los hábitats costeros pueden funcionar como refugios importantes. Muchas de estas áreas consisten en bosques funcionales y cada vez hay más reconocimiento de que los esfuerzos mundiales de conservación deben considerar el valor del hábitat de los suelos funcionales, además de las áreas protegidas, para manejar de manera efectiva los extensos paisajes que mantienen a la biodiversidad. La sensibilidad de los murciélagos de los bosques ante las perturbaciones climáticas y de hábitat hace que sean un taxón indicador útil. Analizamos cómo los microclimas y el manejo forestal influyen sobre el uso de hábitat de 13 especies de murciélagos insectívoros en un refugio climático amplio dentro de un punto caliente de biodiversidad mundial. Examinamos si la actividad de los murciélagos durante la temporada seca de verano es mayor en los bosques en donde la niebla costera proporciona humedad y temperaturas más estables tanto en los árboles maduros como aquellos que son talados con regularidad. Realizamos el monitoreo acústico a escala de paisaje en 20 estudios de sitio y usamos modelos lineales mixtos generalizados para examinar la influencia de las variables del hábitat. Seis especies estuvieron asociadas positivamente con la temperatura nocturna más cálida y cinco especies tuvieron una relación negativa con la humedad o una relación positiva con el déficit climático de humedad. Nuestros resultados sugieren que estos mamíferos pueden tener una mayor capacidad de adaptación climática de lo que se pensaba y, por ahora, que el uso de hábitat puede estar más relacionado con las condiciones óptimas de forrajeo que con la evasión de las temperaturas elevadas y la sequía. También determinamos que 12 de las 13 especies con presencia regional fueron detectadas con regularidad en los puntos de tala comercial. Ya que los murciélagos del bosque tienden a moverse mucho, forrajear a lo largo de grandes distancias y con frecuencia cambiar de nido, debemos abordar la administración de los bosques funcionales para proteger a estas especies.

Flexibility trade-offs in conservation offsets.

Conservation offsets promise cost-effective conservation of biodiversity, especially under economic and environmental change, because they represent a more flexible approach to biodiversity conservation, allowing for the economic development of ecologically valuable land provided that this development is offset by restoration of previously developed areas. The level of flexibility is determined by the trading rules. Lax rules allow for more flexibility, which promises cost savings, but will likely lead to unintended loss of biodiversity. I analyzed the trade-off between economic costs and ecological benefits (biodiversity conservation) in biodiversity offsetting with an ecological-economic model that considered the three main types of offset flexibility: spatial, temporal, and ecosystem type. I sought to examine the influence of ecological and economic conditions on offset flexibility trade-offs. Large variation in the conservation costs and small costs of habitat restoration strongly increased trading activity and reduced the ecological benefit. The ecological benefit was most sensitive to spatial flexibility when a short range of ecological interaction was considered. At a large interaction range, spatial flexibility delivered large cost savings without overly reducing the ecological benefit. Risks and time lags associated with habitat restoration favored an offsetting scheme in which credits are awarded with the initiation of restoration projects rather than their successful completion-given appropriate offsetting multipliers were chosen. Altogether, under scarce resources, the level of flexibility in an offsetting scheme should be chosen by carefully balancing ecological benefits and economic costs.

Compromisos de flexibilidad en las compensaciones por conservación Resumen Las compensaciones por conservación prometen conservar la biodiversidad de forma rentable, especialmente de frente al cambio ambiental y económico. Ya que representan una estrategia más flexible para la conservación de la biodiversidad, esto permite el desarrollo económico de suelo con valor ecológico siempre y cuando este desarrollo esté compensado por la restauración de áreas con desarrollo previo. El nivel de flexibilidad está determinado por las reglas de intercambio. Las reglas laxas permiten una mayor flexibilidad, que promete ahorros, pero probablemente derive en la pérdida no intencionada de la biodiversidad. Analicé los compromisos entre los costos económicos y los beneficios ecológicos (conservación de la biodiversidad) en las compensaciones por biodiversidad con un modelo ecológico-económico que consideraba los tres tipos principales de flexibilidad: espacial, temporal y por tipo de ecosistema. Traté de examinar la influencia de las condiciones ecológicas y económicas sobre los compromisos de flexibilidad en las compensaciones. Una gran variación en los costos de conservación y los pequeños costos de la restauración del hábitat incrementaron fuertemente la actividad de intercambio y redujeron el beneficio ecológico. El beneficio ecológico fue más sensible a la flexibilidad espacial cuando consideré un corto alcance de la interacción ecológica. Con un alcance extenso, la flexibilidad espacial ofreció grandes ahorros son reducir por mucho el beneficio ecológico. Los riesgos y retrasos temporales asociados con la restauración del hábitat favorecieron un esquema de compensaciones en el que los créditos se otorgan al inicio del proyecto de restauración en lugar de con la conclusión exitosa del mismo-siempre y cuando se hayan elegido multiplicadores de compensación adecuados. En conjunto, si se tienen pocos recursos, el nivel de flexibilidad en un esquema de compensaciones debería elegirse con un balance cuidadoso entre los beneficios ecológicos y los costos económicos.

Loss of species and functions in a deforested megadiverse tropical forest.

Tropical species richness is threatened by habitat degradation associated with land-use conversion, yet the consequences for functional diversity remain little understood. Progress has been hindered by difficulties in obtaining comprehensive species-level trait information to characterize entire assemblages and insufficient appreciation that increasing land-cover heterogeneity potentially compensates for species loss. We examined the impacts of tropical deforestation associated with land-use heterogeneity on bird species richness, functional redundancy, functional diversity, and associated components (i.e., alpha diversity, species dissimilarity, and interaction strength of the relationship between abundance and functional dissimilarity). We analyzed over 200 georeferenced bird assemblages in the Atlantic Forest of Brazil. We characterized the functional role of the species of each assemblage and modeled biodiversity metrics as a function of forest cover and land-cover heterogeneity. Replacement of native Atlantic Forest with a mosaic of land uses (e.g., agriculture, pastures, and urbanization) reduced bird species richness in a nonrandom way. Core forest species, or species considered sensitive to edges, tended to be absent in communities in heterogenous environments. Overall, functional diversity and functional redundancy of bird species were not affected by forest loss. However, birds in highly heterogenous habitats were functionally distinct from birds in forest, suggesting a shift in community composition toward mosaic-exclusive species led by land-cover heterogeneity. Threatened species of the Atlantic Forest did not seem to tolerate degraded and heterogeneous environments; they remained primarily in areas with large forest tracts. Our results shed light on the complex effects of native forest transformation to mosaics of anthropogenic landscapes and emphasize the importance of considering the effects of deforestation and land-use heterogeneity when assessing deforestation effects on Neotropical biodiversity.

Pérdida de especies y funciones en un bosque tropical megadiverso deforestado Resumen La riqueza de especies tropicales está amenazada por la degradación asociada con la conversión del uso de suelo, y aun así entendemos muy poco de las consecuencias que esto tiene para la diversidad funcional. El progreso está obstaculizado por las dificultades para obtener información completa de los rasgos a nivel de especie para caracterizar ensamblajes completos y la apreciación insuficiente de que la heterogeneidad creciente de la cobertura del suelo tiene el potencial para compensar la pérdida de especies. Analizamos el impacto que tiene la deforestación tropical asociada con la heterogeneidad del uso de suelo sobre la riqueza de especies de aves, la redundancia funcional, la diversidad funcional y sus componentes asociados (es decir, diversidad alfa, disimilitud de especies y fuerza de interacción de la relación entre la abundancia y la disimilitud funcional). Analizamos más de 200 ensamblajes georreferenciados de aves en el Bosque Atlántico de Brasil. Caracterizamos el papel funcional de las especies de cada ensamblaje y modelamos las medidas de biodiversidad como función de la cobertura forestal y de la heterogeneidad del uso de suelo. La sustitución del Bosque Atlántico nativo con un mosaico de usos de suelo (p. ej.: agricultura, pastura y urbanización) redujo la riqueza de especies de una manera no aleatoria. Las especies nucleares del bosque, o las especies consideradas como sensibles a los bordes, tendieron a estar ausentes en las comunidades de los ambientes heterogéneas. En general, la diversidad y la redundancia funcionales de las especies de aves no se vieron afectadas por la pérdida del bosque. Sin embargo, las aves en los hábitats con alta heterogeneidad eran funcionalmente distintas a las aves de los bosques, lo que sugiere un cambio en la composición x de la comunidad hacia especies exclusivas de mosaicos llevadas por la heterogeneidad de la cobertura del suelo. Las especies amenazadas del Bosque Atlántico no parecieron tolerar el ambiente degradado y heterogéneo pues permanecieron principalmente en las áreas con grandes extensiones de bosque. Nuestros resultados arrojan luz sobre los efectos complejos de la transformación de los bosques nativos en mosaicos de paisajes antropogénicos y recalcan la importancia de considerar los efectos de la deforestación y la heterogeneidad del uso de suelo cuando se evalúan los efectos de la deforestación sobre la biodiversidad neotropical.

Three major steps toward the conservation of freshwater and riparian biodiversity.

Freshwater ecosystems and their bordering wetlands and riparian zones are vital for human society and biological diversity. Yet, they are among the most degraded ecosystems, where sharp declines in biodiversity are driven by human activities, such as hydropower development, agriculture, forestry, and fisheries. Because freshwater ecosystems are characterized by strongly reciprocal linkages with surrounding landscapes, human activities that encroach on or degrade riparian zones ultimately lead to declines in freshwater-riparian ecosystem functioning. We synthesized results of a symposium on freshwater, riparian, and wetland processes and interactions and analyzed some of the major problems associated with improving freshwater and riparian research and management. Three distinct barriers are the lack of involvement of local people in conservation research and management, absence of adequate measurement of biodiversity in freshwater and riparian ecosystems, and separate legislation and policy on riparian and freshwater management. Based on our findings, we argue that freshwater and riparian research and conservation efforts should be integrated more explicitly. Best practices for overcoming the 3 major barriers to improved conservation include more and sustainable use of traditional and other forms of local ecological knowledge, choosing appropriate metrics for ecological research and monitoring of restoration efforts, and mirroring the close links between riparian and freshwater ecosystems in legislation and policy. Integrating these 3 angles in conservation science and practice will provide substantial benefits in addressing the freshwater biodiversity crisis.

Tres grandes pasos hacia la conservación de la biodiversidad ribereña y de agua dulce Resumen Los ecosistemas de agua dulce y los humedales y zonas ribereñas que los bordean son vitales para la sociedad y la biodiversidad. Sin embargo, se encuentran entre los ecosistemas más degradados en donde las declinaciones graves de la biodiversidad son causadas por actividades humanas como el desarrollo hidroeléctrico, la agricultura, la silvicultura y las pesquerías. Puesto que los ecosistemas de agua dulce se caracterizan por tener un vínculo recíproco con los paisajes que los rodean, las actividades humanas que invaden o degradan las zonas ribereñas terminan en la declinación del funcionamiento del ecosistema ribereño de agua dulce. Sintetizamos los resultados de un simposio sobre los procesos e interacciones de agua dulce, ribereños y de humedales y analizamos algunos de los principales problemas asociados con la mejora de la investigación y gestión de agua dulce y ríos. Tres barreras claras son la falta de participación de la población local en la investigación y gestión de la conservación, la ausencia de una medición adecuada de la biodiversidad en los ecosistemas de agua dulce y ribereños, y una legislación y política separadas sobre la gestión ribereña y de agua dulce. Con base en nuestros hallazgos, argumentamos que la investigación y los esfuerzos de conservación de agua dulce y ríos deberían integrarse de manera más explícita. Las mejores prácticas para sobreponerse a las tres grandes barreras incluyen un mayor uso sustentable de los conocimientos tradicionales y otras formas de conocimiento, la selección de medidas apropiadas para la investigación ecológica y el monitoreo de los esfuerzos de restauración y la replicación de los vínculos cercanos entre los ecosistemas ribereños y de agua dulce en la legislación y en las políticas. La integración de estos tres ángulos dentro de las ciencias y prácticas de conservación proporcionará beneficios importantes en la manera de abordar la crisis de la biodiversidad de agua dulce.

Assessing the legal, illegal, and gray ornamental trade of the critically endangered helmeted hornbill.

Monitoring wildlife trade dynamics is an important initial step for conservation action and demand reduction campaigns to reduce illegal wildlife trade. Studies often rely on one data source to assess a species' trade, such as seizures or the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) trade data. Each database provides useful information but is often incomplete. Combining information from multiple sources helps provide a more complete understanding of trade. A recent rapid increase in demand for helmeted hornbill (Rhinoplax vigil) casques (a brightly colored, solid keratinous rostrum) led to its uplisting to critically endangered on the International Union for Conservation of Nature Red List in 2015. However, there is little current information on what factors influence trade trends and what current levels of demand are. We combined data from CITES, seizure records, and previously underused, yet abundant, art and antique auction data to examine the global trade in helmeted hornbill casque products (HHPs). Three decades of auction data revealed that 1027 individual HHPs had been auctioned since 1992; total auction sales were over US$3 million from 1992 to 2021. The number of HHPs auctioned was greatest from 2011 to 2014, just after the global art boom (2009-2011), followed by a decline in volume and price. The auction data also revealed 2 possible markets for HHPs: true antique and speculative, defined by era, price, and trade patterns. Trends in illegal trade matched those of the auction market, but legal trade remained consistently low. Combining data sources from legal, illegal, and gray markets provided an overview of the dynamics of illegal trade in an endangered species. This approach can be applied to other wildlife markets to provide a more complete understanding of trade and demand at the market level to inform future demand reduction campaigns.

Análisis del comercio ornamental legal, ilegal y gris del cálao con casco, especie en peligro crítico Resumen El monitoreo de la dinámica del comercio de especies silvestres es un paso inicial importante para las acciones de conservación y las campañas de reducción de la demanda destinadas a reducir el comercio ilegal de especies silvestres. Los estudios suelen basarse en una sola fuente de datos para evaluar el comercio de una especie, como las incautaciones o los datos comerciales de la Convención sobre el Comercio Internacional de Especies Amenazadas de Fauna y Flora Silvestres (CITES). Cada base de datos proporciona información útil, pero a menudo incompleta. La combinación de información procedente de varias fuentes ayuda a comprender mejor el comercio. Un reciente y rápido aumento de la demanda de cascos (un casquete queratinoso, sólido y de colores brillantes) de cálao con casco (Rhinoplax vigil) hizo que en 2015 se incluyera en la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza como especie en peligro crítico. Sin embargo, existe poca información actual sobre los factores que influyen en las tendencias del comercio y cuáles son los niveles actuales de demanda. Combinamos datos de CITES, registros de incautaciones y datos de subastas de arte y antigüedades previamente poco utilizados, aunque abundantes, para examinar el comercio mundial de productos de casquetes de cálao con casco (CCC). Tres décadas de datos de subastas revelaron que se habían subastado 1,027 CCC individuales desde 1992; las ventas totales en subasta superaron los tres millones de dólares entre 1992 y 2021. El número de CCC subastados fue mayor entre 2011 y 2014, justo después del boom del arte (2009­2011), seguido de un descenso en volumen y precio. Los datos de las subastas también revelaron dos posibles mercados para los CCC: el de las verdaderas antigüedades y el especulativo, definidos por la época, el precio y los patrones de comercio. Las tendencias del comercio ilegal coincidieron con las del mercado de subastas, pero el comercio legal se mantuvo bajo con constancia. Con la combinación de fuentes de datos de mercados legales, ilegales y grises, nuestros datos proporcionaron una visión general de la dinámica del comercio ilegal de una especie amenazada. Este enfoque puede aplicarse a otros mercados de especies silvestres para obtener un conocimiento más completo del comercio y la demanda a nivel de mercado que sirva de base a futuras campañas de reducción de la demanda.

Anthropogenic disturbance driving population decline of a dominant tree in East Asia evergreen broadleaved forests over the last 11,000 years.

Current biodiversity loss is generally considered to have been caused by anthropogenic disturbance, but it is unclear when anthropogenic activities began to affect biodiversity loss. One hypothesis suggests it began with the Industrial Revolution, whereas others propose that anthropogenic disturbance has been associated with biodiversity decline since the early Holocene. To test these hypotheses, we examined the unique vegetation of evergreen broadleaved forests (EBLFs) in East Asia, where humans have affected landscapes since the early Holocene. We adopted a genomic approach to infer the demographic history of a dominant tree (Litsea elongata) of EBLFs. We used Holocene temperature and anthropogenic disturbance factors to calculate the correlation between these variables and the historical effective population size of L. elongata with Spearman statistics and integrated the maximum-entropy niche model to determine the impact of climate change and anthropogenic disturbance on fluctuation in its effective population size. We identified 9 well-defined geographic clades for the populations of L. elongata. Based on the estimated historical population sizes of these clades, all the populations contracted, indicating persistent population decline over the last 11,000 years. Demographic history of L. elongata and human population change, change in cropland use, and change in irrigated rice area were significantly negatively correlated, whereas climate change in the Holocene was not correlated with demographic history. Our results support the early human impact hypothesis and provide comprehensive evidence that early anthropogenic disturbance may contribute to the current biodiversity crisis in East Asia.

Assessing the risk of overexploitation to a tarantula species in the pet trade.

The global pet trade in invertebrates remains poorly understood and underrepresented in policy and research. Tarantulas are a highly traded invertebrate group. Many individuals in trade are wild caught, and trade regulation is often lacking, raising concerns about the effect of trade on local ecosystems and populations. We addressed local concerns surrounding the international trade of Tapinauchenius rasti (Caribbean diamond tarantula), which is endemic to Saint Vincent and the Grenadines. We assessed the extinction risks associated with this widely traded species by analyzing supply of and demand for the species with the COM-B (capability, opportunity, motivation, behavior) model. This model breaks down decision-making into capability, opportunity, and motivation. We interviewed stakeholders throughout the supply chain and analyzed content of an online hobbyist forum and a time series of prices for this species and other tarantulas. In terms of motivation, there was limited preference for the Caribbean diamond tarantula due to its morphology and behavior. In terms of opportunity, the species was readily available, primarily through captive breeding. Collecting wild specimens is challenging due to enforcement measures and logistical difficulties, making it an unprofitable endeavor. In terms of capability, the species was relatively low in price, likely because it is easy to breed in captivity. As a result, the current wildlife trade does not pose a significant threat to the Caribbean diamond tarantula. Our methodology can serve as a valuable tool for assessing potential threats posed by trade to other spider species and possibly other invertebrates. Understanding these threats is crucial for promoting responsible and sustainable trade practices that minimize risks to wild populations while ensuring equitable benefits for communities coexisting with wildlife.

Evaluación del riesgo de sobreexplotación para una especie de tarántula en el mercado de mascotas Resumen El comercio mundial de invertebrados como mascotas todavía es poco conocido y poco representado en las políticas y la investigación. Las tarántulas son un grupo de invertebrados muy comercializado. Muchos ejemplares comercializados son capturados en su entorno natural y a menudo no existe la regulación del comercio, lo que suscita preocupación por el efecto del comercio en los ecosistemas y las poblaciones locales. Abordamos las preocupaciones locales en torno al comercio internacional de Tapinauchenius rasti (tarántula diamante del Caribe), endémica de San Vicente y las Granadinas. Analizamos la oferta y la demanda de la especie con el modelo de comportamiento COM­B para evaluar los riesgos de extinción asociados a esta especie tan comercializada. Este modelo desglosa la toma de decisiones en capacidad, oportunidad y motivación. Entrevistamos a los actores a lo largo de la cadena de suministro y analizamos el contenido de un foro de aficionados en línea y una serie cronológica de precios para esta especie y otras tarántulas. En términos de motivación, hubo una preferencia limitada por la tarántula diamante del Caribe debido a su morfología y comportamiento. En términos de oportunidad, la especie estaba fácilmente disponible, principalmente a través de la cría en cautiverio. La recolección de especímenes silvestres es un reto debido a las medidas judiciales y a las dificultades logísticas, por lo que no resulta rentable. En cuanto a la capacidad, el precio de la especie era relativamente bajo, probablemente porque es fácil de criar en cautiverio. Por lo tanto, el comercio actual de especies silvestres no supone una amenaza significativa para la tarántula diamante del Caribe. Nuestra metodología puede ser una herramienta valiosa para evaluar las amenazas potenciales que el comercio plantea a otras especies de arañas y posiblemente a otros invertebrados. Comprender estas amenazas es crucial para promover prácticas comerciales responsables y sostenibles que minimicen los riesgos para las poblaciones silvestres y garanticen al mismo tiempo beneficios equitativos para las comunidades que coexisten con la vida silvestre.

Examining the structure of plant-lemur interactions in the face of imperfect knowledge.

Biotic interactions, such as plant-animal seed dispersal mutualisms, are essential for ecosystem function. Such interactions are threatened by the possible extinction of the animal partners. Using a data set that includes plant-lemur interactions across Madagascar, we studied the current state of knowledge of these interactions and their structure to determine which plant species are most at risk of losing dispersal services due to the loss of lemurs. We found substantial gaps in understanding of plant-lemur interactions; data were substantially skewed toward a few lemur species and locations. There was also a large gap in knowledge on the interactions of plants and small-bodied or nocturnal lemurs and lemurs outside a few highly studied locations. Of the recorded interactions, a significant portion occurred between lemurs and endemic plants, rather than native or introduced plants. We also found that lemur species tended to primarily consume closely related plant species. Such interaction patterns may indicate the threats to Malagasy endemic plants and highlight how lemur population loss or reductions could affect plant phylogenetic diversity. When examining the impacts of lemur extinction, losing critically endangered species left 164 plant species with no known lemur frugivore partners. Despite phylogenetic patterns in lemur diet, plants for which the only known lemur frugivore is critically endangered were not closely related. These results emphasize the need for further studies to complete our knowledge on these essential interactions and to inform conservation priorities.

Análisis de la estructura de las interacciones entre lémures y plantas de cara al conocimiento incompleto Resumen Las interacciones bióticas, como el mutualismo entre plantas y animales para la dispersión de semillas, son esenciales para que el ecosistema funcione. Dichas interacciones se encuentran amenazadas por la posible extinción del animal que participa en ellas. Usamos un conjunto de datos que incluye las interacciones entre lémures y plantas en Madagascar para estudiar el estado actual del conocimiento de estas interacciones y su estructura. Con lo anterior determinamos cuáles especies botánicas tienen mayor riesgo de perder la dispersión de semillas debido a la extinción de los lémures. Encontramos vacíos sustanciales en el entendimiento de las interacciones entre lémures y plantas; los datos estaban sesgados para unas cuantas especies de lémures y localidades. Hubo un gran vacío de conocimiento para las interacciones entre las plantas y los lémures pequeños o nocturnos y aquellos fuera de unas cuantas localidades estudiadas. De las interacciones registradas, una porción importante ocurrió entre los lémures y plantas endémicas, en lugar de plantas nativas o introducidas. También encontramos que las especies de lémures tienden a consumir especies botánicas con filogenia cercana. Dichos patrones de interacción podrían indicar las amenazas para las plantas endémicas de Madagascar y enfatizar cómo la pérdida o reducción de las poblaciones de lémures podrían afectar la diversidad filogenética de las plantas. Cuando examinamos el impacto de la extinción de los lémures, la pérdida de especies en peligro crítico dejó a 164 especies de plantas sin un lémur frugívoro mutualista. A pesar de los patrones filogenéticos en la dieta de los lémures, las plantas cuyo único lémur frugívoro se encuentra en peligro crítico no tienen una filogenia cercana. Estos resultados resaltan la necesidad de más estudios para completar nuestro conocimiento sobre estas interacciones esenciales y para guiar las prioridades de conservación.