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The single-nucleotide polymorphism rs1990760 in the gene encoding the cytosolic viral sensor IFIH1 results in an amino-acid change (A946T; IFIH1T946) that is associated with multiple autoimmune diseases. The effect of this polymorphism on both viral sensing and autoimmune pathogenesis remains poorly understood. Here we found that human peripheral blood mononuclear cells (PBMCs) and cell lines expressing the risk variant IFIH1T946 exhibited heightened basal and ligand-triggered production of type I interferons. Consistent with those findings, mice with a knock-in mutation encoding IFIH1T946 displayed enhanced basal expression of type I interferons, survived a lethal viral challenge and exhibited increased penetrance in autoimmune models, including a combinatorial effect with other risk variants. Furthermore, IFIH1T946 mice manifested an embryonic survival defect consistent with enhanced responsiveness to RNA self ligands. Together our data support a model wherein the production of type I interferons driven by an autoimmune risk variant and triggered by ligand functions to protect against viral challenge, which probably accounts for its selection within human populations but provides this advantage at the cost of modestly promoting the risk of autoimmunity.
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Autoinmunidad/genética , Infecciones por Cardiovirus/genética , Interferón Tipo I/inmunología , Helicasa Inducida por Interferón IFIH1/genética , Adolescente , Adulto , Animales , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Autoinmunidad/inmunología , Southern Blotting , Infecciones por Cardiovirus/inmunología , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Virus de la Encefalomiocarditis/inmunología , Femenino , Predisposición Genética a la Enfermedad , Células HEK293 , Humanos , Immunoblotting , Helicasa Inducida por Interferón IFIH1/inmunología , Masculino , Ratones , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Virosis/genética , Virosis/inmunología , Adulto JovenRESUMEN
The systematic tuning of crystal lattice parameters to achieve improved kinematic compatibility between different phases is a broadly effective strategy for improving the reversibility, and lowering the hysteresis, of solid-solid phase transformations1-11. (Kinematic compatibility refers to the fitting together of the phases.) Here we present an apparently paradoxical example in which tuning to near perfect kinematic compatibility results in an unusually high degree of irreversibility. Specifically, when cooling the kinematically compatible ceramic (Zr/Hf)O2(YNb)O4 through its tetragonal-to-monoclinic phase transformation, the polycrystal slowly and steadily falls apart at its grain boundaries (a process we term weeping) or even explosively disintegrates. If instead we tune the lattice parameters to satisfy a stronger 'equidistance' condition (which additionally takes into account sample shape), the resulting material exhibits reversible behaviour with low hysteresis. These results show that a diversity of behaviours-from reversible at one extreme to explosive at the other-is possible in a chemically homogeneous ceramic system by manipulating conditions of compatibility in unexpected ways. These concepts could prove critical in the current search for a shape-memory oxide ceramic9-12.
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Antibody inhibitors pose an ongoing challenge to the treatment of subjects with inherited protein deficiency disorders, limiting the efficacy of both protein replacement therapy and corrective gene therapy. Beyond their central role as producers of serum antibody, B cells also exhibit many unique properties that could be exploited in cell therapy applications, notably including antigen-specific recognition and the linked capacity for antigen presentation. Here we employed CRISPR/Cas9 to demonstrate that ex vivo antigen-primed Blimp1-knockout "decoy" B cells, incapable of differentiation into plasma cells, participated in and downregulated host antigen-specific humoral responses after adoptive transfer. Following ex vivo antigen pulse, adoptively transferred high affinity antigen-specific decoy B cells were diverted into germinal centers en masse, thereby reducing participation by endogenous antigen-specific B cells in T-dependent humoral responses and suppressing both cognate and linked antigen-specific IgG following immunization with conjugated antigen. This effect was dose-dependent and, importantly, did not impact concurrent unrelated antibody responses. We demonstrated the therapeutic potential of this approach by treating factor VIII (FVIII)-knockout mice with antigen-pulsed decoy B cells prior to immunization with a FVIII conjugate protein, thereby blunting the production of serum FVIII-specific IgG by an order of magnitude as well as reducing the proportion of animals exhibiting functional FVIII inhibition by 6-fold.
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Bispecific antibodies are an important tool for the management and treatment of acute leukemias. As a next step toward clinical translation of engineered plasma cells, we describe approaches for secretion of bispecific antibodies by human plasma cells. We show that human plasma cells expressing either fragment crystallizable domain-deficient anti-CD19 × anti-CD3 (blinatumomab) or anti-CD33 × anti-CD3 bispecific antibodies mediate T cell activation and direct T cell killing of B acute lymphoblastic leukemia or acute myeloid leukemia cell lines in vitro. We demonstrate that knockout of the self-expressed antigen, CD19, boosts anti-CD19-bispecific secretion by plasma cells and prevents self-targeting. Plasma cells secreting anti-CD19-bispecific antibodies elicited in vivo control of acute lymphoblastic leukemia patient-derived xenografts in immunodeficient mice co-engrafted with autologous T cells. In these studies, we found that leukemic control elicited by engineered plasma cells was similar to CD19-targeted chimeric antigen receptor-expressing T cells. Finally, the steady-state concentration of anti-CD19 bispecifics in serum 1 month after cell delivery and tumor eradication was comparable with that observed in patients treated with a steady-state infusion of blinatumomab. These findings support further development of ePCs for use as a durable delivery system for the treatment of acute leukemias, and potentially other cancers.
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Anticuerpos Biespecíficos , Antígenos CD19 , Células Plasmáticas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Anticuerpos Biespecíficos/farmacología , Animales , Ratones , Antígenos CD19/inmunología , Antígenos CD19/genética , Antígenos CD19/metabolismo , Células Plasmáticas/metabolismo , Células Plasmáticas/inmunología , Línea Celular Tumoral , Linfocitos T/inmunología , Linfocitos T/metabolismo , Complejo CD3/inmunología , Complejo CD3/metabolismo , Complejo CD3/genética , Activación de Linfocitos/inmunología , Citotoxicidad InmunológicaRESUMEN
SignificanceSemiconductor interfaces are among the most important in use in modern technology. The properties they exhibit can either enable or disable the characteristics of the materials they connect for functional performance. While much is known about important junctions involving conventional semiconductors such as Si and GaAs, there are several unsolved mysteries surrounding interfaces between oxide semiconductors. Here we resolve a long-standing issue concerning the measurement of anomalously low dielectric constants in SrTiO3 films with record high electron mobilities. We show that the junction between doped and undoped SrTiO3 required to make dielectric constant measurements masks the dielectric properties of the undoped film. Through modeling, we extract the latter and show that it is much higher than previously measured.
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Background: Endotracheal tube (ETT) occlusion is reported at a higher frequency among coronavirus disease-2019 (COVID-19) patients. Prior to the COVID-19 pandemic, literature examining patient and ventilator characteristics, including humidification, as etiologies of ETT occlusion yielded mixed results. Our study examines the relationship of humidification modality with ETT occlusion in COVID-19 patients undergoing invasive mechanical ventilation (IMV). Methods: We conducted a retrospective chart review of COVID-19 patients requiring IMV at a tertiary care center in New York from April 2020 to April 2021. Teleflex Neptune heated wire heated humidification (HH) and hygroscopic Intersurgical FiltaTherm and Sunmed Ballard 1500 heat and moisture exchangers (HME) were used. Episodes of ETT occlusion were recorded. Univariate and multivariable logistic regression models were used to investigate the relationship between humidification modality and the occurrence of ETT occlusion. Findings: A total of 201 eligible patients were identified. Teleflex HH was utilized in 50.2% of the population and the others Intersurgical and Sunmed HME devices. Median age was 62 years and 78.6% of patients had at least one medical comorbidity. Precisely, 24% of patients experienced an ETT occlusion after a median of 12 days. The HME group was younger (58.5 vs 64 years), predominantly male (75% vs 59.4%), and experienced more total ventilator days than the HH group (24 vs 12). Those using the studied HME devices had significantly higher odds of ETT occlusion (OR 4.4, 95% CI 1.8-10.6, P = .0011). Three patients (6.1%) experienced cardiac arrest as a consequence of their occlusion. There were no deaths directly attributed to ETT occlusion. Conclusions: The studied HME devices were significantly associated with higher odds of ETT occlusion in COVID-19 patients requiring invasive mechanical ventilation. These events are not without significant clinical consequences. Prolonged use of under-performing HME devices remains suspect in the occurrence of ETT occlusions.
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Colicin (Col) plasmid contains colicin encoding genes arranged in an operon controlled by an SOS inducible promoter. Therefore, any external stresses to the host cell can induce the expression of the downstream genes in the Col operon, including a lysis gene. The lysis protein is involved in the extracellular release of colicin through lysis of the producer cells, which causes a decline in culture turbidity. However, it is not yet known that E. coli cells with the native pColE9-J plasmid hold the same level of cell death at the population level following a set of induced conditions. In this study, using a mitomycin C sensitivity assay along with a live dead staining method of detection, we showed that the native pColE9-J plasmid, which unusually carries an extended Col operon (ColE9) containing two lysis genes, did not confer a rapid decline in the culture turbidity following induction with mitomycin C. Interestingly a subset of the cells suffered perturbation of their outer membrane, which was not observed from single lysis mutant (∆celE or ∆celI) cells. This observed heterogeneity in the colicin E9 release leading to differential outer membrane perforation may bring a competitive advantage to these cells in a mixed population.
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Colicinas , Escherichia coli , Mitomicina , Plásmidos , Colicinas/metabolismo , Colicinas/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Mitomicina/farmacología , Plásmidos/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Operón , Antibacterianos/farmacologíaRESUMEN
AbstractEmpirical studies of pediatric clinical ethics cases are scant in the biomedical and bioethics literature. In this study, more than 100 detailed records of clinical ethics consultations spanning from 2000 to 2020 at a moderately sized U.S. Mid-Atlantic children's hospital were abstracted and analyzed. Findings of the analysis were generally consistent with other studies in pediatric clinical ethics, with additional insight into aspects of moral distress associated with cases, family engagement with consultations, and other characteristics of interest also documented. Over the 20-year time frame, ethics consults were completed on average twice a year, with a detectable upward trend. Consultations were requested across the spectrum of services and units within the hospital, with critical care environments represented most frequently and genetic and neurological conditions being the most common primary diagnoses. Ethical analysis most commonly related to questions around the principles of autonomy and beneficence.
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Consultoría Ética , Hospitales Pediátricos , Humanos , Niño , Estados Unidos , Ética Clínica , Autonomía Personal , Análisis Ético , Beneficencia , Masculino , FemeninoRESUMEN
An ergonomics assessment of the physical risk factors in the workplace is instrumental in predicting and preventing musculoskeletal disorders (MSDs). Using Artificial Intelligence (AI) has become increasingly popular for ergonomics assessments because of the time savings and improved accuracy. However, most of the effort in this area starts and ends with producing risk scores, without providing guidance to reduce the risk. This paper proposes a holistic job improvement process that performs automatic root cause analysis and control recommendations for reducing MSD risk. We apply deep learning-based Natural Language Processing (NLP) techniques such as Part of Speech (PoS) tagging and dependency parsing on textual descriptions of the physical actions performed in the job (e.g. pushing) along with the object (e.g. cart) being acted upon. The action-object inferences provide the entry point to an expert-based Machine Learning (ML) system that automatically identifies the targeted work-related causes (e.g. cart movement forces are too high, due to caster size too small) of the identified MSD risk (e.g. excessive shoulder forces). The proposed framework utilises the root causes identified to recommend control strategies (e.g. provide larger diameter casters, minimum diameter 8" or 203 mm) most likely to mitigate risk, resulting in a more efficient and effective job improvement process.
We propose an ergonomics framework that identifies the root causes of MSD risk and recommends control actions. A key insight exploited using artificial intelligence is that when the estimated risk is high for a body joint, the actions of the worker in question and the associated objects constitute valuable information.
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Baeckea frutescens L. has been traditionally used for treating snakebites and is known to possess antifebrile and hemostatic properties. These properties are closely related to wound healing. This study aimed to evaluate the wound healing properties of B. frutescens leaves extract (BFLE) in vitro and in vivo. The in vitro study focused on proliferation, migration, and expression of TGF-ß, IL-1ß, VEGF, and MMP-2 genes and proteins. The in vivo study included excisional wound healing, histology, and tensile strength studies. The ethanolic extract of B. frutescens (BFLE) was tested for its effects on proliferation and migration using keratinocytes (HaCaT) and fibroblasts (BJ) cells. Gene and protein expression related to wound healing were analyzed using real-time PCR and Western blot assays. The wound healing properties of BFLE were evaluated in vivo using Wistar albino rats, focusing on excisional wound healing, histology, and tensile strength studies. The BFLE displayed significant proliferative and migratory effects on keratinocytes and fibroblasts cells, while upregulating the expression of TGF-ß, IL-1ß, VEGF, and MMP-2 genes and proteins. BFLE also exhibited significant wound healing effects on Wistar albino rats' excisional wounds and improved the overall tensile strength. The results suggest that BFLE has strong wound healing properties, as demonstrated by its ability to increase keratinocytes and fibroblasts proliferation and migration, upregulate genes and proteins involved in the wound healing process, and improve wound healing rates and tensile strength. The findings of this study provide important insights into the potential use of B. frutescens as a natural wound healing agent.
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Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function. CARD11 encodes an adaptor protein that expresses dominant-negative and gain-of-function variants associated with distinct immunodeficiencies. Here, we used a "cloning-free" saturation genome editing approach in a diploid cell line to simultaneously score 2,542 variants for decreased or increased function in the region of CARD11 associated with immunodeficiency. We also described an exon-skipping mechanism for CARD11 dominant-negative activity. The classification of reported clinical variants was sensitive (94.6%) and specific (88.9%), which rendered the data immediately useful for interpretation of seven coding and splicing variants implicated in immunodeficiency found in our clinic. This approach is generalizable for variant interpretation in many other clinically actionable genes, in any relevant cell type.
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Proteínas Adaptadoras de Señalización CARD/genética , Variación Genética , Guanilato Ciclasa/genética , Síndromes de Inmunodeficiencia/genética , Adenina/análogos & derivados , Adenina/farmacología , Proteína 10 de la LLC-Linfoma de Células B/genética , Linfocitos B/citología , Línea Celular , Diploidia , Exones , Genes Dominantes , Humanos , Células Jurkat , Linfoma/genética , Subunidad p50 de NF-kappa B/genética , Piperidinas/farmacología , Polimorfismo de Nucleótido Simple , Enfermedades de Inmunodeficiencia Primaria/genética , Sensibilidad y EspecificidadRESUMEN
In the current infodemic, how individuals receive information (channel), who it is coming from (source), and how it is framed can have an important effect on COVID-19 related mitigation behaviors. In light of these challenges presented by the infodemic, Dear Pandemic (DP) was created to directly address persistent questions related to COVID-19 and other health topics in the online environment. This is a qualitative analysis of 3806 questions that were submitted by DP readers to a question box on the Dear Pandemic website between August 30, 2020 and August 29, 2021. Analyses resulted in four themes: the need for clarification of other sources; lack of trust in information; recognition of possible misinformation; and questions on personal decision-making. Each theme reflects an unmet informational need of Dear Pandemic readers, which may be reflective of the broader informational gaps in our science communication efforts.This study highlights the role of an ad hoc risk communication platform in the current environment and uses questions submitted to the Dear Pandemic question box to identify informational needs of DP readers over the course of the COVID-19 pandemic. These findings may help clarify how organizations addressing health misinformation in the digital space can contribute to timely, responsive science communication and improve future communication efforts.
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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Comunicación , ConfianzaRESUMEN
Post-operative oral feeding difficulties in neonates and infants with CHD is common. While pre-operative oral feeding may be normal, oral feeding challenges manifest in the post-operative period without a clearly defined aetiology. The objective of this scoping review was to examine post-operative oral feeding in full-term neonates and infants with a CHD. Electronic databases query (1 January 1975-31 May 2021), hand-search of the reference lists of included studies, contact with experts, and review of relevant conferences were performed to identify quantitative studies evaluating post-operative oral feeding in full-term neonates and infants with a CHD. Associations with additional quantitative variables in these studies were also examined. Twenty-five studies met inclusion criteria. Eighty per cent were cohort studies that utilised retrospective chart review from a single institution. The primary variable of interest in all studies was oral feeding status upon discharge from neonatal hospitalisation. The most common risk factors evaluated with poor feeding at time of discharge were birth weight (36% of included studies), gestational age (44%), duration of post-operative intubation (48%), cardiac diagnosis (40%), and presence of genetic syndrome or chromosomal anomaly (36%). The most common health-related outcomes evaluated were length of hospital stay (40%) and length of ICU stay (16%). Only the health-related outcomes of length of hospital stay and length of ICU stay were consistently significantly associated with poor post-operative oral feeding across studies in this review. A clear aetiology of poor post-operative oral feeding remains unknown.
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Estudios Retrospectivos , Recién Nacido , Humanos , Lactante , Estudios de Cohortes , Edad Gestacional , Peso al NacerRESUMEN
BACKGROUND: Mast cells are involved in many distinct pathologic conditions, suggesting that they recognize and respond to various stimuli and thus require a rich repertoire of cell surface proteins. However, mast cell surface proteomes have not been comprehensively characterized. OBJECTIVE: We aimed to further characterize the mast cell surface proteome to obtain a better understanding of how mast cells function in health and disease. METHODS: We enriched for glycosylated surface proteins expressed in mouse bone marrow-derived cultured mast cells (BMCMCs) and identified them using mass spectrometry analysis. The presence of novel surface proteins in mast cells was validated by real-time quantitative PCR and flow cytometry analysis in BMCMCs and peritoneal mast cells (PMCs). We developed a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing approach to disrupt genes of interest in BMCMCs. RESULTS: The glycoprotein enrichment approach resulted in the identification of 1270 proteins in BMCMCs, 378 of which were localized to the plasma membrane. The most common protein classes among plasma membrane proteins were small GTPases, receptors, and transporters. One such cell surface protein was CD98 heavy chain (CD98hc), encoded by the Slc3a2 gene. Slc3a2 gene disruption resulted in a significant reduction in CD98hc expression, adhesion, and proliferation. CONCLUSIONS: Glycoprotein enrichment coupled with mass spectrometry can be used to identify novel surface molecules in mast cells. Moreover, CD98hc plays an important role in mast cell function.
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Cadena Pesada de la Proteína-1 Reguladora de Fusión/análisis , Mastocitos/química , Proteínas de la Membrana/análisis , Proteoma , Animales , Células Cultivadas , Cadena Pesada de la Proteína-1 Reguladora de Fusión/fisiología , Mastocitos/fisiología , RatonesRESUMEN
Spontaneous production of E colicins is known to occur in only a small fraction of colicinogenic population. The current study aimed to determine if the same holds true for the production of colicin E9 in real time, by investigating the induction dynamics of the promoter of the ColE9 operon which results in the expression of the ColE9 activity and functional genes. A novel fluorescent reporter was constructed which carries the fusion of the ColE9 promoter and the gfpmut2 gene in a low copy number plasmid that was compatible with the native ColE9-J plasmid. Using the fluorescent reporter construct in the non colicinogenic E. coli cells, the induction of the ColE9 promoter was investigated. The current study demonstrates that the spontaneous induction of the ColE9 promoter occurs in a heterogenous manner and this heterogeneity is maintained in a bacterial population for several generations suggesting that it is unlikely due to any irreversible mutation in the bacterial culture. Furthermore, the same investigations were repeated using the colicin E9 producing E. coli cells. Flow cytometry analysis revealed that 7.1 ± 0.68% of the colicin E9 producing E. coli cells expressed GFP albeit only 2.45 ± 0.30% was observed from non colicinogenic E. coli cells. The considerable increase in the number of the fluorescent cells was likely due to the DNase activity of colicin E9 produced by their clonemates, resulting the auto-induction, which can be abolished with the inactivation of the DNase activity of the colicin E9.
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Colicinas , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Colicinas/genética , Colicinas/metabolismo , Desoxirribonucleasas/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Humanos , OperónRESUMEN
OBJECTIVE: Gender-based bias during journal peer review can lead to publication biases and perpetuate gender inequality in science. Double-blind peer review, in which the names of authors and reviewers are masked, may present an opportunity for scientific literature to increase equity and reduce gender-based biases. This systematic review of studies evaluates the impact of double-blind vs single-blind peer review on the publication rates by perceived author gender. DATA SOURCES: The PubMed, Embase, Web of Science, and Scopus electronic databases were searched using the terms "blind," "peer review," "gender," "woman," and "author." All published literature in the English language from database inception through 2020 was queried. STUDY ELIGIBILITY CRITERIA: Prospective experimental and observational studies comparing double-blind to single-blind peer review strategies examining impact on publication decisions by author gender were included. STUDY APPRAISAL AND SYNTHESIS METHODS: The extracted data were primarily descriptive and included information on study design, sample size, primary outcome, major findings, and scientific discipline. The studies were characterized on the basis of design and whether the results demonstrated an impact of double-blind peer review on review scores and publication decision by perceived author gender. This study was registered with the International Prospective Register of Systematic Reviews or PROSPERO. RESULTS: In total, 1717 articles were identified, 123 were reviewed, and 8 were included, encompassing 5 prospective experimental studies and 3 observational studies. Four studies demonstrated a difference in the acceptance rate or review score on the basis of perceived author gender, whereas the other 4 studies demonstrated no differences when the author gender was anonymized. CONCLUSION: Studies evaluating the impact of double-blind peer review on author gender demonstrate mixed results, but there is reasonable evidence that gender bias may exist in scientific publishing and that double-blinding can mitigate its impact. Further evaluation of the processes in place to create the body of evidence that clinicians and researchers rely on is essential to reduce bias, particularly in female-majority fields such as obstetrics and gynecology.
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Revisión por Pares , Sexismo , Femenino , Humanos , Masculino , Método Doble Ciego , Edición , Método Simple CiegoRESUMEN
A better understanding of the social-structural factors that influence HIV vulnerability is crucial to achieve the goal of ending the HIV epidemic by 2030. Given the role of neighborhoods in HIV outcomes, synthesis of findings from such research is key to inform efforts toward HIV eradication. We conducted a systematic review to examine the relationship between neighborhood-level factors (e.g., poverty) and HIV vulnerability (via sexual behaviors and substance use). We searched six electronic databases for studies published from January 1, 2007 through November 30, 2017 (PROSPERO CRD42018084384). We also mapped the studies' geographic distribution to determine whether they aligned with high HIV prevalence areas and/or the "Ending the HIV Epidemic: A Plan for the United States". Fifty-five articles met inclusion criteria. Neighborhood disadvantage, whether measured objectively or subjectively, is one of the most robust correlates of HIV vulnerability. Tests of associations more consistently documented a relationship between neighborhood-level factors and drug use than sexual risk behaviors. There was limited geographic distribution of the studies, with a paucity of research in several counties and states where HIV incidence/prevalence is a concern. Neighborhood influences on HIV vulnerability are the consequence of centuries-old laws, policies and practices that maintain racialized inequities (e.g., racial residential segregation, inequitable urban housing policies). We will not eradicate HIV without multi-level, neighborhood-based approaches to undo these injustices. Our findings inform future research, interventions and policies.
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Infecciones por VIH , Segregación Social , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Características de la Residencia , Asunción de Riesgos , Conducta Sexual , Estados Unidos/epidemiologíaRESUMEN
Only a handful of bird species are known to use foraging tools in the wild. Amongst them, the New Caledonian crow (Corvus moneduloides) stands out with its sophisticated tool-making skills. Despite considerable speculation, the evolutionary origins of this species' remarkable tool behaviour remain largely unknown, not least because no naturally tool-using congeners have yet been identified that would enable informative comparisons. Here we show that another tropical corvid, the 'Alala (C. hawaiiensis; Hawaiian crow), is a highly dexterous tool user. Although the 'Alala became extinct in the wild in the early 2000s, and currently survives only in captivity, at least two lines of evidence suggest that tool use is part of the species' natural behavioural repertoire: juveniles develop functional tool use without training, or social input from adults; and proficient tool use is a species-wide capacity. 'Alala and New Caledonian crows evolved in similar environments on remote tropical islands, yet are only distantly related, suggesting that their technical abilities arose convergently. This supports the idea that avian foraging tool use is facilitated by ecological conditions typical of islands, such as reduced competition for embedded prey and low predation risk. Our discovery creates exciting opportunities for comparative research on multiple tool-using and non-tool-using corvid species. Such work will in turn pave the way for replicated cross-taxonomic comparisons with the primate lineage, enabling valuable insights into the evolutionary origins of tool-using behaviour.
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Cuervos/fisiología , Comportamiento del Uso de la Herramienta , Envejecimiento , Animales , Animales de Zoológico/fisiología , Evolución Biológica , Cognición , Cuervos/clasificación , Femenino , Hawaii , Masculino , Filogenia , Especificidad de la EspecieRESUMEN
This paper provides an analysis of the last 50 years of uterus transplantation (UTx). Animal research on UTx began in the 1960s, aiming to solve tubal factor infertility. The success of in vitro fertilization shifted the focus onto uterine factor infertility. Early research in small and large animals improved following the advent of immunosuppression and established the uterus' ability to tolerate cold ischemia and to function following vessel reanastamosis. Upon the achievement of the first live birth following UTx in 2014, human research has started to focus on reducing donor morbidity, optimal immunosuppression regimes, and the development of deceased donor UTx programmes.
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Infertilidad Femenina , Animales , Femenino , Fertilización In Vitro , Humanos , Infertilidad Femenina/cirugía , Pelvis , Donantes de Tejidos , Útero/trasplanteRESUMEN
Uterine transplantation has evolved rapidly over the last decade. As the number of cases performed increases exponentially worldwide, emerging evidence continues to improve collective knowledge and understanding of the procedure, with the aim of improving both surgical and reproductive outcomes. Although currently restricted to women with absolute uterine factor infertility, increasing awareness as a method of fertility restoration has resulted in a demand for the procedure to be undertaken in transgender women. This manuscript summarizes the recent advances in uterine transplantation, and elaborates further upon the key novel avenues research within the field will focus on over the coming years.