From Eighty Acres and a Mule to Two Thousand Acres and Twenty-Four Row Planters: Anxieties of Growth in the Agriculture Sector from Family Farms

This study investigates the evolution of the family farm between the 1940s until the 2020s, and how the family farm may continue to evolve in future generations. The aim of this study is to investigate the relationship between the changing reality of agriculture and how farmers think about themselves. In the early days of the United States republic, farms were a means of providing a family or localized community with food and resources. These farms participated in an economic exchange that was an early form of capitalism, characterized by meeting needs but not accruing egregious excess. Today’s agricultural system is marked by the pressures to compete in the marketplace, and a shift in cultural values away from balanced reciprocity to the farmer’s individual entrepreneurial spirit. Farmers interviewed in this study expressed a range of emotions and perceptions regarding these shifting cultural values. Many farmers interviewed expressed a sense of anxiety about the growing pressures of the neoliberal market on farmers, the powerlessness that farmers face in the unpredictable nature of the markets, and the loss of hallmark perceptions of previous forms of agriculture, such as balanced reciprocity

Ebola virus disease in West Africa — the first 9 Months of the epidemic and forward projections

BACKGROUND On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern." METHODS By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa - Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14. RESULTS The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R-0) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total. CONCLUSIONS These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months

El análisis de 52 genomas fúngicos aclara la evolución de los estilos de vida de los Agaricales

1 p.Los Agaricomycetes han desarrollado complejas maquinarias enzimáticas que les permiten descomponer los diferentes polímeros vegetales, incluida la lignina. Entre ellos, los Agaricales saprótrofos se caracterizan por su diversidad de hábitats y estilos de vida. El análisis de 52 genomas de Agaricomycetes aquí realizado revela que los Agaricales poseen una gran diversidad de enzimas hidrolíticas y oxidativas para la descomposición de la lignocelulosa. En base a las familias de genes con mayor velocidad evolutiva (dominios de unión a celulosa, glicosil hidrolasa GH43, monooxigenasas líticas de polisacáridos, peroxidasas ligninolíticas, enzimas de la superfamilia de glucosa-metanol-colina oxidasas/deshidrogenasas, lacasas y peroxigenasas), reconstruimos los estilos de vida de los ancestros que dieron lugar a los actuales Agaricomycetes degradadores de lignocelulosa. Los cambios en el conjunto de herramientas enzimáticas de los Agaricales ancestrales se correlacionaron con la evolución de su capacidad para crecer no solo sobre madera, sino también sobre hojarasca de bosques y madera en descomposición, siendo los descomponedores de la hojarasca de praderas el grupo ecofisiológico más reciente. En este contexto, las anteriores familias de enzimas se analizaron en relación con la diversidad de estilos de vida. Las peroxidasas aparecen como un componente central del set enzimático de los Agaricomycetes saprotrófos, consistente con su papel esencial en la degradación de la lignina y sus altas tasas evolutivas. Esto incluye no solo expansiones/pérdidas de genes de peroxidasas, sino también la presencia generalizada en Agaricales de nuevos tipos de peroxidasas que no se encuentran en Polyporales degradadores de madera, y en otros órdenes de Agaricomycetes.Projectos/contratos BIO2017-86559-R, BIO2015-73697-JIN, AGL2014-55971-R, NSF-grant-1457721, CEFOX-031B0831B, PIE-201620E081, ANR-11-LABX-0002-01, US-DOE-DE-AC02-05CH11231Peer reviewe

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder

Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative events (stress-sensitivity) may improve our understanding of the molecular pathways involved, and its association with stress-related illnesses. We sought to generate a proxy for stress-sensitivity through modelling the interaction between SNP allele and MDD status on neuroticism score in order to identify genetic variants that contribute to the higher neuroticism seen in individuals with a lifetime diagnosis of depression compared to unaffected individuals. Meta-analysis of genome-wide interaction studies (GWIS) in UK Biobank (N = 23,092) and Generation Scotland: Scottish Family Health Study (N = 7,155) identified no genome-wide significance SNP interactions. However, gene-based tests identified a genome-wide significant gene, ZNF366, a negative regulator of glucocorticoid receptor function implicated in alcohol dependence (p = 1.48x10-7; Bonferroni-corrected significance threshold p < 2.79x10-6). Using summary statistics from the stress-sensitivity term of the GWIS, SNP heritability for stress-sensitivity was estimated at 5.0%. In models fitting polygenic risk scores of both MDD and neuroticism derived from independent GWAS, we show that polygenic risk scores derived from the UK Biobank stress-sensitivity GWIS significantly improved the prediction of MDD in Generation Scotland. This study may improve interpretation of larger genome-wide association studies of MDD and other stress-related illnesses, and the understanding of the etiological mechanisms underpinning stress-sensitivity

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD

Lifestyle Evolution And Peroxidase Diversity In Agaricales As Revealed By Comparative Genomics

Descripción de 1 páginas de la comunicación oral presentada en Oxizymes2022 10th edition of the international “Oxizymes” meeting. Siena, Italy, July 5-8, 2022Basidiomycetes of the class Agaricomycetes have developed complex enzymatic machineries that allow them to decompose plant polymers, including lignin. Within this group, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles in comparison with fungi from other orders. With the aim of shedding light on the evolution of lignocellulose-decaying lifestyles in Agaricales we conducted a comparative analysis of 52 Agaricomycetes genomes [1]. This study revealed that Agaricales possess a large diversity of hydrolytic and oxidative enzymes. Surprisingly, computer-assisted gene-family evolution analysis of these enzymes revealed that a few oxidoreductase families showed significantly higher evolutionary rates. Based on these gene families we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. According to this, we determined that changes in the oxidative enzymatic toolkit of ancestral Agaricales correlate with the evolution of their ability to grow not only on wood, but also on leaf and grass litter and decayed wood. In this context, the aboye families were analyzed and special attention was paid to peroxidases as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes responsible for lignin degradation. We identified a widespread presence of new ligninolytic peroxidase types in Agaricales, some of them not previously identified in this order, and others also not found in woodrottingPolyporales and other orders of Agaricomycetes. Peroxidase evolution was analyzed in Agaricomycetes by ancestral sequence reconstruction and several major evolutionary pathways were unveiled. The study of the newly identified peroxidases will provide insight into their role in the lignin degradation process. In fact, these studies have already been initiated with the expression and characterization of the first lignin peroxidase identified in Agaricales. [1] Ruiz-Dueñas FJ, Barrasa JM, Sánchez-García M, Camarero S, Miyauchi S, Serrano A, et al., 2021, Mol Biol Evol, 38, 1428-1446.Projects/contracts BI02017-86559-R, BI02015-7369-JIN, AGL2014-55971-R, NSFgrant-1457721 , CEFOX-031 B0831 S, PIE-201620E081 , ANR-11-LABX-0002-01 , US-DOE-DE-AC02-05CH11231N