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1.
Cell ; 186(20): 4289-4309.e23, 2023 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-37683635

RESUMEN

Here, we reveal an unanticipated role of the blood-brain barrier (BBB) in regulating complex social behavior in ants. Using scRNA-seq, we find localization in the BBB of a key hormone-degrading enzyme called juvenile hormone esterase (Jhe), and we show that this localization governs the level of juvenile hormone (JH3) entering the brain. Manipulation of the Jhe level reprograms the brain transcriptome between ant castes. Although ant Jhe is retained and functions intracellularly within the BBB, we show that Drosophila Jhe is naturally extracellular. Heterologous expression of ant Jhe into the Drosophila BBB alters behavior in fly to mimic what is seen in ants. Most strikingly, manipulation of Jhe levels in ants reprograms complex behavior between worker castes. Our study thus uncovers a remarkable, potentially conserved role of the BBB serving as a molecular gatekeeper for a neurohormonal pathway that regulates social behavior.


Asunto(s)
Hormigas , Animales , Hormigas/fisiología , Barrera Hematoencefálica , Encéfalo/metabolismo , Drosophila , Conducta Social , Conducta Animal
2.
Cell ; 184(23): 5807-5823.e14, 2021 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-34739833

RESUMEN

Behavioral plasticity is key to animal survival. Harpegnathos saltator ants can switch between worker and queen-like status (gamergate) depending on the outcome of social conflicts, providing an opportunity to study how distinct behavioral states are achieved in adult brains. Using social and molecular manipulations in live ants and ant neuronal cultures, we show that ecdysone and juvenile hormone drive molecular and functional differences in the brains of workers and gamergates and direct the transcriptional repressor Kr-h1 to different target genes. Depletion of Kr-h1 in the brain caused de-repression of "socially inappropriate" genes: gamergate genes were upregulated in workers, whereas worker genes were upregulated in gamergates. At the phenotypic level, loss of Kr-h1 resulted in the emergence of worker-specific behaviors in gamergates and gamergate-specific traits in workers. We conclude that Kr-h1 is a transcription factor that maintains distinct brain states established in response to socially regulated hormones.


Asunto(s)
Hormigas/genética , Ecdisterona/farmacología , Jerarquia Social , Proteínas de Insectos/metabolismo , Neuronas/metabolismo , Sesquiterpenos/farmacología , Conducta Social , Transcriptoma/genética , Animales , Hormigas/efectos de los fármacos , Hormigas/fisiología , Conducta Animal/efectos de los fármacos , Encéfalo/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Genoma , Neuronas/efectos de los fármacos , Fenotipo , Proteínas Represoras/metabolismo , Transducción de Señal/efectos de los fármacos , Transcriptoma/efectos de los fármacos
3.
Cell ; 184(25): 6081-6100.e26, 2021 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-34861191

RESUMEN

Chimeric antigen receptor (CAR) T cell therapy has achieved remarkable success in hematological malignancies but remains ineffective in solid tumors, due in part to CAR T cell exhaustion in the solid tumor microenvironment. To study dysfunction of mesothelin-redirected CAR T cells in pancreatic cancer, we establish a robust model of continuous antigen exposure that recapitulates hallmark features of T cell exhaustion and discover, both in vitro and in CAR T cell patients, that CAR dysregulation is associated with a CD8+ T-to-NK-like T cell transition. Furthermore, we identify a gene signature defining CAR and TCR dysregulation and transcription factors, including SOX4 and ID3 as key regulators of CAR T cell exhaustion. Our findings shed light on the plasticity of human CAR T cells and demonstrate that genetic downmodulation of ID3 and SOX4 expression can improve the efficacy of CAR T cell therapy in solid tumors by preventing or delaying CAR T cell dysfunction.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Inmunoterapia Adoptiva/métodos , Neoplasias Pancreáticas/terapia , Receptores Quiméricos de Antígenos/inmunología , Animales , Linfocitos T CD8-positivos/citología , Línea Celular Tumoral , Células HEK293 , Humanos , Proteínas Inhibidoras de la Diferenciación/inmunología , Masculino , Ratones , Ratones Noqueados , Ratones Desnudos , Ratones SCID , Proteínas de Neoplasias/inmunología , Factores de Transcripción SOXC/inmunología
4.
Cell ; 170(4): 748-759.e12, 2017 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-28802044

RESUMEN

Social insects are emerging models to study how gene regulation affects behavior because their colonies comprise individuals with the same genomes but greatly different behavioral repertoires. To investigate the molecular mechanisms that activate distinct behaviors in different castes, we exploit a natural behavioral plasticity in Harpegnathos saltator, where adult workers can transition to a reproductive, queen-like state called gamergate. Analysis of brain transcriptomes during the transition reveals that corazonin, a neuropeptide homologous to the vertebrate gonadotropin-releasing hormone, is downregulated as workers become gamergates. Corazonin is also preferentially expressed in workers and/or foragers from other social insect species. Injection of corazonin in transitioning Harpegnathos individuals suppresses expression of vitellogenin in the brain and stimulates worker-like hunting behaviors, while inhibiting gamergate behaviors, such as dueling and egg deposition. We propose that corazonin is a central regulator of caste identity and behavior in social insects.


Asunto(s)
Hormigas/metabolismo , Proteínas de Insectos/metabolismo , Neuropéptidos/metabolismo , Animales , Hormigas/genética , Hormigas/crecimiento & desarrollo , Conducta Animal , Femenino , Regulación del Desarrollo de la Expresión Génica , Masculino , Conducta Social
5.
Genes Dev ; 37(9-10): 398-417, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-37257919

RESUMEN

Eusocial insect reproductive females show strikingly longer life spans than nonreproductive female workers despite high genetic similarity. In the ant Harpegnathos saltator (Hsal), workers can transition to reproductive "gamergates," acquiring a fivefold prolonged life span by mechanisms that are poorly understood. We found that gamergates have elevated expression of heat shock response (HSR) genes in the absence of heat stress and enhanced survival with heat stress. This HSR gene elevation is driven in part by gamergate-specific up-regulation of the gene encoding a truncated form of a heat shock factor most similar to mammalian HSF2 (hsalHSF2). In workers, hsalHSF2 was bound to DNA only upon heat stress. In gamergates, hsalHSF2 bound to DNA even in the absence of heat stress and was localized to gamergate-biased HSR genes. Expression of hsalHSF2 in Drosophila melanogaster led to enhanced heat shock survival and extended life span in the absence of heat stress. Molecular characterization illuminated multiple parallels between long-lived flies and gamergates, underscoring the centrality of hsalHSF2 to extended ant life span. Hence, ant caste-specific heat stress resilience and extended longevity can be transferred to flies via hsalHSF2. These findings reinforce the critical role of proteostasis in health and aging and reveal novel mechanisms underlying facultative life span extension in ants.


Asunto(s)
Hormigas , Longevidad , Animales , Femenino , Longevidad/genética , Hormigas/genética , Drosophila melanogaster/genética , Envejecimiento , Respuesta al Choque Térmico/genética , Mamíferos
6.
Mol Cell ; 77(2): 338-351.e6, 2020 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-31732456

RESUMEN

Ants acquire distinct morphological and behavioral phenotypes arising from a common genome, underscoring the importance of epigenetic regulation. In Camponotus floridanus, "Major" workers defend the colony, but can be epigenetically reprogrammed to forage for food analogously to "Minor" workers. Here, we utilize reprogramming to investigate natural behavioral specification. Reprogramming of Majors upregulates Minor-biased genes and downregulates Major-biased genes, engaging molecular pathways fundamental to foraging behavior. We discover the neuronal corepressor for element-1-silencing transcription factor (CoREST) is upregulated upon reprogramming and required for the epigenetic switch to foraging. Genome-wide profiling during reprogramming reveals CoREST represses expression of enzymes that degrade juvenile hormone (JH), a hormone elevated upon reprogramming. High CoREST, low JH-degrader expression, and high JH levels are mirrored in natural Minors, revealing parallel mechanisms of natural and reprogrammed foraging. These results unveil chromatin regulation via CoREST as central to programming of ant social behavior, with potential far-reaching implications for behavioral epigenetics.


Asunto(s)
Hormigas/genética , Hormigas/fisiología , Conducta Animal/fisiología , Proteínas Co-Represoras/genética , Epigénesis Genética/genética , Proteínas de Insectos/genética , Animales , Cromatina/genética , Genoma/genética , Hormonas Juveniles/genética , Neuronas/fisiología , Conducta Social
7.
Nature ; 588(7838): 436-441, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33328667

RESUMEN

Rivers support some of Earth's richest biodiversity1 and provide essential ecosystem services to society2, but they are often fragmented by barriers to free flow3. In Europe, attempts to quantify river connectivity have been hampered by the absence of a harmonized barrier database. Here we show that there are at least 1.2 million instream barriers in 36 European countries (with a mean density of 0.74 barriers per kilometre), 68 per cent of which are structures less than two metres in height that are often overlooked. Standardized walkover surveys along 2,715 kilometres of stream length for 147 rivers indicate that existing records underestimate barrier numbers by about 61 per cent. The highest barrier densities occur in the heavily modified rivers of central Europe and the lowest barrier densities occur in the most remote, sparsely populated alpine areas. Across Europe, the main predictors of barrier density are agricultural pressure, density of river-road crossings, extent of surface water and elevation. Relatively unfragmented rivers are still found in the Balkans, the Baltic states and parts of Scandinavia and southern Europe, but these require urgent protection from proposed dam developments. Our findings could inform the implementation of the EU Biodiversity Strategy, which aims to reconnect 25,000 kilometres of Europe's rivers by 2030, but achieving this will require a paradigm shift in river restoration that recognizes the widespread impacts caused by small barriers.


Asunto(s)
Ecosistema , Ríos , Agricultura/estadística & datos numéricos , Altitud , Biodiversidad , Conjuntos de Datos como Asunto , Restauración y Remediación Ambiental/métodos , Restauración y Remediación Ambiental/tendencias , Europa (Continente) , Actividades Humanas , Humanos , Modelos Logísticos , Aprendizaje Automático , Densidad de Población , Centrales Eléctricas/provisión & distribución
8.
Blood ; 142(12): 1047-1055, 2023 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-37339585

RESUMEN

The emergence of chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for diffuse large B-cell lymphoma (DLBCL); however, real-world experience reporting outcomes among older patients treated with CAR T-cell therapy is limited. We leveraged the 100% Medicare fee-for-service claims database and analyzed outcomes and cost associated with CAR T-cell therapy in 551 older patients (aged ≥65 years) with DLBCL who received CAR T-cell therapy between 2018 and 2020. CAR T-cell therapy was used in third line and beyond in 19% of patients aged 65 to 69 years and 22% among those aged 70 to 74 years, compared with 13% of patients aged ≥75 years. Most patients received CAR T-cell therapy in an inpatient setting (83%), with an average length of stay of 21 days. The median event-free survival (EFS) following CAR T-cell therapy was 7.2 months. Patients aged ≥75 years had significantly shorter EFS compared with patients aged 65 to 69 and 70 to 74 years, with 12-month EFS estimates of 34%, 43%, and 52%, respectively (P = .002). The median overall survival was 17.1 months, and there was no significant difference by age groups. The median total health care cost during the 90-day follow-up was $352 572 and was similar across all age groups. CAR T-cell therapy was associated with favorable effectiveness, but the CAR T-cell therapy use in older patients was low, especially in patients aged ≥75 years, and this age group had a lower rate of EFS, which illustrates the unmet need for more accessible, effective, and tolerable therapy in older patients, especially those aged ≥75 years.


Asunto(s)
Inmunoterapia Adoptiva , Linfoma de Células B Grandes Difuso , Humanos , Anciano , Estados Unidos/epidemiología , Inmunoterapia Adoptiva/efectos adversos , Medicare , Supervivencia sin Progresión , Antígenos CD19
9.
Nature ; 568(7752): 357-359, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30996316

RESUMEN

During the dawn of chemistry1,2, when the temperature of the young Universe had fallen below some 4,000 kelvin, the ions of the light elements produced in Big Bang nucleosynthesis recombined in reverse order of their ionization potential. With their higher ionization potentials, the helium ions He2+ and He+ were the first to combine with free electrons, forming the first neutral atoms; the recombination of hydrogen followed. In this metal-free and low-density environment, neutral helium atoms formed the Universe's first molecular bond in the helium hydride ion HeH+ through radiative association with protons. As recombination progressed, the destruction of HeH+ created a path to the formation of molecular hydrogen. Despite its unquestioned importance in the evolution of the early Universe, the HeH+ ion has so far eluded unequivocal detection in interstellar space. In the laboratory the ion was discovered3 as long ago as 1925, but only in the late 1970s was the possibility that HeH+ might exist in local astrophysical plasmas discussed4-7. In particular, the conditions in planetary nebulae were shown to be suitable for producing potentially detectable column densities of HeH+. Here we report observations, based on advances in terahertz spectroscopy8,9 and a high-altitude observatory10, of the rotational ground-state transition of HeH+ at a wavelength of 149.1 micrometres in the planetary nebula NGC 7027. This confirmation of the existence of HeH+ in nearby interstellar space constrains our understanding of the chemical networks that control the formation of this molecular ion, in particular the rates of radiative association and dissociative recombination.

10.
Mol Microbiol ; 120(2): 298-306, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37452011

RESUMEN

DNA glycosylases protect genetic fidelity during DNA replication by removing potentially mutagenic chemically damaged DNA bases. Bacterial Lhr proteins are well-characterized DNA repair helicases that are fused to additional 600-700 amino acids of unknown function, but with structural homology to SecB chaperones and AlkZ DNA glycosylases. Here, we identify that Escherichia coli Lhr is a uracil-DNA glycosylase (UDG) that depends on an active site aspartic acid residue. We show that the Lhr DNA helicase activity is functionally independent of the UDG activity, but that the helicase domains are required for fully active UDG activity. Consistent with UDG activity, deletion of lhr from the E. coli chromosome sensitized cells to oxidative stress that triggers cytosine deamination to uracil. The ability of Lhr to translocate single-stranded DNA and remove uracil bases suggests a surveillance role to seek and remove potentially mutagenic base changes during replication stress.


Asunto(s)
Escherichia coli , Uracil-ADN Glicosidasa , Uracil-ADN Glicosidasa/genética , Uracil-ADN Glicosidasa/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Secuencia de Aminoácidos , ADN/metabolismo , Uracilo/química , Reparación del ADN , ADN Helicasas/metabolismo , Proteínas Bacterianas/metabolismo
11.
BMC Plant Biol ; 24(1): 622, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951756

RESUMEN

Hybrid genotypes can provide significant yield gains over conventional inbred varieties due to heterosis or hybrid vigor. However, hybrids can also display unintended negative attributes or phenotypes such as extreme pathogen susceptibility. The necrotrophic pathogen Pyrenophora teres f. maculata (Ptm) causes spot form net blotch, which has caused significant yield losses to barley worldwide. Here, we report on a non-transgressive hybrid susceptibility locus in barley identified between the three parental lines CI5791, Tifang and Golden Promise that are resistant to Ptm isolate 13IM.3. However, F2 progeny from CI5791 × Tifang and CI5791 × Golden Promise crosses exhibited extreme susceptibility. The susceptible phenotype segregated in a ratio of 1 resistant:1 susceptible representing a genetic segregation ratio of 1 parental (res):2 heterozygous (sus):1 parental (res) suggesting a single hybrid susceptibility locus. Genetic mapping using a total of 715 CI5791 × Tifang F2 individuals (1430 recombinant gametes) and 149 targeted SNPs delimited the hybrid susceptibility locus designated Susceptibility to Pyrenophora teres 2 (Spt2) to an ~ 198 kb region on chromosome 5H of the Morex V3 reference assembly. This single locus was independently mapped with 83 CI5791 × Golden Promise F2 individuals (166 recombinant gametes) and 180 genome wide SNPs that colocalized to the same Spt2 locus. The CI5791 genome was sequenced using PacBio Continuous Long Read technology and comparative analysis between CI5791 and the publicly available Golden Promise genome assembly determined that the delimited region contained a single high confidence Spt2 candidate gene predicted to encode a pentatricopeptide repeat-containing protein.


Asunto(s)
Ascomicetos , Mapeo Cromosómico , Hordeum , Enfermedades de las Plantas , Hordeum/genética , Hordeum/microbiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/genética , Ascomicetos/fisiología , Resistencia a la Enfermedad/genética , Fenotipo , Polimorfismo de Nucleótido Simple , Hibridación Genética , Vigor Híbrido/genética , Genotipo
12.
Am Heart J ; 267: 33-43, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37890547

RESUMEN

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.


Asunto(s)
Neoplasias de la Mama , Sistema Cardiovascular , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Aromatasa/uso terapéutico , Estrógenos/uso terapéutico , Corazón
13.
Inorg Chem ; 63(19): 8739-8749, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38696617

RESUMEN

Ground-state and time-dependent density functional theory (TDDFT) calculations with the long-range-corrected, Coulomb-attenuating CAMY-B3LYP exchange-correlation functional and large, all-electron STO-TZ2P basis sets have been used to examine the potential "inverse hypercorrole" character of meso-p-nitrophenyl-appended dicyanidocobalt(III) corrole dianions. The effect is most dramatic for 5,15-bis(p-nitrophenyl) derivatives, where it manifests itself in intense NIR absorptions. The 10-aryl groups in these complexes play a modulatory role, as evinced by experimental UV-visible spectroscopic and electrochemical data for a series of 5,15-bis(p-nitrophenyl) dicyanidocobalt(III) corroles. TDDFT (CAMY-B3LYP) calculations ascribe these features clearly to a transition from the corrole's a2u-like HOMO (retaining the D4h irrep used for metalloporphyrins) to a nitrophenyl-based LUMO. The outward nature of this transition contrasts with the usual phenyl-to-macrocycle direction of charge transfer transitions in many hyperporphyrins and hypercorroles; thus, the complexes studied are aptly described as inverse hypercorroles.

14.
Future Oncol ; : 1-13, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38639552

RESUMEN

Aim: Evaluate the association of race/ethnicity and socioeconomic position (SEP) on emergency department (ED) visits for patients with hepatocellular carcinoma (HCC), which may reflect access to and quality of cancer care. Materials & methods: Patients with HCC identified from a commercial multi-payer claims database between 2015 and 2018 were matched to near-neighborhood social determinants of health (SDOH) and stratified by race/ethnicity and SEP (proxied by annual household income). Analyses evaluated the effect of race/ethnicity and SEP on ED utilization, adjusting for SDOH, demographic and clinical characteristics using multivariable regression methods. Results: A total of 22,247 patients were included. Black and Hispanic patients had 43 and 18% higher ED utilization than White patients at higher-income levels (p < 0.01); these differences were nonsignificant at lower-income. Regardless of income level, Asian patients had lower ED utilization. Conclusion: Further research on the intersectionality between race/ethnicity, SEP and other SDOH may guide structural-level interventions to address health inequities.


Health disparities among racial/ethnic minorities have been observed in patients with hepatocellular carcinoma (HCC). We conducted a real-world retrospective insurance claims study of more than 22,200 adult patients with HCC between 2015 and 2018. We evaluated the association of race/ethnicity and socioeconomic position (measured by income level) with emergency department (ED) utilization. Our study consisted of 69% White, 14% Black, 7% Hispanic, 6% Asian and 4% other patient populations. Black and Hispanic patients had the highest number of ED visits, followed by White and Asian patients. Compared with White patients, ED visits were 27% higher for Black, 17% higher for Hispanic and 36% lower for Asian patients. Compared with low income, middle income was associated with 4% more and high income with 6% less ED use, regardless of race/ethnicity. At higher income levels, Black and Hispanic but not Asian patients demonstrated higher ED use than White patients. These findings suggest that improved socioeconomic position of Black and Hispanic patients may not provide as protective an effect on health outcomes, potentially due to structural health inequities.

15.
Atmos Environ (1994) ; 327: 1-7, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38846931

RESUMEN

The US Environmental Protection Agency (EPA) estimates on-road vehicles emissions using the Motor Vehicle Emission Simulator (MOVES). We developed updated ammonia emission rates for MOVES based on road-side exhaust emission measurements of light-duty gasoline and heavy-duty diesel vehicles. The resulting nationwide on-road vehicle ammonia emissions are 1.8, 2.1, 1.8, and 1.6 times higher than the MOVES3 estimates for calendar years 2010, 2017, 2024, and 2035, respectively, primarily due to an increase in light-duty gasoline vehicle NH3 emission rates. We conducted an air quality simulation using the Community Multi-Scale Air Quality (CMAQv5.3.2) model to evaluate the sensitivity of modeled ammonia and fine particulate matter (PM2.5) concentrations in calendar year 2017 using the updated on-road vehicle ammonia emissions. The average monthly urban ammonia ambient concentrations increased by up to 2.3 ppbv in January and 3.0 ppbv in July. The updated on-road NH3 emission rates resulted in better agreement of modeled ammonia concentrations with 2017 annual average ambient ammonia measurements, reducing model bias by 5.8 % in the Northeast region. Modeled average winter PM2.5 concentrations increased in urban areas, including enhancements of up to 0.5 µg/m3 in the northeast United States. The updated ammonia emission rates have been incorporated in MOVES4 and will be used in future versions of the NEI and EPA's modeling platforms.

16.
BMC Public Health ; 24(1): 2013, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39068431

RESUMEN

BACKGROUND: Evaluating sugar-sweetened beverage (SSB) taxation often relies on simulation models. We assess how assumptions about the response to SSB taxation affect the projected body weight change and subsequent health and economic impacts related to type 2 diabetes mellitus (T2DM) using Germany as an example. METHODS: In the main analysis, we estimated changes in energy intake by age and sex under a 20% value-added tax on SSBs in Germany using marginal price elasticities (PE) and applied an energy equilibrium model to predict body weight changes. We then quantified the impact of several assumption modifications: SSB own-PE adjusted for consumption (M1)/based on alternative meta-analysis (M2); SSB consumption adjusted for underreporting (M3); substitution via marginal (M4a) or adjusted (M4b) cross-PE/as % of calorie change (M4c). We also assessed scenarios with alternative tax rates of 10% (S1) or 30% (S2) and including fruit juice (S3). We calculated overweight and obesity rates per modification and scenario. We simulated the impact on T2DM, associated healthcare costs, and disability-adjusted life years (DALYs) over the lifetime of the 2011 German adult population with a Markov model. Data included official demographics, national surveys, and meta-analyses. RESULTS: A 20% value-added tax in Germany could reduce the number of men and women with obesity by 210,800 [138,800; 294,100] and 80,800 [45,100; 123,300], respectively. Over the population's lifetime, this would lead to modest T2DM-related health and economic impacts (76,700 DALYs [42,500; 120,600] averted; €2.37 billion [1.33; 3.71] costs saved). Policy impacts varied highly across modifications (all in DALYs averted): (M1) 94,800 [51,500; 150,700]; (M2) 164,200 [99,500; 243,500]; (M3) 52,600 [22,500; 91,100]; (M4a) -18,100 [-111,500; 68,300]; (M4b) 25,800 [-31,400; 81,500]; (M4c) 46,700 [25,300; 77,200]. The variability in policy impact related to modifications was similar to the variability between alternative policy scenarios (all in DALYs averted): (S1) 26,400 [9,300; 47,600]; (S2) 126,200 [73,600; 194,500]; (S3) 342,200 [234,200; 430,400]. CONCLUSIONS: Predicted body weight reductions under SSB taxation are sensitive to assumptions by researchers often needed due to data limitations. Because this variability propagates to estimates of health and economic impacts, the resulting structural uncertainty should be considered when using results in decision-making.


Asunto(s)
Diabetes Mellitus Tipo 2 , Bebidas Azucaradas , Impuestos , Humanos , Alemania/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Impuestos/estadística & datos numéricos , Bebidas Azucaradas/economía , Bebidas Azucaradas/estadística & datos numéricos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Peso Corporal , Anciano , Adulto Joven , Política de Salud , Obesidad/epidemiología
17.
PLoS Genet ; 17(9): e1009801, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34550980

RESUMEN

A key question in the rising field of neuroepigenetics is how behavioral plasticity is established and maintained in the developing CNS of multicellular organisms. Behavior is controlled through systemic changes in hormonal signaling, cell-specific regulation of gene expression, and changes in neuronal connections in the nervous system, however the link between these pathways is unclear. In the ant Camponotus floridanus, the epigenetic corepressor CoREST is a central player in experimentally-induced reprogramming of caste-specific behavior, from soldier (Major worker) to forager (Minor worker). Here, we show this pathway is engaged naturally on a large genomic scale during late pupal development targeting multiple genes differentially expressed between castes, and central to this mechanism is the protein tramtrack (ttk), a DNA binding partner of CoREST. Caste-specific differences in DNA binding of ttk co-binding with CoREST correlate with caste-biased gene expression both in the late pupal stage and immediately after eclosion. However, we find a unique set of exclusive Minor-bound genes that show ttk pre-binding in the late pupal stage preceding CoREST binding, followed by caste-specific gene repression on the first day of eclosion. In addition, we show that ttk binding correlates with neurogenic Notch signaling, and that specific ttk binding between castes is enriched for regulatory sites associated with hormonal function. Overall our findings elucidate a pathway of transcription factor binding leading to a repressive epigenetic axis that lies at the crux of development and hormonal signaling to define worker caste identity in C. floridanus.


Asunto(s)
Hormigas/fisiología , Pupa/crecimiento & desarrollo , Animales , Hormigas/genética , Hormigas/crecimiento & desarrollo , Epigénesis Genética , Receptores Notch/metabolismo , Transcriptoma
18.
J Arthroplasty ; 39(7): 1777-1782, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38642851

RESUMEN

BACKGROUND: Symptoms of depression have been associated with greater incapability following total hip arthroplasty (THA). A brief, 2-question, measure of symptoms of depression - the Patient Health Questionnaire-2 (PHQ-2) - may be sufficient to measure associations with the magnitude of incapability during recovery from THA. This study investigated whether preoperative symptoms of depression (measured with the PHQ-2) correlated with levels of incapability 6 weeks and 6 months after THA, accounting for demographic and clinical factors. METHODS: We performed a prospective cohort study across 5 centers and recruited 101 patients undergoing THA, of whom 90 (89%) completed follow-up. Patients completed demographics, a preoperative 2-item (PHQ-2) measure of symptoms of depression, and the Hip Dysfunction and Osteoarthritis Outcome Score for Joint Replacement (HOOS JR) at 6-weeks and 6-months postoperatively. Negative binomial regression models determined factors associated with HOOS JR at 6 weeks and 6 months, accounting for potential confounders. RESULTS: Accounting for potential confounding factors, we found that higher preoperative PHQ-2 scores (reflecting greater symptoms of depression) were associated with lower HOOS JR scores (reflecting a greater level of hip disability) at both 6 weeks (regression coefficient = -0.67, P < .001) and 6 months (regression coefficient = -1.9, P < .001) after THA. CONCLUSIONS: Symptoms of depression on a 2-question preoperative questionnaire are common, and greater symptoms of depression are associated with reduced capability within the first year following THA. These findings support the prioritization of routine mental health assessments before THA. Measuring mindset using relatively brief instruments will be important considering the current shift toward implementing self-reported measures of health status in clinical practice and incorporating them within alternative payment models.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Depresión , Osteoartritis de la Cadera , Humanos , Artroplastia de Reemplazo de Cadera/psicología , Artroplastia de Reemplazo de Cadera/efectos adversos , Femenino , Osteoartritis de la Cadera/cirugía , Osteoartritis de la Cadera/psicología , Masculino , Depresión/etiología , Depresión/psicología , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Periodo Preoperatorio , Encuestas y Cuestionarios , Recuperación de la Función , Resultado del Tratamiento
19.
J Environ Manage ; 370: 122474, 2024 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-39307090

RESUMEN

Inland navigation is one of the most sustainable transport alternatives to help decarbonise the world economy. However, the likely impacts of intensifying inland navigation on freshwater ecosystems are difficult to predict. A global map of knowledge that considers both abiotic and biotic responses to increasing shipping traffic and developing infrastructures is lacking. Deriving general evidence-based assessments is challenging, because most studies on inland navigation impacts are merely descriptive and either consist of local case studies, or address single navigation stressors or specific taxa only. We conducted a systematic mapping of the published literature (1908-2021) to provide a global synthesis of the effects of inland navigation on the biotic and abiotic components of freshwater ecosystems. We show that only half of the reported navigation-related impacts were statistically tested. Navigation itself (vessel operation) had mainly negative effects on native taxa (57%), followed by waterway management (40%), and navigation infrastructures (35%). Navigation has direct negative impacts caused by physical disturbances such as vessel-induced waves, and indirect impacts that facilitate the spread of aquatic invasive species, and altering the abiotic habitat conditions. Thirty percent of the tested relationships showed non-significant impacts on the biotic environment, while in 10% of cases impacts were context-dependent. We identified the main gaps of knowledge, namely (i) impacts of waterway management on communities, (ii) underlying processes of navigation impacts on river ecosystems; and (iii) interactions between multiple navigation factors and cascading effects on multi-taxa responses. These future research directions should improve the diagnosis, mitigate the negative impacts of navigation on rivers and provide guidelines for improving navigated river management.

20.
J Prosthet Dent ; 132(1): 267.e1-267.e10, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38622046

RESUMEN

STATEMENT OF PROBLEM: Denture stomatitis can pose serious health risks, especially to older people. Chemical denture cleaning agents must be effective, yet not adversely affect the longevity of removable dentures. Ready-to-use (RTU) neutral pH electrolyzed oxidizing water (EOW) is an effective biocide against Candida albicans biofilms on denture resins, but the effects of daily disinfection with EOW on the physical and mechanical properties of resins have not been established. PURPOSE: The purpose of this in vitro study was to investigate the effects of simulated long-term exposure to RTU EOW on the color, surface characteristics, and flexural strength of denture base resins. MATERIAL AND METHODS: Heat-polymerized (HP), 3D printed (3D) and computer-aided design and computer-aided manufacture (CAD-CAM)-milled (CC) denture resin specimens (square: 20×20×3.3 mm; beam: 64×10×3.3 mm) were immersed in tap water (TW), RTU EOW (Neutral Anolyte ANK; Envirolyte; EOW), or a commercial denture cleaning tablet solution (Polident 3-Minute; Glaxo SmithKline; PD), mimicking a 5-minute once daily disinfection routine performed up to 3.0 years. Color and surface roughness were recorded (n=3, squares), and changes in color (∆E00) and surface roughness (∆Ra) were calculated. Flexural strength (n=12, beams) and surface hardness (n=18, beams) were measured with a universal testing machine. The fractured surfaces of specimens were examined by scanning electron microscopy and energy dispersive spectroscopy. Data were assessed by performing the Shapiro-Wilk or D'Agostino and Pearson normality tests. Two-way ANOVA or the Kruskal-Wallis test with a post hoc Tukey HSD or Dunn multiple comparisons (α=.05) was used for statistical analyses. RESULTS: No significant changes were found in either color or surface roughness for HP, 3D, and CC resins after 1.5-year and 3.0-year immersion in any of the agents (P>.05). The surface hardness of 3D resins reduced by 14% with TW and by 23% with EOW and PD at 3.0 years. The flexural strengths of all 3 resins were unaffected by 3.0-year immersion (P>.05). CONCLUSIONS: Simulated long-term immersion disinfection with RTU neutral pH EOW did not adversely affect the physical and mechanical properties of HP or CC denture resins.


Asunto(s)
Bases para Dentadura , Limpiadores de Dentadura , Propiedades de Superficie , Agua , Agua/química , Concentración de Iones de Hidrógeno , Limpiadores de Dentadura/química , Ensayo de Materiales , Resistencia Flexional , Humanos , Materiales Dentales/química , Diseño Asistido por Computadora , Técnicas In Vitro , Electrólisis , Resinas Acrílicas/química , Color , Boratos , Sulfatos
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