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1.
Environ Manage ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39294479

RESUMEN

Dense beds of water plants can be perceived as nuisance, but this perception, however, may not be similar for different user categories, and this may affect their willingness-to-pay (WTP) for plant removal. A questionnaire survey was used to test this for residents and visitors and find underlying socio-cultural or economic drivers. We studied five cases where nuisance water plant growth is managed: the rivers Otra (Norway) and Spree (Germany), and the lakes Kemnade (Germany), Grand-Lieu (France), and Hartbeespoort Dam (South Africa). We used a different payment vehicle for residents (annual household tax) and visitors (tourist tax). The survey included questions on days spent on specific types of activity per year, the importance attached to different functions and activities, overall environmental attitude, perception of the plants, socio-demographic respondent characteristics and WTP for increased plant removal. We observed no increase in WTP for increased removal in most sites. The two most important drivers of variation in current WTP were income, and whether respondents were engaged in boating and angling and thus perceived the plants negatively. Variation in WTP among sites was considerable, and mainly related to the mixture of activities among respondents. Differences between residents and visitors were less important than those among sites. Our observations bear importance for water management: information on differences in experienced nuisance among user categories and the frequency of use by these categories is useful as guidance for the design and implementation of any plant removal plan.

2.
Cell ; 187(18): 4877-4889.e15, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39094568

RESUMEN

Innate immune responses to microbial pathogens are regulated by intracellular receptors known as nucleotide-binding leucine-rich repeat receptors (NLRs) in both the plant and animal kingdoms. Across plant innate immune systems, "helper" NLRs (hNLRs) work in coordination with "sensor" NLRs (sNLRs) to modulate disease resistance signaling pathways. Activation mechanisms of hNLRs based on structures are unknown. Our research reveals that the hNLR, known as NLR required for cell death 4 (NRC4), assembles into a hexameric resistosome upon activation by the sNLR Bs2 and the pathogenic effector AvrBs2. This conformational change triggers immune responses by facilitating the influx of calcium ions (Ca2+) into the cytosol. The activation mimic alleles of NRC2, NRC3, or NRC4 alone did not induce Ca2+ influx and cell death in animal cells, suggesting that unknown plant-specific factors regulate NRCs' activation in plants. These findings significantly advance our understanding of the regulatory mechanisms governing plant immune responses.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Calcio , Arabidopsis/inmunología , Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/química , Calcio/metabolismo , Resistencia a la Enfermedad , Inmunidad Innata , Proteínas NLR/metabolismo , Inmunidad de la Planta , Receptores Inmunológicos/metabolismo
3.
J Hazard Mater ; 478: 135412, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39126855

RESUMEN

A prototype air purifier (AP) module has been constructed using bismuth-doped titanium dioxide (Bix-P25: x(%) as Bi/Ti molar ratios of 1.1, 2.1, 3.3, 5.3, and 8.7). The reactive adsorption property of Bix-P25 materials is evaluated against H2S gas at a recirculation rate of 160 L min-1 in a 17 L closed chamber. The AP (Bi5.3-P25) exhibits superior performance against 10 ppm H2S in dry air under dark conditions (i.e., without light irradiation), with a removal efficiency (XH2S)= 99% in 5 mins, reaction kinetic rate (r (at X = 10%))= 7.3 mmol h-1g-1, and partition coefficient= 0.18 mol kg-1 Pa-1. As such, its superiority is evident over the reference AP (P25) filter with XH2S < 10%. The clean air delivery rate (CADR) of AP (Bi5.3-P25) increases noticeably from 9.9 to 17.8 L min-1 with increasing relative humidity (RH) from 0 to 80%, respectively. In contrast, the CADR decreases from 9.9 to 5.8 L min-1 as the H2S increases from 10 to 20 ppm. According to density functional theory (DFT), the presence of H2O vapor enhances the hydroxylation of Bix-P25 surface to promote H2S mineralization through the formation of TiS3 (i.e., thermodynamic reaction of S atom with the catalytic surface). Complete removal of H2S on the Bi5.3-P25 surface is also confirmed consistently through gas chromatography-mass spectrometry (GC-MS), in-situ diffuse reflection infrared spectroscopy (in-situ DRIFTS), and elemental analysis (EA). This work represents the first utilization of Bix-P25 materials fabricated on an AP platform toward the desulfurization of H2S at room temperature (RT). The practical utility of Bix-P25 is overall validated by its eminent role in reactive adsorption and catalytic oxidation (RACO) of H2S from the air.

4.
Comp Med ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39142813

RESUMEN

Enterovirus D68 (EV-D68), a respiratory RNA virus in the family Picornaviridae, is implicated as a potential etiological agent for acute flaccid myelitis in preteen adolescents. The absence of a specific therapeutic intervention necessitates the development of an effective animal model for EV-D68. The AG129 mouse strain, characterized by the double knockout of IFN-α/ß and IFN-γ receptors on the 129 genetic background, has been proposed as a suitable model for EV-D68. The goals of this study were to assess the effect of a nonmouse-adapted EV-D68 strain (US/MO/14-18947, NR-49129) in AG129 (IFN-α/ß and IFN-γ receptors null), A129 (IFN-α/ß receptor null), G129 (IFN-γ receptor null), and the 129 background strain (129S2/SvPasCrl) when infected intraperitoneally at 10 d of age. Both AG129 and A129 strains demonstrated similar clinical signs (paralysis, paresis, lethargy, dyspnea [characterized by prominent abdominal respiration], and morbidity requiring euthanasia) induced by EV-D68. While G129 and 129S2 strains also exhibited susceptibility to EV-D68, the severity of clinical signs was less than in AG129 and A129 strains, and many survived to the experimental endpoint. Histopathological and immunohistochemical data confirmed EV-D68 tropism for the skeletal muscle and spinal cord and suggest that the dyspnea observed in infected mice could be attributed, in part, to lesions in the diaphragmatic skeletal muscles. These findings contribute valuable insights into the pathogenesis of EV-D68 infection in this mouse model and provide investigators with key information on virus dose and mouse strain selection when using this mouse model to evaluate candidate EV-D68 therapeutics.

5.
J Sports Sci ; 42(12): 1072-1080, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39056492

RESUMEN

The objective of this study was to test the vectorelectrocardiographic T-wave characteristics for their associations with oxygen consumption (VO2) and physical performance during a maximal cardiopulmonary exercise test (CPET) in highly trained cross-country skiers. Male highly trained cross-country skiers (n = 30) performed the maximal CPET on the bicycle ergospirometric "Oxycon Pro" system with simultaneous oxygen consumption (VO2) and electrocardiogram recording. The measurements were done at rest; the stage preceding anaerobic threshold (preAnT); peak load; and recovery. The anaerobic threshold was estimated by respiratory exchange ratio. Physical performance was estimated by maximal oxygen consumption (VO2max/kg). VECG characteristics were calculated using Kors transformation procedure. During the test, the magnitudes of T-vector, Tx and Ty components decreased until preAnT, then stayed relatively stable until peak load, and reversed during recovery. In univariate linear regression analysis, T-vector amplitude and Tx, Ty and Tz magnitudes were associated with VO2/kg during the test (p < 0.010). The baseline T-vector characteristics were not associated with physical performance. At the preAnT stage, Tx and T-vector amplitude were associated with VO2max/kg (RC 12.70, 95% CI 0.68-24.73, p = 0.039 and RC 10.64, 95% CI 1.62-19.67, p = 0.023, respectively).


Asunto(s)
Umbral Anaerobio , Electrocardiografía , Prueba de Esfuerzo , Consumo de Oxígeno , Esquí , Humanos , Masculino , Consumo de Oxígeno/fisiología , Prueba de Esfuerzo/métodos , Esquí/fisiología , Umbral Anaerobio/fisiología , Adulto Joven , Adulto , Frecuencia Cardíaca/fisiología , Corazón/fisiología
6.
Artículo en Inglés | MEDLINE | ID: mdl-38982861

RESUMEN

BACKGROUND: Preterm birth (PTB) is a major pregnancy complication. There is evidence that a short cervical length in mid-pregnancy may predict women at increased risk of PTB. AIMS: To evaluate the utility of population-based, transabdominal cervical length (TACL) measurement screening in mid-pregnancy for PTB prediction in women. MATERIALS AND METHODS: A transabdominal approach was initially performed, with a transvaginal (TVCL) approach offered when the TACL was <35 mm, could not be accurately measured, or the pregnancy had risk factors for PTB. TACL was compared to the directly related TVCL, when both were performed at the same assessment. Women with risk factors of PTB were included when they had both TACL and TVCL measurements performed at the same visit. RESULTS: Data were provided for 9355 singleton pregnancies from 13 participating imaging centres. A transabdominal approach was used in 9006 (96.3%), including 682 (7.3%) TVCL combined with TACL. There were 349 (3.7%) women who had TVCL only. The median TACL was longer (40 mm) than the TVCL (38 mm). In 682 paired TACL and TVCL measurements, TACL <35 mm correctly identified 96.2% of pregnancies with TVCL <25 mm, compared with 65.4% of cases when using a TACL <30 mm. A TVCL <25 mm occurred in 59 (0.6%) women. A TACL <35 mm was associated with birth <37 weeks of gestation in 12.1% of women and birth <32 weeks of gestation in 3.9%. CONCLUSIONS: Universal TACL is a feasible option for population screening of cervical length in a low-risk population, progressing to TVCL if the TACL is <35 mm or the cervix cannot be transabdominally accurately measured.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39001651

RESUMEN

INTRODUCTION: Ongoing advances in genetic technology may soon provide prenatal screening for multiple genetic conditions. AIMS: The aims were to investigate what prenatal screening test characteristics women prioritise and their willingness to pay for these tests. METHODS: We designed an online survey incorporating a series of discrete choice scenarios. Dimensions and levels were selected based on existing prenatal tests and a hypothetical prenatal test that could non-invasively detect multiple genetic disorders in pregnancy. Participants were recruited from social media platforms. Data were analysed using conditional logistic regression and latent class analysis (LCA). RESULTS: A total of 219 women completed the survey. Women with higher incomes and those with a tertiary education were willing to pay more than other groups. The maximum willingness to pay was AUD1870 (95% confidence interval: 1630, 2112) for a hypothetical non-invasive test to detect multiple genetic conditions in early pregnancy. An LCA demonstrated considerable heterogeneity in preferences, differing in both overall preference for testing and test characteristics considered most attractive. Among the participants, decision factors cited by 14.5% of participants were the risk of pregnancy loss, making them less likely to undergo testing; for 32.1% participants, accuracy was a major factor, and they were very likely to have testing; for 12.9%, test availability early in pregnancy was a decision factor. CONCLUSIONS: If a non-invasive test that could detect the greatest number of genetic disorders in pregnancy was available, the priorities were test accuracy, risk of pregnancy loss and a test available early in pregnancy.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39010710

RESUMEN

OBJECTIVES: Assess the association of hearing on sex-specific overall mortality and death from acute cardiovascular disease and evaluate if these effects are modulated by postural balance. STUDY DESIGN: Cohort study. SETTING: Otolaryngology department at an academic hospital. METHODS: Patients underwent standard clinical examination, laboratory examination including stabilometry and audiometry. Pure tone average on the best hearing ear was calculated from 0.5, 1, 2, and 3 kHz. Cause of death was retrieved from the Norwegian Cause of Death Registry. RESULTS: A total of 1036 patients (58.8% women) were followed for 26 ± 3 years. In Cox regression analyses for overall mortality adjusted for age, past medical history, and vestibular disease, 10 dB increase in hearing threshold was associated with a 14% increase in mortality among men (hazard ratio 95% confidence interval: 1.02-1.28, P = .02), but no significant association was seen between hearing and mortality in women (0.92-1.15, P = .60). The same analyses for acute cardiovascular death found that a 10 dB increase in hearing threshold was associated with a 57% increase in hazard ratio in men (1.21-2.05, P < .001), but no significant effect of hearing on survival was seen in women (P = .71). Adjusting for postural balance did not change the association between hearing and mortality. CONCLUSION: This study finds hearing threshold is associated with overall mortality and acute cardiovascular death among men, with no such association observed among women. Our findings indicate important differences between men and women and suggest that such differences should be taken into consideration in audiological research.

9.
Pediatr Radiol ; 54(10): 1751-1757, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38913188

RESUMEN

The syndrome of anterior fibroneural stalk, vertebral anomaly, enteric duplication cyst, and diaphragmatic hernia is a manifestation of abnormal notochordal development due to persistence of the neurenteric canal beyond early fetal gestational age. Our description of the third such published case to date supports this novel tetralogy and further illustrates the role of both pre- and postnatal imaging in achieving the diagnosis.


Asunto(s)
Anomalías Múltiples , Hernias Diafragmáticas Congénitas , Notocorda , Humanos , Femenino , Notocorda/diagnóstico por imagen , Notocorda/anomalías , Recién Nacido , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Anomalías Múltiples/diagnóstico por imagen , Defectos del Tubo Neural/diagnóstico por imagen , Ultrasonografía Prenatal/métodos , Imagen Multimodal/métodos , Imagen por Resonancia Magnética/métodos , Diagnóstico Diferencial , Embarazo , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/anomalías , Vértebras Cervicales/diagnóstico por imagen , Vértebras Cervicales/anomalías , Quistes/diagnóstico por imagen , Masculino , Hernia Diafragmática/diagnóstico por imagen
10.
BMJ Case Rep ; 17(6)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38839411

RESUMEN

Cerebriform sebaceous naevus (CSN) is a rare morphological sebaceous naevus variant and challenging to diagnose prenatally due to its flat, smooth and waxy appearance and lack of association with extracutaneous manifestations.A multigravida was referred to our tertiary obstetric unit at 24 weeks of gestation for evaluation of fetal auricular lesions. We were able to further characterise the lesions via serial obstetric ultrasound imaging with the aid of three-dimensional (3D) technology. Although the precise diagnosis prenatally was uncertain, the use of 3D technology allowed the reconstruction of the fetal cutaneous lesions for multidisciplinary assessment to facilitate the development of a neonatal management plan. The diagnosis of CSN was made postnatally on biopsy.


Asunto(s)
Ultrasonografía Prenatal , Humanos , Femenino , Embarazo , Adulto , Nevo Sebáceo de Jadassohn/patología , Nevo Sebáceo de Jadassohn/diagnóstico , Nevo Sebáceo de Jadassohn/diagnóstico por imagen , Recién Nacido , Nevo/diagnóstico por imagen , Nevo/patología , Nevo/diagnóstico , Imagenología Tridimensional , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/diagnóstico , Neoplasias de las Glándulas Sebáceas/patología , Neoplasias de las Glándulas Sebáceas/diagnóstico , Neoplasias de las Glándulas Sebáceas/diagnóstico por imagen
11.
Viruses ; 16(5)2024 05 03.
Artículo en Inglés | MEDLINE | ID: mdl-38793607

RESUMEN

The dengue virus is a single-stranded, positive-sense RNA virus that infects ~400 million people worldwide. Currently, there are no approved antivirals available. CRISPR-based screening methods have greatly accelerated the discovery of host factors that are essential for DENV infection and that can be targeted in host-directed antiviral interventions. In the present study, we performed a focused CRISPR (Clustered Regularly Interspaced Palindromic Repeats) library screen to discover the key host factors that are essential for DENV infection in human Huh7 cells and identified the Protein Activator of Interferon-Induced Protein Kinase (PACT) as a novel pro-viral factor for DENV. PACT is a double-stranded RNA-binding protein generally known to activate antiviral responses in virus-infected cells and block viral replication. However, in our studies, we observed that PACT plays a pro-viral role in DENV infection and specifically promotes viral RNA replication. Knockout of PACT resulted in a significant decrease in DENV RNA and protein abundances in infected cells, which was rescued upon ectopic expression of full-length PACT. An analysis of global gene expression changes indicated that several ER-associated pro-viral genes such as ERN1, DDIT3, HERPUD1, and EIF2AK3 are not upregulated in DENV-infected PACT knockout cells as compared to infected wildtype cells. Thus, our study demonstrates a novel role for PACT in promoting DENV replication, possibly through modulating the expression of ER-associated pro-viral genes.


Asunto(s)
Sistemas CRISPR-Cas , Virus del Dengue , Interacciones Huésped-Patógeno , Proteínas de Unión al ARN , Replicación Viral , Humanos , Línea Celular , Dengue/virología , Virus del Dengue/fisiología , Interacciones Huésped-Patógeno/genética , ARN Viral/genética , ARN Viral/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
12.
Artículo en Inglés | MEDLINE | ID: mdl-38742464

RESUMEN

OBJECTIVES: This study investigated the association between internet use and loneliness among older Chinese adults, and the mediating effects of family support, friend support, and social participation. These associations were evaluated in the context of urban and non-urban geographic settings. METHODS: This study used data from the 2018 wave of the China Longitudinal Ageing Social Survey (N = 10,126), examining samples of urban (n = 3,917) and non-urban (n = 6,209) older adults separately. Linear regression and path analysis within a structural equation modeling framework were employed. RESULTS: Internet use was negatively associated with loneliness for both urban and non-urban residing older adults. Family support and social participation mediated the association between internet use and loneliness for both urban and non-urban residing older Chinese adults, but friend support mediated this association only for urban older residents. DISCUSSION: This study shed light on our understanding of the relationship between internet use and loneliness among older adults in the Chinese context. Also, these findings suggested that digital interventions for loneliness should pay special attention to the different characteristics of urban and non-urban dwelling older Chinese adults.


Asunto(s)
Amigos , Uso de Internet , Soledad , Participación Social , Apoyo Social , Población Urbana , Humanos , Soledad/psicología , Anciano , Masculino , Femenino , China/epidemiología , Población Urbana/estadística & datos numéricos , Participación Social/psicología , Amigos/psicología , Uso de Internet/estadística & datos numéricos , Estudios Longitudinales , Familia/psicología , Población Rural/estadística & datos numéricos , Anciano de 80 o más Años , Persona de Mediana Edad , Apoyo Familiar
13.
Org Lett ; 26(22): 4637-4642, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38805214

RESUMEN

Here we report an efficient route for synthesizing strigolactones (SLs) and their derivatives. Our method relies on a palladium-catalyzed oxidative carbonylation/carbocyclization/carbonylation/alkoxylation cascade reaction, which involves the formation of three new C-C bonds and a new C-O bond while cleaving one C(sp3)-H bond in a single step. With our versatile synthetic strategy, both naturally occurring and artificial SLs were prepared.

14.
J Infect Dis ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713594

RESUMEN

BACKGROUND: Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs). METHODS: We used data from UK Biobank, The Trøndelag Health Study (HUNT), and Michigan Genomics Initiative (MGI) to conduct genome-wide association studies (GWASs) and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs. RESULTS: One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for the females, SCAMP1-AS1 for the males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (OR of 4.84, P = 4.50E-06 and OR of 2.79, P = 3.02E-05, respectively). CONCLUSIONS: We found that genetic variants near TSN was associated with the risk of upper UTIs among females. In addition, we found several genetic loci with suggestive associations with the risk of upper UTIs. Finally, MR analyses found smoking to be a potential causal risk factor for upper UTIs.

15.
Sci Total Environ ; 931: 172960, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38710393

RESUMEN

Aquatic plants (macrophytes) are important for ecosystem structure and function. Macrophyte mass developments are, however, often perceived as a nuisance and are commonly managed by mechanical removal. This is costly and often ineffective due to macrophyte regrowth. There is insufficient understanding about what causes macrophyte mass development, what people who use water bodies consider to be a nuisance, or the potential negative effects of macrophyte removal on the structure and function of ecosystems. To address these gaps, we performed a standardized set of in situ experiments and questionnaires at six sites (lakes, reservoirs, and rivers) on three continents where macrophyte mass developments occur. We then derived monetary values of ecosystem services for different scenarios of macrophyte management ("do nothing", "current practice", "maximum removal"), and developed a decision support system for the management of water courses experiencing macrophyte mass developments. We found that (a) macrophyte mass developments often occur in ecosystems which (unintentionally) became perfect habitats for aquatic plants, that (b) reduced ecosystem disturbance can cause macrophyte mass developments even if nutrient concentrations are low, that (c) macrophyte mass developments are indeed perceived negatively, but visitors tend to regard them as less of a nuisance than residents do, that (d) macrophyte removal lowers the water level of streams and adjacent groundwater, but this may have positive or negative overall societal effects, and that (e) the effects of macrophyte removal on water quality, greenhouse gas emissions, and biodiversity vary, and likely depend on ecosystem characteristics and macrophyte life form. Overall, we found that aquatic plant management often does not greatly affect the overall societal value of the ecosystem, and we suggest that the "do nothing" option should not be easily discarded in the management of perceived nuisance mass developments of aquatic plants.


Asunto(s)
Conservación de los Recursos Naturales , Ecosistema , Conservación de los Recursos Naturales/métodos , Plantas , Ríos , Monitoreo del Ambiente
16.
Malar J ; 23(1): 166, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807105

RESUMEN

BACKGROUND: Deforestation is an important driver of malaria dynamics, with a relevant impact on mosquito ecology, including larval habitat availability, blood-feeding behaviour, and peak biting time. The latter is one of several entomological metrics to evaluate vectorial capacity and effectiveness of disease control. This study aimed to test the effect of forest cover percentage on the peak biting time of Plasmodium-uninfected and infected Nyssorhynchus darlingi females. METHODS: Mosquitoes were captured utilizing human landing catch (HLC) in the peridomestic habitat in field collections carried out in the wet, wet-dry transition, and dry seasons from 2014 to 2017 in areas with active malaria transmission in Amazonian Brazil. The study locations were in rural settlements in areas with the mean annual malaria parasite incidence (Annual Parasite Incidence, API ≥ 30). All Ny. darlingi females were tested for Plasmodium spp. infection using real time PCR technique. Forest cover percentage was calculated for each collection site using QGIS v. 2.8 and was categorized in three distinct deforestation scenarios: (1) degraded, < 30% forest cover, (2) intermediate, 30-70% forest cover, and (3) preserved, > 70% forest cover. RESULTS: The highest number of uninfected female Ny. darlingi was found in degraded landscape-sites with forest cover < 30% in any peak biting time between 18:00 and 0:00. Partially degraded landscape-sites, with (30-70%) forest cover, showed the highest number of vivax-infected females, with a peak biting time of 21:00-23:00. The number of P. falciparum-infected mosquitoes was highest in preserved sites with > 70% forest cover, a peak biting at 19:00-20:00, and in sites with 30-70% forest cover at 22:00-23:00. CONCLUSIONS: Results of this study show empirically that degraded landscapes favour uninfected Ny. darlingi with a peak biting time at dusk (18:00-19:00), whereas partially degraded landscapes affect the behaviour of Plasmodium-infected Ny. darlingi by shifting its peak biting time towards hours after dark (21:00-23:00). In preserved sites, Plasmodium-infected Ny. darlingi bite around dusk (18:00-19:00) and shortly after (19:00-20:00).


Asunto(s)
Conducta Alimentaria , Bosques , Mosquitos Vectores , Animales , Brasil , Femenino , Mosquitos Vectores/fisiología , Mosquitos Vectores/parasitología , Conservación de los Recursos Naturales , Mordeduras y Picaduras de Insectos/epidemiología , Estaciones del Año , Malaria/transmisión
17.
medRxiv ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38645094

RESUMEN

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with NDD. The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). We estimate that variants in this region explain 0.41% of individuals with NDD. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to its contiguous counterpart RNU4-1 and other U4 homologs, supporting RNU4-2's role as the primary U4 transcript in the brain. Overall, this work underscores the importance of non-coding genes in rare disorders. It will provide a diagnosis to thousands of individuals with NDD worldwide and pave the way for the development of effective treatments for these individuals.

18.
Am J Physiol Regul Integr Comp Physiol ; 326(6): R507-R514, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38586888

RESUMEN

Diets varying in macronutrient composition, energy density, and/or palatability may cause differences in outcome of bariatric surgery. In the present study, rats feeding a healthy low-fat (LF) diet or an obesogenic high-fat/sucrose diet (HF/S) were either subjected to Roux-en-Y gastric bypass surgery (RYGB) or sham surgery, and weight loss trajectories and various energy balance parameters were assessed. Before RYGB, rats eating an HF/S (n = 14) diet increased body weight relative to rats eating an LF diet (n = 20; P < 0.01). After RYGB, absolute weight loss was larger in HF/S (n = 6) relative to LF feeding (n = 6) rats, and this was associated with reduced cumulative energy intake (EI; P < 0.05) and increased locomotor activity (LA; P < 0.05-0.001), finally leading to similar levels of reduced body fat content in HF/S and LF rats 3 wk after surgery. Regression analysis revealed that variation in RYGB-induced body weight loss was best explained by models including 1) postoperative cumulative EI and preoperative body weight (R2 = 0.87) and 2) postoperative cumulative EI and diet (R2 = 0.79), each without significant contribution of LA. Particularly rats on the LF diet became transiently more hypothermic and circadianally arrhythmic following RYGB (i.e., indicators of surgery-associated malaise) than HF/S feeding rats. Our data suggest that relative to feeding an LF diet, continued feeding an HF/S diet does not negatively impact recovery from RYGB surgery, yet it promotes RYGB-induced weight loss. The RYGB-induced weight loss is primarily explained by reduced cumulative EI and higher preoperative body weight, leading to comparably low levels of body fat content in HF/S and LF feeding rats.NEW & NOTEWORTHY Relative to feeding an LF diet, continued feeding an HF/S diet does not negatively impact recovery from RYGB surgery in rats. Relative to feeding an LF diet, continued feeding an HF/S diet promotes RYGB-induced weight loss. The RYGB-induced weight loss is primarily explained by reduced cumulative EI and higher preoperative body weight, leading to comparably low levels of body fat content in HF/S and LF feeding rats.


Asunto(s)
Ingestión de Energía , Derivación Gástrica , Ratas Wistar , Pérdida de Peso , Animales , Masculino , Ratas , Metabolismo Energético , Dieta Alta en Grasa , Peso Corporal , Obesidad/fisiopatología , Obesidad/cirugía , Obesidad/metabolismo , Restricción Calórica
19.
Nat Commun ; 15(1): 3469, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658526

RESUMEN

Human parechoviruses (PeV-A) are increasingly being recognized as a cause of infection in neonates and young infants, leading to a spectrum of clinical manifestations ranging from mild gastrointestinal and respiratory illnesses to severe sepsis and meningitis. However, the host factors required for parechovirus entry and infection remain poorly characterized. Here, using genome-wide CRISPR/Cas9 loss-of-function screens, we identify myeloid-associated differentiation marker (MYADM) as a host factor essential for the entry of several human parechovirus genotypes including PeV-A1, PeV-A2 and PeV-A3. Genetic knockout of MYADM confers resistance to PeV-A infection in cell lines and in human gastrointestinal epithelial organoids. Using immunoprecipitation, we show that MYADM binds to PeV-A1 particles via its fourth extracellular loop, and we identify critical amino acid residues within the loop that mediate binding and infection. The demonstrated interaction between MYADM and PeV-A1, and its importance specifically for viral entry, suggest that MYADM is a virus receptor. Knockout of MYADM does not reduce PeV-A1 attachment to cells pointing to a role at the post-attachment stage. Our study suggests that MYADM is a multi-genotype receptor for human parechoviruses with potential as an antiviral target to combat disease associated with emerging parechoviruses.


Asunto(s)
Parechovirus , Infecciones por Picornaviridae , Internalización del Virus , Humanos , Línea Celular , Sistemas CRISPR-Cas , Células HEK293 , Organoides/virología , Organoides/metabolismo , Parechovirus/genética , Parechovirus/metabolismo , Infecciones por Picornaviridae/virología , Infecciones por Picornaviridae/metabolismo , Unión Proteica , Receptores Virales/metabolismo , Receptores Virales/genética
20.
J Infect ; 88(5): 106155, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38574775

RESUMEN

BACKGROUND: Klebsiella pneumoniae species complex (KpSC) bloodstream infections (BSIs) are associated with considerable morbidity and mortality, particularly in elderly and multimorbid patients. Multidrug-resistant (MDR) strains have been associated with poorer outcome. However, the clinical impact of KpSC phylogenetic lineages on BSI outcome is unclear. METHODS: In an 18-month nationwide Norwegian prospective study of KpSC BSI episodes in adults, we used whole-genome sequencing to describe the molecular epidemiology of KpSC, and multivariable Cox regression analysis including clinical data to determine adjusted hazard ratios (aHR) for death associated with specific genomic lineages. FINDINGS: We included 1078 BSI episodes and 1082 bacterial isolates from 1055 patients. The overall 30-day case-fatality rate (CFR) was 12.5%. Median patient age was 73.4, 61.7% of patients were male. Median Charlson comorbidity score was 3. Klebsiella pneumoniae sensu stricto (Kp) (79.3%, n = 858/1082) and K. variicola (15.7%, n = 170/1082) were the dominating phylogroups. Global MDR-associated Kp clonal groups (CGs) were prevalent (25.0%, n = 270/1082) but 78.9% (n = 213/270) were not MDR, and 53.7% (n = 145/270) were community acquired. The major findings were increased risk for death within 30 days in monomicrobial BSIs caused by K. variicola (CFR 16.9%, n = 21; aHR 1.86, CI 1.10-3.17, p = 0.02), and global MDR-associated Kp CGs (CFR 17.0%, n = 36; aHR 1.52, CI 0.98-2.38, p = 0.06) compared to Kp CGs not associated with MDR (CFR 10.1%, n = 46). CONCLUSION: Bacterial traits, beyond antimicrobial resistance, have a major impact on the clinical outcome of KpSC BSIs. The global spread of MDR-associated Kp CGs is driven by other mechanisms than antibiotic selection alone. Further insights into virulence determinants, and their association with phylogenetic lineages are needed to better understand the epidemiology of KpSC infection and clinical outcome.


Asunto(s)
Bacteriemia , Farmacorresistencia Bacteriana Múltiple , Infecciones por Klebsiella , Klebsiella pneumoniae , Filogenia , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Infecciones por Klebsiella/mortalidad , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/epidemiología , Femenino , Anciano , Estudios Prospectivos , Bacteriemia/microbiología , Bacteriemia/mortalidad , Bacteriemia/epidemiología , Persona de Mediana Edad , Anciano de 80 o más Años , Noruega/epidemiología , Secuenciación Completa del Genoma , Factores de Riesgo , Epidemiología Molecular , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Adulto
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