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1.
Mol Cell ; 75(5): 944-956.e6, 2019 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-31326273

RESUMEN

Type III-A CRISPR-Cas surveillance complexes containing multi-subunit Csm effector, guide, and target RNAs exhibit multiple activities, including formation of cyclic-oligoadenylates (cAn) from ATP and subsequent cAn-mediated cleavage of single-strand RNA (ssRNA) by the trans-acting Csm6 RNase. Our structure-function studies have focused on Thermococcus onnurineus Csm6 to deduce mechanistic insights into how cA4 binding to the Csm6 CARF domain triggers the RNase activity of the Csm6 HEPN domain and what factors contribute to regulation of RNA cleavage activity. We demonstrate that the Csm6 CARF domain is a ring nuclease, whereby bound cA4 is stepwise cleaved initially to ApApApA>p and subsequently to ApA>p in its CARF domain-binding pocket, with such cleavage bursts using a timer mechanism to regulate the RNase activity of the Csm6 HEPN domain. In addition, we establish T. onnurineus Csm6 as an adenosine-specific RNase and identify a histidine in the cA4 CARF-binding pocket involved in autoinhibitory regulation of RNase activity.


Asunto(s)
Nucleótidos de Adenina/química , Proteínas Arqueales/química , Proteínas Asociadas a CRISPR/química , Sistemas CRISPR-Cas , Oligorribonucleótidos/química , Ribonucleasas/química , Thermococcus/química , Sitios de Unión , Dominios Proteicos
2.
Proc Natl Acad Sci U S A ; 121(14): e2317492121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38547056

RESUMEN

Energy metabolism is highly interdependent with adaptive cell migration in vivo. Mechanical confinement is a critical physical cue that induces switchable migration modes of the mesenchymal-to-amoeboid transition (MAT). However, the energy states in distinct migration modes, especially amoeboid-like stable bleb (A2) movement, remain unclear. In this report, we developed multivalent DNA framework-based nanomachines to explore strategical mitochondrial trafficking and differential ATP levels during cell migration in mechanically heterogeneous microenvironments. Through single-particle tracking and metabolomic analysis, we revealed that fast A2-moving cells driven by biomimetic confinement recruited back-end positioning of mitochondria for powering highly polarized cytoskeletal networks, preferentially adopting an energy-saving mode compared with a mesenchymal mode of cell migration. We present a versatile DNA nanotool for cellular energy exploration and highlight that adaptive energy strategies coordinately support switchable migration modes for facilitating efficient metastatic escape, offering a unique perspective for therapeutic interventions in cancer metastasis.


Asunto(s)
Amoeba , Línea Celular Tumoral , Movimiento Celular , Fenómenos Físicos
3.
Development ; 149(23)2022 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-36373561

RESUMEN

Leaf meristem is a cell proliferative zone present in the lateral organ primordia. In this study, we examined how cell proliferative zones in primordia of planar floral organs and polar auxin transport inhibitor (PATI)-treated leaf organs differ from those of non-treated foliage leaves of Arabidopsis thaliana, with a focus on the accumulation pattern of ANGUSTIFOLIA3 (AN3) protein, a key element for leaf meristem positioning. We found that PATI-induced leaf shape changes were correlated with cell division angle but not with meristem positioning/size or AN3 localisation. In contrast, different shapes between sepals and petals compared with foliage leaves were associated with both altered meristem position, due to altered AN3 expression patterns, and different distributions of cell division angles. A numerical simulation showed that meristem position majorly affected the final shape but biased cell division angles had a minor effect. Taken together, these results suggest that the unique shapes of different lateral organs depend on the position of the meristem in the case of floral organs and cell division angles in the case of leaf organs with different auxin flow.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Regulación de la Expresión Génica de las Plantas , Meristema/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Ácidos Indolacéticos/metabolismo , Hojas de la Planta/metabolismo , División Celular
4.
Proc Natl Acad Sci U S A ; 119(5)2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-35086930

RESUMEN

Plants are agile, plastic organisms able to adapt to everchanging circumstances. Responding to far-red (FR) wavelengths from nearby vegetation, shade-intolerant species elicit the adaptive shade-avoidance syndrome (SAS), characterized by elongated petioles, leaf hyponasty, and smaller leaves. We utilized end-of-day FR (EODFR) treatments to interrogate molecular processes that underlie the SAS leaf response. Genetic analysis established that PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) is required for EODFR-mediated constraint of leaf blade cell division, while EODFR messenger RNA sequencing data identified ANGUSTIFOLIA3 (AN3) as a potential PIF7 target. We show that PIF7 can suppress AN3 transcription by directly interacting with and sequestering AN3. We also establish that PIF7 and AN3 impose antagonistic control of gene expression via common cis-acting promoter motifs in several cell-cycle regulator genes. EODFR triggers the molecular substitution of AN3 to PIF7 at G-box/PBE-box promoter regions and a switch from promotion to repression of gene expression.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Proteínas de Unión al ADN/metabolismo , Hojas de la Planta/metabolismo , Transactivadores/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Factor VII/genética , Expresión Génica/genética , Regulación de la Expresión Génica de las Plantas/genética , Fitocromo/metabolismo , Regiones Promotoras Genéticas/genética , Transactivadores/genética
5.
BMC Genomics ; 25(1): 348, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38582836

RESUMEN

BACKGROUND: Insecticide resistance (IR) is one of the major threats to malaria vector control programs in endemic countries. However, the mechanisms underlying IR are poorly understood. Thus, investigating gene expression patterns related to IR can offer important insights into the molecular basis of IR in mosquitoes. In this study, RNA-Seq was used to characterize gene expression in Anopheles gambiae surviving exposure to pyrethroids (deltamethrin, alphacypermethrin) and an organophosphate (pirimiphos-methyl). RESULTS: Larvae of An. gambiae s.s. collected from Bassila and Djougou in Benin were reared to adulthood and phenotyped for IR using a modified CDC intensity bottle bioassay. The results showed that mosquitoes from Djougou were more resistant to pyrethroids (5X deltamethrin: 51.7% mortality; 2X alphacypermethrin: 47.4%) than Bassila (1X deltamethrin: 70.7%; 1X alphacypermethrin: 77.7%), while the latter were more resistant to pirimiphos-methyl (1.5X: 48.3% in Bassila and 1X: 21.5% in Djougou). RNA-seq was then conducted on resistant mosquitoes, non-exposed mosquitoes from the same locations and the laboratory-susceptible An. gambiae s.s. Kisumu strain. The results showed overexpression of detoxification genes, including cytochrome P450s (CYP12F2, CYP12F3, CYP4H15, CYP4H17, CYP6Z3, CYP9K1, CYP4G16, and CYP4D17), carboxylesterase genes (COEJHE5E, COE22933) and glutathione S-transferases (GSTE2 and GSTMS3) in all three resistant mosquito groups analyzed. Genes encoding cuticular proteins (CPR130, CPR10, CPR15, CPR16, CPR127, CPAP3-C, CPAP3-B, and CPR76) were also overexpressed in all the resistant groups, indicating their potential role in cross resistance in An. gambiae. Salivary gland protein genes related to 'salivary cysteine-rich peptide' and 'salivary secreted mucin 3' were also over-expressed and shared across all resistant groups. CONCLUSION: Our results suggest that in addition to metabolic enzymes, cuticular and salivary gland proteins could play an important role in cross-resistance to multiple classes of insecticides in Benin. These genes warrant further investigation to validate their functional role in An. gambiae resistance to insecticides.


Asunto(s)
Anopheles , Insecticidas , Malaria , Nitrilos , Piretrinas , Animales , Insecticidas/farmacología , Anopheles/genética , Benin , Organofosfatos/farmacología , Mosquitos Vectores , Piretrinas/farmacología , Resistencia a los Insecticidas/genética , Perfilación de la Expresión Génica
6.
Proc Biol Sci ; 291(2023): 20240101, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38808442

RESUMEN

The early Ediacaran Weng'an biota (Doushantuo Formation, South China) provides a rare window onto the period of Earth history in which molecular timescales have inferred the initial phase of crown-metazoan diversification. Interpretation of the embryo-like fossils that dominate the biota remains contentious because they are morphologically simple and so difficult to constrain phylogenetically. Spiralicellula from the Weng'an biota is distinguished by spiral internal bodies, allied through development to Megasphaera or Helicoforamina and interpreted variously as metazoan embryos, encysting protists, or chlorophycean green algae. Here we show, using X-ray microtomography, that Spiralicellula has a single-layered outer envelope and no more than 32 internal cells, often preserving a nucleus and yolk granules. There is no correlation between the extent of spiral development and the number of component cells; rather, the spiral developed with each palintomic stage, associated with cell disaggregation and reorientation. Evidence for envelope thinning and cell loss was observed in all developmental stages, reflecting non-deterministic shedding of gametes or amoebae. The developmental biology of Spiralicellula is similar to Megasphaera and Helicoforamina, which otherwise exhibit more rounds of palintomy. We reject a crown-metazoan affinity for Spiralicellula and all other components of the Weng'an biota, diminishing the probability of crown-metazoan diversification before the early Ediacaran.


Asunto(s)
Evolución Biológica , Fósiles , Fósiles/anatomía & histología , Animales , China , Microtomografía por Rayos X , Filogenia
7.
J Virol ; 97(2): e0136322, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36688653

RESUMEN

Viral infections alter host cell metabolism and homeostasis; however, the mechanisms that regulate these processes have only begun to be elucidated. We report here that Zika virus (ZIKV) infection activates the antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2), which precedes oxidative stress. Downregulation of Nrf2 or inhibition of glutathione (GSH) synthesis resulted in significantly increased viral replication. Interestingly, 6-amino-nicotinamide (6-AN), a nicotinamide analog commonly used as an inhibitor of the pentose phosphate pathway (PPP), decreased viral replication by over 1,000-fold. This inhibition was neither recapitulated by the knockdown of PPP enzymes, glucose 6-phosphate dehydrogenase (G6PD), or 6-phosphogluconate dehydrogenase (6PGD), nor prevented by supplementation with ribose 5-phosphate. Instead, our metabolomics and metabolic phenotype studies support a mechanism in which 6-AN depletes cells of NAD(H) and impairs NAD(H)-dependent glycolytic steps resulting in inhibition of viral replication. The inhibitory effect of 6-AN was rescued with precursors of the salvage pathway but not with those of other NAD+ biosynthesis pathways. Inhibition of glycolysis reduced viral protein levels, which were recovered transiently. This transient recovery in viral protein synthesis was prevented when oxidative metabolism was inhibited by blockage of the mitochondrial pyruvate carrier, fatty acid oxidation, or glutaminolysis, demonstrating a compensatory role of mitochondrial metabolism in ZIKV replication. These results establish an antagonistic role for the host cell Nrf2/GSH/NADPH-dependent antioxidant response against ZIKV and demonstrate the dependency of ZIKV replication on NAD(H). Importantly, our work suggests the potential use of NAD(H) antimetabolite therapy against the viral infection. IMPORTANCE Zika virus (ZIKV) is a major public health concern of international proportions. While the incidence of ZIKV infections has declined substantially in recent years, the potential for the reemergence or reintroduction remains high. Although viral infection alters host cell metabolism and homeostasis to promote its replication, deciphering the mechanism(s) involved in these processes is important for identifying therapeutic targets. The present work reveals the complexities of host cell redox regulation and metabolic dependency of ZIKV replication. An antagonistic effect of the Nrf2/GSH/NADP(H)-dependent antioxidant response against ZIKV infection and an essential role of NAD(H) metabolism and glycolysis for viral replication are established for the first time. These findings highlight the potential use of NAD(H) antimetabolites to counter ZIKV infection and pathogenesis.


Asunto(s)
Interacciones Microbiota-Huesped , Factor 2 Relacionado con NF-E2 , Replicación Viral , Infección por el Virus Zika , Virus Zika , Humanos , Antioxidantes/metabolismo , Antioxidantes/uso terapéutico , NAD/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción , Proteínas Virales/metabolismo , Replicación Viral/fisiología , Virus Zika/fisiología , Infección por el Virus Zika/tratamiento farmacológico , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/virología , Oxidorreductasas/genética , Técnicas de Silenciamiento del Gen , Células Cultivadas , Interacciones Microbiota-Huesped/fisiología
8.
Brief Bioinform ; 23(6)2022 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-36239380

RESUMEN

In order to identify plant pentatricopeptide repeat (PPR) proteins, a framework of variable selection has been proposed. In fact, it is an effective feature selection strategy that focuses on the performance of classification. Random forest has been used as the classifier with certain variables automatically selected for discrimination between PPR functional and non-functional proteins. However, it is found that samples regarded as PPR functional proteins are wrongly classified in a high rate. In this paper, we plan to improve the framework in order to achieve better classification results. Modifications are made on the framework for better identifying PPR functional proteins. Instead of random forest, a hybrid ensemble classifier is built with its base classifiers derived from six different classification methods. Besides, an incremental strategy and a clustering by search in descending order are alternatively used for feature selection, which can effectively select the most representative variables for identification on PPR proteins. In addition, it can be found that different base classifiers alternately play an important role in the ensemble classifier with feature dimension increasing. The experimental results demonstrate the effectiveness of our improvements.


Asunto(s)
Algoritmos , Proteínas de Plantas , Proteínas de Plantas/genética , Análisis por Conglomerados
9.
New Phytol ; 241(1): 471-489, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37897060

RESUMEN

In this study, we investigate the genetic mechanisms responsible for the loss of anthocyanins in betalain-pigmented Caryophyllales, considering our hypothesis of multiple transitions to betalain pigmentation. Utilizing transcriptomic and genomic datasets across 357 species and 31 families, we scrutinize 18 flavonoid pathway genes and six regulatory genes spanning four transitions to betalain pigmentation. We examined evidence for hypotheses of wholesale gene loss, modified gene function, altered gene expression, and degeneration of the MBW (MYB-bHLH-WD40) trasnscription factor complex, within betalain-pigmented lineages. Our analyses reveal that most flavonoid synthesis genes remain conserved in betalain-pigmented lineages, with the notable exception of TT19 orthologs, essential for the final step in anthocyanidin synthesis, which appear to have been repeatedly and entirely lost. Additional late-stage flavonoid pathway genes upstream of TT19 also manifest strikingly reduced expression in betalain-pigmented species. Additionally, we find repeated loss and alteration in the MBW transcription complex essential for canonical anthocyanin synthesis. Consequently, the loss and exclusion of anthocyanins in betalain-pigmented species appear to be orchestrated through several mechanisms: loss of a key enzyme, downregulation of synthesis genes, and degeneration of regulatory complexes. These changes have occurred iteratively in Caryophyllales, often coinciding with evolutionary transitions to betalain pigmentation.


Asunto(s)
Antocianinas , Caryophyllales , Humanos , Antocianinas/metabolismo , Betalaínas , Caryophyllales/genética , Evolución Biológica , Transcriptoma , Regulación de la Expresión Génica de las Plantas
10.
Insect Mol Biol ; 33(2): 147-156, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37962063

RESUMEN

Geranylgeranyl pyrophosphate (diphosphate) synthase (GGPPS) plays an important role in various physiological processes in insects, such as isoprenoid biosynthesis and protein prenylation. Here, we functionally characterised the GGPPS from the major agricultural lepidopteran pests Spodoptera frugiperda and Helicoverpa armigera. Partial disruption of GGPPS by CRISPR in S. frugiperda decreased embryo hatching rate and larval survival, suggesting that this gene is essential. Functional expression in vitro of Helicoverpa armigera GGPPS in Escherichia coli revealed a catalytically active enzyme. Next, we developed and optimised an enzyme assay to screen for potential inhibitors, such as the zoledronate and the minodronate, which showed a dose-dependent inhibition. Phylogenetic analysis of GGPPS across insects showed that GGPPS is highly conserved but also revealed several residues likely to be involved in substrate binding, which were substantially different in bee pollinator and human GGPPS. Considering the essentiality of GGPPS and its putative binding residue variability qualifies a GGPPS as a novel pesticide target. The developed assay may contribute to the identification of novel insecticide leads.


Asunto(s)
Plaguicidas , Humanos , Animales , Abejas/genética , Farnesiltransferasa/genética , Farnesiltransferasa/metabolismo , Filogenia , Ácido Zoledrónico
11.
Arch Biochem Biophys ; 751: 109822, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38030054

RESUMEN

BACKGROUND: Skin flap transplantation is a routine strategy in plastic and reconstructive surgery for skin-soft tissue defects. Recent research has shown that M2 macrophages have the potential for pro-angiogenesis during tissue healing. METHODS: In our research, we extracted the exosomes from M2 macrophages(M2-exo) and applied the exosomes in the model of skin flap transplantation. The flap survival area was measured, and the choke vessels were assessed by morphological observation. Hematoxylin and eosin (H&E) staining and Immunohistochemistry were applied to assess the neovascularization. The effect of M2-exo on the function of Human umbilical vein endothelial cells (HUVECs) was also investigated. We also administrated 2-methoxyestradiol (2-ME2, an inhibitor of HIF-1α) to explore the underlying mechanism. We tested the effects of M2-Exo on the proliferation of HUVECs through CCK8 assay and EdU staining assay. RESULTS: The survival area and number of micro-vessels in the skin flaps were increased in the M2-exo group. Besides, the dilation rate of choke vessels was also enhanced in the M2-exo group. Additionally, compared with the control group, M2-exo could accelerate the proliferation, migration and tube formation of HUVECs in vitro. Furthermore, the expression of the pro-angiogenesis factors, HIF-1α and VEGFA, were overexpressed with the treatment of the M2-exo. The expression of HIF1AN protein level was decreased in the M2-exo group. Finally, treatment with HIF-1α inhibitor reverses the pro-survival effect of M2-exo on skin flaps by interfering with the HIF1AN/HIF-1α/VEGFA signaling pathway. CONCLUSION: This study showed that M2-exosomes promote skin flap survival by enhancing angiogenesis, with HIF1AN/HIF-1α/VEGFA playing a crucial role in this process.


Asunto(s)
Exosomas , Humanos , Exosomas/metabolismo , Angiogénesis , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Patológica/metabolismo , Neovascularización Fisiológica , Oxigenasas de Función Mixta/metabolismo , Proteínas Represoras/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
12.
Transfusion ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39021332

RESUMEN

BACKGROUND: Transfusion-related acute lung injury (TRALI) remains a major contributor to transfusion-associated mortality. While the pathogenesis of TRALI remains unclear, there is evidence of a role for blood components. We therefore investigated the potential effects of fresh frozen plasma (FFP), cryoprecipitate, and extracellular vesicles (EVs) derived from these blood components, on the viability of human lung microvascular endothelial cells (HLMVECs) in vitro. METHODS: EVs were isolated from FFP and cryoprecipitate using size-exclusion chromatography and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscopy. The potential effects of these blood components and their EVs on HLMVEC viability (determined by trypan blue exclusion) were examined in the presence and absence of neutrophils, either with or without prior treatment of HLMVECs with LPS. RESULTS: EVs isolated from FFP and cryoprecipitate displayed morphological and biochemical properties conforming to latest international criteria. While FFP, cryoprecipitate, and EVs derived from FFP, each reduced HLMVEC viability, no effect was observed for EVs derived from cryoprecipitate. CONCLUSION: Our findings demonstrate clear differences in the effects of FFP, cryoprecipitate, and their respective EVs on HLMVEC viability in vitro. Examination of the mechanisms underlying these differences may lead to an improved understanding of the factors that promote development of TRALI.

13.
Chemphyschem ; 25(18): e202400342, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-38807571

RESUMEN

Some years ago, Jishan Wu reported the synthesis of 8MC and 10MC, two homologues of the cyclopenta-ring-fused oligo(m-phenylene) macrocycles mMC, each behaving as an annulene-within-an-annulene (AWA). This was a surprising result as the AWA behavior is rare. Both molecules have a partial polyradical character, enforced by the quest for restoring some aromatic character of benzene rings. However, that restoration brings back some coupling between the two annulenes. Indeed, we found that the geometry and the magnetically induced currents indicate that, while 8MC does have an AWA character, this is not the case of the larger 10MC. Limitations of the design strategy of AWA molecules should be taken into account in future attempts to prepare novel large coronenes.

14.
Connect Tissue Res ; 65(1): 63-72, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37966352

RESUMEN

The pivotal role of lncRNAs in osteoporosis progression and development necessitates a comprehensive exploration of the functional and precise molecular mechanisms underlying lncRNA SNHG1's regulation of osteoblast differentiation and calcification. The study involved inducing BMSCs cells to differentiate into osteoblasts, followed by transfections of miR-497-5p inhibitors, pcDNA3.1-SNHG1, sh-HIF1AN, miR-497-5p mimics, and respective negative controls into BMSCs. Quantitative PCR (qPCR) was employed to assess the expression of SNHG1 and miR-497-5p. Western Blotting was conducted to measure the levels of short stature-related transcription factor 2 (RUNX2), osteopontin (OPN), osteocalcin (OCN), and HIF1AN. Alkaline phosphatase (ALP) activity was determined using appropriate assay kits. Calcium nodule staining was performed through Alizarin red staining. Dual luciferase reporter gene assays were executed to validate the interaction between SNHG1 and miR-497-5p, as well as HIF1AN. Throughout osteogenic differentiation, there was a down-regulation of SNHG1 and HIF1AN, in contrast to an elevation in miR-497-5p levels. Direct interactions between miR-497-5p and both SNHG1 and HIF1AN were observed. Notably, SNHG1 exhibited the ability to modulate HIF1AN by influencing miR-497-5p, thereby inhibiting osteogenic differentiation. Functioning as a competitive endogenous RNA, lncRNA SNHG1 exerts an inhibitory influence on osteogenic differentiation via the miR-497-5p/HIF1AN axis. This highlights the potential for lncRNA SNHG1 to emerge as a promising therapeutic target for osteoporosis. The study's findings pave the way for a novel target strategy in the future treatment of osteoporosis.


Asunto(s)
MicroARNs , Osteoporosis , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Diferenciación Celular/genética , Osteoporosis/genética , Osteoporosis/metabolismo , Células Cultivadas , Oxigenasas de Función Mixta , Proteínas Represoras
15.
J Sleep Res ; : e14153, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38499951

RESUMEN

Mitochondrial diseases are rare genetic disorders often accompanied by severe sleep disorders. We present the case of a 12-year-old boy diagnosed with a severe primary mitochondrial disease, exhibiting ataxia, spasticity, progressive external ophthalmoplegia, cardiomyopathy and severely disrupted sleep, but no cognitive impairment. Interestingly, his parents reported improved sleep during night train rides. Based on this observation, we installed a rocking bed in the patient's bedroom and performed different interventions, including immersive multimodal vestibular, kinesthetic and auditory stimuli, reminiscent of the sensory experiences encountered during train rides. Over a 5-month period, we conducted four 2-week nocturnal interventions, separated by 1-week washout phases, to determine the subjectively best-perceived stimulation parameters, followed by a final 4-week intervention using the optimal parameters. We assessed sleep duration and quality using the Mini Sleep Questionnaire, monitored pulse rate changes and used videography to document nocturnal interactions between the patient and caregivers. Patient-reported outcome measures, clinical examinations and personal outcomes of specific interests were used to document daytime sleepiness, restlessness, anxiety, fatigue, cognitive performance and physical posture. In the final 4-week intervention, sleep duration increased by 25%, required caregiver interactions reduced by 75%, and caregiving time decreased by 40%. Subjective fatigue, assessed by the Checklist Individual Strength, decreased by 40%, falling below the threshold of severe fatigue. Our study suggests that rocking beds could provide a promising treatment regime for selected patients with persistent severe sleep disorders. Further research is required to validate these findings in larger patient populations with sleep disorders and other conditions.

16.
Malar J ; 23(1): 60, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38413961

RESUMEN

BACKGROUND: When integrated with insecticide-treated bed nets, larval control of Anopheles mosquitoes could fast-track reductions in the incidence of human malaria. However, larval control interventions may deliver suboptimal outcomes where the preferred breeding places of mosquito vectors are not well known. This study investigated the breeding habitat choices of Anopheles mosquitoes in southern Nigeria. The objective was to identify priority sites for mosquito larval management in selected urban and periurban locations where malaria remains a public health burden.  METHODS: Mosquito larvae were collected in urban and periurban water bodies during the wet-dry season interface in Edo, Delta, and Anambra States. Field-collected larvae were identified based on PCR gel-electrophoresis and amplicon sequencing, while the associations between Anopheles larvae and the properties and locations of water bodies were assessed using a range of statistical methods. RESULTS: Mosquito breeding sites were either man-made (72.09%) or natural (27.91%) and mostly drainages (48.84%) and puddles (25.58%). Anopheles larvae occurred in drainages, puddles, stream margins, and a concrete well, and were absent in drums, buckets, car tires, and a water-holding iron pan, all of which contained culicine larvae. Wild-caught Anopheles larvae comprised Anopheles coluzzii (80.51%), Anopheles gambiae sensu stricto (s.s.) (11.54%), and Anopheles arabiensis (7.95%); a species-specific PCR confirmed the absence of the invasive urban malaria vector Anopheles stephensi among field-collected larvae. Anopheles arabiensis, An. coluzzii, and An. gambiae s.s. displayed preferences for turbid, lowland, and partially sunlit water bodies, respectively. Furthermore, An. arabiensis preferred breeding sites located outside 500 m of households, whereas An. gambiae s.s. and An. coluzzii had increased detection odds in sites within 500 m of households. Anopheles gambiae s.s. and An. coluzzii were also more likely to be present in natural water bodies; meanwhile, 96.77% of An. arabiensis were in man-made water bodies. Intraspecific genetic variations were little in the dominant vector An. coluzzii, while breeding habitat choices of populations made no statistically significant contributions to these variations. CONCLUSION: Sibling malaria vectors in the An. gambiae complex display divergent preferences for aquatic breeding habitats in southern Nigeria. The findings are relevant for planning targeted larval control of An. coluzzii whose increasing evolutionary adaptations to urban ecologies are driving the proliferation of the mosquito, and An. arabiensis whose adults typically evade the effects of treated bed nets due to exophilic tendencies.


Asunto(s)
Anopheles , Malaria , Animales , Adulto , Humanos , Anopheles/genética , Mosquitos Vectores , Nigeria , Malaria/epidemiología , Agua , Larva , Cruzamiento
17.
Malar J ; 23(1): 280, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285410

RESUMEN

BACKGROUND: Intensive deployment of insecticide based malaria vector control tools resulted in the rapid evolution of phenotypes resistant to these chemicals. Understanding this process at the genomic level is important for the deployment of successful vector control interventions. Therefore, longitudinal sampling followed by whole genome sequencing (WGS) is necessary to understand how these evolutionary processes evolve over time. This study investigated the change in genetic structure and the evolution of the insecticide resistance variants in natural populations of Anopheles gambiae over time and space from 2012 to 2017 in Burkina Faso. METHODS: New genomic data have been generated from An. gambiae mosquitoes collected from three villages in the western part of Burkina Faso between 2012 and 2017. The samples were whole-genome sequenced and the data used in the An. gambiae 1000 genomes (Ag1000G) project as part of the Vector Observatory. Genomic data were analysed using the analysis pipeline previously designed by the Ag1000G project. RESULTS: The results showed similar and consistent nucleotide diversity and negative Tajima's D between An. gambiae sensu stricto (s.s.) and Anopheles coluzzii. Principal component analysis (PCA) and the fixation index (FST) showed a clear genetic structure in the An. gambiae sensu lato (s.l.) species. Genome-wide FST and H12 scans identified genomic regions under divergent selection that may have implications in the adaptation to ecological changes. Novel voltage-gated sodium channel pyrethroid resistance target-site alleles (V402L, I1527T) were identified at increasing frequencies alongside the established alleles (Vgsc-L995F, Vgsc-L995S and N1570Y) within the An. gambiae s.l. POPULATIONS: Organophosphate metabolic resistance markers were also identified, at increasing frequencies, within the An. gambiae s.s. populations from 2012 to 2017, including the SNP Ace1-G280S and its associated duplication. Variants simultaneously identified in the same vector populations raise concerns about the long-term efficacy of new generation bed nets and the recently organophosphate pirimiphos-methyl indoor residual spraying in Burkina Faso. CONCLUSION: These findings highlighted the benefit of genomic surveillance of malaria vectors for the detection of new insecticide resistance variants, the monitoring of the existing resistance variants, and also to get insights into the evolutionary processes driving insecticide resistance.


Asunto(s)
Anopheles , Resistencia a los Insecticidas , Mosquitos Vectores , Secuenciación Completa del Genoma , Resistencia a los Insecticidas/genética , Anopheles/genética , Anopheles/efectos de los fármacos , Animales , Burkina Faso , Mosquitos Vectores/genética , Mosquitos Vectores/efectos de los fármacos , Estudios Longitudinales , Evolución Molecular , Insecticidas/farmacología , Malaria/transmisión
18.
Artículo en Inglés | MEDLINE | ID: mdl-38265282

RESUMEN

In 2014, it was reported that the bacterial genus name Rhodococcus Zopf 1891 was illegitimate due to the priority of the cyanobacterial genus name Rhodococcus Hansgirg 1884. Since that time, the consequences of this conclusion have been largely ignored, whilst changes have been made to relevant Rules of the International Code of Nomenclature of Prokaryotes, including significant changes to the way in which the Code treats the names of members of Cyanobacteriota. Given the complexity of the nomenclatural issues, we request the opinion of the Judicial Commission of the International Committee on Systematics of Prokaryotes as to whether the genus name Rhodococcus Zopf 1891 (Approved Lists 1980) is illegitimate.


Asunto(s)
Ácidos Grasos , Rhodococcus , Filogenia , Análisis de Secuencia de ADN , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Composición de Base , Ácidos Grasos/química
19.
Scand J Gastroenterol ; 59(2): 213-217, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37698190

RESUMEN

BACKGROUND: For small gastric subepithelial tumours originating from the muscularis propria, there is no uniform standard for selecting the best endoscopic resection method. OBJECTIVE: To compare the efficacy and safety of endoscopic snare resection with a transparent cap (ESR-C) and endoscopic snare resection with an elastic band (ESR-EB) for small gastric subepithelial tumours originating from the muscularis propria to determine which method is more suitable for these tumours. METHODS: The data from small gastric subepithelial tumours originating from the muscularis propria treated from Jan 2020 to Dec 2022 were collected. A total of 34 eligible patients were enrolled. Sixteen of these patients were treated with ESR-C, and eighteen were treated with ESR-EB. The general clinical characteristics, tumour location, tumour size,growth pattern,operation time, complete resection rate, and complication rate were compared between the two groups. RESULTS: There was no difference in age, sex, tumour location, tumour size, growth pattern, or histological diagnosis after resection (p > 0.05). There was no significant difference in operation time, complete resection rate, or follow-up time (p > 0.05). Eight patients (50.5%) in the ESR-C group had complications (6 perforations and 2 bleeding), and 2 (11.11%) in the ESR-EB group had complications (2 perforations). There were significant differences between the two groups (p = 0.037). All perforations were successfully treated. No recurrence or metastasis was observed in either group during the follow-up period. CONCLUSION: Both ESR-C and ESR-EB are effective and safe in treating small gastric subepithelial tumours originating from the muscularis propria. However, ESR-EB can significantly reduce the incidence of complications. ESR-EB is likely a better option for small gastric subepithelial tumours originating from the muscularis propria.


Asunto(s)
Tumores del Estroma Gastrointestinal , Neoplasias Gástricas , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Neoplasias Gástricas/patología , Gastroscopía/métodos , Ligadura , Mucosa Gástrica/cirugía , Mucosa Gástrica/patología , Tumores del Estroma Gastrointestinal/patología
20.
Conserv Biol ; : e14309, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842291

RESUMEN

Religious environmentalism relies upon religious texts and leadership to promote effective and long-lasting change for environmental problems, such as responsible use and conservation of natural resources and biodiversity. World religions note the importance of biodiversity and humanity's responsibility in stewarding biodiversity as a member of ecological communities. We reviewed Quranic verses that relate to biodiversity and align with United Nations Sustainable Development Goals (SDGs). The Holy Quran was reviewed in electronic and hard copy formats, and verses related to biodiversity were translated to English and tabulated by Qur'anic chapter, verse, and narrative citation. Twenty-one Qur'anic verses were identified that addressed biodiversity. Scriptures were divided into 5 groups that addressed provision of resources, governance or stewardship of resources, nature as a teacher, and human life in nature's communities or described creation of biodiversity. Qur'anic verses were aligned with 4 SDGs (goals 12-15), which address sustainable consumption of natural resources, global climate change, life in marine environments, and life in terrestrial environments, including freshwater ecosystems. This alignment demonstrates the interconnectedness of life, that conservation of biodiversity is referenced in the Quran, and how positive management of natural recourses can be beneficial to Muslim communities on local, national, and global scales. Positive movement toward ecofriendly practices, sound environmental resource use and management, biodiversity conservation, and governmental policies on conservation can be promoted through scriptures from the Holy Qur'an.


Énfasis en la importancia de la conservación de la biodiversidad con el Sagrado Corán Resumen El ambientalismo religioso depende de los textos y el liderazgo religioso para promover un cambio efectivo y duradero de los problemas ambientales, como el uso y conservación de los recursos naturales y la biodiversidad. Las religiones del mundo destacan la importancia de la biodiversidad y la responsabilidad de la humanidad en el cuidado de la biodiversidad como miembros de las comunidades ecológicas. Revisamos los versos del Corán que se relacionan con la biodiversidad y que se alinean con los Objetivos de Desarrollo Sustentable (ODGs) de las Naciones Unidas. Revisamos el Sagrado Corán en formato físico y electrónico y tradujimos al inglés los versos relacionados con la biodiversidad para luego tabularlos según la cita del capítulo, verso y narrativa del Corán. Identificamos 21 versos del Corán en los que se aborda la biodiversidad. Clasificamos las escrituras en cinco grupos de acuerdo con si abordan el suministro de recursos, la administración o cuidado de los recursos, a la naturaleza como docente y a la vida humana dentro de las comunidades naturales o si describen la creación de la biodiversidad. Los versos del Corán se alinearon con cuatro de los ODGs (del 12 al 15), lo cuales abordan el consumo sustentable de los recursos naturales, el cambio climático mundial y la vida marina y terrestre, incluyendo los ecosistemas de agua dulce. Esta alineación demuestra la interconexión de la vida, que el Corán tiene referencias a la conservación de la biodiversidad y cómo la gestión positiva de los recursos naturales puede ser benéfica para las comunidades musulmanes a escala local, nacional y mundial. El Sagrado Corán puede usarse para promover un movimiento positivo hacia las prácticas amigables con el ambiente, el uso y manejo sensato de los recursos naturales, la conservación de la biodiversidad y políticas gubernamentales para la conservación.

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