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1.
PLoS Pathog ; 15(9): e1008085, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31568486

RESUMEN

Human parasitic nematodes are the causative agents of lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness), diseases that are endemic to more than 80 countries and that consistently rank in the top ten for the highest number of years lived with disability. These filarial nematodes have evolved an obligate mutualistic association with an intracellular bacterium, Wolbachia, a symbiont that is essential for the successful development, reproduction, and survival of adult filarial worms. Elimination of the bacteria causes adult worms to die, making Wolbachia a primary target for developing new interventional tools to combat filariases. To further explore Wolbachia as a promising indirect macrofilaricidal drug target, the essential cellular processes that define the symbiotic Wolbachia-host interactions need to be identified. Genomic analyses revealed that while filarial nematodes encode all the enzymes necessary for glycolysis, Wolbachia does not encode the genes for three glycolytic enzymes: hexokinase, 6-phosphofructokinase, and pyruvate kinase. These enzymes are necessary for converting glucose into pyruvate. Wolbachia, however, has the full complement of genes required for gluconeogenesis starting with pyruvate, and for energy metabolism via the tricarboxylic acid cycle. Therefore, we hypothesized that Wolbachia might depend on host glycolysis to maintain a mutualistic association with their parasitic host. We did conditional experiments in vitro that confirmed that glycolysis and its end-product, pyruvate, sustain this symbiotic relationship. Analysis of alternative sources of pyruvate within the worm indicated that the filarial lactate dehydrogenase could also regulate the local intracellular concentration of pyruvate in proximity to Wolbachia and thus help control bacterial growth via molecular interactions with the bacteria. Lastly, we have shown that the parasite's pyruvate kinase, the enzyme that performs the last step in glycolysis, could be a potential novel anti-filarial drug target. Establishing that glycolysis is an essential component of symbiosis in filarial worms could have a broader impact on research focused on other intracellular bacteria-host interactions where the role of glycolysis in supporting intracellular survival of bacteria has been reported.


Asunto(s)
Brugia/metabolismo , Brugia/microbiología , Ácido Pirúvico/metabolismo , Wolbachia/metabolismo , Animales , Brugia/genética , Brugia Malayi/genética , Brugia Malayi/metabolismo , Brugia Malayi/microbiología , Brugia pahangi/genética , Brugia pahangi/metabolismo , Brugia pahangi/microbiología , Femenino , Filariasis/metabolismo , Filariasis/microbiología , Filariasis/parasitología , Genes de Helminto , Glucólisis , Interacciones Microbiota-Huesped , Interacciones Huésped-Parásitos , Humanos , Masculino , Simbiosis , Wolbachia/genética
2.
PLoS Pathog ; 15(9): e1008041, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31553770

RESUMEN

Filariae are parasitic nematodes that are transmitted to their definitive host as third-stage larvae by arthropod vectors like mosquitoes. Filariae cause diseases including: lymphatic filariasis with distressing and disturbing symptoms like elephantiasis; and river blindness. Filarial diseases affect millions of people in 73 countries throughout the topics and sub-tropics. The drugs available for mass drug administration, (ivermectin, albendazole and diethylcarbamazine), are ineffective against adult filariae (macrofilariae) at the registered dosing regimen; this generates a real and urgent need to identify effective macrofilaricides. Emodepside, a veterinary anthelmintic registered for treatment of nematode infections in cats and dogs, is reported to have macrofilaricidal effects. Here, we explore the mode of action of emodepside using adult Brugia malayi, one of the species that causes lymphatic filariasis. Whole-parasite motility measurement with Worminator and patch-clamp of single muscle cells show that emodepside potently inhibits motility by activating voltage-gated potassium channels and that the male is more sensitive than the female. RNAi knock down suggests that emodepside targets SLO-1 K channels. We expressed slo-1 isoforms, with alternatively spliced exons at the RCK1 (Regulator of Conductance of Potassium) domain, heterologously in Xenopus laevis oocytes. We discovered that the slo-1f isoform, found in muscles of males, is more sensitive to emodepside than the slo-1a isoform found in muscles of females; and selective RNAi of the slo-1a isoform in female worms increased emodepside potency. In Onchocerca volvulus, that causes river blindness, we found two isoforms in adult females with homology to Bma-SLO-1A and Bma-SLO-1F at the RCK1 domain. In silico modeling identified an emodepside binding pocket in the same RCK1 region of different species of filaria that is affected by these splice variations. Our observations show that emodepside has potent macrofilaricidal effects and alternative splicing in the RCK1 binding pocket affects potency. Therefore, the evaluation of potential sex-dependent effects of an anthelmintic compound is of importance to prevent any under-dosing of one or the other gender of nematodes once given to patients.


Asunto(s)
Brugia Malayi/efectos de los fármacos , Brugia Malayi/fisiología , Depsipéptidos/farmacología , Filaricidas/farmacología , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Empalme Alternativo , Secuencia de Aminoácidos , Animales , Sitios de Unión/genética , Brugia Malayi/genética , Femenino , Filariasis/tratamiento farmacológico , Filariasis/parasitología , Técnicas de Silenciamiento del Gen , Humanos , Canales de Potasio de Gran Conductancia Activados por el Calcio/química , Canales de Potasio de Gran Conductancia Activados por el Calcio/genética , Masculino , Modelos Moleculares , Movimiento/efectos de los fármacos , Movimiento/fisiología , Músculos/efectos de los fármacos , Músculos/fisiología , Péptidos/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Homología de Secuencia de Aminoácido , Factores Sexuales
3.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-34502059

RESUMEN

The increased research activity aiming at improved delivery of pharmaceutical molecules indicates the expansion of the field. An efficient therapeutic delivery approach is based on the optimal choice of drug-carrying vehicle, successful targeting, and payload release enabling the site-specific accumulation of the therapeutic molecules. However, designing the formulation endowed with the targeting properties in vitro does not guarantee its selective delivery in vivo. The various biological barriers that the carrier encounters upon intravascular administration should be adequately addressed in its overall design to reduce the off-target effects and unwanted toxicity in vivo and thereby enhance the therapeutic efficacy of the payload. Here, we discuss the main parameters of remote-controlled drug delivery systems: (i) key principles of the carrier selection; (ii) the most significant physiological barriers and limitations associated with the drug delivery; (iii) major concepts for its targeting and cargo release stimulation by external stimuli in vivo. The clinical translation for drug delivery systems is also described along with the main challenges, key parameters, and examples of successfully translated drug delivery platforms. The essential steps on the way from drug delivery system design to clinical trials are summarized, arranged, and discussed.


Asunto(s)
Portadores de Fármacos/química , Liberación de Fármacos , Animales , Ensayos Clínicos como Asunto , Portadores de Fármacos/efectos adversos , Portadores de Fármacos/toxicidad , Humanos , Materiales Inteligentes/química
4.
Int J Mol Sci ; 21(7)2020 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-32230871

RESUMEN

Flow cytometry nowadays is among the main working instruments in modern biology paving the way for clinics to provide early, quick, and reliable diagnostics of many blood-related diseases. The major problem for clinical applications is the detection of rare pathogenic objects in patient blood. These objects can be circulating tumor cells, very rare during the early stages of cancer development, various microorganisms and parasites in the blood during acute blood infections. All of these rare diagnostic objects can be detected and identified very rapidly to save a patient's life. This review outlines the main techniques of visualization of rare objects in the blood flow, methods for extraction of such objects from the blood flow for further investigations and new approaches to identify the objects automatically with the modern deep learning methods.


Asunto(s)
Separación Celular/métodos , Aprendizaje Profundo , Diagnóstico por Imagen/métodos , Citometría de Flujo/métodos , Automatización , Circulación Sanguínea , Separación Celular/instrumentación , Rastreo Celular , Diagnóstico por Imagen/instrumentación , Pruebas Diagnósticas de Rutina , Citometría de Flujo/instrumentación , Colorantes Fluorescentes , Enfermedades Hematológicas/diagnóstico , Humanos , Magnetismo , Células Neoplásicas Circulantes/patología , Enfermedades Raras/diagnóstico , Coloración y Etiquetado/métodos
5.
Molecules ; 25(7)2020 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-32225028

RESUMEN

The development of novel materials and approaches for effective energy consumption and the employment of renewable energy sources is one of the current trends in modern material science. With this respect, the number of researches is focused on the effective harvesting and storage of solar energy for various applications. Phase change materials (PCMs) are known to be able to store thermal energy of the sunlight due to adsorption and release of latent heat through reversible phase transitions. Therefore, PCMs are promising as functional additives to construction materials and paints for advanced thermoregulation in building and industry. However, bare PCMs have limited practical applications. Organic PCMs like paraffins suffer from material leakage when undergoing in a liquid state while inorganic ones like salt hydrates lack long-term stability after multiple phase transitions. To avoid this, the loading of PCMs in porous matrices are intensively studied along with the thermal properties of the resulted composites. The loading of PCMs in microcontainers of natural porous or layered clay materials appears as a simple and cost-effective method of encapsulation significantly improving the shape and cyclic stability of PCMs. Additionally, the inclusion of functional clay containers into construction materials allows for improving their mechanical and flame-retardant properties. This article summarizes the recent progress in the preparation of composites based on PCM-loaded clay microcontainers along with their future perspectives as functional additives in thermo-regulating materials.


Asunto(s)
Arcilla/química , Termodinámica , Algoritmos , Tierra de Diatomeas/química , Energía Geotérmica , Calor , Caolín/química , Silicatos de Magnesio/química , Modelos Moleculares , Modelos Teóricos , Transición de Fase , Porosidad , Conductividad Térmica
6.
FASEB J ; 30(10): 3501-3514, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27363426

RESUMEN

Nematodes lack a heme biosynthetic pathway and must acquire heme from exogenous sources. Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme-responsive genes (HRGs) have been characterized within the free-living nematode Caenorhabditis elegans, we have undertaken the first study of heme transport in Brugia malayi, a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter B. malayi HRG-1 (BmHRG-1) is indeed functional in B. malayi In addition, BmHRG-1 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that BmHRG-1, BmHRG-2, and BmMRP-5 (all orthologs of HRGs in C. elegans) are down-regulated in heme-treated B. malayi, as compared to non-heme-treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in B. malayi (BmHRG-3-6) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode B. malayi is capable of transporting exogenous heme.-Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode Brugia malayi.


Asunto(s)
Brugia Malayi , Hemo/inmunología , Homeostasis/fisiología , Animales , Caenorhabditis elegans , Interferencia de ARN
7.
Proc Natl Acad Sci U S A ; 109(25): E1638-46, 2012 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-22645363

RESUMEN

Wolbachia are widespread and abundant intracellular symbionts of arthropods and filarial nematodes. Their symbiotic relationships encompass obligate mutualism, commensalism, parasitism, and pathogenicity. A consequence of these diverse associations is that Wolbachia encounter a wide range of host cells and intracellular immune defense mechanisms of invertebrates, which they must evade to maintain their populations and spread to new hosts. Here we show that autophagy, a conserved intracellular defense mechanism and regulator of cell homeostasis, is a major immune recognition and regulatory process that determines the size of Wolbachia populations. The regulation of Wolbachia populations by autophagy occurs across all distinct symbiotic relationships and can be manipulated either chemically or genetically to modulate the Wolbachia population load. The recognition and activation of host autophagy is particularly apparent in rapidly replicating strains of Wolbachia found in somatic tissues of Drosophila and filarial nematodes. In filarial nematodes, which host a mutualistic association with Wolbachia, the use of antibiotics such as doxycycline to eliminate Wolbachia has emerged as a promising approach to their treatment and control. Here we show that the activation of host nematode autophagy reduces bacterial loads to the same magnitude as antibiotic therapy; thus we identify a bactericidal mode of action targeting Wolbachia that can be exploited for the development of chemotherapeutic agents against onchocerciasis, lymphatic filariasis, and heartworm.


Asunto(s)
Autofagia , Simbiosis , Wolbachia/fisiología , Animales , Proteínas Bacterianas/metabolismo , Brugia Malayi/metabolismo , Brugia Malayi/microbiología , Línea Celular/metabolismo , Drosophila melanogaster/metabolismo , Nematodos/microbiología , Fracciones Subcelulares/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/metabolismo
8.
Cell Microbiol ; 15(4): 520-6, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23210448

RESUMEN

Wolbachia pipientis is a widespread intracellular bacterial symbiont of arthropods and is common in insects. One of their more exotic and unexpected hosts is the filarial nematodes, notable for the parasites responsible for onchocerciasis (river blindness), lymphatic filariasis (elephantiasis) and dirofilariasis (heartworm). Wolbachia are only present in a subgroup of the filarial nematodes and do not extend to other groups of nematodes either parasitic or free-living. In the medically and veterinary important species that host Wolbachia, the symbiont has become an essential partner to key biological processes in the life of the nematode to the point where antibiotic elimination of the bacteria leads to a potent and effective anti-filarial drug treatment. We review the cellular and molecular basis of Wolbachia filarial interactions and highlight the key processes provided by the endosymbiont upon which the nematodes have become entirely dependent. This dependency is primarily restricted to periods of the lifecycle with heavy metabolic demands including growth and development of larval stages and embryogenesis in the adult female. Also, the longevity of filarial parasites is compromised following depletion of the symbiont, which for the first time has delivered a safe and effective treatment to kill adult parasites with antibiotics.


Asunto(s)
Filarioidea/microbiología , Simbiosis , Wolbachia/fisiología , Animales , Antibacterianos/farmacología , Filarioidea/fisiología , Análisis de Supervivencia , Wolbachia/efectos de los fármacos , Wolbachia/crecimiento & desarrollo
9.
Pharmaceutics ; 16(2)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38399310

RESUMEN

Onchocerciasis and lymphatic filariasis are two neglected tropical diseases caused by filarial nematodes that utilize insect vectors for transmission to their human hosts. Current control strategies are based on annual or biannual mass drug administration (MDA) of the drugs Ivermectin or Ivermectin plus Albendazole, respectively. These drug regimens kill the first-stage larvae of filarial worms (i.e., microfilariae) and interrupt the transmission of infections. MDA programs for these microfilaricidal drugs must be given over the lifetime of the filarial adult worms, which can reach 15 years in the case of Onchocerca volvulus. This is problematic because of suboptimal responses to ivermectin in various endemic regions and inefficient reduction of transmission even after decades of MDA. There is an urgent need for the development of novel alternative treatments to support the 2030 elimination goals of onchocerciasis and lymphatic filariasis. One successful approach has been to target Wolbachia, obligatory endosymbiotic bacteria on which filarial worms are dependent for their survival and reproduction within the human host. A 4-6-week antibiotic therapy with doxycycline, for example, resulted in the loss of Wolbachia that subsequently led to extensive apoptosis of somatic cells, germline, embryos, and microfilariae, as well as inhibition of fourth-stage larval development. However, this long-course regimen has limited use in MDA programs. As an alternative approach to the use of bacteriostatic antibiotics, in this study, we focused on autophagy-inducing compounds, which we hypothesized could disturb various pathways involved in the interdependency between Wolbachia and filarial worms. We demonstrated that several such compounds, including Niclosamide, an FDA-approved drug, Niclosamide ethanolamine (NEN), and Rottlerin, a natural product derived from Kamala trees, significantly reduced the levels of Wolbachia in vitro. Moreover, when these compounds were used in vivo to treat Brugia pahangi-infected gerbils, Niclosamide and NEN significantly decreased adult worm survival, reduced the release of microfilariae, and decreased embryonic development depending on the regimen and dose used. All three drugs given orally significantly reduced Wolbachia loads and induced an increase in levels of lysosome-associated membrane protein in worms from treated animals, suggesting that Niclosamide, NEN, and Rottlerin were effective in causing drug-induced autophagy in these filarial worms. These repurposed drugs provide a new avenue for the clearance of adult worms in filarial infections.

10.
Biomedicines ; 12(2)2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38398045

RESUMEN

The effect of an extremely low frequency alternating magnetic field (ELF AMF) at frequencies of 17, 48, and 95 Hz at 100 mT on free and internalized 4T1 breast cancer cell submicron magnetic mineral carriers with an anticancer drug, mitoxantrone, was shown. The alternating magnetic field (100 mT; 17, 48, 95 Hz; time of treatment-10.5 min with a 30 s delay) does not lead to the significant destruction of carrier shells and release of mitoxantrone or bovine serum albumin from them according to the data of spectrophotometry, or the heating of carriers in the process of exposure to magnetic fields. The most optimal set of factors that would lead to the suppression of proliferation and survival of cells with anticancer drug carriers on the third day (in comparison with the control and first day) is exposure to an alternating magnetic field of 100 mT in a pulsed mode with a frequency of 95 Hz. The presence of magnetic nanocarriers in cell lines was carried out by a direct label-free method, space-resolved Brillouin light scattering (BLS) spectrometry, which was realized for the first time. The analysis of the series of integrated BLS spectra showed an increase in the magnetic phase in cells with a growth in the number of particles per cell (from 10 to 100) after their internalization. The safety of magnetic carriers in the release of their constituent ions has been evaluated using atomic absorption spectrometry.

11.
Front Microbiol ; 15: 1346068, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38362501

RESUMEN

Lymphatic filariasis and onchocerciasis are two major neglected tropical diseases that are responsible for causing severe disability in 50 million people worldwide, whilst veterinary filariasis (heartworm) is a potentially lethal parasitic infection of companion animals. There is an urgent need for safe, short-course curative (macrofilaricidal) drugs to eliminate these debilitating parasite infections. We investigated combination treatments of the novel anti-Wolbachia azaquinazoline small molecule, AWZ1066S, with benzimidazole drugs (albendazole or oxfendazole) in up to four different rodent filariasis infection models: Brugia malayi-CB.17 SCID mice, B. malayi-Mongolian gerbils, B. pahangi-Mongolian gerbils, and Litomosoides sigmodontis-Mongolian gerbils. Combination treatments synergised to elicit threshold (>90%) Wolbachia depletion from female worms in 5 days of treatment, using 2-fold lower dose-exposures of AWZ1066S than monotherapy. Short-course lowered dose AWZ1066S-albendazole combination treatments also delivered partial adulticidal activities and/or long-lasting inhibition of embryogenesis, resulting in complete transmission blockade in B. pahangi and L. sigmodontis gerbil models. We determined that short-course AWZ1066S-albendazole co-treatment significantly augmented the depletion of Wolbachia populations within both germline and hypodermal tissues of B. malayi female worms and in hypodermal tissues in male worms, indicating that anti-Wolbachia synergy is not limited to targeting female embryonic tissues. Our data provides pre-clinical proof-of-concept that sub-seven-day combinations of rapid-acting novel anti-Wolbachia agents with benzimidazole anthelmintics are a promising curative and transmission-blocking drug treatment strategy for filarial diseases of medical and veterinary importance.

12.
PLoS Pathog ; 7(11): e1002351, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22072969

RESUMEN

Filarial nematodes maintain a mutualistic relationship with the endosymbiont Wolbachia. Depletion of Wolbachia produces profound defects in nematode development, fertility and viability and thus has great promise as a novel approach for treating filarial diseases. However, little is known concerning the basis for this mutualistic relationship. Here we demonstrate using whole mount confocal microscopy that an immediate response to Wolbachia depletion is extensive apoptosis in the adult germline, and in the somatic cells of the embryos, microfilariae and fourth-stage larvae (L4). Surprisingly, apoptosis occurs in the majority of embryonic cells that had not been infected prior to antibiotic treatment. In addition, no apoptosis occurs in the hypodermal chords, which are populated with large numbers of Wolbachia, although disruption of the hypodermal cytoskeleton occurs following their depletion. Thus, the induction of apoptosis upon Wolbachia depletion is non-cell autonomous and suggests the involvement of factors originating from Wolbachia in the hypodermal chords. The pattern of apoptosis correlates closely with the nematode tissues and processes initially perturbed following depletion of Wolbachia, embryogenesis and long-term sterilization, which are sustained for several months until the premature death of the adult worms. Our observations provide a cellular mechanism to account for the sustained reductions in microfilarial loads and interruption of transmission that occurs prior to macrofilaricidal activity following antibiotic therapy of filarial nematodes.


Asunto(s)
Antibacterianos/farmacología , Apoptosis , Brugia Malayi/microbiología , Filariasis/parasitología , Wolbachia/efectos de los fármacos , Wolbachia/fisiología , Animales , Antibacterianos/uso terapéutico , Brugia Malayi/citología , Brugia Malayi/efectos de los fármacos , Brugia Malayi/metabolismo , Caspasa 3/biosíntesis , Doxiciclina/farmacología , Femenino , Filariasis/tratamiento farmacológico , Gerbillinae/parasitología , Proteínas del Helminto/biosíntesis , Humanos , Etiquetado Corte-Fin in Situ , Larva/microbiología , Masculino , Simbiosis , Tetraciclina/farmacología
13.
Microbiol Spectr ; 11(6): e0218023, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37811984

RESUMEN

IMPORTANCE: Arthropod-borne viruses are emerging pathogens that are spread widely by mosquitos. Zika virus is an arbovirus that can infect humans and be transmitted from an infected mother to the fetus, potentially leading to microcephaly in infants. One promising strategy to prevent disease caused by arboviruses is to target the insect vector population. Recent field studies have shown that mosquito populations infected with Wolbachia bacteria suppress arbovirus replication and transmission. Here, we describe how intracellular bacteria redirect resources within their host cells and suppress Zika virus replication at the cellular level. Understanding the mechanism behind Wolbachia-induced interference of arbovirus replication could help advance strategies to control arbovirus pathogens in insect vectors and human populations.


Asunto(s)
Aedes , Arbovirus , Wolbachia , Infección por el Virus Zika , Virus Zika , Animales , Humanos , Aedes/microbiología , Mosquitos Vectores/microbiología , Replicación Viral , Colesterol
14.
Nat Commun ; 14(1): 6500, 2023 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-37838705

RESUMEN

Several important human infectious diseases are caused by microscale-sized parasitic nematodes like filarial worms. Filarial worms have their own spatial tissue organization; to uncover this tissue structure, we need methods that can spatially resolve these miniature specimens. Most filarial worms evolved a mutualistic association with endosymbiotic bacteria Wolbachia. However, the mechanisms underlying the dependency of filarial worms on the fitness of these bacteria remain unknown. As Wolbachia is essential for the development, reproduction, and survival of filarial worms, we spatially explored how Wolbachia interacts with the worm's reproductive system by performing a spatial characterization using Spatial Transcriptomics (ST) across a posterior region containing reproductive tissue and developing embryos of adult female Brugia malayi worms. We provide a proof-of-concept for miniature-ST to explore spatial gene expression patterns in small sample types, demonstrating the method's ability to uncover nuanced tissue region expression patterns, observe the spatial localization of key B. malayi - Wolbachia pathway genes, and co-localize the B. malayi spatial transcriptome in Wolbachia tissue regions, also under antibiotic treatment. We envision our approach will open up new avenues for the study of infectious diseases caused by micro-scale parasitic worms.


Asunto(s)
Enfermedades Transmisibles , Parásitos , Wolbachia , Animales , Femenino , Humanos , Parásitos/genética , Transcriptoma , Antibacterianos/metabolismo , Perfilación de la Expresión Génica , Wolbachia/genética , Wolbachia/metabolismo , Simbiosis/genética
15.
Polymers (Basel) ; 15(18)2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37765611

RESUMEN

Antibiotic-loaded bone cement (ALBC) has become an indispensable material in orthopedic surgery in recent decades, owing to the possibility of drugs delivery to the surgical site. It is applied for both infection prophylaxis (e.g., in primary joint arthroplasty) and infection treatment (e.g., in periprosthetic infection). However, the introduction of antibiotic to the polymer matrix diminishes the mechanical strength of the latter. Moreover, the majority of the loaded antibiotic remains embedded in polymer and does not participate in drug elution. Incorporation of the various additives to ALBC can help to overcome these issues. In this paper, four different natural micro/nanoscale materials (halloysite, nanocrystalline cellulose, micro- and nanofibrillated cellulose) were tested as additives to commercial Simplex P bone cement preloaded with vancomycin. The influence of all four materials on the polymerization process was comprehensively studied, including the investigation of the maximum temperature of polymerization, setting time, and monomer leaching. The introduction of the natural additives led to a considerable enhancement of drug elution and microhardness in the composite bone cements compared to ALBC. The best combination of the polymerization rate, monomer leaching, antibiotic release, and microhardness was observed for the sample containing nanofibrillated cellulose (NFC).

16.
Materials (Basel) ; 16(19)2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37834594

RESUMEN

Organic phase-change materials (PCMs) hold promise in developing advanced thermoregulation and responsive energy systems owing to their high latent heat capacity and thermal reliability. However, organic PCMs are prone to leakages in the liquid state and, thus, are hardly applicable in their pristine form. Herein, we encapsulated organic PCM n-Octadecane into polyurethane capsules via polymerization of commercially available polymethylene polyphenylene isocyanate and polyethylene glycol at the interface oil-in-water emulsion and studied how various n-Octadecane feeding affected the shell formation, capsule structure, and latent heat storage properties. The successful shell polymerization and encapsulation of n-Octadecane dissolved in the oil core was verified by confocal microscopy and Fourier-transform infrared spectroscopy. The mean capsule size varied from 9.4 to 16.7 µm while the shell was found to reduce in thickness from 460 to 220 nm as the n-Octadecane feeding increased. Conversely, the latent heat storage capacity increased from 50 to 132 J/g corresponding to the growth in actual n-Octadecane content from 25% to 67% as revealed by differential scanning calorimetry. The actual n-Octadecane content increased non-linearly along with the n-Octadecane feeding and reached a plateau at 66-67% corresponded to 3.44-3.69 core-to-monomer ratio. Finally, the capsules with the reasonable combination of structural and thermal properties were evaluated as a thermoregulating additive to a commercially available paint.

17.
Polymers (Basel) ; 15(23)2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-38231929

RESUMEN

Adsorption of organic phase-change materials (PCMs) by the porous matrix of microfibrillar cellulose (MFC) is a simple and versatile way to prepare shape-stable phase-change composites, which are promising as sustainable thermoregulating additives to construction materials. However, due to MFC inherent morphology, the resulting composites have relatively low poured density that complicates their introduction in sufficient amounts, for instance, into mortar mixes. Unlike MFC, fungal mycelium has, by an order, less fibrils thickness and, thus, possesses significantly higher poured density. Herein, we studied the feasibility of fungal mycelium-based matrices as alternative biopolymeric porous supports for preparation of sustainable and shape-stable phase-change composites. Two methods were employed to prepare the porous mycelium-based supports. The first one was the solid-state fermentation, which resulted in partial biotransformation of MFCs to mycelium hyphae, while the second one was the liquid-state surface fermentation, used to cultivate the reference matrix of Trametes hirsuta hyphae. The phase-change composites were prepared by adsorption of model organic PCMs on porous biopolymer matrices. The mass ratio of support/PCM was 40/60 wt%. The composites were studied with respect to their structure, composition, poured density, latent heat storage properties, and thermal and shape stability. The employment of the partially transformed to mycelium-hyphae MFC fibers was found to be a suitable way to prepare phase-change composites with improved poured density while preserving a reasonable latent heat capacity and shape stability as compared to the MFC/PCM composites.

18.
J Bacteriol ; 194(7): 1840, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22408242

RESUMEN

Although bacteria of the genus Wolbachia induced significant extended phenotypes to infected hosts, most molecular mechanisms involved are still unknown. To gain insight into the bacterial genetic determinants, we sequenced the whole genome of Wolbachia wAlbB strain, a commensal obligate intracellular of the tiger mosquito Aedes albopictus.


Asunto(s)
Aedes/microbiología , Genoma Bacteriano , Insectos Vectores/microbiología , Wolbachia/genética , Aedes/fisiología , Animales , Secuencia de Bases , Insectos Vectores/fisiología , Datos de Secuencia Molecular , Filogenia , Simbiosis , Wolbachia/clasificación , Wolbachia/aislamiento & purificación , Wolbachia/fisiología
19.
Langmuir ; 28(33): 12275-81, 2012 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-22812404

RESUMEN

The development of the microelectronics industry requires a new element basis with reduced size and increased functionality. The most important components in modern microelectronic integrated circuits are passive elements. One of the key challenges in order to improve the functionality of integrated circuits is to increase the quality of passive elements composing them. In this paper we suggest a novel approach to increase the quality factor Q of inductors by the surface modification and functionalization of the metal components. Ultrasound induced surface modification of metal wires led to the formation of a porous surface structure, which further can be functionalized with magnetite nanoparticles using layer-by-layer assembly technique. The surface modification and deposition of magnetite nanoparticles was investigated with SEM, XRD, and contact angle measurements. Additionally, inductance and resistance measurements, as the main parameters determining the Q-factor of inductors, were carried out. Samples with high number of magnetic nanoparticle-polyelectrolyte bilayers demonstrate a significant increase in inductance and a slight decrease in resistance in comparison to uncoated ones. The combination of these factors led to enhancement the Q-factor of the investigated inductive elements.

20.
mBio ; 13(4): e0118222, 2022 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-35862784

RESUMEN

Wolbachia is a heritable alphaproteobacterial symbiont of arthropods and nematodes, famous for its repertoire of host manipulations, including cytoplasmic incompatibility. To be vertically transmitted, Wolbachia must efficiently colonize the female germ line, although somatic tissues outside the gonads are also infected. In Drosophila spp., Wolbachia is usually distributed systemically in multiple regions of the adult fly, but in some neotropical hosts, Wolbachia's only somatic niches are cerebral bacteriocyte-like structures and the ovarian follicle cells. In their recent article, Strunov and colleagues (A. Strunov, K. Schmidt, M. Kapun, and W. J. Miller. mBio 13:e03863-21, 2022, https://doi.org/10.1128/mbio.03863-21) compared the development of Drosophila spp. with systemic or restricted infections and demonstrated that the restricted pattern is determined in early embryogenesis by an apparently novel autophagic process, involving intimate interactions of Wolbachia with the endoplasmic reticulum. This work has implications not only for the evolution of neotropical Drosophila spp. but also for our understanding of how Wolbachia infections are controlled in other native or artificial hosts.


Asunto(s)
Nematodos , Wolbachia , Animales , Encéfalo , Drosophila/microbiología , Femenino , Simbiosis
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