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1.
Proteins ; 92(3): 356-369, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37881117

RESUMEN

The fusion of haemagglutinin-neuraminidase (HN) protein of peste des petits ruminant (PPR) virus with signaling lymphocyte activation molecules (SLAM) host cell receptor consequences the virus entry and multiplication inside the host cell. The use of synthetic SLAM homologous peptides (i.e., molecular decoy for HN protein of PPR virus) may check PPR infection at the preliminary stage. Hence, the predicted SLAM homologous peptides using bioinformatics tools were synthesized by solid phase chemistry with standard Merrifield's 9-fluorenylmethoxycarbonyl (Fmoc) chemistry and were purified by reverse phase high performance liquid chromatography. The secondary structures of synthesized peptides were elucidated by circular dichroism spectroscopy. The in vitro interactions of these peptides were studied through indirect Enzyme Linked Immuno Sorbent Assay (ELISA) and visual surface plasmon UV-visible spectroscopy. The SLAM homologous peptides were able to interact with the peste des petits ruminant virus (PPRV) with varying binding efficiency. The interaction of SLAM homologous peptide with the PPR virus was ascertained by the change in the plasmon color from red wine to purple during visual detection and also by bathochromic shift in absorbance spectra under UV-visible spectrophotometry. The cytotoxic and anti-PPRV effect of these peptides were also evaluated in B95a cell line using PPR virus (Sungri/96). The cytotoxic concentration 50 (CC50 ) value of each peptide was greater than 1000 µg mL-1 . The anti-PPRV efficiency of SLAM-22 was relatively high among SLAM homologous peptides, SLAM-22 at 25 µg mL-1 concentration showed a reduction of more than log10 3 virus titer by priming of B95a cell line while the use of SLAM-15 and Muco-17 at the same concentration dropped virus titer from log10 4.8 to log10 2.5 and log10 3.1 respectively. The concentration of SLAM homologous peptide (25 µg mL-1 ) to exert its anti-PPRV effect was much less than its CC50 level (>1000 µg mL-1 ). Therefore, the synthetic SLAM homologous peptides may prove to be better agents to target PPRV.


Asunto(s)
Peste de los Pequeños Rumiantes , Virus de la Peste de los Pequeños Rumiantes , Animales , Virus de la Peste de los Pequeños Rumiantes/metabolismo , Peste de los Pequeños Rumiantes/metabolismo , Línea Celular , Proteínas Virales/metabolismo , Péptidos/farmacología , Péptidos/metabolismo , Cabras
2.
Biomacromolecules ; 25(9): 5809-5818, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39113404

RESUMEN

Cellulose acetate (CA), a prominent water-soluble derivative of cellulose, is a promising biodegradable ingredient that has applications in films, membranes, fibers, drug delivery, and more. In this work, we present a molecularly informed field-theoretic model for CA to explore its phase behavior in aqueous solutions. By integrating atomistic details into large-scale field-theoretic simulations via the relative entropy coarse-graining framework, our approach enables efficient calculations of CA's miscibility window as a function of the degree of substitution (DS) of cellulose hydroxyl groups with acetate side chains. This allows us to capture the intricate phase behavior of CA, particularly its unique miscibility at intermediate substitution, without relying on experimental input. Additionally, the model directly probes CA solution behavior specific to the relative DS at C2, C3, and C6 alcohol sites, providing insights for the rational design of water-soluble CA for diverse applications. This work demonstrates a promising integration of molecularly informed field theories, complementing wet-lab experimentation, for engineering the next-generation polymeric materials with precisely tailored properties.


Asunto(s)
Celulosa , Agua , Celulosa/química , Celulosa/análogos & derivados , Agua/química , Solubilidad , Simulación de Dinámica Molecular
3.
Anal Biochem ; 671: 115157, 2023 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-37061113

RESUMEN

With the exception of plants, almost all living organisms synthesize neuraminidase/sialidase. It is a one among the crucial proteins that controls how virulent a microorganism is. An essential enzyme in orthomyxoviruses and paramyxoviruses that destroys receptors is neuraminidase. It plays a number of roles throughout the viral life cycle in addition to one that involves the release of progeny virus particles. This protein is an important target for therapeutic interventions and diagnostic assays. Neuraminidase inhibitors effectively prevent the spread of disease and viral infection. Sensitive, quick, and inexpensive high throughput assays are needed to screen for specific neuraminidase inhibitory chemicals. To characterize the neuraminidase catalytic activity, however, the traditional assays are still the most common in laboratories. This review gives a brief overview of these neuraminidase assays and recent, innovative developments, particularly those involving biosensors.


Asunto(s)
Neuraminidasa , Orthomyxoviridae , Animales , Humanos , Antivirales , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Guanidinas
4.
Eur Phys J E Soft Matter ; 46(9): 75, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37665423

RESUMEN

The self-assembly and phase separation of mixtures of polyelectrolytes and surfactants are important to a range of applications, from formulating personal care products to drug encapsulation. In contrast to systems of oppositely charged polyelectrolytes, in polyelectrolyte-surfactant systems the surfactants micellize into structures that are highly responsive to solution conditions. In this work, we examine how the morphology of micelles and degree of polyelectrolyte adsorption dynamically change upon varying the mixing ratio of charged and neutral surfactants. Specifically, we consider a solution of the cationic polyelectrolyte polydiallyldimethylammonium, anionic surfactant sodium dodecyl sulfate, neutral ethoxylated surfactants (C[Formula: see text]EO[Formula: see text]), sodium chloride salt, and water. To capture the chemical specificity of these species, we leverage recent developments in constructing molecularly informed field theories via coarse-graining from all-atom simulations. Our results show how changing the surfactant mixing ratios and the identity of the nonionic surfactant modulates micelle size and surface charge, and as a result dictates the degree of polyelectrolyte adsorption. These results are in semi-quantitative agreement with experimental observations on the same system.

5.
J Chem Phys ; 159(24)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38149742

RESUMEN

The critical micelle concentration (CMC) is a crucial parameter in understanding the self-assembly behavior of surfactants. In this study, we combine simulation and experiment to demonstrate the predictive capability of molecularly informed field theories in estimating the CMC of biologically based protein surfactants. Our simulation approach combines the relative entropy coarse-graining of small-scale atomistic simulations with large-scale field-theoretic simulations, allowing us to efficiently compute the free energy of micelle formation necessary for the CMC calculation while preserving chemistry-specific information about the underlying surfactant building blocks. We apply this methodology to a unique intrinsically disordered protein platform capable of a wide variety of tailored sequences that enable tunable micelle self-assembly. The computational predictions of the CMC closely match experimental measurements, demonstrating the potential of molecularly informed field theories as a valuable tool to investigate self-assembly in bio-based macromolecules systematically.


Asunto(s)
Proteínas Intrínsecamente Desordenadas , Micelas , Tensoactivos , Simulación por Computador
6.
J Environ Manage ; 345: 118901, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37688958

RESUMEN

Increasing irrigation demand has heavily relied on groundwater use, especially in places with highly variable water supplies that are vulnerable to drought. Groundwater management in agriculture is becoming increasingly challenging given the growing effects from overdraft and groundwater depletion worldwide. However, multiple challenges emerge when seeking to develop sustainable groundwater management in irrigated systems, such as trade-offs between the economic revenues from food production and groundwater resources, as well as the broad array of uncertainties in food-water systems. In this study we explore the applicability of Evolutionary Multi-Objective Direct Policy Search (EMODPS) to identify adaptive irrigation policies that water agencies and farmers can implement including operational decisions related to land use and groundwater use controls as well as groundwater pumping fees. The EMODPS framework yields state-aware, adaptive policies that respond dynamically as system state conditions change, for example with variable surface water (e.g., shifting management strategies across wet versus dry years). For this study, we focus on the Semitropic Water Storage district located in the San Joaquin Valley, California to provide broader insights relevant to ongoing efforts to improve groundwater sustainability in the state. Our findings demonstrate that adaptive irrigation policies can achieve sufficiently flexible groundwater management to acceptably balance revenue and sustainability goals across a wide range of uncertain future scenarios. Among the evaluated policy decisions, pumping restrictions and reductions in inflexible irrigation demands from tree crops are actions that can support dry-year pumping while maximizing groundwater storage recovery during wet years. Policies suggest that an adaptive pumping fee is the most flexible decision to control groundwater pumping and land use.


Asunto(s)
Conservación de los Recursos Naturales , Agua Subterránea , Abastecimiento de Agua , Agricultura , Incertidumbre
7.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35443534

RESUMEN

CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is considered a potential independent risk factor for cardiovascular disease. Increased carotid intima-media thickness (CIMT) is a sign of early atherosclerosis and is linked to an increased risk of myocardial infarction, stroke, and peripheral vascular disease. AIM: To study correlation between CIMT and NAFLD and its association with increase in grades of NAFLD. Material and Study Design: An observational case control study of 40 cases and 40 controls (age and sex matched) was done. The difference of CIMT between the two groups was analysed. CIMT was also measured among the various grades of NAFLD cases. MATERIALS AND METHODS: 40 cases with NAFLD and 40 controls falling within the age group of 18-45 years were taken in the study. Patients with history of significant alcohol consumption, acute or chronic liver disease, diabetes mellitus, hypertension, malignancy, hypothyroidism and having dyslipidaemia, CAD and stroke were excluded from the study. All the subjects underwent abdominal and carotid ultrasound in order to assess NAFLD and CIMT measurement. The left and right common carotid artery was examined using PHILIPS HD11XE high-definition ultrasound system equipped with a 3-12 MHz linear array transducer in B mode. OBSERVATION AND RESULTS: There was a statistically significant difference between the 2 groups in terms of CIMT with a p value of <0.001. The mean CIMT in the Case group was 0.86 mm while in Control group was 0.52 mm. There was a significant difference between the 3 Grades of NAFLD in terms of CIMT with a p value of <0.001 with maximum CIMT being in Grade 3 of NAFLD. Body Mass Index, Alanine Transaminase, Aspartate Transaminase, Alkaline Phosphatase, Total Cholesterol, Triglycerides, Low Density Lipoprotein were also found to have statistical significant difference between cases and controls. Age, gender, Blood pressure, Fasting Blood Sugar, HbA1c, Hemoglobin, Total leucocyte Count, Platelet count, Serum Bilirubin, Total protein and Albumin were found to be statistically insignificantly different between cases and controls. CONCLUSION: CIMT is increased in NAFLD patients. Increase in CIMT is significantly correlated with increasing grades of NAFLD. Hence CIMT can be used as screening tests in NALFD patients to assess cardiovascular risks.


Asunto(s)
Infarto del Miocardio , Enfermedad del Hígado Graso no Alcohólico , Accidente Cerebrovascular , Adolescente , Adulto , Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Humanos , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Factores de Riesgo , Accidente Cerebrovascular/complicaciones , Adulto Joven
8.
Bioorg Chem ; 108: 104633, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33513476

RESUMEN

8-Hydroxyquinoline (8-HQ) is a significant heterocyclic scaffold in organic and analytical chemistry because of the properties of chromophore and is used to detect various metal ions and anions. But from the last 2 decades, this moiety has been drawn great attention of medicinal chemists due to its significant biological activities. Synthetic modification of 8-hydroxyquinoline is under exploration on large scale to develop more potent target-based broad spectrum drug molecules for the treatment of several life-threatening diseases such as anti-cancer, HIV, neurodegenerative disorders, etc. Metal chelation properties of 8-hydroxyquinoline and its derivatives also make these potent drug candidates for the treatment of various diseases. This review comprises 8-hydroxyquinoline derivatives reported in the literature in last five years (2016-2020) and we anticipate that it will assist medicinal chemists in the synthesis of novel and pharmacologically potent agents for various therapeutic targets, mainly anti-proliferative, anti-microbial, anti-fungal and anti-viral as well as for the treatment of neurodegenerative disorders.


Asunto(s)
Antiinfecciosos/farmacología , Antineoplásicos/farmacología , Neoplasias/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Oxiquinolina/farmacología , Antiinfecciosos/química , Antineoplásicos/química , Bacterias/efectos de los fármacos , Química Farmacéutica , Hongos/efectos de los fármacos , Humanos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Fármacos Neuroprotectores/química , Oxiquinolina/química , Virus/efectos de los fármacos
9.
J Trop Pediatr ; 65(1): 29-38, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29506083

RESUMEN

The WHO Integrated Management of Childhood Illnesses-HIV (IMCI-HIV) algorithm and its regional adaptation have shown variable performance in clinically identifying HIV-infected children with lack of validation in low prevalence areas. Addition of certain 'parental factors' (proxy indicators of parental HIV) may improve its utility. In this study, children aged 2 months to 5 years were enrolled into Group A (n = 1000, 'suspected symptomatic HIV infected' children as per the IMNCI-HIV algorithm) and group B (n = 50, children newly diagnosed with HIV infection). Parental factors were asked and HIV infection was tested for in Group A. For Group B, retrospective data were collected regarding IMNCI-HIV algorithm signs and parental factors. Utility of individual and various combinations of IMNCI-HIV signs and parental factors to predict HIV status was evaluated. Results showed that incorporating parental factors to IMNCI-HIV algorithm improved its sensitivity and positive predictive value in identifying HIV-infected children while maintaining the same sensitivity.


Asunto(s)
Servicios de Salud del Niño/organización & administración , Prestación Integrada de Atención de Salud/métodos , Infecciones por VIH/diagnóstico , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Padres , Atención Primaria de Salud/métodos , Adulto , Algoritmos , Niño , Preescolar , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/terapia , Humanos , India/epidemiología , Lactante , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Masculino , Estudios Retrospectivos
10.
Langmuir ; 34(5): 2006-2013, 2018 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-29303275

RESUMEN

Colloidal particles at complex fluid interfaces and within films assemble to form ordered structures with high degrees of symmetry via interactions that include capillarity, elasticity, and other fields like electrostatic charge. Here we study microparticle interactions within free-standing smectic-A films, in which the elasticity arising from the director field distortion and capillary interactions arising from interface deformation compete to direct the assembly of motile particles. New colloidal assemblies and patterns, ranging from 1D chains to 2D aggregates, sensitive to the initial wetting conditions of particles at the smectic film, are reported. This work paves the way to exploiting LC interfaces as a means to direct spontaneously formed, reconfigurable, and optically active materials.

11.
Langmuir ; 32(10): 2360-8, 2016 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-26901492

RESUMEN

Despite its importance in many applications and processes, a complete and unified view on how nano- and microscale asperities influence hydrodynamic interactions has yet to be reached. In particular, the effects of surface structure can be expected to become more dominant when the length scale of the asperities or textures becomes comparable to that of the fluid flow. Here we analyze the hydrodynamic drainage of a viscous silicone oil squeezed between a smooth plane and a surface decorated with hexagonal arrays of lyophilic microsized cylindrical posts. For all micropost arrays studied, the periodicity of the structures was much larger than the separation range of our measurements. In this thin channel geometry, we find the hydrodynamic drainage and separation forces for the micropost arrays cannot be fully described by existing boundary condition models for interfacial slip or a no-slip shifted plane. Instead, our results show that the influence of the microposts on the hydrodynamic drag exhibits three distinct regimes as a function of separation. For large separations, a no slip boundary condition (Reynolds theory) is observed for all surfaces until a critical (intermediate) separation, below which the position of the no-slip plane scales with surface separation until reaching a maximum, just before contact. Below this separation, a sharp decrease in the no-slip plane position then suggests that a boundary condition of a smooth surface is recovered at contact.

12.
J Obstet Gynaecol Res ; 41(9): 1478-82, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26013913

RESUMEN

Unicornuate uterus with rudimentary horn occurs due to failure of complete development and partial fusion of one of the Müllerian ducts. Pregnancy in a non-communicating rudimentary horn is extremely rare, with a reported incidence of 1 in 76 000-150 000 pregnancies, and usually terminates in rupture during the first or second trimester. Clinical diagnosis of rudimentary horn pregnancy in a woman with history of normal vaginal delivery in prior gestations is difficult. The role of sonography, and more recently, magnetic resonance imaging, in the presurgical diagnosis of rudimentary horn pregnancy is established. We present a case of magnetic resonance imaging diagnosis of 20-week pregnancy in the unruptured non-communicating rudimentary horn in a patient with previous history of two full-term normal vaginal deliveries. The novelty of the case lies in the fact that there was associated torsion of the gravid rudimentary horn and ipsilateral ovary, which has not been reported previously.


Asunto(s)
Enfermedades del Ovario/diagnóstico por imagen , Anomalía Torsional/diagnóstico por imagen , Anomalías Urogenitales/diagnóstico por imagen , Útero/anomalías , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Embarazo , Segundo Trimestre del Embarazo , Útero/diagnóstico por imagen
13.
AIDS Care ; 26(7): 865-71, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24266437

RESUMEN

The objective of this study is to assess adherence to antiretroviral therapy (ART) in HIV-infected children using the pill count method, and determine factors leading to adherence failure. Records of 106 children living with HIV (CLHIV) age <15 years and on ART for >6 months were reviewed. Average adherence to ART by pill count method over preceding six months was calculated and re-assessed by 3-day recall method. The caregivers of 105 children and one child himself were interviewed about the problems encountered while giving ART. Median age of enrolled children was 104 (inter-quartile range [IQR] 77.3-133.8) months. Median duration of ART was 25 (IQR 16-35) months. The desired adherence level of >95% during six months of review assessed by pill count was achieved in 95.3% children. The 3-day recall method yielded >95% adherence in 99% children (p ≤ .001). Caregivers of 59 children (56.2%) reported multiple problems while administering drugs. In most instances, problems encountered were related to family/caregivers, the commonest being multiple caregivers, job constraints and death/illness in the family. In conclusion, we found a very high level of adherence to ART in CLHIV. Poor adherence was mainly associated with issues related to the family/caregivers.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Cuidadores , Niño , Femenino , Humanos , India , Masculino , Encuestas y Cuestionarios
14.
J Mater Chem B ; 12(36): 9037-9049, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39158475

RESUMEN

The present study provides insight into the differential response of a benzimidazole-malononitrile fluorescent "Turn-ON" probe on interaction with two structurally similar proteins, BSA and HSA. Compound 6 shows more sensitivity towards the two SAs, which is completely lost in the case of compound 7, synthesized by substitution on 6. The aggregates of compound 6 show absorption maxima at 385 nm and weak emission maxima at 565 nm. Compound 6 forms a new emission band at 475 nm on gradual addition of BSA (200 µM) along with a slight increase in the emission band at 565 nm. However, on addition of HSA (50 µM), a new band at 475 nm is formed. In contrast to BSA, in the case of HSA, 50% quenching is observed in the emission band of compound 6 at 565 nm. The new band formed on the interaction of 6 with BSA shows four-fold more enhancement compared to HSA. Furthermore, the mechanism of interaction of 6 with serum albumin has been investigated through lifetime-fluorescence analysis, site-selective drug experiments, dynamic light scattering, FE-SEM, FT-IR, etc. Molecular docking studies and site marker drug displacement experiments reveal differential interactions of 6 towards the two structurally similar proteins. Aggregates of 6 with an average hydrodynamic size of 100-190 nm are disassembled on adding BSA and HSA, and the size of the serum albumin and 6 complex decreases to 10-20 nm, revealing the ligand's encapsulation in the serum albumin cavity. Practical applicability for the quantitative detection of HSA in human urine samples is also demonstrated. The high binding affinity, sensitivity, selectivity and differential response of probe 6 towards two serum albumins (HSA and BSA) and significant quantification of HSA in urine samples shows the potential ability of this probe in medical applications.


Asunto(s)
Colorantes Fluorescentes , Simulación del Acoplamiento Molecular , Albúmina Sérica Bovina , Albúmina Sérica Humana , Humanos , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Bovinos , Albúmina Sérica Humana/química , Albúmina Sérica Humana/orina , Albúmina Sérica Humana/metabolismo , Animales , Espectrometría de Fluorescencia , Estructura Molecular , Bencimidazoles/química
15.
ChemMedChem ; 19(15): e202400114, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38676621

RESUMEN

In the present study, naphthalimide-pyrazole-benzothiazole based fluorescent analogs were synthesized by substituting different primary and secondary amines on the naphthalimide nucleus and were evaluated for their sensitivity and selectivity towards serum albumin. Among various synthesized analogues compound 25 showed the most significant change with serum albumin and was further studied for selective detection and mode of interaction with serum albumin. Here, we compared the binding interaction of fluorescent probe 25 for variation/detection of two 76 % structurally resembling proteins HSA and BSA, by spectroscopic experiments. The compound shows more selectivity for HSA and BSA with a higher binding constant and evident visible change in the emission spectra of two serum albumins among different bioanalytes. The mode of interaction of 25 with human serum albumin and bovine serum albumin was investigated by FT-IR, circular dichroism, and DLS techniques to find out the change in the microenvironment and variation in the structure of serum albumin proteins. Higher binding affinity and specific selectivity of 25 with a limit of detection of 0.69 µM and 1.4 µM towards HSA and BSA compared to other bioanalytes make it a significant fluorescent probe for quantitatively detecting serum albumins at the very early stage of many fatal diseases.


Asunto(s)
Colorantes Fluorescentes , Simulación del Acoplamiento Molecular , Naftalimidas , Albúmina Sérica Bovina , Albúmina Sérica Humana , Espectrometría de Fluorescencia , Naftalimidas/química , Naftalimidas/síntesis química , Humanos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Albúmina Sérica Bovina/química , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Sitios de Unión , Bovinos , Estructura Molecular , Animales , Unión Proteica , Dicroismo Circular , Benzotiazoles/química , Benzotiazoles/síntesis química , Albúmina Sérica/química , Albúmina Sérica/metabolismo
16.
Cancer Gene Ther ; 31(9): 1357-1379, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39039193

RESUMEN

Trk (NTRK) receptor and NTRK gene fusions are oncogenic drivers of a wide variety of tumors. Although Trk receptors are typically activated at the cell surface, signaling of constitutive active Trk and diverse intracellular NTRK fusion oncogenes is barely investigated. Here, we show that a high intracellular abundance is sufficient for neurotrophin-independent, constitutive activation of TrkB kinase domains. In HEK293 cells, constitutive active TrkB kinase and an intracellular NTRK2-fusion oncogene (SQSTM1-NTRK2) reduced actin filopodia dynamics, phosphorylated FAK, and altered the cell morphology. Atypical cellular responses could be mimicked with the intracellular kinase domain, which did not activate the Trk-associated MAPK/ERK pathway. In glioblastoma-like U87MG cells, expression of TrkB or SQSTM1-NTRK2 reduced cell motility and caused drastic changes in the transcriptome. Clinically approved Trk inhibitors or mutating Y705 in the kinase domain, blocked the cellular effects and transcriptome changes. Atypical signaling was also seen for TrkA and TrkC. Moreover, hallmarks of atypical pTrk kinase were found in biopsies of Nestin-positive glioblastoma. Therefore, we suggest Western blot-like immunoassay screening of NTRK-related (brain) tumor biopsies to identify patients with atypical panTrk or phosphoTrk signals. Such patients could be candidates for treatment with NTRK inhibitors such as Larotrectinhib or Entrectinhib.


Asunto(s)
Proteínas de Fusión Oncogénica , Receptor trkB , Humanos , Receptor trkB/metabolismo , Receptor trkB/genética , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Línea Celular Tumoral , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Células HEK293 , Transducción de Señal , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patología , Movimiento Celular/genética
17.
J Indian Assoc Pediatr Surg ; 18(3): 115-7, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24019643

RESUMEN

A renal tumor in a 14-month- old child, who was initially diagnosed as mesoblastic nephroma, but on review post surgery was diagnosed as hyper-differentiated metanephric stromal tumor, with its excellent prognostic outcome. An attempt is made to document imaging features that may enable one to suspect this rare condition. The literature is reviewed with emphasis on its distinction from its look-alikes in the pediatric age group.

18.
Sci Robot ; 8(79): eadg3792, 2023 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-37343076

RESUMEN

Most soft robots are pneumatically actuated and fabricated by molding and assembling processes that typically require many manual operations and limit complexity. Furthermore, complex control components (for example, electronic pumps and microcontrollers) must be added to achieve even simple functions. Desktop fused filament fabrication (FFF) three-dimensional printing provides an accessible alternative with less manual work and the capability of generating more complex structures. However, because of material and process limitations, FFF-printed soft robots often have a high effective stiffness and contain a large number of leaks, limiting their applications. We present an approach for the design and fabrication of soft, airtight pneumatic robotic devices using FFF to simultaneously print actuators with embedded fluidic control components. We demonstrated this approach by printing actuators an order of magnitude softer than those previously fabricated using FFF and capable of bending to form a complete circle. Similarly, we printed pneumatic valves that control a high-pressure airflow with low control pressure. Combining the actuators and valves, we demonstrated a monolithically printed electronics-free autonomous gripper. When connected to a constant supply of air pressure, the gripper autonomously detected and gripped an object and released the object when it detected a force due to the weight of the object acting perpendicular to the gripper. The entire fabrication process of the gripper required no posttreatment, postassembly, or repair of manufacturing defects, making this approach highly repeatable and accessible. Our proposed approach represents a step toward complex, customized robotic systems and components created at distributed fabricating facilities.

19.
Protein J ; 42(6): 685-697, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37421558

RESUMEN

The lack of specific antiviral therapy and complications associated with the existing peste des petits ruminants (PPR) vaccines accentuates the search of novel antiviral blocking agents in order to curtail the PPR infection at initial level. The synthetic hemagglutinin-neuraminidase (HN) homologous peptides may compete with the natural HN protein of PPR virus for binding to signaling lymphocytic activation molecule (SLAM) receptor, consequently, may disrupt peste des petits ruminants virus (PPRV) at entry level. Therefore, insilico analysis, synthesis, purification and subsequent characterization of HN homologous peptides were conducted in this study. The HN homologous peptides were synthesized by means of solid phase chemistry and were purified by reversed-phase-high performance liquid chromatography. The mass as well as sequence of HN homologous peptides were assessed by mass spectroscopy while its secondary structure was elucidated by circular dichroism spectroscopy. The binding (interaction) efficacy of HN homologous peptides with PPRV antibodies was assessed via indirect enzyme linked immunosorbent assay, visual detection test (red wine to purple), bathochromic shift under UV-Vis spectrophotometry and lateral flow immunochromatographic strip test. The antiviral properties and cytotoxicity of these peptides were also assessed in B95a cell line with changes in cytopathic effect and titer of PPRV (Sungri/96). The presence of green fluorescein isothiocyanate over the B95a cell surface pointed towards the binding of HN homologous peptides with surface SLAM receptor. Moreover, the intact beta sheet configuration in water and lower cytotoxicity [cytotoxic concentration 50 (CC50) > 1000 µg/ml] of these peptides signifies its in vivo use. Among HN homologous peptides, the binding efficacy and antiviral properties of pep A was relatively high in comparison to pep B and Pep ppr peptides. The prerequisite concentration of HN homologous peptides (pep A = 12.5 µg/ml; pep B = 25 µg/ml; pep ppr = 25 µg/ml) to exemplify its antiviral effect was much lower than its CC50 level. Hence, this study signifies the therapeutic potential of synthetic HN homologous peptides.

20.
ACS Macro Lett ; 12(6): 787-793, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37220638

RESUMEN

Pressure-sensitive adhesives (PSAs) based on poly(acrylate) chemistry are common in a wide variety of applications, but the absence of backbone degradability causes issues with recycling and sustainability. Here, we report a strategy to create degradable poly(acrylate) PSAs using simple, scalable, and functional 1,2-dithiolanes as drop-in replacements for traditional acrylate comonomers. Our key building block is α-lipoic acid, a natural, biocompatible, and commercially available antioxidant found in various consumer supplements. α-Lipoic acid and its derivative ethyl lipoate efficiently copolymerize with n-butyl acrylate under conventional free-radical conditions leading to high-molecular-weight copolymers (Mn > 100 kg mol-1) containing a tunable concentration of degradable disulfide bonds along the backbone. The thermal and viscoelastic properties of these materials are practically indistinguishable from nondegradable poly(acrylate) analogues, but a significant reduction in molecular weight is realized upon exposure to reducing agents such as tris (2-carboxyethyl) phosphine (e.g., Mn = 198 kg mol-1 → 2.6 kg mol-1). By virtue of the thiol chain ends produced after disulfide cleavage, degraded oligomers can be further cycled between high and low molecular weights through oxidative repolymerization and reductive degradation. Transforming otherwise persistent poly(acrylates) into recyclable materials using simple and versatile chemistry could play a pivotal role in improving the sustainability of contemporary adhesives.

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