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1.
Cureus ; 16(5): e60633, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38903375

RESUMO

Folliculitis decalvans (FD) is a rare type of inflammatory scalp disorder that leads to scarring alopecia. It is classified as primary neutrophilic cicatricial alopecia. FD presents a challenging scenario in clinical dermatology due to its rarity, resistance to treatment, and potential for scarring alopecia. This inflammatory scalp disorder primarily affects middle-aged adults, predominantly males. While its exact pathogenesis remains uncertain, a deficient host immune response to Staphylococcus aureus infection is hypothesized. Therapeutic interventions for FD pose difficulties, with limited treatment options available A 58-year-old female patient presented with a history of follicular papules that gradually progressed to form clusters of pustules, crusting, and hemorrhagic lesions with tufting of hairs on the crown area of the scalp, and was diagnosed with FD. Considering isotretinoin's role in inhibiting abnormal keratinization and inflammation, and rifampicin's ability to eradicate S. aureus, the combination of both provides a comprehensive approach to tackling the underlying factors contributing to FD. Despite previous unsuccessful treatments, combination therapy with isotretinoin and rifampicin yielded a remarkable outcome, prompting further exploration of this approach.

2.
Life Sci ; 351: 122778, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879157

RESUMO

Even though the genus Mycobacterium is a diverse group consisting of a majority of environmental bacteria known as non-tuberculous mycobacteria (NTM), it also contains some of the deadliest pathogens (Mycobacterium tuberculosis) in history associated with chronic disease called tuberculosis (TB). Formation of biofilm is one of the unique strategies employed by mycobacteria to enhance their ability to survive in hostile conditions. Biofilm formation by Mycobacterium species is an emerging area of research with significant implications for understanding its pathogenesis and treatment of related infections, specifically TB. This review provides an overview of the biofilm-forming abilities of different species of Mycobacterium and the genetic factors influencing biofilm formation with a detailed focus on M. tuberculosis. Biofilm-mediated resistance is a significant challenge as it can limit antibiotic penetration and promote the survival of dormant mycobacterial cells. Key genetic factors promoting biofilm formation have been explored such as the mmpL genes involved in lipid transport and cell wall integrity as well as the groEL gene essential for mature biofilm formation. Additionally, biofilm-mediated antibiotic resistance and pathogenesis highlighting the specific niches, sites of infection along with the possible mechanisms of biofilm dissemination have been discussed. Furthermore, drug targets within mycobacterial biofilm and their role as potential biomarkers in the development of rapid diagnostic tools have been highlighted. The review summarises the current understanding of the complex nature of Mycobacterium biofilm and its clinical implications, paving the way for advancements in the field of disease diagnosis, management and treatment against its multi-drug resistant species.


Assuntos
Biofilmes , Biofilmes/crescimento & desenvolvimento , Humanos , Mycobacterium/genética , Mycobacterium tuberculosis/genética , Farmacorresistência Bacteriana/genética , Tuberculose/microbiologia , Tuberculose/genética , Tuberculose/tratamento farmacológico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Animais
3.
J Bacteriol ; : e0011924, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837341

RESUMO

RsgA (small ribosomal subunit, 30S, GTPase), a late-stage biogenesis factor, releases RbfA from 30S-RbfA complex. Escherichia coli ΔrsgA (deleted for rsgA) shows a slow growth phenotype and an increased accumulation of 17S rRNA (precursor of 16S rRNA) and the ribosomal subunits. Here, we show that the rescue of the ΔrsgA strain by multicopy infB (IF2) is enhanced by simultaneous overexpression of initiator tRNA (i-tRNA), suggesting a role of initiation complex formation in growth rescue. The synergistic effect of IF2/i-tRNA is accompanied by increased processing of 17S rRNA (to 16S), and protection of the 16S rRNA 3'-minor domain. Importantly, we show that an IF2-binding anticonvulsant drug, lamotrigine (Ltg), also rescues the ΔrsgA strain growth. The rescue is accompanied by increased processing of 17S rRNA, protection of the 3'-minor domain of 16S rRNA, and increased 70S ribosomes in polysome profiles. However, Ltg becomes inhibitory to the ΔrsgA strain whose growth was already rescued by an L83R mutation in rbfA. Interestingly, like wild-type infB, overproduction of LtgRinfB alleles (having indel mutations in their domain II) also rescues the ΔrsgA strain (independent of Ltg). Our observations suggest the dual role of IF2 in rescuing the ΔrsgA strain. First, together with i-tRNA, IF2 facilitates the final steps of processing of 17S rRNA. Second, a conformer of IF2 functionally compensates for RsgA, albeit poorly, during 30S biogenesis. IMPORTANCE: RsgA is a late-stage ribosome biogenesis factor. Earlier, infB (IF2) was isolated as a multicopy suppressor of the Escherichia coli ΔrsgA strain. How IF2 rescued the strain growth remained unclear. This study reveals that (i) the multicopy infB-mediated growth rescue of E. coli ΔrsgA and the processing of 17S precursor to 16S rRNA in the strain are enhanced upon simultaneous overexpression of initiator tRNA and (ii) a conformer of IF2, whose occurrence increases when IF2 is overproduced or when E. coli ΔrsgA is treated with Ltg (an anticonvulsant drug that binds to domain II of IF2), compensates for the function of RsgA. Thus, this study reveals yet another role of IF2 in ribosome biogenesis.

4.
Environ Res ; 255: 119141, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754606

RESUMO

The increasing air pollution in the urban atmosphere is adversely impacts the environment, climate and human health. The alarming degradation of air quality, atmospheric conditions, economy and human life due to air pollution needs significant in-depth studies to ascertain causes, contributions and impacts for developing and implementing an effective policy to combat these issues. This work lies in its multifaceted approach towards comprehensive understanding and mitigating severe pollution episodes in Delhi and its surrounding areas. We investigated the aerosol dynamics in the post-monsoon season (PMS) from 2019 to 2022 under the influence of both crop residue burning and meteorological conditions. The study involves a broad spectrum of factors, including PM2.5 concentrations, active fire events, and meteorological parameters, shedding light on previously unexplored studies. The average AOD550 (0.79) and PM2.5 concentration (140.12 µg/m³) were the highest in 2019. PM2.5 was higher from mid-October to mid-November each year, exceeding the WHO guideline of 15 µg/m³ (24 h) by 27-34 times, signifying a public health emergency. A moderate to strong correlation between PM2.5 and AOD was found (r = 0.65) in 2021. The hotspot region accounts for almost 50% (2019), 47.51% (2020), 57.91% (2021) and 36.61% (2022) of the total fire events. A statistically significant negative non-linear correlation (r) was observed between wind speed (WS) and both AOD and PM2.5 concentration, influencing air quality over the region. HYSPLIT model and Windrose result show the movement of air masses predominated from the North and North-West direction during PMS. This study suggest to promotes strategies such as alternative waste management, encouraging modern agricultural practices in hot-spot regions, and enforcing strict emission norms for industries and vehicles to reducing air pollution and its detrimental effects on public health in the region and also highlights the need for future possibilities of research to attract the global attention.


Assuntos
Aerossóis , Poluentes Atmosféricos , Monitoramento Ambiental , Material Particulado , Índia , Aerossóis/análise , Material Particulado/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Estações do Ano , Poluição do Ar/análise , Incêndios , Produtos Agrícolas
5.
3 Biotech ; 14(6): 153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38742228

RESUMO

Genus Ophiorrhiza has recently emerged as one of the promising sources of Camptothecin (CPT), an antitumour monoterpene indole alkaloid. It possesses CPT in its every part and has a relatively short life span. To determine whether differentiation plays any role in the synthesis and/or accumulation of CPT, the concentration of CPT was analyzed across various tissues of Ophiorrhiza rugosa var. decumbens obtained through both direct as well as indirect modes of regeneration. The results revealed that the plants obtained from both types of regeneration showed similar levels of CPT. It was also observed that with differentiation, the accumulation of CPT increases, as the callus, being an undifferentiated mass of cells, had only traces of CPT. In contrast, the completely differentiated in-vitro plant obtained from it showed a significantly higher percentage of CPT in shoots (0.22% dry weight) and roots (0.247% dw). The CPT when analyzed after hardening, varied among different organs of the plant. It was also observed that the inflorescence accumulated the highest concentration of CPT (0.348% dw) once the flowering began, accompanied by a decrease in remaining organs. This decrease may result from CPT being mobilized to the inflorescence as a chemical defense mechanism. These findings allowed us to determine the ideal plant harvesting age for CPT extraction. The findings could be used to decide the right stage of plant harvest, which is just before the onset of blooming. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03999-4.

6.
Food Funct ; 15(11): 5987-5999, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38742436

RESUMO

The considerable value of whey is evident from its significant potential applications and contributions to the functional food and nutraceutical market. The by-products were individually obtained during functional chhurpi and novel soy chhurpi cheese production using defined lactic acid bacterial strains of Sikkim Himalaya's traditional chhurpi. Hydrolysis of substrate proteins by starter proteinases resulted in a comparable peptide content in whey and soy whey which was associated with antioxidant and ACE inhibition potential. Peptidome analysis of Lactobacillus delbrueckii WS4 whey and soy whey revealed the presence of several bioactive peptides including the multifunctional peptides PVVVPPFLQPE and YQEPVLGPVRGPFPIIV. In silico analyses predicted the antihypertensive potential of whey and soy whey peptides with strong binding affinity for ACE active sites. QSAR models predicted the highest ACE inhibition potential (IC50) for the ß-casein-derived decapeptide PVRGPFPIIV (0.95 µM) and the Kunitz trypsin inhibitor protein-derived nonapeptide KNKPLVVQF (16.64 µM). Chhurpi whey and soy whey can be explored as a valuable source of diverse and novel bioactive peptides for applications in designer functional foods development.


Assuntos
Lactobacillus delbrueckii , Peptídeos , Lactobacillus delbrueckii/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Queijo/microbiologia , Queijo/análise , Soro do Leite/química , Alimento Funcional , Antioxidantes/farmacologia , Antioxidantes/química , Proteínas do Soro do Leite/química
7.
Heliyon ; 10(10): e31116, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38799742

RESUMO

The emergence of multidrug-resistant mycobacterial strains is a significant crisis that has led to higher treatment failure rates and more toxic and expensive medications for tuberculosis (TB). The urgent need to develop novel therapeutics has galvanized research interest towards developing alternative antimicrobials such as silver nanoparticles (AgNPs). The current study focused on the anti-mycobacterial activity of green-synthesized AgNPs and its polyethylene glycol encapsulated derivative (PEG-AgNPs) with improved stability using the leaves extract of Clerodendrum serratum. Different characterization methods were used to analyze them. DLS analysis revealed a lower polydispersity index of PEG-AgNPs, suggesting a more uniform size distribution than that of AgNPs. The HR-TEM results revealed that the AgNPs and PEG-AgNPs have predominantly spherical shapes in the size range of 9-35 nm and 15-60 nm, respectively, while positive values of Zeta potential indicate their stability. FTIR-ATR analysis confirmed the presence of functional groups responsible for reducing and capping the bio-reduced AgNPs, whereas the XRD data established its crystalline nature. Impressively, the PEG-AgNPs exhibited maximum inhibitory activity against different Tubercular and Non-Tuberculous Mycobacterium species i.e., Mycobacterium smegmatis, Mycobacterium fortuitum and Mycobacterium marinum, relative to those of AgNPs and Linezolid. The flow cytometry assay showed that the anti-mycobacterial action was mediated by an increase in cell wall permeability. Notably, the results of AFM confirm their ability to inhibit mycobacterial biofilm significantly. We demonstrated the nontoxic nature of these AgNPs, explicated by the absence of hemolytic activity against human RBCs. Overall, the results suggest that PEG-AgNPs could offer a novel therapeutic approach with potential anti-mycobacterial activity and can overcome the limitations of existing TB therapies.

8.
BMJ Open ; 14(5): e085126, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816052

RESUMO

BACKGROUND: Hospital electronic patient records (EPRs) offer the opportunity to exploit large-scale routinely acquired data at relatively low cost and without selection. EPRs provide considerably richer data, and in real-time, than retrospective administrative data sets in which clinical complexity is often poorly captured. With population ageing, a wide range of hospital specialties now manage older people with multimorbidity, frailty and associated poor outcomes. We, therefore, set-up the Oxford and Reading Cognitive Comorbidity, Frailty and Ageing Research Database-Electronic Patient Records (ORCHARD-EPR) to facilitate clinically meaningful research in older hospital patients, including algorithm development, and to aid medical decision-making, implementation of guidelines, and inform policy. METHODS AND ANALYSIS: ORCHARD-EPR uses routinely acquired individual patient data on all patients aged ≥65 years with unplanned admission or Same Day Emergency Care unit attendance at four acute general hospitals serving a population of >800 000 (Oxfordshire, UK) with planned extension to the neighbouring Berkshire regional hospitals (>1 000 000). Data fields include diagnosis, comorbidities, nursing risk assessments, frailty, observations, illness acuity, laboratory tests and brain scan images. Importantly, ORCHARD-EPR contains the results from mandatory hospital-wide cognitive screening (≥70 years) comprising the 10-point Abbreviated-Mental-Test and dementia and delirium diagnosis (Confusion Assessment Method-CAM). Outcomes include length of stay, delayed transfers of care, discharge destination, readmissions and death. The rich multimodal data are further enhanced by linkage to secondary care electronic mental health records. Selection of appropriate subgroups or linkage to existing cohorts allows disease-specific studies. Over 200 000 patient episodes are included to date with data collection ongoing of which 129 248 are admissions with a length of stay ≥1 day in 64 641 unique patients. ETHICS AND DISSEMINATION: ORCHARD-EPR is approved by the South Central Oxford C Research Ethics Committee (ref: 23/SC/0258). Results will be widely disseminated through peer-reviewed publications and presentations at conferences, and regional meetings to improve hospital data quality and clinical services.


Assuntos
Comorbidade , Registros Eletrônicos de Saúde , Humanos , Idoso , Bases de Dados Factuais , Fragilidade/epidemiologia , Feminino , Idoso de 80 Anos ou mais , Masculino , Envelhecimento , Reino Unido/epidemiologia , Avaliação Geriátrica/métodos
9.
Cureus ; 16(3): e55763, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586795

RESUMO

Pityriasis versicolor (PV) also referred to as Peter Elam's disease or tinea versicolor is caused by the Malassezia species which is a chronic-relapsing widespread mycosis. The most common sites involved are the shoulders, upper arms, back, upper trunk, and chest. Atrophying PV is a very rare variant that has rarely been reported in the Indian literature. Hence, in this case report, a 29-year-old male presented with chief complaints of multiple asymptomatic, light-colored lesions over his chest, shoulder, and arms for three months. On examination, multiple well-defined hypopigmented macules of varying sizes with fine scales were observed on the patient's chest, shoulders, and arms. Dermoscopic examination revealed nonuniform perifollicular hypopigmentation with clearly demarcated borders, patchy scaling, and inconspicuous ridges and furrows. Moreover, a histopathological examination was performed that reported flattening of rete ridges along with fungal hyphae and spores which consequently confirmed the diagnosis. The medical intervention with antifungal agents was prescribed by the dermatologist, after which the lesion was completely resolved and the follow-up period reported no recurrence of the lesions demonstrating positive outcomes. In conclusion, diagnosing atrophic PV which is a rare variant of PV can be challenging. Hence, accurate diagnosis along with appropriate and adequate intervention can lead to the resolution of the condition and can prevent its recurrence.

10.
Cureus ; 16(3): e56152, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618325

RESUMO

Minimally invasive dermatosurgical procedures have revolutionized the field of dermatology, offering patients effective treatment options with reduced risks and downtime. This review provides a comprehensive overview of these procedures, beginning with their definition and historical context. We classify minimally invasive techniques, including both surgical and nonsurgical approaches, and explore their wide-ranging applications in cosmetic and therapeutic dermatology. Patient selection, preoperative assessment, techniques, clinical outcomes, and comparisons with traditional surgical methods are thoroughly examined. The implications for clinical practice are discussed, emphasizing the importance of integrating minimally invasive techniques into dermatologic care to enhance patient outcomes. Furthermore, areas for future research are identified, highlighting the need for ongoing studies to optimize techniques, evaluate long-term outcomes, and explore emerging technologies. Overall, this review underscores the significance of minimally invasive dermatosurgical procedures in advancing dermatologic practice and improving patient care.

11.
Appl Microbiol Biotechnol ; 108(1): 279, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564031

RESUMO

A novel L-rhamnose isomerase was identified and cloned from an extreme-temperature aquatic habitat metagenome. The deduced amino acid sequence homology suggested the possible source of this metagenomic sequence to be Chloroflexus islandicus. The gene expression was performed in a heterologous host, Escherichia coli, and the recombinant protein L-rhamnose isomerase (L-RIM) was extracted and purified. The catalytic function of L-RIM was characterized for D-allulose to D-allose bioconversion. D-Allose is a sweet, rare sugar molecule with anti-tumour, anti-hypertensive, cryoprotective, and antioxidative properties. The characterization experiments showed L-RIM to be a Co++- or Mn++-dependent metalloenzyme. L-RIM was remarkably active (~ 80%) in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges. Optimal L-RIM activity with D-allulose as the substrate occurred at pH 7.0 and 75 °C. The enzyme was found to be excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively. L-RIM catalysis conducted at slightly acidic pH of 6.0 and 70 °C achieved biosynthesis of about 30 g L-1 from 100 g L-1 D-allulose in 3 h. KEY POINTS: • The present study explored an extreme temperature metagenome to identify a novel gene that encodes a thermostable l-rhamnose isomerase (L-RIM) • L-RIM exhibits substantial (80% or more) activity in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges • L-RIM is excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively.


Assuntos
Aldose-Cetose Isomerases , Frutose , Glucose , Anti-Hipertensivos , Escherichia coli/genética
12.
Int J Biol Macromol ; 267(Pt 2): 131565, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38614184

RESUMO

Endopolygalacturonases are crucial pectinases known for their efficient and sustainable pectin depolymerization activities. The present study identified a novel gene encoding endopolygalacturonase from an acidic mine tailing metagenome. The putative gene showed a maximum identity of 67.55 % with an uncharacterized peptide sequence from Flavobacterium fluvii. The gene was cloned and expressed in a heterologous host, E. coli. Biochemical characterization of the novel endopolygalacturonase enzyme variant (EPHM) showed maximum activity at 60 °C and at 5.0 pH, while retaining 50 % activity under the temperature and pH range of 20 °C to 70 °C for 6 h, and 3.0 to 10.0 for 3 h, respectively. The enzyme exhibited tolerance to different metal ions. EPHM was characterized for the depolymerization of methylated pectin into pectic oligosaccharides. Further, its utility was established for fruit juice clarification, as endorsed by high transmittance, significant viscosity reduction, and release of reducing sugars in the treated fruit juice samples.


Assuntos
Sucos de Frutas e Vegetais , Pectinas , Poligalacturonase , Pectinas/metabolismo , Pectinas/química , Poligalacturonase/metabolismo , Poligalacturonase/química , Poligalacturonase/genética , Sucos de Frutas e Vegetais/análise , Concentração de Íons de Hidrogênio , Temperatura , Clonagem Molecular , Polimerização , Oligossacarídeos/química
13.
Mitochondrion ; 76: 101876, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599301

RESUMO

Ribosome biogenesis, involving processing/assembly of rRNAs and r-proteins is a vital process. In Saccharomyces cerevisiae mitochondria, ribosomal small subunit comprises 15S rRNA (15S). While the 15S 5'-end processing uses Ccm1p and Pet127p, the mechanisms of the 3'-end processing remain unclear. We reveal involvement of Rmd9p in safeguarding/processing 15S 3'-end. Rmd9p deficiency results in a cleavage at a position 183 nucleotides upstream of 15S 3'-end, and in the loss of the 3'-minor domain. Rmd9p binds to the sequences in the 3'-end region of 15S, and a genetic interaction between rmd9 and dss1 indicates that Rmd9p regulates/limits mtEXO activity during the 3'-end spacer processing.


Assuntos
RNA Ribossômico , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Mitocôndrias/metabolismo , Mitocôndrias/genética , Processamento de Terminações 3' de RNA , Processamento Pós-Transcricional do RNA , RNA Fúngico/metabolismo , RNA Fúngico/genética , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética
14.
Cureus ; 16(1): e52361, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38361716

RESUMO

Klippel-Trenaunay syndrome (KTS) is a rare genetic syndrome comprising an abnormal development of soft tissues and the lymphovascular system with bony overgrowth, venous malformation, and port wine stains. We present an interesting case of a three-year-old child brought to our hospital with a swollen limb and raised skin lesions associated with bleeding from minor trauma. Most of the clinical characteristics of KTS were seen in our patient, including arteriovenous, soft tissue, capillary, and lymphatic abnormalities. The diagnosis of KTS is based on clinical examinations and imaging investigations. He had gross hypertrophy of the left lower limb with measurable lengthening compared to the opposite limb. Ultrasonography of the left limb revealed soft tissue hypertrophy with abnormal venous communication. The management of KTS is mainly symptomatic and should be approached conservatively if the patient has functional limbs without edema, bleeding, ulceration, or pain.

15.
Environ Sci Pollut Res Int ; 31(12): 18871-18886, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38353821

RESUMO

The Betwa River Basin (BRB), a sub-basin of the River Yamuna, is the oldest flowing water system in Central India. The water quality of the rivers are under stress, hence regular monitoring and appraisal is required to know the health of the rivers. Factor analysis and principal component analysis (FA/PCA) multivariate statistical techniques were used to extract three and four varimax factors that explained 96.408 and 100.00 percent of the total variance in water quality, respectively. Cluster analysis (CA) categorizes observed items into distinct quality categories based on correlations between stations and years. Point industrial/sewage effluents, diffuse pollution as runoff from arable land, erosion, and natural source pollution contribute to the pollution of the BRB. As a result, water quality is threatened or impaired, and conditions often departed from natural or desirable levels at Rajghat, Garrauli, Mohana, and Shahijina stations. According to the Canadian Council of Ministers of the Environment Water Quality Index (CCME-WQI), the surface water quality at the Rajghat and Mohana stations corresponds to fair ecological status. However, the surface water quality of the Garrauli and Shahijina stations has a marginal water quality as per CCME-WQI. From 1985 to 2018, the Shahijina had the most considerable load of nutrients and organic matter, as determined by the CCME-WQI and by comparing the water quality data. A thorough examination had revealed a fluctuating trend in the BRB pollution, particularly at all stations. Results indicate that between 1985 and 2018, the only defense mechanism of the river was the auto purification mechanism, which is strongly influenced by the drought, point pollution source, and extreme meteorological events that probably cause these fluctuations.


Assuntos
Poluentes Químicos da Água , Qualidade da Água , Rios , Monitoramento Ambiental/métodos , Canadá , Análise por Conglomerados , Poluentes Químicos da Água/análise
16.
Sci Adv ; 10(6): eadi1367, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38324691

RESUMO

Several kinesin-5 motors (kinesin-5s) exhibit bidirectional motility. The mechanism of such motility remains unknown. Bidirectional kinesin-5s share a long N-terminal nonmotor domain (NTnmd), absent in exclusively plus-end-directed kinesins. Here, we combined in vivo, in vitro, and cryo-electron microscopy (cryo-EM) studies to examine the impact of NTnmd mutations on the motor functions of the bidirectional kinesin-5, Cin8. We found that NTnmd deletion mutants exhibited cell viability and spindle localization defects. Using cryo-EM, we examined the structure of a microtubule (MT)-bound motor domain of Cin8, containing part of its NTnmd. Modeling and molecular dynamic simulations based on the cryo-EM map suggested that the NTnmd of Cin8 interacts with the C-terminal tail of ß-tubulin. In vitro experiments on subtilisin-treated MTs confirmed this notion. Last, we showed that NTnmd mutants are defective in plus-end-directed motility in single-molecule and antiparallel MT sliding assays. These findings demonstrate that the NTnmd, common to bidirectional kinesin-5s, is critical for their bidirectional motility and intracellular functions.


Assuntos
Cinesinas , Proteínas de Saccharomyces cerevisiae , Cinesinas/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Microscopia Crioeletrônica , Microtúbulos/química
17.
J Lipid Res ; 65(3): 100519, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38354857

RESUMO

Metabolic syndrome affects more than one in three adults and is associated with increased risk of diabetes, cardiovascular disease, and all-cause mortality. Muscle insulin resistance is a major contributor to the development of the metabolic syndrome. Studies in mice have linked skeletal muscle sarcoplasmic reticulum (SR) phospholipid composition to sarcoplasmic/endoplasmic reticulum Ca2+-ATPase activity and insulin sensitivity. To determine if the presence of metabolic syndrome alters specific phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in human SR, we compared SR phospholipid composition in skeletal muscle from sedentary subjects with metabolic syndrome and sedentary control subjects without metabolic syndrome. Both total PC and total PE were significantly decreased in skeletal muscle SR of sedentary metabolic syndrome patients compared with sedentary controls, particularly in female participants, but there was no difference in the PC:PE ratio between groups. Total SR PC levels, but not total SR PE levels or PC:PE ratio, were significantly negatively correlated with BMI, waist circumference, total fat, visceral adipose tissue, triglycerides, fasting insulin, and homeostatic model assessment for insulin resistance. These findings are consistent with the existence of a relationship between skeletal muscle SR PC content and insulin resistance in humans.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Adulto , Humanos , Feminino , Animais , Camundongos , Retículo Sarcoplasmático/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/metabolismo , Músculo Esquelético/metabolismo , Fosfolipídeos/metabolismo , Fosfatidilcolinas/metabolismo
18.
J Biomol Struct Dyn ; 42(3): 1533-1543, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37079006

RESUMO

Human Lymphatic filariasis is caused by parasitic nematodes Wuchereria bancrofti, Brugia malayi, and Brugia timori. Protein disulfide isomerase (PDI), a redox-active enzyme, helps to form and isomerize the disulfide bonds, thereby acting as a chaperone. Such activity is essential for activating many essential enzymes and functional proteins. Brugia malayi protein disulfide isomerase (BmPDI) is crucial for parasite survival and an important drug target. Here, we used a combination of spectroscopic and computational analysis to study the structural and functional changes in the BmPDI during unfolding. Tryptophan fluorescence data revealed two well-separated transitions during the unfolding process, suggesting that the unfolding of the BmPDI is non-cooperative. The binding of the fluorescence probe 8-anilino-1-naphthalene sulfonic acid dye (ANS) validated the results obtained by the pH unfolding. The dynamics of molecular simulation performed at different pH conditions revealed the structural basis of BmPDI unfolding. Detailed analysis suggested that under different pH, both the global structure and the conformational dynamics of the active site residues were differentially altered. Our multiparametric study reveals the differential dynamics and collective motions of BmPDI unfolding, providing insights into its structure-function relationship.Communicated by Ramaswamy H. Sarma.


Assuntos
Brugia Malayi , Animais , Humanos , Isomerases de Dissulfetos de Proteínas , Desdobramento de Proteína , Domínio Catalítico , Relação Estrutura-Atividade
19.
J Pediatr Surg ; 59(4): 605-609, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38142192

RESUMO

INTRODUCTION: In hydronephrosis due to pelviureteric junction obstruction (PUJO), an obstruction to urine flow may lead to increased pelvic pressure, which may cause interstitial fibrosis and renal impairment. Recently, there have been reports on renal pelvic assessment using ultrasound elastography (USE). This study was conducted to see if USE can evaluate PUJO and if it can be correlated to the findings of the dynamic renal nuclear scan. MATERIAL AND METHODS: In this observational study, only patients with unilateral PUJO underwent acoustic radiation force impulse (ARFI) elastography. A rectangular region of interest (ROI) measuring 5 × 10 mm was positioned on the cortex region of the upper, mid, and lower poles of the affected kidney. Three valid measurements were obtained, from which a mean value was calculated. A dynamic renal nuclear scan using Technetium-99m ethylene dicysteine (EC or TC99 m EC) was obtained and split renal function (SRF) was used for comparison. RESULTS: In the group of 20 patients, the mean age was 3.37 years. The mean SRF of the affected kidney was 26.65 %, and the corresponding USE value was 0.45 kpa. The Spearman's rho correlation coefficient for SRF and USE was 1 and 0.672, respectively (p = 0.001). Elastography was not feasible if SRF was less than 20 %. CONCLUSION: USE may be able to comment on the renal functional status of hydronephrosis. If USE is reported as non-feasible, it may suggest that renal function is grossly compromised. It may serve as an alternative diagnostic modality for renal functional evaluation. LEVEL OF EVIDENCE: Level II, Prospective Cohort Study.


Assuntos
Técnicas de Imagem por Elasticidade , Hidronefrose , Hidronefrose/congênito , Rim Displásico Multicístico , Obstrução Ureteral , Humanos , Pré-Escolar , Estudos Prospectivos , Rim/diagnóstico por imagem , Obstrução Ureteral/diagnóstico por imagem , Obstrução Ureteral/complicações , Hidronefrose/diagnóstico por imagem , Hidronefrose/etiologia , Cintilografia
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