scholarly journals AKR1A1 Variant Associated With Schizophrenia Causes Exon Skipping, Leading to Loss of Enzymatic Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Kyoka Iino ◽  
Kazuya Toriumi ◽  
Riko Agarie ◽  
Mitsuhiro Miyashita ◽  
Kazuhiro Suzuki ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Negative Symptoms ◽  
Frameshift Mutation ◽  
Exon Skipping ◽  
Drug Resistant ◽  
Treatment Resistant ◽  
Drug Excretion ◽  
Flat Affect ◽  
Whole Blood Cells ◽  
And Control

Schizophrenia is a heterogeneous psychiatric disorder characterized by positive symptoms such as hallucinations and delusions, negative symptoms such as anhedonia and flat affect, and cognitive impairment. Recently, glucuronate (GlucA) levels were reported to be significantly higher in serum of patients with schizophrenia than those in healthy controls. The accumulation of GlucA is known to be related to treatment-resistant schizophrenia, since GlucA is known to promote drug excretion by forming conjugates with drugs. However, the cause of GlucA accumulation remains unclear. Aldo-keto reductase family one member A1 (AKR1A1) is an oxidoreductase that catalyzes the reduction of GlucA. Genetic loss of AKR1A1 function is known to result in the accumulation of GlucA in rodents. Here, we aimed to explore genetic defects in AKR1A1 in patients with schizophrenia, which may result in the accumulation of GlucA. We identified 28 variants of AKR1A1 in patients with schizophrenia and control subjects. In particular, we identified a silent c.753G > A (rs745484618, p. Arg251Arg) variant located at the first position of exon 8 to be associated with schizophrenia. Using a minigene assay, we found that the c.753G > A variant induced exon 8 skipping in AKR1A1, resulting in a frameshift mutation, which in turn led to truncation of the AKR1A1 protein. Using the recombinant protein, we demonstrated that the truncated AKR1A1 completely lost its activity. Furthermore, we showed that AKR1A1 mRNA expression in the whole blood cells of individuals with the c.753G > A variant tended to be lower than that in those without the variants, leading to lower AKR activity. Our findings suggest that AKR1A1 carrying the c.753G > A variant induces exon skipping, leading to a loss of gene expression and enzymatic activity. Thus, GlucA patients with schizophrenia with the c.753G > A variant may show higher GlucA levels, leading to drug-resistant schizophrenia, since drug excretion by GlucA is enhanced.

scholarly journals A New Class of Cell Wall-Recycling l , d -Carboxypeptidase Determines β-Lactam Susceptibility and Morphogenesis in Acinetobacter baumannii

mBio ◽  
2021 ◽  
Author(s):  
Yunfei Dai ◽  
Victor Pinedo ◽  
Amy Y. Tang ◽  
Felipe Cava ◽  
Edward Geisinger
Keyword(s):  
Immune Response ◽  
Cell Wall ◽  
Enzymatic Activity ◽  
Acinetobacter Baumannii ◽  
Drug Resistant ◽  
Content Type ◽  
New Class ◽  
Recycling Pathway ◽  
And Control ◽  
Cell Wall Recycling

To grow efficiently, resist antibiotics, and control the immune response, bacteria recycle parts of their cell wall. A key step in the typical recycling pathway is the reuse of cell wall peptides by an enzyme known as an l , d -carboxypeptidase (LDC). Acinetobacter baumannii , an “urgent-threat” pathogen causing drug-resistant sepsis in hospitals, was previously thought to lack this enzymatic activity due to absence of a known LDC homolog.

scholarly journals Activity and Mechanism of Action of Antifungal Peptides from Microorganisms: A Review

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3438
Author(s):  
Tianxi Li ◽  
Lulu Li ◽  
Fangyuan Du ◽  
Lei Sun ◽  
Jichao Shi ◽  
...  
Keyword(s):  
Mechanisms Of Action ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Important Research ◽  
Factors Affecting ◽  
Natural Substances ◽  
Therapeutic Drugs ◽  
Antifungal Peptides ◽  
Control Work ◽  
And Control

Harmful fungi in nature not only cause diseases in plants, but also fungal infection and poisoning when people and animals eat food derived from crops contaminated with them. Unfortunately, such fungi are becoming increasingly more resistant to traditional synthetic antifungal drugs, which can make prevention and control work increasingly more difficult to achieve. This means they are potentially very harmful to human health and lifestyle. Antifungal peptides are natural substances produced by organisms to defend themselves against harmful fungi. As a result, they have become an important research object to help deal with harmful fungi and overcome their drug resistance. Moreover, they are expected to be developed into new therapeutic drugs against drug-resistant fungi in clinical application. This review focuses on antifungal peptides that have been isolated from bacteria, fungi, and other microorganisms to date. Their antifungal activity and factors affecting it are outlined in terms of their antibacterial spectra and effects. The toxic effects of the antifungal peptides and their common solutions are mentioned. The mechanisms of action of the antifungal peptides are described according to their action pathways. The work provides a useful reference for further clinical research and the development of safe antifungal drugs that have high efficiencies and broad application spectra.

scholarly journals Perfil Epidemiológico dos Isolamentos dos Microrganismos ‘Problema’

2019 ◽  
Vol 32 (9) ◽  
pp. 600
Author(s):  
Pedro Atilano Carvalho ◽  
Ana Monteiro ◽  
Bruno Almeida ◽  
Filomena Horta Correia ◽  
Vera Resende ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Beta Lactamase ◽  
Drug Resistant ◽  
Streptococcus Pneumonia ◽  
Extended Spectrum Beta Lactamase ◽  
The North ◽  
Male Patients ◽  
Epidemiological Profile ◽  
Healthcare Associated ◽  
And Control

Introduction: Infections are a major problem and the presence of drug-resistant microorganisms has significant clinical and economic impact. The present study aims to evaluate the epidemiological profile of “problem” microorganisms isolated in a hospital in the north of Portugal.Material and Methods: All isolated microorganisms were analyzed, between January 2014 and June 2015. Data obtained was then processed using statistical software.Results: We analyzed 8146 microbiological isolations and found a prevalence of 23% of ‘problem’ microorganisms (in descending order of frequency: Enterococcus, Pseudomonas, Staphylococcus aureus e Streptococcus pneumonia), 57.55% of which isolated in male patients. The most frequent mechanism of drug resistance for the overall sample was the production of extended-spectrum beta-lactamase, and resistance to oxacillin for ‘problem’ microorganisms.Discussion: In this sample, we observed a much higher prevalence of ‘problem’ microorganisms than that reported in other countries, which shows the need of improvement of surveillance mechanisms and treatment of these cases. Microorganisms that showed higher resistance were Staphylococcus aureus (resistant to oxacillin) and Enterococcus (resistant to vancomycin). Those were isolated in patients with a higher mean age compared to non-resistant microorganisms. Most of these microorganisms were isolated in hospitalized patients or intermediate and intensive care units, what relates them with healthcare associated infections.Conclusion: The prevalence of infection by ‘problem’ microorganisms during the studied period was 23%. The detection and control of the spread of these microorganisms are paramount due to its impact on health costs, morbidity and survival of patients.

scholarly journals Memory in health and in schizophrenia

2013 ◽  
Vol 15 (4) ◽  
pp. 399-410 ◽  
Keyword(s):  
Sex Differences ◽  
Social Cognition ◽  
Episodic Memory ◽  
Cognitive Neuroscience ◽  
Negative Symptoms ◽  
Behavioral Science ◽  
Present Evidence ◽  
Memory Processing ◽  
Flat Affect ◽  
History Of

Memory is an important capacity needed for survival in a changing environment, and its principles are shared across species. These principles have been studied since the inception of behavioral science, and more recently neuroscience has helped understand brain systems and mechanisms responsible for enabling aspects of memory. Here we outline the history of work on memory and its neural underpinning, and describe the major dimensions of memory processing that have been evaluated by cognitive neuroscience, focusing on episodic memory. We present evidence in healthy populations for sex differences-females outperforming in verbal and face memory, and age effects-slowed memory processes with age. We then describe deficits associated with schizophrenia. Impairment in schizophrenia is more severe in patients with negative symptoms-especially flat affect-who also show deficits in measures of social cognition. This evidence implicates medial temporal and frontal regions in schizophrenia.

scholarly journals What is the mechanism for persistent coexistence of drug-susceptible and drug-resistant strains of Streptococcus pneumoniae ?

2009 ◽  
Vol 7 (47) ◽  
pp. 905-919 ◽  
Author(s):  
Caroline Colijn ◽  
Ted Cohen ◽  
Christophe Fraser ◽  
William Hanage ◽  
Edward Goldstein ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Infectious Diseases ◽  
Multiple Infection ◽  
Drug Resistant ◽  
Host Interactions ◽  
Resistant Strains ◽  
Neutral Models ◽  
Drug Resistant Strains ◽  
And Control

The rise of antimicrobial resistance in many pathogens presents a major challenge to the treatment and control of infectious diseases. Furthermore, the observation that drug-resistant strains have risen to substantial prevalence but have not replaced drug-susceptible strains despite continuing (and even growing) selective pressure by antimicrobial use presents an important problem for those who study the dynamics of infectious diseases. While simple competition models predict the exclusion of one strain in favour of whichever is ‘fitter’, or has a higher reproduction number, we argue that in the case of Streptococcus pneumoniae there has been persistent coexistence of drug-sensitive and drug-resistant strains, with neither approaching 100 per cent prevalence. We have previously proposed that models seeking to understand the origins of coexistence should not incorporate implicit mechanisms that build in stable coexistence ‘for free’. Here, we construct a series of such ‘structurally neutral’ models that incorporate various features of bacterial spread and host heterogeneity that have been proposed as mechanisms that may promote coexistence. We ask to what extent coexistence is a typical outcome in each. We find that while coexistence is possible in each of the models we consider, it is relatively rare, with two exceptions: (i) allowing simultaneous dual transmission of sensitive and resistant strains lets coexistence become a typical outcome, as does (ii) modelling each strain as competing more strongly with itself than with the other strain, i.e. self-immunity greater than cross-immunity. We conclude that while treatment and contact heterogeneity can promote coexistence to some extent, the in-host interactions between strains, particularly the interplay between coinfection, multiple infection and immunity, play a crucial role in the long-term population dynamics of pathogens with drug resistance.

AMR: effective infection prevention and control measures

2019 ◽  
Vol 30 (8) ◽  
pp. 390-395
Author(s):  
Naomi Fleming
Keyword(s):  
Antimicrobial Resistance ◽  
Prevention And Control ◽  
Infection Prevention ◽  
Control Measures ◽  
Infection Prevention And Control ◽  
Drug Resistant ◽  
Practice Nurses ◽  
Prevention And Control Measures ◽  
Spread Of Infection ◽  
And Control

Antimicrobial resistance is on the rise. As more infections are becoming resistant to antibiotic treatment, it would benefit practice nurses to be aware of the effective measures they can use to prevent the spread of infection, explains Naomi Fleming When micro-organisms are exposed to an antimicrobial, more susceptible organisms succumb, leaving behind those resistant to the antimicrobial. They can then pass on resistance to their offspring. The use and misuse of antimicrobials has increased the number and types of resistant organisms. As a result, standard treatments become ineffective and infections persist and may spread. Infection prevention and control (IPC) is key to reducing demand for antimicrobial use and reducing the acquisition of antimicrobial resistance. Poor IPC can increase the spread of drug-resistant infections. Interventions such as effective hand hygiene and vaccination have significant potential to limit opportunities for drug-resistant strains to emerge. Effective leadership is vital and nurses are central to promoting IPC, leading on IPC compliance and ensuring uptake of vaccination in primary care.

scholarly journals Treatment Resistant Hypertension

2015 ◽  
Vol 25 (4) ◽  
pp. 495 ◽  
Author(s):  
Brent M. Egan
Keyword(s):  
Resistant Hypertension ◽  
Treatment Options ◽  
Diuretic Therapy ◽  
Clinical Information ◽  
Treatment Resistant ◽  
Antihypertensive Medications ◽  
Optimal Therapy ◽  
Medication Costs ◽  
And Control ◽  
Measurement Artifacts

<p>Treatment resistant hypertension (TRH) is defined by office blood pressure (BP) uncontrolled on ≥3 or controlled on ≥4 antihypertensive medications, preferably at optimal doses and including a diuretic. Apparent (a)TRH is used when optimal therapy, adherence, and measurement artifacts are unknown. Among treated hy­pertensives, ~30% of uncontrolled and 10% of controlled individuals have aTRH, with a higher prevalence in Blacks than other race-ethnicity groups. In ≥50% of aTRH patients, BP measurement artifacts (‘office’ TRH), suboptimal regimens, or suboptimal adher­ence are present, ie, pseudo-resistance. While patients with ‘office’ TRH have fewer cardiovascular events than those with ‘true’ TRH, no evidence confirms that patients with suboptimal regimens or adherence are spared. Averaging several office BPs obtained with an automated monitor can reduce ‘office’ TRH. Home or ambulatory BP monitoring can identify office resistance. Prescribing ≥3 different antihypertensive medication classes, eg, thiazide-type diuret­ic, renin-angiotensin blocker and calcium antagonist at ≥50% of maximum recom­mended doses reasonably defines optimal therapy. Intensifying diuretic therapy, eg, adding an aldosterone antagonist, is effec­tive for many TRH patients who are volume expanded. Clinical information, hemody­namic and renin-guided therapeutics can inform other treatment options. Attention to adverse effects, medication costs, and pill burden can improve adherence and control. Patients with aTRH and suspected second­ary hypertension should be evaluated. Inter­fering substances or medications should be discontinued. These approaches will identify or correct the problem in ~80% of aTRH patients. Referral to a hypertension special­ist and newer therapeutic approaches are options for TRH patients who cannot take or do not respond to optimal therapy. <em>Ethn Dis. </em>2015;25(4):495-498; doi:10.18865/ ed.25.4.495</p>

scholarly journals FUNGICIDA METALAXIL NA MICROBIOTA E NA ATIVIDADE ENZIMÁTICA DO SOLO

2004 ◽  
Vol 14 ◽  
Author(s):  
ALEX MORETINI ◽  
ANDREA MARIA SPESSOTO ◽  
ITAMAR SOARES DE MELO
Keyword(s):  
Acid Phosphatase ◽  
Enzymatic Activity ◽  
Soil Microorganisms ◽  
Bacterial Population ◽  
Sao Paulo ◽  
Clay Soils ◽  
São Paulo ◽  
Fungal Population ◽  
And Control

Foram estudados os efeitos do metalaxil sobre a microbiota de solos coletados nos municípios paulistas de Aguai, Estiva Gerbi e Jaguariúna (Brasil), suplementados com doses de 3 e 30 µg i.a. g-1 de metalaxil pelo período de 32 dias. Populações de bactérias, actinomicetos e fungos foram monitoradas mediante contagem em placas com meios de cultura seletivos e pela atividade enzimática da fosfatase ácida (Pase) e desidrogenase (Dhase). A Pase foi avaliada pelo método da p-nitrofenilfosfatase e a Dhase pela quantificação do vermelho formazan produzido. Houve predominância de populações bacterianas em todos os solos, sendo os maiores valores de UFC g-1 observados nos solos suplementados com a dose de 30 µg i.a. g-1 de metalaxil. Populações de fungos apresentaram acentuado decréscimo após a incorporação do composto. A atividade Dhase foi inibida pela presença de metalaxil nos solos arenoso e controle. No solo argiloso houve acréscimo dessa atividade, mais significativo no período de 7 a 21 dias, nas duas doses de suplementação avaliadas. A atividade da Pase foi inibida em todos os três solos. METALAXIL ON SOIL MICROBIOT AND ENZYMATIC ACTIVITY Abstract The effects of Metalaxyl on soil microorganisms collected in Sao Paulo districts of Aguai, Estiva, Gerbi and Jaguariuna (Brazil), supplemented with doses of 3 and 30 µg a.i g-1 for the period of 32 days were studied. Bacterial, actinomycets and fungi were monitored by plate counting and by acid phosphatase (Pase) and dehydrogenase enzymatic activity (Dhase). The Pase was evaluated by the method of p-nitrophenilphosphatase and the Dhase by the quantification of the produced red formazan. Predominance of bacterial population was observed in all soils, being the higher values of CFU g-1 observed in soils supplemented with the dose of 30 µg a.i g-1 of Metalaxyl. Fungal population presented accentuated decrease after compost incorporation. Dhase activity was inhibited by the presence of Metalaxyl in sandy and control soils. In clay soils the activity was incremented, being more significant in the period of 7 to 21 days, in both supplementation doses. Pase activity was inhibited in all three soils.

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