Challenges and opportunities to understanding genetics of fungal diseases: towards a functional genomics approach

Infectious diseases are a leading cause of morbidity and mortality worldwide and human pathogens have long been recognized as one of the main sources of evolutionary pressure, resulting in a high variable genetic background in immune-related genes. The study of the genetic contribution to infectious diseases has undergone tremendous advances over the last decades. Here, focusing on genetic predisposition to fungal diseases, we provide an overview of the available approaches for studying human genetic susceptibility to infections, reviewing current methodological and practical limitations. We describe how the classical methods available, such as family-based studies and candidate-gene studies, have contributed to the discovery of crucial susceptibility factors for fungal infections. We will also discuss the contribution of novel unbiased approaches to the field, highlighting their success but also their limitations for the fungal immunology field. Finally, we show how a systems genomics approach can overcome those limitations and can lead to efficient prioritization and identification of genes and pathways with a critical role in susceptibility to fungal diseases. This knowledge will help stratify patients at risk groups and, subsequently, develop early appropriate prophylactic and treatment strategies.

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Nanoarchitectures in Management of Fungal Diseases: An Overview

Applied Sciences ◽

10.3390/app11157119 ◽

2021 ◽

Vol 11 (15) ◽

pp. 7119

Author(s):

Vijay Mishra ◽

Manvendra Singh ◽

Yachana Mishra ◽

Nitin Charbe ◽

Pallavi Nayak ◽

...

Keyword(s):

Polymer Nanocomposites ◽

Metallic Nanoparticles ◽

Antifungal Agents ◽

Carbon Nanomaterials ◽

Fungal Infections ◽

Polymeric Nanoparticles ◽

Treatment Strategies ◽

Chemical Compounds ◽

Antifungal Drugs ◽

Fungal Diseases

Fungal infections, from mild itching to fatal infections, lead to chronic diseases and death. Antifungal agents have incorporated chemical compounds and natural products/phytoconstituents in the management of fungal diseases. In contrast to antibacterial research, novel antifungal drugs have progressed more swiftly because of their mild existence and negligible resistance of infections to antifungal bioactivities. Nanotechnology-based carriers have gained much attention due to their magnificent abilities. Nanoarchitectures have served as excellent carriers/drug delivery systems (DDS) for delivering antifungal drugs with improved antifungal activities, bioavailability, targeted action, and reduced cytotoxicity. This review outlines the different fungal diseases and their treatment strategies involving various nanocarrier-based techniques such as liposomes, transfersomes, ethosomes, transethosomes, niosomes, spanlastics, dendrimers, polymeric nanoparticles, polymer nanocomposites, metallic nanoparticles, carbon nanomaterials, and nanoemulsions, among other nanotechnological approaches.

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Systemic processes in influenza in fection, as a triggers of the development of somatic pathology in patients at risk

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid40886 ◽

2015 ◽

Vol 20 (4) ◽

pp. 47-53

Author(s):

E. G Deeva ◽

T. G Zubkova ◽

N. V Dunaeva ◽

S. Zh Koltsebaeva ◽

G. Yu Chelaeva ◽

...

Keyword(s):

At Risk ◽

Neurological Diseases ◽

Influenza Infection ◽

Critical Role ◽

Risk Groups ◽

Patients At Risk ◽

Triggering Factor ◽

Complicated Course ◽

Severe Infections ◽

The One

Pathogenetic mechanisms of influenza infection on the one hand are the triggering factor of certain diseases (asthma, neurological diseases and others.), on the other hand they worsen the course of concomitant somatic pathology, leading to severe, complicated course of infection and lethal outcomes in high-risk groups. The two components of the flu - a syndrome of systemic inflammation, which is manifested in the overproduction of cytokines and generalized vascular thrombosis syndrome (VTS) are the most important components of the pathogenesis of influenza and play a critical role in the development of severe infections, especially in patients with a history ofpremorbid background. Analysis of the pathogenic mechanisms of diseases, at risk, is necessary for the development of a comprehensive targeted tactics prevention, treatment and medical examination that will prevent mortality in these groups.

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Fungal infections in haemato-oncology

10.1093/med/9780198755388.003.0032 ◽

2017 ◽

Author(s):

Philipp Koehler ◽

Oliver A. Cornely

Keyword(s):

Fungal Infection ◽

Invasive Fungal Infection ◽

Fungal Infections ◽

Bone Marrow Failure ◽

Treatment Strategies ◽

Underlying Disease ◽

Haematopoietic Stem Cell ◽

Graft Versus Host ◽

Patients At Risk ◽

Work Up

Invasive fungal infections on haemato-oncology wards present a major challenge. Patients at risk for invasive fungal infection usually have a compromised immune system due to bone marrow failure caused by underlying disease, prolonged neutropenia after intensive chemotherapy, or immunosuppression after haematopoietic stem cell transplantation to avoid graft-versus-host disease. Three major entities—invasive candidiasis, invasive aspergillosis, and mucormycosis—account for the majority of fungal infections. Here, we describe specific host and therapeutic factors predisposing to invasive fungal infection in the haemato-oncology setting. Clinical presentation is highly variable and dependent on the underlying pathogen, organ involvement, and site of infection. Diagnosis is mainly based on radiographic imaging combined with microbiological and histopathological work-up. Various prophylaxis and treatment strategies have been developed, and the evidence for these is discussed.

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Role of Internal Medicines in the Management of Infections w.s.r. to Viral and Fungal Diseases: A Review

Himalayan Journal of Health Sciences ◽

10.22270/hjhs.v6i3.102 ◽

2021 ◽

pp. 10-13

Author(s):

Neeraj Kanungo ◽

Vijayata Kanungo ◽

Ajit Kumar Ojha

Keyword(s):

Infectious Diseases ◽

General Health ◽

Viral Infections ◽

Fungal Infections ◽

Modern Science ◽

Health Problems ◽

Fungal Diseases ◽

Pathological Conditions ◽

Microbial Toxins

Ayurveda works towards the prevention and management of various health problems, Ayurveda also suggests many natural ways to promote general health. Ayurveda in this regards provides several modalities for controlling infectious diseases which described as Sankramak Roga in Ayurveda. As per Ayurveda these Sankramak Roga mainly arises due to the vitiated state of Doshas and this vitiation arises by microbial toxins in case of infectious diseases. Therefore Doshas pacifying medicines recommended controlling infections. Ayurveda drugs like Kapura, Neema, Guduchi, Tulsi and Vacha, etc. helps to treat such pathological conditions. The present scenario of pandemic disaster requires an approach where Ayurveda and modern science can join hand together to combat against this situation. The consequences of viral infections also increases susceptibility towards other infections i.e.; fungal diseases. Considering these all facts this article explored Ayurveda as well as modern approaches for the management of various types of Sankramak Roga w.s.r. to viral and fungal infections.

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The Role of Glyoxalase in Glycation and Carbonyl Stress Induced Metabolic Disorders

Current Protein and Peptide Science ◽

10.2174/1389203721666200505101734 ◽

2020 ◽

Vol 21 (9) ◽

pp. 846-859

Author(s):

Mohd Saeed ◽

Mohd Adnan Kausar ◽

Rajeev Singh ◽

Arif J. Siddiqui ◽

Asma Akhter

Keyword(s):

Protein Misfolding ◽

Covalent Binding ◽

Critical Role ◽

Enzymatic Reaction ◽

Treatment Strategies ◽

Bioactive Molecules ◽

Carbonyl Stress ◽

Defense System ◽

Pathological Conditions ◽

Age Related

Glycation refers to the covalent binding of sugar molecules to macromolecules, such as DNA, proteins, and lipids in a non-enzymatic reaction, resulting in the formation of irreversibly bound products known as advanced glycation end products (AGEs). AGEs are synthesized in high amounts both in pathological conditions, such as diabetes and under physiological conditions resulting in aging. The body’s anti-glycation defense mechanisms play a critical role in removing glycated products. However, if this defense system fails, AGEs start accumulating, which results in pathological conditions. Studies have been shown that increased accumulation of AGEs acts as key mediators in multiple diseases, such as diabetes, obesity, arthritis, cancer, atherosclerosis, decreased skin elasticity, male erectile dysfunction, pulmonary fibrosis, aging, and Alzheimer’s disease. Furthermore, glycation of nucleotides, proteins, and phospholipids by α-oxoaldehyde metabolites, such as glyoxal (GO) and methylglyoxal (MGO), causes potential damage to the genome, proteome, and lipidome. Glyoxalase-1 (GLO-1) acts as a part of the anti-glycation defense system by carrying out detoxification of GO and MGO. It has been demonstrated that GLO-1 protects dicarbonyl modifications of the proteome and lipidome, thereby impeding the cell signaling and affecting age-related diseases. Its relationship with detoxification and anti-glycation defense is well established. Glycation of proteins by MGO and GO results in protein misfolding, thereby affecting their structure and function. These findings provide evidence for the rationale that the functional modulation of the GLO pathway could be used as a potential therapeutic target. In the present review, we summarized the newly emerged literature on the GLO pathway, including enzymes regulating the process. In addition, we described small bioactive molecules with the potential to modulate the GLO pathway, thereby providing a basis for the development of new treatment strategies against age-related complications.

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Sarcopenia and Malnutrition Screening in Female Osteoporosis Patients—A Cross-Sectional Study

Journal of Clinical Medicine ◽

10.3390/jcm10112344 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2344

Author(s):

Franca Genest ◽

Dominik Rak ◽

Elisa Bätz ◽

Kerstin Ott ◽

Lothar Seefried

Keyword(s):

At Risk ◽

Risk Groups ◽

Cross Sectional Study ◽

Mineral Density ◽

Cross Sectional ◽

Functional Deficits ◽

Complementary Approach ◽

Study Results ◽

Patients At Risk ◽

Not At Risk

Sarcopenia and malnutrition are important determinants of increased fracture risk in osteoporosis. SARC-F and MNA-SF are well-established questionnaires for identifying patients at risk for these conditions. We sought to evaluate the feasibility and potential added benefit of such assessments as well as the actual prevalence of these conditions in osteoporosis patients. We conducted a cross-sectional, single-center study in female osteoporosis patients ≥ 65 years (SaNSiBaR-study). Results of the sarcopenia (SARC-F) and malnutrition (MNA-SF) screening questionnaires were matched with a functional assessment for sarcopenia and data from patients’ medical records. Out of 107 patients included in the analysis, a risk for sarcopenia (SARC-F ≥ 4 points) and a risk for malnutrition (MNA-SF ≤ 11 points) was found in 33 (30.8%) and 38 (35.5%) patients, respectively. Diagnostic overlap with coincident indicative findings in both questionnaires was observed in 17 patients (16%). As compared to the respective not-at-risk groups, the mean short physical performance battery (SPPB) score was significantly reduced in both patients at risk for sarcopenia (7.0 vs. 10.9 points, p < 0.001) and patients at risk for malnutrition (8.7 vs. 10.5 points, p = 0.005). Still, confirmed sarcopenia according to EWGSOP2 criteria was present in only 6 (6%) of all 107 patients, with only 3 of them having an indicative SARC-F score. Bone mineral density was not significantly different in any of the at-risk groups at any site. In summary, applying SARC-F and MNA-SF in osteoporosis patients appears to be a complementary approach to identify individuals with functional deficits.

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Towards Scalable Economic Photovoltaic Potential Analysis Using Aerial Images and Deep Learning

Energies ◽

10.3390/en14133800 ◽

2021 ◽

Vol 14 (13) ◽

pp. 3800

Author(s):

Sebastian Krapf ◽

Nils Kemmerzell ◽

Syed Khawaja Haseeb Khawaja Haseeb Uddin ◽

Manuel Hack Hack Vázquez ◽

Fabian Netzler ◽

...

Keyword(s):

Deep Learning ◽

System Analysis ◽

State Of The Art ◽

Critical Role ◽

Semantic Segmentation ◽

Energy System ◽

Aerial Images ◽

Potential Analysis ◽

3D Data ◽

Challenges And Opportunities

Roof-mounted photovoltaic systems play a critical role in the global transition to renewable energy generation. An analysis of roof photovoltaic potential is an important tool for supporting decision-making and for accelerating new installations. State of the art uses 3D data to conduct potential analyses with high spatial resolution, limiting the study area to places with available 3D data. Recent advances in deep learning allow the required roof information from aerial images to be extracted. Furthermore, most publications consider the technical photovoltaic potential, and only a few publications determine the photovoltaic economic potential. Therefore, this paper extends state of the art by proposing and applying a methodology for scalable economic photovoltaic potential analysis using aerial images and deep learning. Two convolutional neural networks are trained for semantic segmentation of roof segments and superstructures and achieve an Intersection over Union values of 0.84 and 0.64, respectively. We calculated the internal rate of return of each roof segment for 71 buildings in a small study area. A comparison of this paper’s methodology with a 3D-based analysis discusses its benefits and disadvantages. The proposed methodology uses only publicly available data and is potentially scalable to the global level. However, this poses a variety of research challenges and opportunities, which are summarized with a focus on the application of deep learning, economic photovoltaic potential analysis, and energy system analysis.

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Craniofacial Diseases Caused by Defects in Intracellular Trafficking

Genes ◽

10.3390/genes12050726 ◽

2021 ◽

Vol 12 (5) ◽

pp. 726

Author(s):

Chung-Ling Lu ◽

Jinoh Kim

Keyword(s):

Endoplasmic Reticulum ◽

Membrane Proteins ◽

Intracellular Trafficking ◽

Critical Role ◽

Treatment Strategies ◽

Soluble Proteins ◽

Genes Encoding ◽

Membrane Bound ◽

Signaling Receptors ◽

Craniofacial Morphogenesis

Cells use membrane-bound carriers to transport cargo molecules like membrane proteins and soluble proteins, to their destinations. Many signaling receptors and ligands are synthesized in the endoplasmic reticulum and are transported to their destinations through intracellular trafficking pathways. Some of the signaling molecules play a critical role in craniofacial morphogenesis. Not surprisingly, variants in the genes encoding intracellular trafficking machinery can cause craniofacial diseases. Despite the fundamental importance of the trafficking pathways in craniofacial morphogenesis, relatively less emphasis is placed on this topic, thus far. Here, we describe craniofacial diseases caused by lesions in the intracellular trafficking machinery and possible treatment strategies for such diseases.

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A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma

BioData Mining ◽

10.1186/s13040-021-00261-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qian Yan ◽

Wenjiang Zheng ◽

Boqing Wang ◽

Baoqian Ye ◽

Huiyan Luo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

High Risk ◽

Risk Score ◽

Immune Cells ◽

Prognostic Model ◽

Risk Groups ◽

Low Risk ◽

Prognostic Performance ◽

Immune Related Genes

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

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Primary immune deficiencies with defects in neutrophil function

Hematology ◽

10.1182/asheducation-2016.1.43 ◽

2016 ◽

Vol 2016 (1) ◽

pp. 43-50 ◽

Cited By ~ 25

Author(s):

Mary C. Dinauer

Keyword(s):

Fungal Infections ◽

Leukocyte Adhesion ◽

Genetic Disorders ◽

Clinical Manifestations ◽

Treatment Strategies ◽

Adaptor Protein ◽

Invasive Fungal Disease ◽

Neutrophil Function ◽

Microbial Pathogens ◽

Immune Deficiencies

Abstract Immune deficiencies resulting from inherited defects in neutrophil function have revealed important features of the innate immune response. Although sharing an increased susceptibility to bacterial and fungal infections, these disorders each have distinctive features in their clinical manifestations and characteristic microbial pathogens. This review provides an update on several genetic disorders with impaired neutrophil function, their pathogenesis, and treatment strategies. These include chronic granulomatous disease, which results from inactivating mutations in the superoxide-generating nicotinamide dinucleotide phosphate oxidase. Superoxide-derived oxidants play an important role in the control of certain bacterial and fungal species, and also contribute to the regulation of inflammation. Also briefly summarized are updates on leukocyte adhesion deficiency, including the severe periodontal disease characteristic of this disorder, and a new immune deficiency associated with defects in caspase recruitment domain–containing protein 9, an adaptor protein that regulates signaling in neutrophils and other myeloid cells, leading to invasive fungal disease.

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