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Topic Review
JAMM Deubiquitinating Enzymes in Disease
Deubiquitinating enzymes (DUBs) are a group of proteases that are important for maintaining cell homeostasis by regulating the balance between ubiquitination and deubiquitination. As the only known metalloproteinase family of DUBs, JAB1/MPN/Mov34 metalloenzymes (JAMMs) are specifically associated with tumorigenesis and immunological and inflammatory diseases at multiple levels. The far smaller numbers and distinct catalytic mechanism of JAMMs render them attractive drug targets. Several JAMM inhibitors have been successfully developed and have shown promising therapeutic efficacy. 
  • 786
  • 22 Jul 2022
Topic Review
Genetics of Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclerosis (fALS) forms 10% of the cases. In 1993, the first causative gene (SOD1) of fALS was identified. With rapid advances in genetics, over fifty potentially causative or disease-modifying genes have been found in ALS so far. Accordingly, routine diagnostic tests should encompass the oldest and most frequently mutated ALS genes as well as several new important genetic variants in ALS.
  • 786
  • 07 Jan 2021
Topic Review
The Alter Retina
Alternative splicing of mRNA is an essential mechanism to regulate and increase the diversity of the transcriptome and proteome. Alternative splicing frequently occurs in a tissue- or time-specific manner, contributing to differential gene expression between cell types during development. Neural tissues present extremely complex splicing programs and display the highest number of alternative splicing events. As an extension of the central nervous system, the retina constitutes an excellent system to illustrate the high diversity of neural transcripts. The retina expresses retinal specific splicing factors and produces a large number of alternative transcripts, including exclusive tissue-specific exons, which require an exquisite regulation. In fact, a current challenge in the genetic diagnosis of inherited retinal diseases stems from the lack of information regarding alternative splicing of retinal genes, as a considerable percentage of mutations alter splicing or the relative production of alternative transcripts. Modulation of alternative splicing in the retina is also instrumental in the design of novel therapeutic approaches for retinal dystrophies, since it enables precision medicine for specific mutations.
  • 785
  • 22 Sep 2021
Topic Review
Coronary Heart Disease
Coronary heart disease is a public health problem and is one of the leading causes of loss of quality of life, disability, and death worldwide. A widely used therapeutic option for the treatment of coronary disease worldwide is coronary artery bypass grafting (CABG). A CABG seems to be very beneficial for patients, since in addition to the positive quality of life results, other studies indicate that it positively influences the occurrence of depression [30], can lead to the disappearance of symptoms for around 15 years, decreases death resulting from other causes, reduces hospital admission, and reduces death due to cardiovascular factors.
  • 785
  • 20 Nov 2020
Topic Review
Peptide Libraries with Antimicrobial Activity
Authors describe how by coupling emerging in silico and experimental tools it is possible to create novel peptide libraries with potential antimicrobial activity. This is in response to the growing public health concern pose by multiresistant microbial strains that take millions of lives annually on a global scale. The in silico tools include emerging artificial intelligence algorithms that allow searching for novel sequences in extremely large databases. Once identified, the required membrane activity can be estimated by looking at the interactions with model lipid bilayers via molecular dynamics (MD) simulations. Experimentally, the sequences can be expressed on the surface of yeasts by the surface display technology and subsequently screened in a high-throughput manner aided by microfluidic systems capable of separating out the most active peptides by precisely monitoring changes in optical properties in-line and real-time. 
  • 785
  • 24 May 2021
Topic Review
Fosfomycin as Partner Drug
Fosfomycin is being increasingly prescribed intravenously for multidrug‐resistant bacterial infections, usually administered as a partner drug. The knowledge of fosfomycin pharmacodynamicinteractions (synergistic, additive, indifferent and antagonistic effect) is fundamental for a properclinical management of severe bacterial infections. We performed a systematic review to point outfosfomycin’s synergistic properties.
  • 785
  • 02 Nov 2020
Topic Review
Complement and IgA Nephropathy
Primary IgA nephropathy (IgAN) is a leading cause of chronic kidney disease and kidney failure for which there is no disease-specific treatment. However, this could change, since novel therapeutic approaches are currently being assessed in clinical trials, including complement-targeting therapies. An improved understanding of the role of the lectin and the alternative pathway of complement in the pathophysiology of IgAN has led to the development of these treatment strategies. Recently, in a phase 2 trial, treatment with a blocking antibody against mannose-binding protein-associated serine protease 2 (MASP-2, a crucial enzyme of the lectin pathway) was suggested to have a potential benefit for IgAN. Now in a phase 3 study, this MASP-2 inhibitor for the treatment of IgAN could mark the start of a new era of complement therapeutics where common diseases can be treated with these drugs. The clinical development of complement inhibitors requires a better understanding by physicians of the biology of complement, the pathogenic role of complement in IgAN, and complement-targeted therapies.
  • 785
  • 01 Nov 2021
Topic Review
Alcohol Use Disorder and the Brain
Alcohol use disorder (AUD) can be defined as a chronically relapsing disorder characterized by the compulsion to ingest alcohol, the loss of control in limiting alcohol intake despite adverse health, social, and occupational consequences, and the emergence of a negative emotional state that can involve feelings of anxiety, irritability, and dysphoria when access to alcohol is prevented, reflecting a state of motivational withdrawal.
  • 785
  • 31 May 2022
Topic Review
Electromagnetic Microrobotic Platforms for Biomedical Applications
Magnetic microrobotics is a promising technology for improving minimally invasive surgery (MIS) with the ambition of enhancing patient care and comfort. The potential benefits include limited incisions, less hemorrhaging and postoperative pain, and faster recovery time. To achieve this, a key issue relies on the design of a proper electromagnetic actuation (EMA) setup which is based on the use of magnetic sources. The magnetic field and its gradient generated by the EMA platform is then used to induce magnetic torque and force for microrobot manipulations inside the human body. Like any control systems, the EMA system must be adapted to the given controlled microrobot and customized for the application. 
  • 785
  • 24 Jan 2022
Topic Review
Hepatitis B Virus Nucleocapsid
Hepatitis B virus (HBV) is a small enveloped DNA virus which replicates its tiny 3.2 kb genome by reverse transcription inside an icosahedral nucleocapsid, formed by a single ~180 amino acid capsid, or core, protein (Cp). HBV causes chronic hepatitis B (CHB), a severe liver disease responsible for nearly a million deaths each year. Dynamic changes in Cp chemical modification and capsid conformation are crucial in the viral life-cycle and represent a promising new antiviral target.
  • 784
  • 07 Mar 2022
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