Risk of Seizure Aggravation after COVID-19 Vaccinations in Patients with Epilepsy.

Although Coronavirus disease 2019 (COVID-19) vaccinations are generally recommended for persons with epilepsy (PwE), a significant vaccination gap remains due to patient concerns over the risk of post-vaccination seizure aggravation (PVSA). In this single-centre, retrospective cohort study, we aimed to determine the early (7-day) and delayed (30-day) risk of PVSA, and to identify clinical predictors of PVSA among PwE. Adult epilepsy patients aged ≥18 years without a history of COVID-19 infection were recruited from a specialty epilepsy clinic in early 2022.

Diagnostic Challenges of Lyme Neuroborreliosis in Inpatient Neurology: A Case Series.

Lyme disease is a multisystem disorder transmitted through the Ixodes tick and is most commonly diagnosed in northeastern and mid-Atlantic states, Wisconsin, and Minnesota, though its disease borders are expanding in the setting of climate change. Approximately 10%-15% of untreated Lyme disease cases will develop neurologic manifestations of Lyme neuroborreliosis (LNB). Due to varying presentations, LNB presents diagnostic challenges and is associated with a delay to treatment.

Mesoscopic and macroscopic investigation of a dolomitic marble subjected to thermal damage.

Thermal loading is an important factor that could lead to the weakening and deterioration of rock materials. Understanding the thermal properties of rocks and their evolution under different high temperatures is important in the post-fire-hazard evaluation and cultural heritage conservation. Yet it is challenging to understand the evolution of thermally-induced changes in rock properties and to quantitatively study degrees of thermal damage when samples are limited.

Exploring relations between plant photochemical quantum parameters and unsaturated soil water retention for biochars and pith amended soils.

Sustainable biomaterials such as natural fibers and biochars have been increasingly used in green infrastructures such as landfill covers for its dual-advantages of climate change mitigation and waste management. The existing studies did not systematically discuss the comparison on how biochar (stable carbon) and fiber (likely degradable), influence plant growth and water retention abilities in unsaturated soils. Also, the effect of photochemistry in the amended soils has rarely been investigated.

Seepage characteristics of three-layered landfill cover system constituting fly-ash under extreme ponding condition.

A multi-layered final cover system is constructed over the landfill after it reaches its full capacity to minimize water ingress into the underlying hazardous waste. Three layered landfill cover are designed for areas experiencing very humid climatic conditions. Under the effects of climate change, the occurrences of extreme rainfall events become more frequent and this has resulted in catastrophic floods and hence extreme ponding.

SERious Surprises for ADP-Ribosylation Specificity: HPF1 Switches PARP1 Specificity to Ser Residues.

In this issue of Molecular Cell, Bonfiglio et al. (2017) demonstrate that histone PARylation factor 1 (HPF1) is required for PARP1 to attach ADP-ribose groups onto the hydroxyl oxygen of the Ser residues of target substrates, including both PARP1 itself and histones. Here, mechanisms and implications of this unexpected, O-linked ADP-ribosylation are speculated on.

Divergent Effects of miR-181 Family Members on Myocardial Function Through Protective Cytosolic and Detrimental Mitochondrial microRNA Targets.

Background: MicroRNA (miRNA) is a type of noncoding RNA that can repress the expression of target genes through posttranscriptional regulation. In addition to numerous physiologic roles for miRNAs, they play an important role in pathophysiologic processes affecting cardiovascular health. Previously, we reported that nuclear encoded microRNA (miR-181c) is present in heart mitochondria, and importantly, its overexpression affects mitochondrial function by regulating mitochondrial gene expression.

Mechanisms of hydrogen sulfide removal by ground granulated blast furnace slag amended soil.

Ground granulated blast furnace slag (GGBS) amended soil has been found able to remove gaseous hydrogen sulfide (HS). However, how HS is removed by GGBS amended soil and why GGBS amended soil can be regenerated to remove HS are not fully understood. In this study, laboratory column tests together with chemical analysis were conducted to investigate and reveal the mechanisms of HS removal process in GGBS amended soil.

ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence.

Chikungunya virus (CHIKV), an Old World alphavirus, is transmitted to humans by infected mosquitoes and causes acute rash and arthritis, occasionally complicated by neurologic disease and chronic arthritis. One determinant of alphavirus virulence is nonstructural protein 3 (nsP3) that contains a highly conserved MacroD-type macrodomain at the N terminus, but the roles of nsP3 and the macrodomain in virulence have not been defined. Macrodomain is a conserved protein fold found in several plus-strand RNA viruses that binds to the small molecule ADP-ribose.

CircRNAs: a regulator of cellular stress.

Circular RNAs (CircRNAs) were first identified as a viroid and later found to also be an endogenous RNA splicing product in eukaryotes. In recent years, a series of RNA-sequencing analyses from a diverse range of eukaryotes have shed new light on these eukaryotic circRNAs, revealing dynamic expression patterns in various developmental stages and physiological conditions. In this review, we focus on circRNAs implicated in stress response pathways and explore potential mechanisms underlying their regulation.

ADPriboDB: The database of ADP-ribosylated proteins.

ADP-ribosylation refers to the addition of one or more ADP-ribose units onto proteins post-translationally. This protein modification is often added by ADP-ribosyltransferases, commonly known as PARPs, but it can also be added by other enzymes, including sirtuins or bacterial toxins. While past literature has utilized a variety of methods to identify ADP-ribosylated proteins, recent proteomics studies bring the power of mass spectrometry to determine sites of the modification.

ENPP1 processes protein ADP-ribosylation in vitro.

ADP-ribosylation is a conserved post-translational protein modification that plays a role in all major cellular processes, particularly DNA repair, transcription, translation, stress response and cell death. Hence, dysregulation of ADP-ribosylation is linked to the physiopathology of several human diseases including cancers, diabetes and neurodegenerative disorders. Protein ADP-ribosylation can be reversed by the macrodomain-containing proteins PARG, TARG1, MacroD1 and MacroD2, which hydrolyse the ester bond known to link proteins to ADP-ribose as well as consecutive ADP-ribose subunits; targeting this bond can thus result in the complete removal of the protein modification or the conversion of poly(ADP-ribose) to mono(ADP-ribose).

Dynamic regulation of RNA editing in human brain development and disease.

RNA editing is increasingly recognized as a molecular mechanism regulating RNA activity and recoding proteins. Here we surveyed the global landscape of RNA editing in human brain tissues and identified three unique patterns of A-to-I RNA editing rates during cortical development: stable high, stable low and increasing. RNA secondary structure and the temporal expression of adenosine deaminase acting on RNA (ADAR) contribute to cis- and trans-regulatory mechanisms of these RNA editing patterns, respectively.

RNA Granules and Diseases: A Case Study of Stress Granules in ALS and FTLD.

RNA granules are microscopically visible cellular structures that aggregate by protein-protein and protein-RNA interactions. Using stress granules as an example, we discuss the principles of RNA granule formation, which rely on the multivalency of RNA and multi-domain proteins as well as low-affinity interactions between proteins with prion-like/low-complexity domains (e.g.

Nudix hydrolases degrade protein-conjugated ADP-ribose.

ADP-ribosylation refers to the transfer of the ADP-ribose group from NAD(+) to target proteins post-translationally, either attached singly as mono(ADP-ribose) (MAR) or in polymeric chains as poly(ADP-ribose) (PAR). Though ADP-ribosylation is therapeutically important, investigation of this protein modification has been limited by a lack of proteomic tools for site identification. Recent work has demonstrated the potential of a tag-based pipeline in which MAR/PAR is hydrolyzed down to phosphoribose, leaving a 212 Dalton tag at the modification site.

The Promise of Proteomics for the Study of ADP-Ribosylation.

ADP-ribosylation is a post-translational modification where single units (mono-ADP-ribosylation) or polymeric chains (poly-ADP-ribosylation) of ADP-ribose are conjugated to proteins by ADP-ribosyltransferases. This post-translational modification and the ADP-ribosyltransferases (also known as PARPs) responsible for its synthesis have been found to play a role in nearly all major cellular processes, including DNA repair, transcription, translation, cell signaling, and cell death. Furthermore, dysregulation of ADP-ribosylation has been linked to diseases including cancers, diabetes, neurodegenerative disorders, and heart failure, leading to the development of therapeutic PARP inhibitors, many of which are currently in clinical trials.

Methods for studying microRNA functions during stress.

Constituting 5 % of the human genome, microRNAs represent a sizeable class of gene regulators that is predicted to control the expression of at least 60 % of all protein-coding RNAs. Dysregulation of microRNA function results in developmental defects and pathological diseases such as cancers and neurological disorders. Intriguingly, many phenotypes of microRNA deficiencies are subdued in normal condition but manifested apparently upon stress.

Proteomics approaches to identify mono-(ADP-ribosyl)ated and poly(ADP-ribosyl)ated proteins.

ADP-ribosylation refers to the addition of one or more ADP-ribose units onto protein substrates and this protein modification has been implicated in various cellular processes including DNA damage repair, RNA metabolism, transcription, and cell cycle regulation. This review focuses on a compilation of large-scale proteomics studies that identify ADP-ribosylated proteins and their associated proteins by MS using a variety of enrichment strategies. Some methods, such as the use of a poly(ADP-ribose)-specific antibody and boronate affinity chromatography and NAD(+) analogues, have been employed for decades while others, such as the use of protein microarrays and recombinant proteins that bind ADP-ribose moieties (such as macrodomains), have only recently been developed.

Impact of an antimicrobial stewardship program on patients with acute bacterial skin and skin structure infections.

Purpose: The impact of an antimicrobial stewardship program (ASP) on the management of therapy and hospital resources for patients with acute bacterial skin and skin structure infections (ABSSSIs) at a community teaching hospital was evaluated.

Methods: A retrospective, observational chart review was performed to evaluate the impact of the ASP on patients admitted to Akron City Hospital with a diagnosis of ABSSSI between February 1 and August 20, 2012. Information on patient demographic characteristics, comorbidities, ABSSSI subtype, antibiotic therapy, microbiology, surgical interventions, and ASP recommendations was collected from medical records and the ASP intervention log.

Phosphoproteomic approach to characterize protein mono- and poly(ADP-ribosyl)ation sites from cells.

Poly(ADP-ribose), or PAR, is a cellular polymer implicated in DNA/RNA metabolism, cell death, and cellular stress response via its role as a post-translational modification, signaling molecule, and scaffolding element. PAR is synthesized by a family of proteins known as poly(ADP-ribose) polymerases, or PARPs, which attach PAR polymers to various amino acids of substrate proteins. The nature of these polymers (large, charged, heterogeneous, base-labile) has made these attachment sites difficult to study by mass spectrometry.

Poly(ADP-ribose): an organizer of cellular architecture.

Distinct properties of poly(ADP-ribose)-including its structural diversity, nucleation potential, and low complexity, polyvalent, highly charged nature-could contribute to organizing cellular architectures. Emergent data indicate that poly(ADP-ribose) aids in the formation of nonmembranous structures, such as DNA repair foci, spindle poles, and RNA granules. Informatics analyses reported here show that RNA granule proteins enriched for low complexity regions, which aid self-assembly, are preferentially modified by poly(ADP-ribose), indicating how poly(ADP-ribose) could direct cellular organization.

Does an emergency visit to the ER make microRNAs stronger during stress?

In this issue of Molecular Cell, Wu et al. (2013) report the identification of GW182-independent microRNA complexes that confer stronger repression upon serum starvation; interestingly, these complexes are associated with polyribosomes and the endoplasmic reticulum.

Quantifying Argonaute proteins in and out of GW/P-bodies: implications in microRNA activities.

MicroRNAs (miRNAs) are a class of ∼22nt non-coding RNAs that regulate the translational potential and stability of mRNAs. Though constituting only 1-4% of human genes, miRNAs are predicted to regulate more than 60% of all mRNAs. The action of miRNAs is mediated through their associations with Argonaute proteins and mRNA targets.

Methods for purification of proteins associated with cellular poly(ADP-ribose) and PARP-specific poly(ADP-ribose).

Poly(ADP-ribose) (pADPr) is a posttranslational modification that regulates protein function through two major mechanisms: covalent modification of acceptor proteins and noncovalent binding of proteins to pADPr. pADPr is synthesized by a family of enzymes called poly(ADP-ribose) polymerases (PARPs) that are themselves major targets of pADPr modification. Here, we outline two methods for the purification of pADPr-binding proteins via pADPr purification under native conditions: purification of cellular pADPr and pADPr covalently linked to specific PARPs.