Mitochondrial Dysfunction and Barth Syndrome
Shamim I. Ahmad in Handbook of Mitochondrial Dysfunction, 2019
Investigations of different yeast lines, representing 21 distinct and conserved human TAZ pathogenic variants, have established seven functional classes of TAZ genetic variation. The first and the largest class, includes variants that result in the production of little to no functional TAZ. The remaining classes include; (2) Mitochondrial mislocalization and aggregate prone; (3) Impaired macromolecular assembly; (4) Catalytically null; (5) Hypomorphs with residual transacylase activity; (6) Degradation due to impaired folding and assembly; and (7) Temperature sensitive71,72. Distinct loss of function (LOF) classes with potential for residual TAZ function suggest a possible genotype-phenotype correlation; however, prior clinical phenotyping studies have not identified such a relationship71,72.
Manufacturing and Standardizing Allergen Extracts in Europe
Richard F. Lockey, Dennis K. Ledford in Allergens and Allergen Immunotherapy, 2014
The first international initiative on allergen standardization was based on the Danish Allergen Standardization 1976 program [4], which was published as part of the Nordic Guidelines in 1989 [5]. The Nordic Guidelines established the first regulatory requirements for allergen extracts. The guideline introduced the biological unit (BU), based on skin testing, for potency measures. Each manufacturer was instructed to produce an in-house reference preparation (IHRP), adjust the potency of BU, and use the IHRP for batch-to-batch control using scientifically based laboratory testing. The significance of using the major allergen content for the biological activity, recognized in the early 1990s, was established in the WHO Position Paper [6]. Current regulations and requirements for authorization are described in the Monograph on Allergen Products [7] of the European Pharmacopoeia and in the European Medicines Agency’s (EMA) Guideline on Allergen Products [8]; an overview of current regulatory documents can be found in Ref. 9. This chapter describes important issues in the control of source materials and in the preparation of extracts as part of the standardization process the way it is performed in Europe. The procedures differ from those used in the United States, as does the selection of extracts for vaccination in common allergy practice (see Chapter 20).
Manufacturing and standardizing allergen extracts in Europe
Richard F. Lockey, Dennis K. Ledford in Allergens and Allergen Immunotherapy, 2020
Skin testing in humans is the principle underlying the establishment of biological units of allergen extract potency. Several units are used. In Europe, the potency unit is based on the dose of allergen that results in a wheal comparable in size to the wheal produced by a given concentration of histamine. This unit was originally called histamine equivalent prick (HEP). The Nordic Guidelines introduced the biological unit (BU) [5]. One thousand BU is the equivalent of 1 HEP.
Proteomics and plant biology: contributions to date and a look towards the next decade
Published in Expert Review of Proteomics, 2021
A good definition should be the starting point of a scientific review, as I learnt from my Professors and Mentors, and recommend to my students. So, let us start this chapter by defining ‘Proteomics’. Proteomics can be defined as being the scientific discipline or methodology whose object of study or research is the proteome, understood as the total set of protein species or proteoforms (Through the manuscript, the term proteins, as synonymous of genes, and protein species or proteoforms, as the different products of a specific gene due to posttranscriptional and posttranslational events [alternative splicing, frame reading, PTMs], will be used.) present in a biological unit (subcellular fraction, cell, tissue, organ, individual, ecosystem, or derived in vitro total or purified extracts), at a time point of the developmental stages, and under specific environmental conditions. It can also refer to a structural or functional group of proteins (proteases, phosphoproteome, membrane proteins, etc.). In the broadest sense, proteomics techniques include not only those based on mass spectrometry, as the core platform, but also those of structural biochemistry (X-ray diffraction, cryoelectron microscopy, NMR), antibody-based, Edman sequencing, the two-hybrid yeast system, and even those of wide genomics approaches. However, MS-based platforms are those discussed in this review. Some scientists claim that other MS alternatives do exist and that they should be exploited, presenting, among other characteristics, higher sensitivity [3].
Analyzing clustered count data with a cluster-specific random effect zero-inflated Conway–Maxwell–Poisson distribution
Published in Journal of Applied Statistics, 2018
Hyoyoung Choo-Wosoba, Somnath Datta
Out of 39,656 genes, the gene ID, ‘GRMZM2G327208’ is selected to represent the case of v>1. This gene ID consists of 64 observations including 44 zeros, 9 ones, 8 twos, 1 threes, and 2 fours. A joint model is applied to analyze the data with a ZICMP framework including an random intercept accounting for correlations within each root. Since the total numbers of read counts over genes are different among biological units (in this case, individual replicate for each root), the model needs to be adjusted for normalizing the data by adding an offset term into the link function of the count part. The offset term is calculated by summing all read counts for each biological unit. Thus, our adjusted count part link function becomes
The phosphoinositide code is read by a plethora of protein domains
Published in Expert Review of Proteomics, 2021
Michael Overduin, Troy A. Kervin
Membranes are read by protein domains that selectively bind the lipids that uniquely mark each subcellular organelle and plasma membrane compartment. These conserved domains mediate reversible attachment of proteins to membranes in order to facilitate the assembly and disassembly of signaling and trafficking complexes in response to changes in lipid concentration and locality. The best characterized are the FYVE, PH, and PX domain superfamilies, which exemplify the PI code that controls eukaryotic membrane recognition [1–3]. This overview of the literature reveals a growing array of soluble, folded domains, which are known to recognize various PI lipids and thus localize and mediate signaling, macromolecular assembly, and trafficking functions on most eukaryotic membrane-bound compartments (Table 1).