The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.

Evaluation of the central nervous system (CNS) in the developing mouse presents unique challenges, given the complexity of ontogenesis, marked structural reorganization over very short distances in 3 dimensions each hour, and numerous developmental events susceptible to genetic and environmental influences. Developmental defects affecting the brain and spinal cord arise frequently both in utero and perinatally as spontaneous events, following teratogen exposure, and as sequelae to induced mutations and thus are a common factor in embryonic and perinatal lethality in many mouse models. Knowledge of normal organ and cellular architecture and differentiation throughout the mouse’s life span is crucial to identify and characterize neurodevelopmental lesions. By providing a well-illustrated overview summarizing major events of normal in utero and perinatal mouse CNS development with examples of common developmental abnormalities, this annotated, color atlas can be used to identify normal structure and histology when phenotyping genetically engineered mice and will enhance efforts to describe and interpret brain and spinal cord malformations as causes of mouse embryonic and perinatal lethal phenotypes. The schematics and images in this atlas illustrate major developmental events during gestation from embryonic day (E)7.5 to E18.5 and after birth from postnatal day (P)1 to P21.

Predatory journals—also called fraudulent, deceptive, or pseudo-journals—are publications that claim to be legitimate scholarly journals but misrepresent their publishing practices. Some common forms of predatory publishing practices include falsely claiming to provide peer review, hiding information about article processing charges, misrepresenting members of the journal’s editorial board, and other violations of copyright or scholarly ethics. Because of their increasing prevalence, this article aims to provide helpful information for authors on how to identify and avoid predatory journals.

In humans, congenital heart diseases are common. Since the rapid progression of transgenic technologies, the mouse has become the major animal model of defective cardiovascular development. Moreover, genetically modified mice frequently die in utero, commonly due to abnormal cardiovascular development. A variety of publications address specific developmental stages or structures of the mouse heart, but a single reference reviewing and describing the anatomy and histology of cardiac developmental events, stage by stage, has not been available. The aim of this color atlas, which demonstrates embryonic/fetal heart development, is to provide a tool for pathologists and biomedical scientists to use for detailed histological evaluation of hematoxylin and eosin (H&E)-stained sections of the developing mouse heart with emphasis on embryonic days (E) 11.5–18.5. The selected images illustrate the main structures and developmental events at each stage and serve as reference material for the confirmation of the chronological age of the embryo/early fetus and assist in the identification of any abnormalities. An extensive review of the literature covering cardiac development pre-E11.5 is summarized in the introduction. Although the focus of this atlas is on the descriptive anatomic and histological development of the normal mouse heart from E11.5 to E18.5, potential embryonic cardiac lesions are discussed with a list of the most common transgenic pre- and perinatal heart defects. Representative images of hearts at E11.5–15.5 and E18.5 are provided in Figures 2–4, 6, 8, and 9. A complete set of labeled images (Figures E11.5–18.5) is available on the CD enclosed in this issue of Toxicologic Pathology. All digital images can be viewed online at https://niehsimages.epl-inc.com with the username “ToxPath” and the password “embryohearts.”

Historically, there has been confusion relating to the diagnostic nomenclature for individual cell death. Toxicologic pathologists have generally used the terms “single cell necrosis” and “apoptosis” interchangeably. Increased research on the mechanisms of cell death in recent years has led to the understanding that apoptosis and necrosis involve different cellular pathways and that these differences can have important implications when considering overall mechanisms of toxicity, and, for these reasons, the separate terms of apoptosis and necrosis should be used whenever differentiation is possible. However, it is also recognized that differentiation of the precise pathway of cell death may not be important, necessary, or possible in routine toxicity studies and so a more general term to indicate cell death is warranted in these situations. Morphological distinction between these two forms of cell death can sometimes be straightforward but can also be challenging. This article provides a brief discussion of the cellular mechanisms and morphological features of apoptosis and necrosis as well as guidance on when the pathologist should use these terms. It provides recommended nomenclature along with diagnostic criteria (in hematoxylin and eosin [H&E]-stained sections) for the most common forms of cell death (apoptosis and necrosis). This document is intended to serve as current guidance for the nomenclature of cell death for the International Harmonization of Nomenclature and Diagnostic Criteria Organ Working Groups and the toxicologic pathology community at large. The specific recommendations are: Use necrosis and apoptosis as separate diagnostic terms. Use modifiers to denote the distribution of necrosis (e.g., necrosis, single cell; necrosis, focal; necrosis, diffuse; etc.). Use the combined term apoptosis/single cell necrosis when There is no requirement or need to split the processes, or When the nature of cell death cannot be determined with certainty, or When both processes are present together. The diagnosis should be based primarily on the morphological features in H&E-stained sections. When needed, additional, special techniques to identify and characterize apoptosis can also be used.