Whether the mutations act in a predominantly neomorphic (production of toxic DSBs) or dominant-negative (reduction of sphingolipid synthesis) manner, or if the two mechanisms overlap to generate pathology remain unclear.
20 Indeed, pathologists currently generate pathology reports prospectively as part of the clinical process, and our use of electronic data feeds from our service provider is an example of how clinical data can be directly captured for clinical or research use without the need for manual data entry.
One working definition of biological aging is the set of endogenously generated pathologies that increase in later life [ 56].
However, as we have seen here, a growing number of obesity researchers are calling attention to the fact that environmental conditions have shifted so drastically with the widespread availability of calorie-dense foods that negative feedback mechanisms are failing, generating pathology.
Recent studies have demonstrated that M. tuberculosis actively interferes with the apoptosis of infected cells in vitro as a means of virulence, and that dysregulation of the host's lipid metabolism is a major pathway for generating pathology and promoting necrosis over apoptosis [ 9, 10].
Wild organisms are exposed to complex mixtures of chemicals (Hayes et al. 2006) and other environmental conditions (Edwards et al. 2006) that can obfuscate a causal link between abnormalities and a particular toxic agent or generate novel pathologies not identified in controlled laboratory studies.
The recent approval of mitochondrial replacement therapies is one promising approach to treating these diseases, but the mito-nuclear interactions resulting from such 'three-parent babies' raise the possibility of unintended interactions between mtDNA and nDNA SNPs that could generate novel pathologies (Reinhardt et al., 2013).
More interestingly, studies have demonstrated that NLRP3 inflammasome activation is critical for the induction of allergic airway inflammation in bronchial asthma, with increased understanding of how adaptive and innate immunity generate downstream pathology of allergic inflammation.
Traumatic events, such as wildfires, can generate psychiatric pathology among the exposed section of the population, i.e., those who are most vulnerable owing to their specific temperamental and neurobiological characteristics, which would act as vulnerability factors ("vulnerability/stress model").
In addition, decrease in placental weight in As exposed females could be due to an impairment in placental vasculogenesis [ 36], reduction of cytotrophoblastic plugging, and syncytium formation caused by oxidative stress which could generate placental pathology and/or preeclampsia [ 37– 37].
