Investigating Fluctuating Asymmetry of the Larval Damselfly, Calopteryx maculata (Odonata: Calopterigidae)

Fluctuating asymmetry (FA), or subtle random deviations from perfect bilateral symmetry, has recently become a useful tool in allowing researchers to understand more about an organism\u27s health, fitness, developmental stability and environmental stressors. Ultimately, FA studies can be used as an indirect measurement of the quality of an aquatic system over time. We measured and examined the femur segments of the larval damselfly, Calopteryx maculata from sites on the Town, Hockomock, and Salisbury Plain Rivers, of Plymouth County, Massachusetts to determine FA levels. After accounting for measurement error, preliminary results show that variations in symmetry are not correlated to individual trait size. Also, the Hockomock River site showed FA levels thee times higher than the Salisbury Plain river, and twice that of the Town River. Finally, severe femur deformation of some individuals at all sites suggests that other, more serious developmental or environmental factors may be inhibiting normal development. Results from a simple two-way ANOVA of differences in right and left femur segments and a KolmogorovSmirnov test for normality strongly suggest that the first femur of C. maculata is a useful trait for FA measurement

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death

A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the Black Death in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic evidence for a receptor-interacting protein (RIP) kinase-caspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-β (TLR4-TRIF). Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1β, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing. Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1β and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents. Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge. Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death. We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection

Mutations causing medullary cystic kidney disease type 1 (MCKD1) lie in a large VNTR in MUC1 missed by massively parallel sequencing

While genetic lesions responsible for some Mendelian disorders can be rapidly discovered through massively parallel sequencing (MPS) of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple Mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing, and de novo assembly, we found that each of six MCKD1 families harbors an equivalent, but apparently independently arising, mutation in sequence dramatically underrepresented in MPS data: the insertion of a single C in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (~1.5-5 kb), GC-rich (>80%), coding VNTR in the mucin 1 gene. The results provide a cautionary tale about the challenges in identifying genes responsible for Mendelian, let alone more complex, disorders through MPS

Mutations causing medullary cystic kidney disease type 1 (MCKD1) lie in a large VNTR in MUC1 missed by massively parallel sequencing

While genetic lesions responsible for some Mendelian disorders can be rapidly discovered through massively parallel sequencing (MPS) of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple Mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing, and de novo assembly, we found that each of six MCKD1 families harbors an equivalent, but apparently independently arising, mutation in sequence dramatically underrepresented in MPS data: the insertion of a single C in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (~1.5-5 kb), GC-rich (>80%), coding VNTR in the mucin 1 gene. The results provide a cautionary tale about the challenges in identifying genes responsible for Mendelian, let alone more complex, disorders through MPS

Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing

Although genetic lesions responsible for some mendelian disorders can be rapidly discovered through massively parallel sequencing of whole genomes or exomes, not all diseases readily yield to such efforts. We describe the illustrative case of the simple mendelian disorder medullary cystic kidney disease type 1 (MCKD1), mapped more than a decade ago to a 2-Mb region on chromosome 1. Ultimately, only by cloning, capillary sequencing and de novo assembly did we find that each of six families with MCKD1 harbors an equivalent but apparently independently arising mutation in sequence markedly under-represented in massively parallel sequencing data: the insertion of a single cytosine in one copy (but a different copy in each family) of the repeat unit comprising the extremely long (~1.5–5 kb), GC-rich (>80%) coding variable-number tandem repeat (VNTR) sequence in the MUC1 gene encoding mucin 1. These results provide a cautionary tale about the challenges in identifying the genes responsible for mendelian, let alone more complex, disorders through massively parallel sequencing.National Institutes of Health (U.S.) (Intramural Research Program)National Human Genome Research Institute (U.S.)Charles University (program UNCE 204011)Charles University (program PRVOUK-P24/LF1/3)Czech Republic. Ministry of Education, Youth, and Sports (grant NT13116-4/2012)Czech Republic. Ministry of Health (grant NT13116-4/2012)Czech Republic. Ministry of Health (grant LH12015)National Institutes of Health (U.S.) (Harvard Digestive Diseases Center, grant DK34854

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Forgiveness and Suicidal Behavior in Primary Care: Mediating Role of Future Orientation

Forgiveness, a cognitive-emotional and behavioral reduction of negative responses to offenses, is directly related to less suicide risk, but may be indirectly related via its relation with future orientation, the ability to envision a positive future. In 100 rural primary care patients, we examined the association between self-forgiveness, other-forgiveness, and forgiveness by God and suicidal behavior, with future orientation as a mediator. Forgiveness was related to greater future orientation and, in turn, to, less suicidal behavior. Addressing the past may promote adaptive views of the future and reduce suicide risk, results suggesting potential temporal and forgiveness-based points for suicide prevention

Perceived Stress and Suicidal Behaviors in College Students: Conditional Indirect Effects of Depressive Symptoms and Mental Health Stigma

Suicide is a significant public health concern and the second leading cause of death for college students. Perceived stress, depression, and mental health stigma are established risk factors for suicidal behavior; however, their interrelationships are unknown. Data were collected from 913 collegiate housing residents (70.8% female; N = 646). Using data from self-report measures, depressive symptoms were examined as a mediator of the relation between stress and suicidal behavior, along with the moderating effect of mental health stigma. Depressive symptoms partially mediated the stress–suicide linkage, and mental health stigma was a significant moderator of the associations between stress and depression, depression and suicidal behavior, and stress and suicidal behavior. Stigmatized attitudes toward mental health treatment, including fear of social repercussion, may exacerbate the deleterious impact of stress on psychopathology and suicide risk. Individual-level therapeutic strategies targeting stress and psychopathology, as well as public health approaches that directly address and attempt to reduce mental health stigma, may reduce suicide risk in college students

Perceived Stress and Suicidal Behaviors in College Students: Conditional Indirect Effects of Depressive Symptoms and Mental Health Stigma

Suicide is a significant public health concern and the second leading cause of death for college students. Perceived stress, depression, and mental health stigma are established risk factors for suicidal behavior; however, their interrelationships are unknown. Data were collected from 913 collegiate housing residents (70.8% female; N = 646). Using data from self-report measures, depressive symptoms were examined as a mediator of the relation between stress and suicidal behavior, along with the moderating effect of mental health stigma. Depressive symptoms partially mediated the stress–suicide linkage, and mental health stigma was a significant moderator of the associations between stress and depression, depression and suicidal behavior, and stress and suicidal behavior. Stigmatized attitudes toward mental health treatment, including fear of social repercussion, may exacerbate the deleterious impact of stress on psychopathology and suicide risk. Individual-level therapeutic strategies targeting stress and psychopathology, as well as public health approaches that directly address and attempt to reduce mental health stigma, may reduce suicide risk in college students