Racial differences in scleroderma among women in Michigan

Objective. To examine racial differences in disease onset, extent, manifestations, and survival among women with scleroderma. Methods. A retrospective cohort study of women with scleroderma, diagnosed in Michigan between 1980 and 1991, was conducted. Clinical, laboratory, and demographic data were abstracted from the patients' medical records. Results. A total of 514 women with scleroderma were identified: 117 (23%) were black and 397 (77%) were white. Among black women, the mean age at diagnosis was lower (44.5 years versus 51.5 years; P 40 mm/hour ( P < 0.001) were more frequent among black women, while white women were more likely to have digital infarctions ( P < 0.001). Survival at 7 years from diagnosis was 72.5% among black women and 77.6% among white women. Age-adjusted survival was significantly reduced among black women ( P = 0.033), most likely because of increased diffuse involvement. Survival among those with renal or pulmonary involvement was also significantly reduced. Conclusion. Black women with scleroderma were significantly more likely than white women to develop diffuse disease, be diagnosed at a younger age, have a higher incidence of inflammatory features, and have a worse age-adjusted survival rate.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37812/1/1780400421_ftp.pd

George Hirschenberger Interview, January 31, 2014

George Hirschenberger discusses what drew him to the University of Montana from Chicago, Illinois (his birthplace), and graduating from the College of Forestry with a degree in Range Management. He talks about his time as a student and two instructors, Melvin Morris and Lee Eddleman, who both impacted his studies and future career at the Bureau of Land Management where he worked for 36 years. Hirschenberger shares stories about the rivalry between the Forestry School and the Law School and describes the pranks the two schools played on each other.https://scholarworks.umt.edu/collegeofforestry_oralhistory/1007/thumbnail.jp

Sexual Assault and the Mens Rea Problem: The Empathic Approach

133 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1999.The defense of consent and the alleged difficulty of determining if a victim has given consent prevent the crime of rape from being congruent with women's experience of it. If the perpetrator of a rape mistakenly believes that the victim has consented, the perpetrator fails to have the necessary criminal intent, or mens rea, and thus cannot be held culpable for the crime. I consider the appropriateness of holding these persons to a standard of negligence, ultimately concluding that this standard of liability fails to characterize the mental state of perpetrators of these crimes. I then argue that the real problem is not that perpetrators are incapable of distinguishing between consent and nonconsent, but rather their failure to distinguish between legitimate consent and a form of a pseudo-consent I call Implicit Sexual Consent. Once a victim gives what the perpetrator takes to be a sign of compliance with this form of consent, she finds herself party to an irrevocable sexual contract. I maintain that the most effective means of combating the belief in this type of consent is for the law to modify its current conception of consent. In particular, I hold that in addition to consent, we ought to ensure that sexual partner take care to not cause each other harm. In short, sexual partners must treat each other with empathy.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Sexual Assault and the Mens Rea Problem: The Empathic Approach

133 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1999.The defense of consent and the alleged difficulty of determining if a victim has given consent prevent the crime of rape from being congruent with women's experience of it. If the perpetrator of a rape mistakenly believes that the victim has consented, the perpetrator fails to have the necessary criminal intent, or mens rea, and thus cannot be held culpable for the crime. I consider the appropriateness of holding these persons to a standard of negligence, ultimately concluding that this standard of liability fails to characterize the mental state of perpetrators of these crimes. I then argue that the real problem is not that perpetrators are incapable of distinguishing between consent and nonconsent, but rather their failure to distinguish between legitimate consent and a form of a pseudo-consent I call Implicit Sexual Consent. Once a victim gives what the perpetrator takes to be a sign of compliance with this form of consent, she finds herself party to an irrevocable sexual contract. I maintain that the most effective means of combating the belief in this type of consent is for the law to modify its current conception of consent. In particular, I hold that in addition to consent, we ought to ensure that sexual partner take care to not cause each other harm. In short, sexual partners must treat each other with empathy.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Near-Native Visualization of SARS-CoV-2 Induced Membrane Remodeling and Virion Morphogenesis

Infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the COVID-19 pandemic, leads to profound remodeling of cellular membranes, promoting viral replication and virion assembly. A full understanding of this drastic remodeling and the process of virion morphogenesis remains lacking. In this study, we applied room temperature transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) tomography to visualize the SARS-CoV-2 replication factory in Vero cells, and present our results in comparison with published cryo-EM studies. We obtained cryo-EM-like clarity of the ultrastructure by employing high-pressure freezing, freeze substitution (HPF-FS) and embedding, allowing room temperature visualization of double-membrane vesicles (DMVs) in a near-native state. In addition, our data illustrate the consecutive stages of virion morphogenesis and reveal that SARS-CoV-2 ribonucleoprotein assembly and membrane curvature occur simultaneously. Finally, we show the tethering of virions to the plasma membrane in 3D, and that accumulations of virus particles lacking spike protein in large vesicles are most likely not a result of defective virion assembly at their membrane. In conclusion, this study puts forward a room-temperature EM technique providing near-native ultrastructural information about SARS-CoV-2 replication, adding to our understanding of the interaction of this pandemic virus with its host cell

Deletion of Six3 in post-proliferative neurons produces weakened SCN circadian output, improved metabolic function, and dwarfism in male mice.

ObjectiveThe increasing prevalence of obesity makes it important to increase the understanding of the maturation and function of the neuronal integrators and regulators of metabolic function.MethodsBehavioral, molecular, and physiological analyses of transgenic mice with Sine oculis 3 (Six3) deleted in mature neurons using the Synapsincreallele.ResultsConditional deletion of the homeodomain transcription factor Six3 in mature neurons causes dwarfism and weakens circadian wheel-running activity rhythms but increases general activity at night, and improves metabolic function, without impacting pubertal onset or fertility in males. The reduced growth in 6-week-old Six3fl/fl:Synapsincre (Six3syn) males correlates with increased somatostatin (SS) expression in the hypothalamus and reduced growth hormone (GH) in the pituitary. In contrast, 12-week-old Six3syn males have increased GH release, despite an increased number of the inhibitory SS neurons in the periventricular nucleus. GH is important in glucose metabolism, muscle function, and bone health. Interestingly, Six3syn males have improved glucose tolerance at 7, 12, and 18 weeks of age, which, in adulthood, is associated with increased % lean mass and increased metabolic rates. Further, 12-week-old Six3syn males have reduced bone mineralization and a lower bone mineral density, indicating that reduced GH levels during early life cause a long-term reduction in bone mineralization.ConclusionOur study points to the novel role of Six3 in post-proliferative neurons to regulate metabolic function through SS neuron control of GH release

Regulation of STING activity in DNA sensing by ISG15 modification

Summary: Sensing of human immunodeficiency virus type 1 (HIV-1) DNA is mediated by the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling axis. Signal transduction and regulation of this cascade is achieved by post-translational modifications. Here we show that cGAS-STING-dependent HIV-1 sensing requires interferon-stimulated gene 15 (ISG15). ISG15 deficiency inhibits STING-dependent sensing of HIV-1 and STING agonist-induced antiviral response. Upon external stimuli, STING undergoes ISGylation at residues K224, K236, K289, K347, K338, and K370. Inhibition of STING ISGylation at K289 suppresses STING-mediated type Ⅰ interferon induction by inhibiting its oligomerization. Of note, removal of STING ISGylation alleviates gain-of-function phenotype in STING-associated vasculopathy with onset in infancy (SAVI). Molecular modeling suggests that ISGylation of K289 is an important regulator of oligomerization. Taken together, our data demonstrate that ISGylation at K289 is crucial for STING activation and represents an important regulatory step in DNA sensing of viruses and autoimmune responses