Roles of mechanistic target of rapamycin and transforming growth factor-B signaling in the molting gland (Y-organ) of the blackback land crab, Gecarcinus lateralis

Molting in decapod crustaceans is controlled by molt-inhibiting hormone (MIH), an eyestalk neuropeptide that suppresses production of ecdysteroids by a pair of molting glands (Y-organs or YOs). Eyestalk ablation (ESA) activates the YOs, which hypertrophy and increase ecdysteroid secretion. At mid premolt, which occurs 7–14 days post-ESA, the YO transitions to the committed state; hemolymph ecdysteroid titers increase further and the animal reaches ecdysis ~ 3 weeks post-ESA. Two conserved signaling pathways, mechanistic target of rapamycin (mTOR) and transforming growth factor-β (TGF-β), are expressed in the Gecarcinus lateralis YO. Rapamycin, an mTOR antagonist, inhibits YO ecdysteroidogenesis in vitro. In this study, rapamycin lowered hemolymph ecdysteroid titer in ESA G. lateralis in vivo; levels were significantly lower than in control animals at all intervals (1–14 days post-ESA). Injection of SB431542, an activin TGF-β receptor antagonist, lowered hemolymph ecdysteroid titers 7 and 14 days post-ESA, but had no effect on ecdysteroid titers at 1 and 3 days post-ESA. mRNA levels of mTOR signaling genes Gl-mTOR, Gl-Akt, and Gl-S6k were increased by 3 days post-ESA; the increases in Gl-mTOR and Gl-Akt mRNA levels were blocked by SB431542. Gl-elongation factor 2 and Gl-Rheb mRNA levels were not affected by ESA, but SB431542 lowered mRNA levels at Days 3 and 7 post-ESA. The mRNA level of an activin TGF-β peptide, Gl-myostatin-like factor (Mstn), increased 5.5-fold from 0 to 3 days post-ESA, followed by a 50-fold decrease from 3 to 7 days post-ESA. These data suggest that (1) YO activation involves an up regulation of the mTOR signaling pathway; (2) mTOR is required for YO commitment; and (3) a Mstn-like factor mediates the transition of the YO from the activated to the committed state

Understanding factors relevant to poor sleep and coping methods in people with schizophrenia

Background Sleep disruption is pervasive in people with schizophrenia, but few studies have explored their sleep experiences. This study aims to identify factors relevant to sleep problems and explore coping methods used by community-dwelling people with schizophrenia. Methods Eighteen participants with schizophrenia were recruited from three mental health centers in Taiwan. They completed a semi-structured interview and the Pittsburgh Sleep Quality Index (PSQI) assessment. The Person-Environment-Occupation model offered a framework to assess factors related to sleep. Thematic analysis was used for the qualitative data analysis. Results Factors related to sleep were classified under person, environment, and occupation domains. The person domain included three subthemes: psychiatric symptoms, unpleasant emotions, and frustration about sleep. The environment domain included three subthemes: sensory intrusions from the environment, quality of bedding, and roommates. The occupation domain included sleep interruption and sleep preparation. There were notable discrepancies in sleep quality between the participants’ narratives and their PSQI global scores. Regarding coping methods for poor sleep, sleep medication was the primary strategy while some participants also used other strategies, such as modifying the environment, adjusting routines, or engaging in activities that improve sleep quality. Conclusions Psychiatric symptoms and nightmares were identified as unique sleep disruptions in people with schizophrenia, and poor economic status was also found to impact their sleep. The sleep quality of people with schizophrenia tends to be poor, as identified by the PSQI, even though they may have positive perceptions of their sleep quality. Our participants appeared to prefer to take hypnotics to address their sleep problems, which may be due to limited knowledge about alternatives. Mental health professionals are encouraged to receive training in the application of non-pharmacological approaches to support their clients’ issues related to sleep

A Pilot Study Exploring Gender Differences in Residents’ Strategies for Establishing Mentoring Relationships

BACKGROUND: Mentoring is important throughout a physician's career and has been noted to be particularly important during residency training. Other studies suggest that women may experience difficulty in finding mentors. PURPOSE: This study explored gender-specific differences in residents' mentoring experiences. METHODS: The authors conducted two focus groups at the University of Pittsburgh in July, 2004. One group was composed of 12 female residents; the other was composed of nine male residents. Discussions were audiotaped and transcribed. Two investigators coded the transcripts and identified emerging themes. RESULTS: Residents of both genders cited multiple barriers to mentoring. Men's strategies for finding mentors were more numerous than women's and included identifying mentors through research, similar interests, friendship, and networking. Female strategies were limited and included identifying mentors through "word of mouth" and work experiences. Women described more passive approaches for finding a mentor than men. CONCLUSIONS: Female residents may lack strategies and initiatives for finding mentors. Residency programs should create opportunities for residents to develop mentoring relationships, with special attention paid to gender differences

The Landscape of Long Non-Coding RNA Dysregulation and Clinical Relevance in Muscle Invasive Bladder Urothelial Carcinoma.

Bladder cancer is one of the most common cancers in the United States, but few advancements in treatment options have occurred in the past few decades. This study aims to identify the most clinically relevant long non-coding RNAs (lncRNAs) to serve as potential biomarkers and treatment targets for muscle invasive bladder cancer (MIBC). Using RNA-sequencing data from 406 patients in The Cancer Genome Atlas (TCGA) database, we identified differentially expressed lncRNAs in MIBC vs. normal tissues. We then associated lncRNA expression with patient survival, clinical variables, oncogenic signatures, cancer- and immune-associated pathways, and genomic alterations. We identified a panel of 20 key lncRNAs that were most implicated in MIBC prognosis after differential expression analysis and prognostic correlations. Almost all lncRNAs we identified are correlated significantly with oncogenic processes. In conclusion, we discovered previously undescribed lncRNAs strongly implicated in the MIBC disease course that may be leveraged for diagnostic and treatment purposes in the future. Functional analysis of these lncRNAs may also reveal distinct mechanisms of bladder cancer carcinogenesis

KEAP1 Cancer Mutants: A Large-Scale Molecular Dynamics Study of Protein Stability.

We have performed 280 μs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experimentally, painting a more complete picture of their mutagenic effects. Notably, blade-wise analysis of the Kelch domain points to stability as a possible target of cancer in KEAP1. Interestingly, structural analysis of the R470C ANCHOR mutant, the most prevalent missense mutation in KEAP1, revealed no significant change in structural stability or NRF2 binding site dynamics, possibly indicating an covalent modification as this mutant\u27s mode of action

Fitness costs of herbicide resistance across natural populations of the common morning glory, Ipomoea purpurea

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134117/1/evo13016_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134117/2/evo13016.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134117/3/evo13016-sup-0001-FigS1.pd

Poster 285 High Prevalence of Cranial Asymmetry May Exist in Infants with Neonatal Brachial Plexus Palsy (NBPP)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147206/1/pmr2s184b.pd

(Re)negotiating and (Re)envisioning Our Feminist Journeys: A Collaborative Autoethnography of Five Women of Color Doctoral Students

This study utilizes critical collaborative autoethnography to explore the development, identity, and experiences as a feminist from five Women of Color doctoral students. Given that existing research on the experiences of doctoral women of color remains sparse, the purpose of this study is to expand the knowledge by highlighting and validating the lived experiences of doctoral women of color in the academy from a feminist perspective. Through the use of collaborative autoethnography, the authors explore and interrogate their individual journeys as self-identified or aspiring feminists. The findings present the living reality and complexity involving history, contexts, intersection of identities, conflicts, inter-/intra-racial coalition, and activism through these Women of Color doctoral students

Poster 285 High Prevalence of Cranial Asymmetry May Exist in Infants with Neonatal Brachial Plexus Palsy (NBPP)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147206/1/pmr2s184b.pd