Finite mixture clustering of human tissues with different levels of IGF-1 splice variants mRNA transcripts

BACKGROUND: This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a finite mixture of multivariate Gaussian densities. However, given we had more technical replicates from the same tissue for each quantitative measurement, we also employed a finite mixture of linear mixed models, with tissue-specific random effects. RESULTS: A panel of human tissues was analysed through quantitative real-time PCR methods, to quantify the relative amount of mRNA encoding different IGF-1 alternative splicing variants. After an appropriate, preliminary, equalization of the quantitative data, we provided an estimate of the distribution of the observed concentrations for the different IGF-1 mRNA splice variants in the cohort of tissues by employing suitable kernel density estimators. We observed that the analysed IGF-1 mRNA splice variants were characterized by multimodal distributions, which could be interpreted as describing the presence of several sub-population, i.e. potential tissue clusters. In this context, a formal clustering approach based on a finite mixture model (FMM) with Gaussian components is proposed. Due to the presence of potential dependence between the technical replicates (originated by repeated quantitative measurements of the same mRNA splice isoform in the same tissue) we have also employed the finite mixture of linear mixed models (FMLMM), which allowed to take into account this kind of within-tissue dependence. CONCLUSIONS: The FMM and the FMLMM provided a convenient yet formal setting for a model-based clustering of the human tissues in sub-populations, characterized by homogeneous values of concentrations of the mRNAs for one or multiple IGF-1 alternative splicing isoforms. The proposed approaches can be applied to any cohort of tissues expressing several alternatively spliced mRNAs generated by the same gene, and can overcome the limitations of clustering methods based on simple comparisons between splice isoform expression levels

Increased circulating levels of interleukin-6 induce perturbation in redox-regulated signaling cascades in muscle of dystrophic mice

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease in which dystrophin gene is mutated, resulting in dysfunctional or absent dystrophin protein. The pathology of dystrophic muscle includes degeneration, necrosis with inflammatory cell invasion, regeneration, and fibrous and fatty changes. Nevertheless, the mechanisms by which the absence of dystrophin leads to muscle degeneration remain to be fully elucidated. An imbalance between oxidant and antioxidant systems has been proposed as a secondary effect of DMD. However, the significance and precise extent of the perturbation in redox signaling cascades is poorly understood. We report that mdx dystrophic mice are able to activate a compensatory antioxidant response at the presymptomatic stage of the disease. In contrast, increased circulating levels of IL-6 perturb the redox signaling cascade, even prior to the necrotic stage, leading to severe features and progressive nature of muscular dystrophy

Letter from Nancy Pelosi to Sam Farr, August 5, 1993

Letter from Congresswoman Nancy Pelosi concerning funding for the establishment of a CSU campus at Ford Ord.https://digitalcommons.csumb.edu/samfarr_corr_all/1004/thumbnail.jp

When Women Succeed, America Succeeds

Leader Pelosi\u27s speech, delivered at the Hastings Women\u27s Law Journal 25th Anniversary Symposium, discusses the recently-launched When Women Succeed, America Succeeds campaign that places female empowerment at the center of a successful society and economy. Ms. Pelosi emphasized three fundamental issues that most affect the position of women in the workforce: pay equity, paid sick leave, and affordable quality child care. The successful resolution of those three issues is the key to the success of women and the U.S

Reducing CIED lead dislodgements: Faithful alignment to small things

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147189/1/pace13545.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147189/2/pace13545_am.pd

Secure and user-friendly display of schedule in a meeting room

Meeting and conference rooms in offices are equipped with video conferencing equipment that includes a screen that displays meetings scheduled in the room, e.g., on an idle screen display. The displayed schedules can include meeting titles or codes. If a visitor enters the meeting room, such display can potentially reveal information that is confidential to the organization. This disclosure describes techniques to automatically determine whether display of meeting-related information is appropriate. External meetings are identified based on available contextual information, e.g., meeting attendees, agenda/notes, room location, schedules of adjacent rooms, etc. Ahead of external meetings in a room, schedule information is hidden from the idle screen