Investigating Neural Substrates of Visual Motion Sensitivity in Deaf Individuals

The aim of this thesis has been to explore neural substrates of enhanced far-peripheral visual motion processing in congenitally deaf adults. To do this, psychophysical measures were used as well as novel fMRI stimulus delivery methods to record responses to stimu- lation in the far-peripheral visual field. For the first time, far-peripheral visual field mapping measured an extended representa- tion of the visual field (72 ◦) in early visual cortex in deaf and hearing individuals. Using this method, unique evidence of plasticity within the cortical surface area distribution of visual field representations in the primary visual cortex was found in congenitally deaf adults, biased towards the far-peripheral visual field. Furthermore, neural responses to far-peripheral stimuli were measured in visual motion processing areas V5/MT+ and V6, and in auditory regions. Results show novel and dis- tinctive differences in response profiles in auditory, but not visual regions between deaf and hearing participants, indicating crossmodal plasticity in deaf participants, specific to coherent but not incoherent global optic flow field motion stimuli. Most importantly, the aim of the thesis was to relate neural measures to behavioural per- formance of motion perception. The results show evidence that unimodal plasticity in V1 and activation in visual motion areas V5/MT+ and V6 are not related to performance in two visual motion tasks (local motion detection and global motion direction discrimina- tion), but that response inhibition and excitation levels in auditory regions are related to motion processing performance in deaf and hearing individuals. In summary, the findings described in this thesis show for the first time that congenital deafness leads to plastic changes within primary visual cortex. In addition, auditory but not visual motion regions are recruited differentially between deaf and hearing individu- als, depending on the motion type, and this activation shows a trending relationship with visual motion performance in both groups

Carbon Free Boston: Buildings Technical Report

Part of a series of reports that includes: Carbon Free Boston: Summary Report; Carbon Free Boston: Social Equity Report; Carbon Free Boston: Technical Summary; Carbon Free Boston: Transportation Technical Report; Carbon Free Boston: Waste Technical Report; Carbon Free Boston: Energy Technical Report; Carbon Free Boston: Offsets Technical Report; Available at http://sites.bu.edu/cfb/OVERVIEW: Boston is known for its historic iconic buildings, from the Paul Revere House in the North End, to City Hall in Government Center, to the Old South Meeting House in Downtown Crossing, to the African Meeting House on Beacon Hill, to 200 Clarendon (the Hancock Tower) in Back Bay, to Abbotsford in Roxbury. In total, there are over 86,000 buildings that comprise more than 647 million square feet of area. Most of these buildings will still be in use in 2050. Floorspace (square footage) is almost evenly split between residential and non-residential uses, but residential buildings account for nearly 80,000 (93 percent) of the 86,000 buildings. Boston’s buildings are used for a diverse range of activities that include homes, offices, hospitals, factories, laboratories, schools, public service, retail, hotels, restaurants, and convention space. Building type strongly influences energy use; for example, restaurants, hospitals, and laboratories have high energy demands compared to other commercial uses. Boston’s building stock is characterized by thousands of turn-of-the-20th century homes and a postWorld War II building boom that expanded both residential buildings and commercial space. Boston is in the midst of another boom in building construction that is transforming neighborhoods across the city. [TRUNCATED]Published versio

Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma

BACKGROUND. MicroRNA regulate mRNA levels in a tissue specific way, either by inducing degradation of the transcript or by inhibiting translation or transcription. Putative mRNA targets of microRNA identified from seed sequence matches are available in many databases. However, such matches have a high false positive rate and cannot identify tissue specificity of regulation. RESULTS. We describe a simple method to identify direct mRNA targets of microRNA dysregulated in cancers from expression level measurements in patient matched tumor/normal samples. The word "direct" is used here in a strict sense to: a) represent mRNA which have an exact seed sequence match to the microRNA in their 3'UTR, b) the seed sequence match is strictly conserved across mouse, human, rat and dog genomes, c) the mRNA and microRNA expression levels can distinguish tumor from normal with high significance and d) the microRNA/mRNA expression levels are strongly and significantly anti-correlated in tumor and/or normal samples. We apply and validate the method using clear cell Renal Cell Carcinoma (ccRCC) and matched normal kidney samples, limiting our analysis to mRNA targets which undergo degradation of the mRNA transcript because of a perfect seed sequence match. Dysregulated microRNA and mRNA are first identified by comparing their expression levels in tumor vs normal samples. Putative dysregulated microRNA/mRNA pairs are identified from these using seed sequence matches, requiring that the seed sequence be conserved in human/dog/rat/mouse genomes. These are further pruned by requiring a strong anti-correlation signature in tumor and/or normal samples. The method revealed many new regulations in ccRCC. For instance, loss of miR-149, miR-200c and mir-141 causes gain of function of oncogenes (KCNMA1, LOX), VEGFA and SEMA6A respectively and increased levels of miR-142-3p, miR-185, mir-34a, miR-224, miR-21 cause loss of function of tumor suppressors LRRC2, PTPN13, SFRP1, ERBB4, and (SLC12A1, TCF21) respectively. We also found strong anti-correlation between VEGFA and the miR-200 family of microRNA: miR-200a*, 200b, 200c and miR-141. Several identified microRNA/mRNA pairs were validated on an independent set of matched ccRCC/normal samples. The regulation of SEMA6A by miR-141 was verified by a transfection assay. CONCLUSIONS. We describe a simple and reliable method to identify direct gene targets of microRNA in any cancer. The constraints we impose (strong dysregulation signature for microRNA and mRNA levels between tumor/normal samples, evolutionary conservation of seed sequence and strong anti-correlation of expression levels) remove spurious matches and identify a subset of robust, tissue specific, functional mRNA targets of dysregulated microRNA.Cancer Institute of New Jersy; New Jersey Commission for Cacner Research; Lineberger Comprehensive Cancer Center Tissue Procurement and Genomics Core Facility; Crawford Fun