Surface water-- groundwater interaction : the spatial organization of hydrologic processes over complex terrain

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2000.Includes bibliographical references (p. 232-242).by Karen Plaut Berger.Ph.D

Does STAT5a Have an Effect on BMAL1 Levels in Mammary Epithelial Cells?

The mammary gland is a very important organ for reproduction in mammals because it produces milk which serves as the primary source of nutrients for newly-born offspring. Previous studies suggest that its development is regulated by circadian clocks, biochemical oscillators that generate circadian rhythms (the body’s internal clock). The circadian system plays a major role in homeostasis, coordinating the body’s internal physiology and synchronizing it with the external environment. Our lab showed that levels of the BMAL1 protein, a core clock component, increased in the mammary gland at the onset of lactation. Treatment of mammary epithelial cells (HC11) with the hormone prolactin significantly increased BMAL1 levels. We hypothesize that the secretion of prolactin during lactogenesis induces expression of BMAL1 in the mouse mammary gland through the STAT5a signaling pathway. The objective of the project was to determine the effect of different amounts of STAT5a protein on BMAL1 levels with and without prolactin treatment. For this experiment, western blot analysis was used to measure STAT5a and BMAL1 levels in wild type HC11 cells and in HC11 cell lines that were genetically modified to: 1) express very high levels of STAT5a (STAT5a-OE), 2) express a mutant form of STAT5a that is inactive (STAT5a-dnl), and 3) delete the BMAL1 gene (BMAL1 KO). Our first round of analysis showed that overexpressing STAT5a increased BMAL1 protein levels, especially in cells differentiated by prolactin. Results from this experiment would allow us to better understand the relationship between mammary gland development and the circadian system

Relationship Between Sleep Quality, Depression Symptoms, and Blood Glucose in Pregnant Women

Sleep quality during pregnancy affects maternal/child health. We aimed to assess changes in sleep quality during pregnancy and determine its relationship to maternal mood, blood glucose, and work schedule among primiparous women. We conducted a prospective/longitudinal/observational study. Ninety-two pregnant women were recruited from Midwestern hospital. Mood and sleep quality data were collected using Edinburgh Postnatal Depression Scale/Pittsburgh Sleep Quality Index at Gestational Weeks 22 and 32. Forty-three women completed the study. Twenty-six women (63%) were African American and the mean age was 23.64 (SD = 3.82) years. Rate of poor sleep quality increased during pregnancy with 25% of women had scores indicative of depression symptoms. Poor sleep quality score was related to mood scores (p < .05) and work schedule. Blood glucose was not significantly related to sleep duration. In conclusion, poor sleep quality during pregnancy was associated with poor mood and work schedule, suggesting that interventions targeting mental health and lifestyles are needed

Unique N170 Signatures to Words and Faces in Deaf ASL Signers Reflect Experience-Specific Adaptations During Early Visual Processing

Previous studies with deaf adults reported reduced N170 waveform asymmetry to visual words, a finding attributed to reduced phonological mapping in left-hemisphere temporal regions compared to hearing adults. An open question remains whether this pattern indeed results from reduced phonological processing or from general neurobiological adaptations in visual processing of deaf individuals. Deaf ASL signers and hearing nonsigners performed a same-different discrimination task with visually presented words, faces, or cars, while scalp EEG time-locked to the onset of the first item in each pair was recorded. For word recognition, the typical left-lateralized N170 in hearing participants and reduced left-sided asymmetry in deaf participants were replicated. The groups did not differ on word discrimination but better orthographic skill was associated with larger N170 in the right hemisphere only for deaf participants. Face recognition was characterized by unique N170 signatures for both groups, and deaf individuals exhibited superior face discrimination performance. Laterality or discrimination performance effects did not generalize to the N170 responses to cars, confirming that deaf signers are not inherently less lateralized in their electrophysiological responses to words and critically, giving support to the phonological mapping hypothesis. P1 was attenuated for deaf participants compared to the hearing, but in both groups, P1 selectively discriminated between highly learned familiar objects – words and faces versus less familiar objects – cars. The distinct electrophysiological signatures to words and faces reflected experience-driven adaptations to words and faces that do not generalize to object recognition

Delayed Lactogenesis II is Associated With Lower Sleep Efficiency and Greater Variation in Nightly Sleep Duration in the Third Trimester

Background: Metabolic and hormonal disturbances are associated with sleep disturbances and delayed onset of lactogenesis II. Research aims: The aim of this study was to measure sleep using wrist actigraphy during gestation weeks 22 and 32 to determine if sleep characteristics were associated with blood glucose, body mass index, gestational related disease, delayed onset of lactogenesis II, or work schedule. Methods: Demographic data were collected at study intake from primiparous women who wore a wrist actigraph during gestation weeks 22 (n = 50) and 32 (n = 44). Start and end sleep time, total nighttime sleep, sleep efficiency, wake after sleep onset, and sleep fragmentation were measured. Night to night variability was assessed with the root mean square of successive difference. Blood glucose levels, body mass index, and gestational disease data were abstracted from medical charts. Timing of lactogenesis II was determined by survey. Results: Between gestation week 22 and 32, sleep efficiency decreased and fragmentation increased (p < .05). During gestation week 32, blood glucose was negatively correlated with sleep duration, and positively related to fragmentation (p < .05). Women who experienced delayed lactogenesis II had lower sleep efficiency and greater fragmentation (p < .05), and greater night-to-night variability in sleep start and end time, efficiency, and duration during gestation week 32 (p < .05). Conclusion: Women with better sleep efficiency and more stable nightly sleep time are less likely to experience delayed onset of lactogenesis II. Interventions to improve sleep may improve maternal health and breastfeeding adequacy

The anterior temporal lobes support residual comprehension in Wernicke’s aphasia

Wernicke’s aphasia occurs following a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke’s aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used fMRI to investigate the neural basis of written word and picture semantic processing in Wernicke’s aphasia, with the wider aim of examining how the semantic system is altered following damage to the classical comprehension regions. Twelve participants with Wernicke’s aphasia and twelve control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and ROI analysis in Wernicke’s aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke’s aphasia group displayed an “over-activation” in comparison to control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke’s aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results concord with models which indicate that the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions

Molecular Signatures Reveal Circadian Clocks May Orchestrate the Homeorhetic Response to Lactation

Genes associated with lactation evolved more slowly than other genes in the mammalian genome. Higher conservation of milk and mammary genes suggest that species variation in milk composition is due in part to the environment and that we must look deeper into the genome for regulation of lactation. At the onset of lactation, metabolic changes are coordinated among multiple tissues through the endocrine system to accommodate the increased demand for nutrients and energy while allowing the animal to remain in homeostasis. This process is known as homeorhesis. Homeorhetic adaptation to lactation has been extensively described; however how these adaptations are orchestrated among multiple tissues remains elusive. To develop a clearer picture of how gene expression is coordinated across multiple tissues during the pregnancy to lactation transition, total RNA was isolated from mammary, liver and adipose tissues collected from rat dams (n = 5) on day 20 of pregnancy and day 1 of lactation, and gene expression was measured using Affymetrix GeneChips. Two types of gene expression analysis were performed. Genes that were differentially expressed between days within a tissue were identified with linear regression, and univariate regression was used to identify genes commonly up-regulated and down-regulated across all tissues. Gene set enrichment analysis showed genes commonly up regulated among the three tissues enriched gene ontologies primary metabolic processes, macromolecular complex assembly and negative regulation of apoptosis ontologies. Genes enriched in transcription regulator activity showed the common up regulation of 2 core molecular clock genes, ARNTL and CLOCK. Commonly down regulated genes enriched Rhythmic process and included: NR1D1, DBP, BHLHB2, OPN4, and HTR7, which regulate intracellular circadian rhythms. Changes in mammary, liver and adipose transcriptomes at the onset of lactation illustrate the complexity of homeorhetic adaptations and suggest that these changes are coordinated through molecular clocks

Transcriptome Analysis of Epithelial and Stromal Contributions to Mammogenesis in Three Week Prepartum Cows

Transcriptome analysis of bovine mammary development has provided insight into regulation of mammogenesis. However, previous studies primarily examined expression of epithelial and stromal tissues combined, and consequently did not account for tissue specific contribution to mammary development. Our objective was to identify differences in gene expression in epithelial and intralobular stromal compartments. Tissue was biopsied from non-lactating dairy cows 3 weeks prepartum, cut into explants and incubated for 2 hr with insulin and hydrocortisone. Epithelial and intralobular stromal tissues were isolated with laser capture microdissection. Global gene expression was measured with Bovine Affymetrix GeneChips, and data were preprocessed using RMA method. Moderated t-tests from gene-specific linear model analysis with cell type as a fixed effect showed more than 3,000 genes were differentially expressed between tissues (P<0.05; FDR<0.17). Analysis of epithelial and stromal transcriptomes using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathways Analysis (IPA) showed that epithelial and stromal cells contributed distinct molecular signatures. Epithelial signatures were enriched with gene sets for protein synthesis, metabolism and secretion. Stromal signatures were enriched with genes that encoded molecules important to signaling, extracellular matrix composition and remodeling. Transcriptome differences also showed evidence for paracrine interactions between tissues in stimulation of IGF1 signaling pathway, stromal reaction, angiogenesis, neurogenesis, and immune response. Molecular signatures point to the dynamic role the stroma plays in prepartum mammogenesis and highlight the importance of examining the roles of cell types within the mammary gland when targeting therapies and studying mechanisms that affect milk production

Swim-Training Changes the Spatio-Temporal Dynamics of Skeletogenesis in Zebrafish Larvae (Danio rerio)

Fish larvae experience many environmental challenges during development such as variation in water velocity, food availability and predation. The rapid development of structures involved in feeding, respiration and swimming increases the chance of survival. It has been hypothesized that mechanical loading induced by muscle forces plays a role in prioritizing the development of these structures. Mechanical loading by muscle forces has been shown to affect larval and embryonic bone development in vertebrates, but these investigations were limited to the appendicular skeleton. To explore the role of mechanical load during chondrogenesis and osteogenesis of the cranial, axial and appendicular skeleton, we subjected zebrafish larvae to swim-training, which increases physical exercise levels and presumably also mechanical loads, from 5 until 14 days post fertilization. Here we show that an increased swimming activity accelerated growth, chondrogenesis and osteogenesis during larval development in zebrafish. Interestingly, swim-training accelerated both perichondral and intramembranous ossification. Furthermore, swim-training prioritized the formation of cartilage and bone structures in the head and tail region as well as the formation of elements in the anal and dorsal fins. This suggests that an increased swimming activity prioritized the development of structures which play an important role in swimming and thereby increasing the chance of survival in an environment where water velocity increases. Our study is the first to show that already during early zebrafish larval development, skeletal tissue in the cranial, axial and appendicular skeleton is competent to respond to swim-training due to increased water velocities. It demonstrates that changes in water flow conditions can result into significant spatio-temporal changes in skeletogenesis