Meiosis is a specialized form of cell division where chromosomes are duplicated once and segregated twice, in order to reduce the chromosome number by half to generate haploid gametes. In contrast to mitosis, oocyte meiosis in many species occurs in the absence of centrosomes, the microtubule organizing centers that nucleate...
Short interfering RNAs (siRNAs) and microRNAs (miRNAs) are both processed from longer, double-stranded RNA (dsRNA) presursors by a member of the Dicer (Dcr) family of proteins. siRNAs generally arise from perfectly base-paired dsRNAs, whereas miRNAs are excised from 60-70 nt pre-miRNA hairpins containing multiple bulges and mismatches within the duplexed...
Pain normally subserves a vital role in the survival of the organism by prompting the avoidance of situations associated with tissue damage. However, the sensation of pain can become dissociated from its normal physiological role when the pain-sensing nervous system becomes hypersensitive, a condition known as neuropathic pain. Currently available...
Previous research has shown that creative insight problem-solving is distinct from systematic analytical problem-solving. Behaviorally, a positive mood has shown to facilitate insights but without knowing the processes that are fundamental to insight, the mechanisms as to how a positive mood facilitates insights have remained unspecified. Here, we investigate the...
TGF-β has been named the molecular Jekyll and Hyde of cancer due to its ability to both suppress and promote tumor development. Components of the TGF-β signaling pathway are often mutated in cancer to inhibit the tumor suppressor roles of TGF-β. Our lab studies how a 3-alanine deletion in the...
The studies in this thesis are directed towards defining the signaling mechanisms that regulate astrogliosis after SCI and towards developing potential therapeutic techniques for modifying this process. The central hypothesis is that alteration of the extracellular milieu after SCI can limit the deleterious effects of glial scar formation and enhance...
Latent membrane protein 2A (LMP2A) and LMP2B are viral proteins expressed during Epstein-Barr virus (EBV) latency in EBV-infected B cells both in cell culture and in vivo. Although Lyn has been shown to be important in mediating LMP2A signaling, it is still unclear if Lyn is used preferentially or if...
Herpes simplex virus (HSV) infection of host cells requires virus attachment to the cell surface and subsequent membrane fusion between the virus envelope and host cell membrane to deliver the nucleocapsid containing the viral genome into the host cell. A proposed mechanism for HSV glycoprotein-induced membrane fusion is gD binding...
A pyramidal neuron receives thousands of inputs spread throughout its dendritic tree, which it must integrate into a decision about whether or not to fire action-potential output. Since action potentials are the primary means by which these neurons communicate with their network partners, understanding this input-output relationship is critical for...
Synapses in the central nervous system vary widely in how they transmit and store information. The properties of short-term and long-term plasticity, in particular, seem to be specific for each class of synapse studied. The types of plasticity expressed at a particular synapse determine how it processes, transmits and possibly...
PilD is an enzyme that processes prepilins that are part of the type II protein secretion apparatus and the type IV piliation machinery. Using a <em>Legionella pneumophila pilDlacZ</em> fusion strain to measure transcription, we observed a 20% increase in beta-galactosidase levels at 30°C vs. 37°C. At 25°C and 17°C vs....
Epstein Barr Virus (EBV) is associated with malignancies of lymphoid and epithelial origin. While the precise role of EBV in oncogenesis remains elusive, latent membrane protein 2A (LMP2A) is detected in all EBV-associated malignancies, implicating LMP2A in their pathogenesis. Interestingly, LMP2A is expressed in EBV-associated malignancies such as Burkitt's Lymphoma,...
Many ion channels are localized in specific subcellular domain of the neurons, and the proper localization is critical for the function of ion channels. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (h channels) are asymmetrically distributed in the CA1 pyramidal neurons, enriched in the distal apical dendrites. H current, generated by h...
The growth cone is a highly specialized motile structure with a distinctive and dynamically variable morphology. Current understanding of actin-based protrusive motility has been formulated in terms of the dendritic nucleation/array treadmilling model for lamellipodial protrusion and the convergent-elongation model for filopodial protrusion, that were based upon results obtained primarily...
HspB2 was discovered as a chaperone of muscular dystrophy protein kinase (DMPK) and originally named, DMPK binding protein (MKBP) and presently called HspB2. Functionally, MKBP binds to DMPK and stabilizes its kinase activity, thereby accelerating the progression of muscular dystrophy. Although other binding partners of HspB2 have been found, the...
A comprehensive understanding of how image processing occurs in the primary visual cortex (V1) requires learning what aspects of neuronal responses are driven by strong feed-forward input from the lateral geniculate nucleus (LGN), and what aspects arise due to the densely recurrent network operating within the cortex itself. From an...
Activin, a member of the TGF-b superfamily, controls a variety of physiological events from the cell cycle to reproductive health. Activin activates the Smad signaling pathway through ActRII/B and ALK4 receptors. The regulation of activin signaling is carried out in part by the inhibitor protein follistatin. The mechanistic details of...
Gonadotropin releasing hormone (GnRH) neurons comprise the final pathway through which the central nervous system exerts its control over the hypothalamic-pituitary-gonadal (HPG) axis. GnRH is released in a pulsatile manner, and conveyed to the anterior pituitary gland to stimulate synthesis and secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating...
The response to reduced levels of oxygen (hypoxia) is essential for embryonic development by promoting the proper formation of vascular networks. Conversely, hypoxia also promotes the development of pathophysiological processes such as pulmonary hypertension and cancer. The main mediator of responses to hypoxia within the cell is the transcription factor...
Initial studies described the ability of CD4+CD25+ T regulatory (Treg) cells in suppressing autoimmune diseases in animal models. An emerging interest has focused on the potential role of Treg cells in cancer development and progression as they have been shown to suppress anti-tumor immunity. In the present study, CD4+CD25- T...