Assessment of pregnancy in the late-gestation mare using digital infrared thermography.

The objective of this study was to investigate use of digital infrared thermal imaging (DITI) to determine whether surface temperature gradient differences exist between pregnant and nonpregnant mares as a noncontact method to determine pregnancy status. On the day measurements were collected, each pregnant mare (n=10; beginning at 292.4+/-1.

Association of cardiovascular factors and Alzheimer's disease plasma amyloid-beta protein in subjective memory complainers.

A strong link is indicated between cardiovascular disease (CVD) and risk for developing Alzheimer's disease (AD), which may be exacerbated by the major AD genetic risk factor apolipoprotein Eepsilon4 (APOEepsilon4). Since subjective memory complaint (SMC) may potentially be an early indicator for cognitive decline, we examined CVD risk factors in a cohort of SMC. As amyloid-beta (Abeta) is considered to play a central role in AD, we hypothesized that the CVD risk profile (increased LDL, reduced HDL, and increased body fat) would be associated with plasma Abeta levels.

Phosphorylation of the amino-terminal region of X11L regulates its interaction with APP.

X11-like (X11L) is neuronal adaptor protein that interacts with the amyloid beta-protein precursor (APP) and regulates its metabolism. The phosphotyrosine interaction/binding (PI/PTB) domain of X11L interacts with the cytoplasmic region of APP695. We found that X11L-APP interaction is enhanced in osmotically stressed cells and X11L modification is required for the enhancement.

nELAV proteins alteration in Alzheimer's disease brain: a novel putative target for amyloid-beta reverberating on AbetaPP processing.

Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). Indeed, we found that the content of nELAV proteins is significantly decreased along with clinical dementia progression in the hippocampi of AD brains, where it inversely correlates with the amount of amyloid-beta (Abeta). To check the direct influence of Abeta on nELAV, we performed in vitro experiments using human SH-SY5Y cells, finding that Abeta(1-42) specifically determines nELAV proteins reduction.

Regulation of forkhead transcription factor FoxO3a contributes to calorie restriction-induced prevention of Alzheimer's disease-type amyloid neuropathology and spatial memory deterioration.

Forkhead transcription factor FoxO3a, also known as DAF-16 in Caenorhabditis elegans, is a key regulator of the insulin receptor (IR)/insulin-like growth factor-I signaling pathway mediated extension of life span in worms and yeast. In this study, we report that calorie restriction (CR)-mediated activation of the IR signaling pathway leads to hyperphosphorylation of FoxO3a transcription factor and, consequently, its exclusion from the nucleus. This inactivation of FoxO3a activity is correlated with attenuation of Alzheimer's disease (AD)-type amyloid neuropathology and with preservation of spatial reference memory in the Tg2576 mouse model of AD.

Enhanced generation of Alzheimer's amyloid-beta following chronic exposure to phorbol ester correlates with differential effects on alpha and epsilon isozymes of protein kinase C.

Alzheimer's amyloid precursor protein (APP) sorting and processing are modulated through signal transduction mechanisms regulated by protein phosphorylation. Notably, protein kinase C (PKC) appears to be an important component in signaling pathways that control APP metabolism. PKCs exist in at least 11 conventional and unconventional isoforms, and PKCalpha and PKCepsilon isoforms have been specifically implicated in controlling the generation of soluble APP and amyloid-beta (Abeta) fragments of APP, although identification of the PKC substrate phospho-state-sensitive effector proteins remains challenging.

X11 proteins regulate the translocation of amyloid beta-protein precursor (APP) into detergent-resistant membrane and suppress the amyloidogenic cleavage of APP by beta-site-cleaving enzyme in brain.

X11 and X11-like proteins (X11L) are neuronal adaptor proteins whose association to the cytoplasmic domain of amyloid beta-protein precursor (APP) suppresses the generation of amyloid beta-protein (Abeta) implicated in Alzheimer disease pathogenesis. The amyloidogenic, but not amyloidolytic, metabolism of APP was selectively increased in the brain of mutant mice lacking X11L (Sano, Y., Syuzo-Takabatake, A.

Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology.

Objective: To examine the association between treatment for diabetes and Alzheimer disease (AD) neuropathology.

Methods: This postmortem study matched 124 subjects with diabetes to 124 without diabetes from the Mount Sinai School of Medicine Brain Bank, on age (mean = 81.2 + 9.

Association of alleles carried at TNFA -850 and BAT1 -22 with Alzheimer's disease.

Background: Inflammatory changes are a prominent feature of brains affected by Alzheimer's disease (AD). Activated glial cells release inflammatory cytokines which modulate the neurodegenerative process. These cytokines are encoded by genes representing several interleukins and TNFA, which are associated with AD.

Comparison of the reproducibility of quantitative cardiac left ventricular assessments in healthy volunteers using different MRI scanners: a multicenter simulation.

Purpose: To derive reproducibility assessments of ejection fraction (EF) and left ventricular mass (LVM) from short-axis cardiac MR images acquired at single and multiple time-points on different 1.5T scanner models.

Materials And Methods: Images of 15 healthy volunteers were acquired twice using a Magnetom Avanto scanner (Siemens, Erlangen, Germany) and once using a Signa Excite scanner (General Electric, Milwaukee, WI, USA) over four months, and analyzed using ARGUS and MASS Analysis+ software, respectively.

Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer's mouse model.

Mitochondrial dysfunction, oxidative stress and reductions in thiamine-dependent enzymes have been implicated in multiple neurological disorders including Alzheimer's disease (AD). Experimental thiamine deficiency (TD) is an established model for reducing the activities of thiamine-dependent enzymes in brain. TD diminishes thiamine-dependent enzymes throughout the brain, but produces a time-dependent selective neuronal loss, glial activation, inflammation, abnormalities in oxidative metabolism and clusters of degenerating neurites in only specific thalamic regions.

MRI comparison of quantitative left ventricular structure, function and measurement reproducibility in patient cohorts with a range of clinically distinct cardiac conditions.

Aim: Quantitative MRI assessments of cardiac structure and function are possible and potentially useful for longitudinal clinical monitoring. The aim of this study was to compare the magnitude and repeatability of left ventricular (LV) ejection fraction (EF) and mass (LVM) measurements in patients with clinically distinct cardiac conditions.

Materials And Methods: Patients were recruited into four groups: (i) congestive heart failure (CHF), (ii) left ventricular hypertrophy (LVH), (iii) recent post myocardial infarct (PMI), and (iv) healthy normal volunteers (HNV).

Evidence against roles for phorbol binding protein Munc13-1, ADAM adaptor Eve-1, or vesicle trafficking phosphoproteins Munc18 or NSF as phospho-state-sensitive modulators of phorbol/PKC-activated Alzheimer APP ectodomain shedding.

Background: Shedding of the Alzheimer amyloid precursor protein (APP) ectodomain can be accelerated by phorbol esters, compounds that act via protein kinase C (PKC) or through unconventional phorbol-binding proteins such as Munc13-1. We have previously demonstrated that application of phorbol esters or purified PKC potentiates budding of APP-bearing secretory vesicles at the trans-Golgi network (TGN) and toward the plasma membrane where APP becomes a substrate for enzymes responsible for shedding, known collectively as alpha-secretase(s). However, molecular identification of the presumptive "phospho-state-sensitive modulators of ectodomain shedding" (PMES) responsible for regulated shedding has been challenging.

RNA editing of the human herpesvirus 8 kaposin transcript eliminates its transforming activity and is induced during lytic replication.

Human herpesvirus 8 is the etiologic agent associated with Kaposi's sarcoma and primary effusion lymphoma (PEL). The K12 RNA, which produces as many as three variants of the kaposin protein, as well as a microRNA, is the most abundant transcript expressed in latent Kaposi's sarcoma-associated herpesvirus infection, and yet it is also induced during lytic replication. The portion of the transcript that includes the microRNA and the kaposin A sequence has been shown to have tumorigenic potential.

Prepartum milking effects on parlour behaviour, endocrine and immune responses in Holstein heifers.

Transition of primiparous heifers to the milking herd is a period with multiple stressors. The objective of these studies was to determine effects of parlour experience and prepartum milking (pre-milking) on behavioural and physiological indicators of stress after calving. Two experiments were conducted, one was in a free-stall housing confinement system and the second was in a modified grazing system.

Alzheimer's presenilin 1 modulates sorting of APP and its carboxyl-terminal fragments in cerebral neurons in vivo.

Studies in continuously cultured cells have established that familial Alzheimer's disease (FAD) mutant presenilin 1 (PS1) delays exit of the amyloid precursor protein (APP) from the trans-Golgi network (TGN). Here we report the first description of PS1-regulated APP trafficking in cerebral neurons in culture and in vivo. Using neurons from transgenic mice or a cell-free APP transport vesicle biogenesis system derived from the TGN of those neurons, we demonstrated that knocking-in an FAD-associated mutant PS1 transgene was associated with delayed kinetics of APP arrival at the cell surface.

The relationship between vaginal electrical impedence and hormone profiles during pregnancy and parturition of a white rhinoceros (Ceratotherium simum simum).

In this study, an attempt was made to use vaginal electrical impedance to predict calving in a female white rhinoceros (Ceratotherium simum simum) and to determine the relationship between vaginal electrical impedance and hormonal profiles during pregnancy. The principle behind vaginal electrical impedance is that a change in the ionic balance of vaginal and cervical mucus occurs in response to changes in reproductive hormones. Three times weekly vaginal electrical impedance readings and fecal samples were collected from midgestation to calving (a 6-mo period).

A clinical MRI investigation of the relationship between kidney volume measurements and renal function in patients with renovascular disease.

Recent improvements in MR image acquisition and post-processing techniques have allowed quantitative kidney volume measurements to be derived from patient studies. These morphological indices can provide "snapshot" assessments that may be related to kidney function. The study objective was to measure cortical and total kidney volumes in patients with renovascular disease (RVD) using contrast-enhanced MR angiography (CE-MRA) in order to assess the reproducibility of the technique and to investigate associations between volumes and renal function as measured by glomerular filtration rate (GFR) calculations.

Physiological mouse brain Abeta levels are not related to the phosphorylation state of threonine-668 of Alzheimer's APP.

Background: Amyloid-beta peptide species ending at positions 40 and 42 (Abeta40, Abeta42) are generated by the proteolytic processing of the Alzheimer's amyloid precursor protein (APP). Abeta peptides accumulate in the brain early in the course of Alzheimer's disease (AD), especially Abeta42. The cytoplasmic domain of APP regulates intracellular trafficking and metabolism of APP and its carboxyl-terminal fragments (CTFalpha, CTFbeta).

Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus).

Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-beta (Abeta) neuropathology in the mouse models of AD. Moreover, we found that promotion of the NAD+-dependent SIRT1 mediated deacetylase activity, a key regulator in CR extension of life span, may be a mechanism by which CR influences AD-type neuropathology. In this study we continued to explore the role of CR in AD-type brain amyloidosis in Squirrel monkeys (Saimiri sciureus).

A phase 2 study of tramiprosate for cerebral amyloid angiopathy.

Background And Purpose: No treatments have been identified to lower the risk of intracerebral hemorrhage due to cerebral amyloid angiopathy (CAA). A potential approach to prevention is the use of agents that interfere with the pathogenic cascade initiated by the beta-amyloid peptide (Abeta). Tramiprosate (3-amino-1-propanesulfonic acid) is a candidate molecule shown in preclinical studies to reduce CAA in a transgenic mouse model.

Sorting through the cell biology of Alzheimer's disease: intracellular pathways to pathogenesis.

During the first 100 years of Alzheimer's disease research, this devastating and intractable disorder has been characterized at the clinical, histological, and molecular levels. Nevertheless, many key mechanistic questions remain unanswered. Here we will emphasize the importance of the cell biology of Alzheimer's disease, reviewing the relevant literature that has expanded our mechanistic understanding, with a particular focus on pathways regulating protein sorting.

The role of presenilin and its interacting proteins in the biogenesis of Alzheimer's beta amyloid.

The biogenesis and accumulation of the beta amyloid protein (Abeta) is a key event in the cascade of oxidative and inflammatory processes that characterises Alzheimer's disease. The presenilins and its interacting proteins play a pivotal role in the generation of Abeta from the amyloid precursor protein (APP). In particular, three proteins (nicastrin, aph-1 and pen-2) interact with presenilins to form a large multi-subunit enzymatic complex (gamma-secretase) that cleaves APP to generate Abeta.