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Biomedical subjects

A Mogilner

Publications and source records attributed to A Mogilner.

18 recordsLinked to original sources
PubMed2003

Analysis of actin dynamics at the leading edge of crawling cells: implications for the shape of keratocyte lamellipodia.

Leading edge protrusion is one of the critical events in the cell motility cycle and it is believed to be driven by the assembly of the actin network. The concept of dendritic nucleation of actin filaments provides a basis for understanding the organization and dynamics of the actin network at the molecular level. At a larger scale, the dynamic geometry of the cell edge has been described in terms of the graded radial extension model, but this level of description has not yet been linked to the molecular dynamics. Here, we measure the graded distribution of actin filament density along the leading edge of fish epidermal keratocytes. We develop a mathematical model relating dendritic nucleation to the long-range actin distribution and the shape of the leading edge. In this model, a steady-state graded actin distribution evolves as a result of branching, growth and capping of actin filaments in a finite area of the leading edge. We model the shape of the leading edge as a product of the extension of the actin network, which depends on actin filament density. The feedback between the actin density and edge shape in the model results in a cell shape and an actin distribution similar to those experimentally observed. Thus, we explain the stability of the keratocyte shape in terms of the self-organization of the branching actin network.

Actins↗
PubMed2003

A force balance model of early spindle pole separation in Drosophila embryos.

The formation and function of the mitotic spindle depends upon force generation by multiple molecular motors and by the dynamics of microtubules, but how these force-generating mechanisms relate to one another is unclear. To address this issue we have modeled the separation of spindle poles as a function of time during the early stages of spindle morphogenesis in Drosophila embryos. We propose that the outward forces that drive the separation of the spindle poles depend upon forces exerted by cortical dynein and by microtubule polymerization, and that these forces are antagonized by a C-terminal kinesin, Ncd, which generates an inward force on the poles. We computed the sum of the forces generated by dynein, microtubule polymerization, and Ncd, as a function of the extent of spindle pole separation and solved an equation relating the rate of pole separation to the net force. As a result, we obtained graphs of the time course of spindle pole separation during interphase and prophase that display a reasonable fit to the experimental data for wild-type and motor-inhibited embryos. Among the novel contributions of the model are an explanation of pole separation after simultaneous loss of Ncd and dynein function, and the prediction of a large value for the effective centrosomal drag that is needed to fit the experimental data. The results demonstrate the utility of force balance models for explaining certain mitotic movements because they explain semiquantitatively how the force generators drive a rapid initial burst of pole separation when the net force is great, how pole separation slows down as the force decreases, and how a stable separation of the spindle poles characteristic of the prophase steady state is achieved when the force reaches zero.

Animals↗
PubMed2002

Neurophysiological modulation of the subthalamic nucleus by pallidal stimulation in Parkinson's disease.

OBJECTIVES: Current models of basal ganglia dysfunction in Parkinson's disease suggest a pivotal role of subthalamic nucleus (STN) hyperactivity. There is a direct excitatory output to the globus pallidus internus (GPi), which in turn hyperinhibits the motor thalamus and leads to a lack of cortical facilitation. The model, however, does not address the reciprocal influence of GPi on STN activity. METHODS: Measurement of immediate changes in STN single cell activity after GPi deep brain stimulation (DBS). RESULTS: An opposite effect of GPi DBS in the dorsal versus ventral STN was found. There was an almost exclusive reduction of firing rate in the dorsal region of the STN, whereas the cells in the ventral region exhibited facilitation similar to the recordings from the substantia nigra pars reticulata. CONCLUSION: Although these findings require confirmation, they suggest that the current theories of GPi DBS action, which do not include a GPi-STN modulation, are most likely incomplete.

Aged↗
PubMed2001

Pattern formation and traveling waves in myxobacteria: theory and modeling.

Recent experiments have provided new quantitative measurements of the rippling phenomenon in fields of developing myxobacteria cells. These measurements have enabled us to develop a mathematical model for the ripple phenomenon on the basis of the biochemistry of the C-signaling system, whereby individuals signal by direct cell contact. The model quantitatively reproduces all of the experimental observations and illustrates how intracellular dynamics, contact-mediated intercellular communication, and cell motility can coordinate to produce collective behavior. This pattern of waves is qualitatively different from that observed in other social organisms, especially Dictyostelium discoideum, which depend on diffusible morphogens.

Models, Biological↗
PubMed2001

Structural changes in the neck linker of kinesin explain the load dependence of the motor's mechanical cycle.

The two-headed motor protein kinesin hydrolyzes ATP and moves on microtubule tracks towards the plus end. The motor develops speeds and forces of the order of hundreds of nanometers per second and piconewtons, respectively. Recently, the dependence of the velocity, the dissociation rate and the displacement variance on the load and the ATP concentration were measured in vitro for individual kinesin molecules (Coppin et al., 1997; Visscher et al., 1999) over a wide range of forces. The structural changes in the kinesin motor that drive motility were discovered by Rice et al. (1999). Here we present a phenomenological model for force generation in kinesin based on the bi-stable, nucleotide-dependent behavior of the neck linker. We demonstrate that the model explains the mechanical, kinetic and statistical (experimental) data of Coppin et al. (1997). We also discuss the relationship between the model results and experimental data of Visscher et al. (1999).

Adenosine Diphosphate↗
PubMed2001

Non-local concepts and models in biology.

In this paper, we consider local and non-local spatially explicit mathematical models for biological phenomena. We show that, when rate differences between fast and slow local dynamics are great enough, non-local models are adequate simplifications of local models. Non-local models thus avoid describing fast processes in mechanistic detail, instead describing the effects of fast processes on slower ones. As a consequence, non-local models are helpful to biologists because they describe biological systems on scales that are convenient to observation, data collection, and insight. We illustrate these arguments by comparing local and non-local models for the aggregation of hypothetical organisms, and we support theoretical ideas with concrete examples from cell biology and animal behavior.

Animal Communication↗
PubMed2001

Complications of deep brain stimulation surgery.

Although technological advances have reduced device-related complications, DBS surgery still carries a significant risk of transient and permanent complications. We report our experience in 86 patients and 149 DBS implants. Patients with Parkinson's disease, essential tremor and dystonia were treated. There were 8 perioperative, 8 postoperative, 9 hardware-related complications and 4 stimulation-induced side effects. Only 5 patients (6%) sustained some persistent neurological sequelae, however, 26 of the 86 patients undergoing 149 DBS implants in this series experienced some untoward event with the procedure. Although there were no fatalities or permanent severe disabilities encountered, it is important to extend the informed consent to include all potential complications.

Accessory Nerve Diseases↗
PubMed1998

Force generation in RNA polymerase.

RNA polymerase (RNAP) is a processive molecular motor capable of generating forces of 25-30 pN, far in excess of any other known ATPase. This force derives from the hydrolysis free energy of nucleotides as they are incorporated into the growing RNA chain. The velocity of procession is limited by the rate of pyrophosphate release. Here we demonstrate how nucleotide triphosphate binding free energy can rectify the diffusion of RNAP, and show that this is sufficient to account for the quantitative features of the measured load-velocity curve. Predictions are made for the effect of changing pyrophosphate and nucleotide concentrations and for the statistical behavior of the system.

Adenosine Triphosphatases↗
PubMed1998

Nocardia abscess of the choroid plexus: clinical and pathological case report.

OBJECTIVE: Cerebral Nocardia abscesses are rare, accounting for approximately 1 to 2% of all cerebral abscesses. Prompt aggressive surgical treatment involving craniotomy and excision of these lesions has been advocated by many authors, because these lesions have significantly higher morbidity and mortality rates than do most other cerebral abscesses. We report an atypical presentation of cerebral nocardiosis localized to the choroid plexus of the lateral ventricle. CLINICAL PRESENTATION: A 56-year-old man presented with a 3-week history of fever, cough, and progressive headache and an ensuing 3-day history of progressive lethargy, confusion, and gait ataxia. Radiographic studies demonstrated a loculated contrast-enhancing left lateral ventricular lesion with significant perilesional parenchymal edema that was thought preoperatively to be a neoplasm. INTERVENTION: The patient underwent a craniotomy for resection of the lesion. Intraoperatively, a reddish gray lesion with purulent exudate was encountered within the left lateral ventricle intimately adherent to the choroid plexus as well as to the ependyma and subependymal veins. A frozen section demonstrated an organizing abscess wall. The lesion was resected in its entirety, and multiple cultures were sent for analysis. CONCLUSION: Microbiology cultures grew Nocardia asteroides. A course of intravenous antibiotics was started, which included trimethoprim-sulfamethoxazole, amikacin, and ceftriaxone. Two weeks after surgery, at the time of discharge, the patient's neurological status had improved considerably. Although Nocardia abscesses have been documented to occur throughout the central nervous system, the presentation of a lesion confined to the choroid plexus of the lateral ventricle with significant parenchymal edema is unusual and demonstrates that Nocardia abscesses must be considered in the differential diagnosis of a contrast-enhancing intraventricular mass lesion involving the choroid plexus.

Brain Abscess↗
PubMed1998

Unemployment and underemployment in 1996 graduates of New York City gastroenterology training programs.

OBJECTIVE: Based on anecdotal reports of young gastroenterologists facing extreme difficulty in finding a job, we sought to gain information about the success of newly trained gastroenterologists in finding employment in their subspecialty, and to find any possible predictors of unemployment. METHODS: We surveyed all fellows finishing basic or advanced gastroenterology fellowship training in New York City in June 1996. Data were collected on unemployment, underemployment (practicing less than half-time gastroenterology), and also type of job, employment terms, training program, medical school, gender, and satisfaction with job plans. RESULTS: Of the 59 study subjects who sought gastroenterology employment in the United States, data were collected on all of them (100%). Fifteen subjects (25%) were unemployed. An additional 10 subjects (17%) were underemployed. Of the 24 subjects expecting to be associates in a group practice, eight (33%) had either no signed contract, were underemployed, or both. Programs that did not participate in the National Residency Matching Program were more likely to have both unemployed and underemployed graduates. CONCLUSION: Unemployment among newly trained gastroenterologists in New York City is very high. Also, there is substantial underemployment, and this phenomenon needs to be taken into account when studying the workforce.

Data Collection↗
PubMed1996

Cell motility driven by actin polymerization.

Certain kinds of cellular movements are apparently driven by actin polymerization. Examples include the lamellipodia of spreading and migrating embryonic cells, and the bacterium Listeria monocytogenes, that propels itself through its host's cytoplasm by constructing behind it a polymerized tail of cross-linked actin filaments. Peskin et al. (1993) formulated a model to explain how a polymerizing filament could rectify the Brownian motion of an object so as to produce unidirectional force (Peskin, C., G. Odell, and G. Oster. 1993. Cellular motions and thermal fluctuations: the Brownian ratchet. Biophys. J. 65:316-324). Their "Brownian ratchet" model assumed that the filament was stiff and that thermal fluctuations affected only the "load," i.e., the object being pushed. However, under many conditions of biological interest, the thermal fluctuations of the load are insufficient to produce the observed motions. Here we shall show that the thermal motions of the polymerizing filaments can produce a directed force. This "elastic Brownian ratchet" can explain quantitatively the propulsion of Listeria and the protrusive mechanics of lamellipodia. The model also explains how the polymerization process nucleates the orthogonal structure of the actin network in lamellipodia.

Actins↗
PubMed1996

Central motor loop oscillations in parkinsonian resting tremor revealed by magnetoencephalography.

A variety of clinical and experimental findings suggest that parkinsonian resting tremor results from the involuntary activation of a central mechanism normally used for the production of rapid voluntary alternating movements. However, such central motor loop oscillations have never been directly demonstrated in parkinsonian patients. Using magnetoencephalography, we recorded synchronized and tremor-related neuromagnetic activity over wide areas of the frontal and parietal cortex. The spatial and temporal organization of this activity was studied in seven patients suffering from early-stage idiopathic Parkinson's disease (PD). Single equivalent current dipole (ECD) analysis and fully three-dimensional distributed source solutions (magnetic field tomography, MFT) were used in this analysis. ECD and MFT solutions were superimposed on high-resolution MRI. The findings indicate that 3 to 6 Hz tremor in PD is accompanied by rhythmic subsequent electrical activation at the diencephalic level and in lateral premotor, somatomotor, and somatosensory cortex. Tremor-evoked magnetic activity can be attributed to source generators that were previously described for voluntary movements. The interference of such slow central motor loop oscillations with voluntary motor activity may therefore constitute a pathophysiologic link between tremor and bradykinesia in PD.

Aged↗
PubMed1996

Selecting a common direction. II. Peak-like solutions representing total alignment of cell clusters.

The problem of alignment of cells (or other objects) that interact in an angle-dependent way was described in Mogilner and Edelstein-Keshet (1995). In this sequel we consider in detail a special limiting case of nearly complete alignment. This occurs when the rotational diffusion of individual objects becomes very slow. In this case, the motion of the objects is essentially deterministic, and the individuals or objects tend to gather in clusters at various orientations. (Numerical solutions show that the angular distribution develops sharp peaks at various discrete orientations.) To understand the behaviour of the deterministic models with analytic tools, we represent the distribution as a number of delta-like peaks. This approximation of a true solution by a set of (infinitely sharp) peaks will be referred to as the peak ansatz. For weak but nonzero angular diffusion, the peaks are smoothed out. The analysis of this case leads to a singular perturbation problem which we investigate. We briefly discuss other applications of similar techniques.

Animals↗
PubMed1994

Neuromagnetic studies of the lip area of primary somatosensory cortex in humans: evidence for an oscillotopic organization.

Magnetic trigeminal somatosensory responses from human subjects were recorded using a 14-channel magnetoencephalographic system. Sensory stimuli comprising a 15-ms vibration at frequencies of 50 Hz, 150 Hz and 250 Hz were given at randomized interstimulus intervals. Using a single dipole model, the neuronal sources of the evoked responses were determined, and mapped onto magnetic resonance images of each subject. Source localization analysis was based on the main peak of the averaged signal (M55). All of the sources were located deep in the anterior bank of the postcentral gyrus, corresponding to area 3b of somatosensory cortex SI. In all cases, the source for the upper lip was significantly higher in the vertical axis (0.6-1.1 cm) than for the lower lip, while the lower lip stimulation produced a larger response than the upper lip. Furthermore, statistically significant differences were found between the locations of the dipoles evoked by different frequency stimulation. The location of the response shifted with change in stimulation frequency, showing a trend among all subjects with medial shift between 150 and 250 Hz for both upper and lower lip. The accuracy of source localization calculated from magnetic fields ranged between +/- 0.9 and +/- 3.0 mm (SEM). These results demonstrate (1) that a large area of the somatosensory cortex is utilized for lip representation and (2) that the spatial displacement of the trigeminal somatosensory response may be related to the discrimination of frequency.

Adult↗
PubMed1993

Somatosensory cortical plasticity in adult humans revealed by magnetoencephalography.

Microelectrode recordings in adult mammals have clearly demonstrated that somatosensory cortical maps reorganize following peripheral nerve injuries and functional modifications; however, such reorganization has never been directly demonstrated in humans. Using magnetoencephalography, we have been able to demonstrate the somatotopic organization of the hand area in normal humans with high spatial precision. Somatosensory cortical plasticity was detected in two adults who were studied before and after surgical separation of webbed fingers (syndactyly). The presurgical maps displayed shrunken and nonsomatotopic hand representations. Within weeks following surgery, cortical reorganization occurring over distances of 3-9 mm was evident, correlating with the new functional status of their separated digits. In contrast, no modification of the somatosensory map was observed months following transfer of a neurovascular skin island flap for sensory reconstruction of the thumb in two subjects in whom sensory transfer failed to occur.

Adult↗
PubMed1991

Magnetic field tomography of coherent thalamocortical 40-Hz oscillations in humans.

This paper introduces the use of magnetic field tomography (MFT), a noninvasive technique based on distributed source analysis of magnetoencephalography data, which makes possible the three-dimensional reconstruction of dynamic brain activity in humans. MFT has a temporal resolution better than 1 msec and a spatial accuracy of 2-5 mm at the cortical level, which deteriorates to 1-3 cm at depths of 6 cm or more. MFT is used here to visualize the origin of a spatiotemporally organized pattern of coherent 40-Hz electrical activity. This coherence, initially observed during auditory input, was proposed to be generated by recurrent corticothalamic oscillation. In support of this hypothesis, we illustrate well-defined 40-Hz coherence between cortical-subcortical sites with a time shift that is consistent with thalamocortical conduction times. Studies on Alzheimer patients indicate that, while a similar activity pattern is present, the cortical component is reduced in these subjects.

Adult↗
PubMedDate not supplied

Awareness and attitudes concerning BRCA gene testing.

BACKGROUND: The availability of a commercial test for the breast cancer susceptibility genes, BRCA1 and BRCA2, has generated interest in both the medical community and the general public. METHODS: Patients and family members were approached in the waiting room and asked to fill out an anonymous questionnaire about their awareness of breast cancer genes and breast cancer gene testing, and their desire to be tested. chi2 analysis was used to analyze frequencies between groups. RESULTS: A total of 354 women completed a questionnaire concerning the breast cancer genes BRCA1 and BRCA2. The very young, the very old, and African-Americans were the least informed in terms of awareness of the genes and the availability of testing for the breast cancer susceptibility genes. Jewish people, people with a college education or beyond, people earning more than $30,000 a year, and Caucasians were more aware of the genes and of testing for these genes. Interest in being tested was similar in all groups, except for participants over 60 and those who had only an elementary-school education. CONCLUSIONS: Information concerning the breast cancer susceptibility genes has not reached the general public uniformly. A concerted effort is needed if this information is to be passed on to those people at risk.

Adult↗