The laws of genetics.

It used to be that high technology meant nuclear physics and missile systems, and presented the threat of physical destruction. Today, high tech means biotechnology and electronic communication systems, and the focus has shifted to concerns about more subtle problems like loss of privacy, inability to control personal information, and the discriminations and other adversities that often follow

Deposition of general ellipsoidal particles

We present a systematic overview of granular deposits composed of ellipsoidal particles with different particle shapes and size polydispersities. We study the density and anisotropy of such deposits as functions of size polydispersity and two shape parameters that fully describe the shape of a general ellipsoid. Our results show that, while shape influences significantly the macroscopic properties of the deposits, polydispersity plays apparently a secondary role. The density attains a maximum for a particular family of non-symmetrical ellipsoids, larger than the density observed for prolate or oblate ellipsoids. As for anisotropy measures, the contact forces show are increasingly preferred along the vertical direction as the shape of the particles deviates for a sphere. The deposits are constructed by means of an efficient molecular dynamics method, where the contact forces are efficiently and accurately computed. The main results are discussed in the light of applications for porous media models and sedimentation processes.Comment: 7 pages, 8 figure

Sculpting the hippocampus from within: stress, spines, and CRH.

Learning and memory processes carried out within the hippocampus are influenced by stress in a complex manner, and the mechanisms by which stress modulates the physiology of the hippocampus are not fully understood. This review addresses how the production and release of the neuropeptide corticotropin-releasing hormone (CRH) within the hippocampus during stress influences neuronal structure and hippocampal function. CRH functions in the contexts of acute and chronic stresses taking place during development, adulthood and aging. Current challenges are to uncover how the dynamic actions of CRH integrate with the well-established roles of adrenal-derived steroid stress hormones to shape the cognitive functions of the hippocampus in response to stress

Calculation of the Density of States Using Discrete Variable Representation and Toeplitz Matrices

A direct and exact method for calculating the density of states for systems with localized potentials is presented. The method is based on explicit inversion of the operator $E-H$. The operator is written in the discrete variable representation of the Hamiltonian, and the Toeplitz property of the asymptotic part of the obtained {\it infinite} matrix is used. Thus, the problem is reduced to the inversion of a {\it finite} matrix

Diffusional Relaxation in Random Sequential Deposition

The effect of diffusional relaxation on the random sequential deposition process is studied in the limit of fast deposition. Expression for the coverage as a function of time are analytically derived for both the short-time and long-time regimes. These results are tested and compared with numerical simulations.Comment: 9 pages + 2 figure

How do the many etiologies of West syndrome lead to excitability and seizures? The corticotropin releasing hormone excess hypothesis.

West syndrome (WS) is associated with diverse etiological factors. This fact has suggested that there must be a 'final common pathway' for these etiologies, which operates on the immature brain to result in WS only at the maturational state present during infancy. Any theory for the pathogenesis of WS has to account for the unique features of this disorder. For example, how can a single entity have so many etiologies? Why does WS arise only in infancy, even when a known insult had occurred prenatally, and why does it disappear? Why is WS associated with lasting cognitive dysfunction? And, importantly, why do these seizures--unlike most others--respond to treatment by a hormone, ACTH? The established hormonal role of ACTH in human physiology is to function in the neuroendocrine cascade of the responses to all stressful stimuli, including insults to the brain. As part of this function, ACTH is known to suppress the production of corticotropin releasing hormone (CRH), a peptide that is produced in response to diverse insults and stressors.The many etiologies of WS all lead to activation of the stress response, including increased production and secretion of the stress-neurohormone CRH. CRH has been shown, in infant animal models, to cause severe seizures and death of neurons in areas involved with learning and memory. These effects of CRH are restricted to the infancy period because the receptors for CRH, which mediate its action on neurons, are most abundant during this developmental period. ACTH administration is known to inhibit production and release of CRH via a negative feedback mechanism. Therefore, the efficacy of ACTH for WS may depend on its ability to decrease the levels of the seizure-promoting stress-neurohormone CRH.This CRH-excess theory for the pathophysiology of WS is consistent not only with the profile of ACTH effects, but also with the many different 'causes' of WS, with the abnormal ACTH levels in the cerebrospinal fluid of affected infants and with the spontaneous disappearance of the seizures. Furthermore, if CRH is responsible for the seizures, and CRH-mediated neuronal injury contributes to the worsened cognitive outcome of individuals with WS, then drugs which block the actions of CRH on its receptors may provide a better therapy for this disorder

The Influence of Unpredictable, Fragmented Parental Signals on the Developing Brain

Mental illnesses originate early in life, governed by environmental and genetic factors. Because parents are a dominant source of signals to the developing child, parental signals - beginning with maternal signals in utero - are primary contributors to children’s mental health. Existing literature on maternal signals has focused almost exclusively on their quality and valence (e.g. maternal depression, sensitivity). Here we identify a novel dimension of maternal signals: their patterns and especially their predictability/unpredictability, as an important determinant of children’s neurodevelopment. We find that unpredictable maternal mood and behavior presage risk for child and adolescent psychopathology. In experimental models, fragmented/unpredictable maternal care patterns directly induce aberrant synaptic connectivity and disturbed maturation of cognitive and emotional brain circuits, with commensurate memory problems and anhedonia-like behaviors. Together, our findings across species demonstrate that patterns of maternal signals influence brain circuit maturation, promoting resilience or vulnerability to mental illness

Dexamethasone Attenuates Hyperexcitability Provoked by Experimental Febrile Status Epilepticus.

The role of neuroinflammation in the mechanisms of epilepsy development is important because inflammatory mediators provide tractable targets for intervention. Inflammation is intrinsically involved in the generation of childhood febrile seizures (FSs), and prolonged FS [febrile status epilepticus (FSE)] precedes a large proportion of adult cases of temporal lobe epilepsy (TLE). As TLE is often refractory to therapy and is associated with serious cognitive and emotional problems, we investigated whether its development can be prevented using anti-inflammatory strategies. Using an immature rat model of FSE [experimental FSE (eFSE)], we administered dexamethasone (DEX), a broad anti-inflammatory agent, over 3 d following eFSE. We assessed eFSE-provoked hippocampal network hyperexcitability by quantifying the presence, frequency, and duration of hippocampal spike series, as these precede and herald the development of TLE-like epilepsy. We tested whether eFSE provoked hippocampal microgliosis, astrocytosis, and proinflammatory cytokine production in male and female rats and investigated blood-brain barrier (BBB) breaches as a potential contributor. We then evaluated whether DEX attenuated these eFSE sequelae. Spike series were not observed in control rats given vehicle or DEX, but occurred in 41.6% of eFSE-vehicle rats, associated with BBB leakage and elevated hippocampal cytokines. eFSE did not induce astrocytosis or microgliosis but provoked BBB disruption in 60% of animals. DEX significantly reduced spike series prevalence (to 7.6%) and frequency, and abrogated eFSE-induced cytokine production and BBB leakage (to 20%). These findings suggest that a short, postinsult intervention with a clinically available anti-inflammatory agent potently attenuates epilepsy-predicting hippocampal hyperexcitability, potentially by minimizing BBB disruption and related neuroinflammation