Annotated interictal discharges in intracranial EEG sleep data and related machine learning detection scheme.

Interictal epileptiform discharges (IEDs) such as spikes and sharp waves represent pathological electrophysiological activities occurring in epilepsy patients between seizures. IEDs occur preferentially during non-rapid eye movement (NREM) sleep and are associated with impaired memory and cognition. Despite growing interest, most studies involving IED detections rely on visual annotations or employ simple amplitude threshold approaches.

Quantification of Osteoclasts in Culture, Powered by Machine Learning.

osteoclastogenesis is a central assay in bone biology to study the effect of genetic and pharmacologic cues on the differentiation of bone resorbing osteoclasts. To date, identification of TRAP+ multinucleated cells and measurements of osteoclast number and surface rely on a manual tracing requiring specially trained lab personnel. This task is tedious, time-consuming, and prone to operator bias.

Rich cell-type-specific network topology in neocortical microcircuitry.

Uncovering structural regularities and architectural topologies of cortical circuitry is vital for understanding neural computations. Recently, an experimentally constrained algorithm generated a dense network reconstruction of a ∼0.3-mm volume from juvenile rat somatosensory neocortex, comprising ∼31,000 cells and ∼36 million synapses.

Biogerontology research in Israel.

Studies on biogerontology in Israel are reviewed in relation to the academic and medical research setup, as well as to a variety of gerontological bodies that contribute to promotion of the research. Studies on the biology of aging are outlined with a view also on the relevance and possible applications to medicine. The various topics encompass longevity-associated genes, effects of calorie restriction, including studies on the experimental model of the alpha-MUPA mutant mouse, as well as basic issues regarding the central nervous system and skeletal tissues.

Past-future information bottleneck in dynamical systems.

Biological systems need to process information in real time and must trade off accuracy of presentation and coding costs. Here we operationalize this trade-off and develop an information-theoretic framework that selectively extracts information of the input past that is predictive about the output future, obtaining a generalized eigenvalue problem. Thereby, we unravel the input history in terms of structural phase transitions corresponding to additional dimensions of a state space.

The minimum information principle and its application to neural code analysis.

The study of complex information processing systems requires appropriate theoretical tools to help unravel their underlying design principles. Information theory is one such tool, and has been utilized extensively in the study of the neural code. Although much progress has been made in information theoretic methodology, there is still no satisfying answer to the question: "What is the information that a given property of the neural population activity (e.

Correlations between groups of premotor neurons carry information about prehension.

How distinct parameters are bound together in brain activity is unknown. Combination coding by interneuronal interactions is one possibility, but, to coordinate parameters, interactions between neuronal pairs must carry information about them. To address this issue, we recorded neural activity from multiple sites in the premotor cortices of monkeys that memorized reach direction and grasp type followed by actual prehension.

Evidence-based roads to the promotion of health in old age.

The increase in life expectancy, along with the accompanying ongoing increase in the proportion and absolute numbers of nonagenarians and centenarians have set forth the curiosity regarding the question of the quality of health in very old age. Studies on that issue have pointed to the fact that the very old people are actually healthier than originally predicted on the basis of the earlier studies on aging. Current efforts are thus invested in elucidating the possible basis of health in the very old people, as well as better understanding of potential causes of frailty and common diseases in old age.

Protein synthesis inhibitors and the chemical chaperone TMAO reverse endoplasmic reticulum perturbation induced by overexpression of the iodide transporter pendrin.

An outcome of overloading of the endoplasmic reticulum (ER) folding machinery is a perturbation in ER function and the formation of intracellular aggregates. The latter is a key pathogenic factor in numerous diseases known as ER storage diseases. Here, we report that heterologous overexpression of the green fluorescent protein-tagged iodide transporter pendrin (GFP-PDS) perturbs folding and degradation processes in the ER.

What accounts for the wide variation in life span of genetically identical organisms reared in a constant environment?

Individual organisms show marked variability in life span, even when they are of the same genotype and are raised in a common environment protected from extrinsic hazards. This intrinsic variability of life span is thought to arise from the stochastic nature of the cellular and molecular mechanisms controlling development and ageing. In this article we review what is currently understood about the factors underlying the variability of life span and consider the implications for research that aims to improve the predictability of health in old age.

The voyage to healthy longevity: from experimental models to the ultimate goal.

Understanding mechanisms underlying longevity, and endeavor towards the specific goals of alleviating frailty in old age, require a comprehensive approach that considers the various theoretical and experimental approaches, as well as compiling the data on humans. This logistic has underlined the program of the conference, and is reflected in the present special issue. Considerable volume of data now point to distinct genes that are associated with exceptional longevity in humans, as reflected from the articles in this volume.

Tumor necrosis factor promotes human T-cell development in nonobese diabetic/severe combined immunodeficient mice.

A major problem after clinical hematopoietic stem cell transplantations is poor T-cell reconstitution. Studying the mechanisms underlying this concern is hampered, because experimental transplantation of human stem and progenitor cells into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice usually results in low T-lymphocyte reconstitution. Because tumor necrosis factor alpha (TNFalpha) has been proposed to play a role in T-lineage commitment and differentiation in vitro, we investigated its potential to augment human T-cell development in vivo.

Age related microsatellite instability in T cells from healthy individuals.

Many immune functions decline with age and may jeopardize the elderly, as illustrated, for example by the significantly higher mortality rate from influenza in old age. Although innate and humoral immunity are affected by aging, it is the T cell compartment, which manifests most alterations. The mechanisms behind these alterations are still unclear, and several explanations have been offered including thymic involution and Telomere attrition leading to cell senescence.

T cells and aging, January 2002 update.

Age-related changes in the immune system may contribute to morbidity and mortality due to decreased resistance to infection and, possibly, certain cancers in the aged. Many studies mostly performed in mice, rats and man but also including monkeys and dogs have established that age-associated immune decline is characterized by decreases in both humoral and cellular responses. The former may be largely a result of the latter, because observed changes both in the B cell germline-encoded repertoire and the age-associated decrease in somatic hypermutation of the B cell antigen receptors are now known to be critically affected by helper T cell aging.

Hematopoietic cells and replicative senescence.

Replicative senescence describes the finite cell replicative capacity in response to chronic proliferative stimulation. A key element in this process is the shortening of the telomeres, which to a major extent is caused by the lack of expression of telomerase. Whereas this situation has been well documented for a variety of somatic cell types, the question of whether stem cells "senesce" in the course of enforced chronic sequential divisions is as yet unresolved.

The center for multidisciplinary research in aging (CMRA) at Ben Gurion University of the Negev in Israel.

The Center for Multidisciplinary Research in Aging (CMRA) was established at Ben Gurion University of the Negev (BGU) in Beer Sheva in 2000, to promote research in the different disciplines of gerontology and geriatrics. It benefits from the special features of that university compared to other academic institutions in Israel and from the regional uniqueness of its location, in the southern part of Israel. CMRA serves as a comprehensive outreach unit for collaborative projects, as well as training programs and organization of professional meetings on aging.

Haematopoietic stem cell ageing.

The question of whether haematopoietic stem cells age has raised considerable controversy, and has been re-opened recently, as a result of the growing interest in stem cells for transplantation and gene therapy. Studies have focused on the generation of different blood cell elements and the capacity for self-renewal; properties that characterize stem cells. Taken together, it appears that basal haematopoiesis is maintained throughout life, yet, the capacity to cope with haematological stress is decreased in advanced age.

Ageing and the mismatch repair system.

Age-related accumulation of mutations has been extensively documented, and it has been proposed as one of the prominent causes of malignancies in old age. The present review is focused on the particular case of DNA mismatch repair system (MMR), that has drawn increased attention for its possible relevance to malignancy. We also report on our own observations on an age-associated genomic instability that develops with age in the MMR system.

Biogerontology research in Israel.

The article describes the special features of gerontology research that has been expanding for five decades in Israel, and outlines the research in the biology of aging, covering a wide spectrum of areas and topics. A variety of associations, institutes and centers that have been established over the years play an important role in furthering the research and academic training.

Effect of aging on cytokine production in normal and experimental systemic lupus erythematosus-afflicted mice.

Aging mice of strains susceptible to the induction of experimental systemic lupus erythematosus (SLE) develop a milder disease than young animals. To find out whether the decrease in susceptibility to disease is due to age-associated changes in cytokine profile, we first examined the secretion of cytokines by healthy mice aged 2-15 months. A gradual age-related decline in the levels of interleukin (IL)-2 and interferon (IFN) gamma, and an increase in IL-4, IL-10, IL-1, and tumor necrosis factor (TNF) alpha were observed.

AlphaMUPA mice: a transgenic model for increased life span.

AlphaMUPA is a line of transgenic mice that, compared with their wild type (WT) counterparts, spontaneously eat less (approximately 20%) and live longer (average approximately 20%), thus resembling dietary-restricted (DR) mice. Here, we show that body temperature was significantly reduced in alphaMUPA compared with WT throughout a wide range of ages. Plasma corticosterone was significantly higher in young alphaMUPA compared to young WT; however, it significantly declined in aged alphaMUPA, but not in aged WT.

Hematopoietic stem cells and aging.

The question of whether hematopoietic stem cells are altered in aging has been the subject of considerable controversy for over two decades. The substantial advancement of knowledge on hematopoietic stem cells and developmental hematology in the last few years has reopened this issue for critical analysis. Dynamic changes have been noted regarding the anatomic site and the function of hematopoietic cells, from the early embryo to old age.