Bioelectrical signals and ion channels in the modeling of multicellular patterns and cancer biophysics

Bioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level

Optimization of Fast Penetration Tests for Rheology Control in 3D Printing Concrete

3D printing concrete must meet demanding requirements in terms of its rheology, which also needs to evolve to adapt to each stage of the printing process. As a result, a thorough control of the rheology during printing is essential for its success. However, the rheological characteristics of 3D-printed con-crete (particularly its yield stress) differ significantly from those displayed by conventional ones. Thus, conventional laboratory tools are generally not suitable for the measurement range required by 3D-printed concretes. Also, for a test method to be applicable for the monitoring of 3D printing, extra requirements must be met, such as being fast, simple and with little sample preparation. This work presents the use of fast penetration tests as a simple method for in situ control of the yield stress of 3D-printed concrete. The study is initially focused on the identification of parameters that may affect the robustness and repeatability of the test for various penetration probe geometries. For this purpose, several tests were carried out on non-aging pure plastic materials (i.e. clays) using penetration probes of different geometries and sizes and varying the test conditions (penetration speed, user and sample shape). The results indicate that the robustness and dispersion of the results are closely related to the geometry of the penetration probe. In that sense, probe geometries that minimize the user dependence and present an adequate size compared to the sample and aggregate size provided optimal results. The clays were tested by additional methods (squeeze test and pocket vane) to obtain equivalence between penetration forces and yield stress. Finally, the method feasibility was tested on 3D printed samples and compared with the results obtained by pocket vane tests

Targeted ablation and reorganization of the principal preplate neurons and their neuroblasts identified by golli promoter transgene expression in the neocortex of mice

The present study delineates the cellular responses of dorsal pallium to targeted genetic ablation of the principal preplate neurons of the neocortex. Ganciclovir treatment during prenatal development (E11–E13; where E is embryonic day) of mice selectively killed cells with shared S-phase vulnerability and targeted expression of a GPT [golli promoter transgene, linked to HSV-TK (herpes simplex virus-thymidine kinase), τ-eGFP (τ-enhanced green fluorescent protein) and lacZ (lacZ galactosidase) reporters] localized in preplate neurons. Morphogenetic fates of attacked neurons and neuroblasts, and their successors, were assessed by multiple labelling in time-series comparisons between ablated (HSV-TK+/0) and control (HSV-TK0/0) littermates. During ablation generation, neocortical growth was suppressed, and compensatory reorganization of non-GPT ventricular zone progenitors of dorsal pallium produced replacements for killed GPT neuroblasts. Replacement and surviving GPT neuroblasts then produced replacements for killed GPT neurons. Near-normal restoration of their complement delayed the settlement of GPT neurons into the reconstituted preplate, which curtailed the outgrowth of pioneer corticofugal axons. Based on this evidence, we conclude that specific cell killing in ablated mice can eliminate a major fraction of GPT neurons, with insignificant bystander killing. Also, replacement GPT neurons in ablated mice originate exclusively by proliferation from intermediate progenitor GPT neuroblasts, whose complement is maintained by non-GPT progenitors for inductive regulation of the total complement of GPT neurons. Finally, GPT neurons in both normal and ablated mice meet all morphogenetic criteria, including the ‘outside-in’ vertical gradient of settlement, presently used to identify principal preplate neurons. In ablated mice, delayed organization of these neurons desynchronizes and isolates developing neocortex from the rest of the brain, and permanently impairs its connectivity

Limb-shaking transient ischemic attacks: case report and review of literature

BACKGROUND: Limb shaking Transient Ischemic Attack is a rare manifestation of carotid-occlusive disease. The symptoms usually point towards a seizure like activity and misdiagnosed as focal seizures. On careful history the rhythmic seizure like activity reveals no Jacksonian march mainly precipitated by maneuvers which lead to carotid compression. We here present a case of an elderly gentleman who was initially worked up as suffering from epileptic discharge and then later on found to have carotid occlusion. CASE PRESENTATION: Elderly gentleman presented with symptoms of rhythmic jerky movements of the left arm and both the lower limbs. Clinical suspicion of focal epilepsy was made and EEG, MRI-Brain with MRA were done. EEG and MRI-Brain revealed normal findings but the MRA revealed complete occlusion of right internal carotid artery. On a follow-up visit jerky movements of the left arm were precipitated by hyperextension and a tremor of 3–4 Hz was revealed. Based on this the diagnosis of low flow TIA was made the patient was treated conservatively with adjustment of his anti-hypertensive and anti-platelet medications. CONCLUSION: Diagnosis of limb-shaking TIA is important and should be differentiated from other disorders presenting as tremors. Timely diagnosis is important as these patients are shown to benefit from reperfusion procedures either surgical or radiological reducing their risk of stroke

Long-term prognosis of symptomatic isolated middle cerebral artery disease in Korean stroke patients

<p>Abstract</p> <p>Background</p> <p>This study aimed to investigate the long-term mortality and recurrence rate of stroke in first-time stroke patients with symptomatic isolated middle cerebral artery disease (MCAD) under medical management.</p> <p>Methods</p> <p>We identified 141 first ever stroke patients (mean age, 64.4 ± 12.5 years; 53% male) with symptomatic isolated MCAD. MCAD was defined as significant stenosis of more than 50% or occlusion of the MCA as revealed by MR angiography. The median follow-up was 27.7 months. We determined a cumulative rate of stroke recurrence and mortality by Kaplan-Meier survival analyses and sought predictors using the Cox proportional hazard model.</p> <p>Results</p> <p>The cumulative composite outcome rate (stroke recurrence or any-cause death) was 14%, 19%, 22%, and 28% at years 1, 2, 3, and 5, respectively. The annual recurrence rate of stroke was 4.1%. The presence of diabetes mellitus was the only significant independent predictor of stroke recurrence or any cause of death in multivariate analyses of Cox proportional hazard model adjusted for any plausible potential confounding factors.</p> <p>Conclusions</p> <p>We estimated the long-term prognosis of stroke patients with isolated symptomatic MCAD under current medical management in Korea. Diabetes mellitus was found to be a significant predictor for stroke recurrence and mortality.</p

Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium

<p>Abstract</p> <p>Background</p> <p>The modulation of gap junctional communication between tumor cells and between tumor and vascular endothelial cells during tumorigenesis and metastasis is complex. The notion of a role for loss of gap junctional intercellular communication in tumorigenesis and metastasis has been controversial. While some of the stages of tumorigenesis and metastasis, such as uncontrolled cell division and cellular detachment, would necessitate the loss of intercellular junctions, other stages, such as intravasation, endothelial attachment, and vascularization, likely require increased cell-cell contact. We hypothesized that, in this multi-stage scheme, connexin-43 is centrally involved as a cell adhesion molecule mediating metastatic tumor attachment to the pulmonary endothelium.</p> <p>Methods</p> <p>Tumor cell attachment to pulmonary vasculature, tumor growth, and connexin-43 expression was studied in metastatic lung tumor sections obtained after tail-vein injection into nude mice of syngeneic breast cancer cell lines, overexpressing wild type connexin-43 or dominant-negatively mutated connexin-43 proteins. High-resolution immunofluorescence microscopy and Western blot analysis was performed using a connexin-43 monoclonal antibody. Calcein Orange Red AM dye transfer by fluorescence imaging was used to evaluate the gap junction function.</p> <p>Results</p> <p>Adhesion of breast cancer cells to the pulmonary endothelium increased with cancer cells overexpressing connexin-43 and markedly decreased with cells expressing dominant-negative connexin-43. Upregulation of connexin-43 was observed in tumor cell-endothelial cell contact areas <it>in vitro </it>and <it>in vivo</it>, and in areas of intratumor blood vessels and in micrometastatic foci.</p> <p>Conclusion</p> <p>Connexin-43 facilitates metastatic 'homing' by increasing adhesion of cancer cells to the lung endothelial cells. The marked upregulation of connexin-43 in tumor cell-endothelial cell contact areas, whether in preexisting 'homing' vessels or in newly formed tumor vessels, suggests that connexin-43 can serve as a potential marker of micrometastases and tumor vasculature and that it may play a role in the early incorporation of endothelial cells into small tumors as seeds for vasculogenesis.</p

Growth and mortality estimates of Sardinella brasiliensis in the southeastern Brazilian Bight

Length frequency analisys were applied for sardine data collected from commercial catches throughout the southeastern Brazilian coast in 1977-1987. Age/length keys were obtained by otolith ring countings and utilized to transform length into age composition. Growth parameters were estimated by the von Bertalanffy growth equation using age and length data for each year and for all the period of investigation. The mean growth parameters for the entire period were estimated as L&#8734; = 271 mm and K= 0.59 year-1. Instantaneous total mortality (Z) coefficients per year were estimated using catch curves and methods based on the mean length of the fish caught. Total mortality rate for the entire period was obtained through the average of the annual values. Natural mortality (M) was estimated using the Paul/s empirical equation (1980a), and fishing mortality (F) by the difference between total and natural mortality values.The results were Z = 3.6 year-1; M = 0.96 year-1; and F= 2.6 year-1.Estudo sobre o crescimento e a mortalidade de Sardinella brasiliensis, da costa sudeste do Brasil, foi realizado para o período 1977 a 1987. As análises foram efetuadas a partir de dados existentes sobre distribuições de freqüência de comprimento de amostras da captura comercial. Chaves idade/comprimento, construidas a partir de leitura de anéis de crescimento em otólitos, dentro do Programa Integrado de Estudos Biológicos sobre a Sardinha - PIEBS, foram utilizadas para transformar as distribuiçes de comprimento em idade. Os parâmetros de crescimento da equação de von Bertalanffy foram estimados, anualmente e para o período como um todo, a partir de métodos que utilizam dados de idade e comprimento. Os parâmetros médios encontrados para o período foram: L&#8734; = 271 mm e K= 0,59 ano-1. Os coeficientes instantâneos de mortalidade total (Z) anuais foram calculados pelas curvas de captura e por métodos baseados no comprimento médio dos indivíduos nas capturas. A mortalidade total para todo o período foi obtida pela média dos valores anuais. O coeficiente instantâneo de mortalidade natural (M) foi estimado pela equação empírica de Pauly (1980a), usando um fator de correção de 0,8 para clupeoides, e o coeficiente instantâneo de mortalidade por pesca (F), pela diferença entre a mortalidade total e a natural. Os valores encontrados foram: Z= 3,6 ano-1, M = 0,96 ano-1 e F= 2,6 ano-1