Small Groups Of Cells Research Articles

Building the gateway to consciousness—about the development of the thalamus

The thalamus is a twinned bulb-shaped structures that form at the top of the brainstem on either side of the third ventricle. The thalamic complex is located in the posterior forebrain and includes the prethalamus and thalamus (formerly known as ventral thalamus and dorsal thalamus, respectively). This complex is the major sensory relay station of the brain, receiving all inputs (except olfaction) and connecting reciprocally with the overlying cortex therefore, Crick and Koch (2003) has described the thalamus as “the gateway to consciousness.” Although, the thalamus has been anatomically characterized in vertebrates the underlying genetic mechanism leading to the formation of this complex brain area is largely unknown. In this special issue we tried to cover many aspects describing the development of the posterior forebrain i.e., the thalamus. The posterior forebrain can be subdivided in the epithalamus, the prethalamus (Figure ​(Figure1,1, indicated in yellow), the thalamus (Figure ​(Figure1,1, indicated in green), and the pretectum. Mechanisms regulating the formation and setting the boundaries between them are described in the article of Chatterjee and Li (2012). The crucial structure for the development of the thalamus is a small group of cells secreting different signaling molecules and is localized at the intrathalamic boundary, the zona limitans intrathalamica (ZLI). This cell population has been termed the mid-diencephalic organizer (MDO) or alternatively as ZLI organizer. The MDO releases three different families of signaling factors, Shh, Wnt, and Fgf. This network has been described in the articles of Hagemann and Scholpp (2012) focusing mainly on events in zebrafish and in Martinez-Ferre and Martinez (2012), who describe the situation in chick. Both group described that the principal signal of the MDO is Shh, which is conserved in different animals (Figure ​(Figure1,1, expression domain of Shh indicated in red). Therefore, we elucidate the function of Shh in mice more in detail in two articles. Epstein (2012) focuses in his article on the description of the function of this signaling factor, whereas Haddad-Tovolli et al. (2012) focuses on the regulators downstream of Shh signaling, the GLI transcription factors. Pre-patterning of the thalamic tissue is essential for the axonal projections of the thalamus and the most important axonal output of this structure is the thalamo-cortical projection. Price et al. (2012) and Grant et al. (2012) review recent progress of the development of these projections and axonal guidance. The zebrafish serves as a novel vertebrate model organism in thalamic development, however, the comparability to the mammalian systems is difficult. In a comparative review (Mueller, 2012) summarizes anatomical similarities and differences of the thalamus in different model organisms. Dorsally adjacent to the thalamus is the location of the habenula. The development of the connection to the thalamic tissue has been elucidated by two articles from Beretta et al. (2012) and Aizawa et al. (2011). Figure 1 Development of the thalamus in vertebrates. After our opinion, the special issue “Building the gateway to consciousness—about the development of the thalamus” summarizes recent efforts in understanding the formation of thalamus in vertebrates and we carefully selected carefully articles covering the entire field. However, it is impossible to elucidate any aspect in sufficient detail and we would like to apologize to our colleagues for potential gaps. We wish all scientist as much as fun in reading the articles as we had in assembling it and sincerely hope that this special issue helps the field of thalamus development to find the scientific recognition it deserves.

Incidence of preclinical manifestations of mantle cell lymphoma and mantle cell lymphoma in situ in reactive lymphoid tissues

Recently, the occurrence of cyclin D1-positive B cells with mantle cell lymphoma phenotype in the inner mantle zones of morphologically inconspicuous lymph nodes has been described and termed mantle cell lymphoma 'in situ'. Prevalence and clinical significance of this lesion and related minimal mantle cell lymphoma infiltrates in reactive lymphoid tissues of healthy individuals, and of mantle cell lymphoma patients are unknown. All 1292 reactive lymph nodes from unselected consecutive surgical specimens of 131 patients without a history of lymphoma obtained over a 3-month period were stained for cyclin D1. In addition, all morphologically reactive lymph nodes and benign-appearing extranodal lymphoid infiltrates of patients diagnosed with mantle cell lymphoma in the years 2000–2011 were studied. Samples predating the lymphoma diagnosis for at least 2 months were available from 37/423 (9%) patients. A mantle cell lymphoma 'in situ' was not identified in any of the two groups. However, in four patients with subsequent mantle cell lymphoma diagnosis, an early manifestation of mantle cell lymphoma was detected retrospectively, antedating the lymphoma diagnosis for 2–86 months. In six mantle cell lymphoma patients, only small groups of cyclin D1-positive cells in morphologically reactive extranodal infiltrates were detected >2 months before the diagnosis of mantle cell lymphoma (range 3–59 months). Mantle cell lymphoma 'in situ' is an extremely rare phenomenon in morphologically reactive lymph nodes, in line with the low prevalence of t(11;14)-positive cells described in the peripheral blood of a healthy population. In mantle cell lymphoma patients, however, immunohistochemically detectable infiltrates of mantle cell lymphoma cells antedating the lymphoma diagnosis were found in a significant proportion of cases (10/37=27%). These consisted either of early mantle cell lymphoma with mantle zone growth pattern, or small extranodal accumulations of cyclin D1+ cells, whereas typical mantle cell lymphoma 'in situ' was not detected.

Prognostic Significance of EpCAM-Positive Disseminated Tumor Cells in Rectal Cancer Patients With Stage I Disease

Here we evaluated the prevalence and prognostic impact of epithelial cell adhesion molecule (EpCAM)-positive disseminated tumor cells (DTCs) in stage I rectal cancer. Further we tested the association of these single tumor cells or small tumor cell groups with the extent of peritumoral lymphangiogenesis. A total of 845 regional lymph nodes (LN) of 44 patients classified as negative on conventional histopathology were retrospectively reanalyzed with immunohistochemistry (IHC) using the monoclonal antibody Ber-Ep4 directed against EpCAM for the detection of DTCs. The degree of lymphangiogenesis in the primary tumors was assessed by IHC of the primary tumor tissue using the monoclonal antibody D2-40, which reacts with the lymphatic endothelium. The IHC results were correlated with clinico-pathologic parameters and clinical follow-up data. EpCAM-positive DTCs in LNs were detected in 8 (18.2%) of the 44 patients. During a median follow-up of 59 months, 3 (37.5%) of the 8 patients with EpCAM-positive DTCs relapsed, whereas none of the DTC-negative patients developed tumor recurrence (P=0.004). Survival analysis revealed a significant effect of the prevalence of DTCs on overall survival (P=0.0009) and on recurrence-free survival (P=0.0001). Finally, the prevalence of EpCAM-positive DTCs in perirectal LNs was significantly correlated with a high density of peritumoral lymphatic vessels (P=0.015). Our results show that DTCs may occur in stage I of rectal cancer and are associated with poor prognosis. Their occurrence seems to be linked to a high density of newly formed lymphatic vessel at the primary tumor site. According to our data, patients with DTCs in their LN might benefit from adjuvant therapy.

Abstract 9940: Novel Function of the P2y/cysteinyl-leukotriene Receptor Gpr17 in Recruitment of Circulating and Resident Myofibroblast Progenitors Following Acute Myocardial Infarction

Background - GPR17 is a G i -coupled dual receptor activated by uracil-nucleotides and cysteinyl-leukotrienes, families of signaling molecules massively released into hypoxic tissues. In the normal heart GPR17 expression has been reported, while its role during ischemia is totally unknown. Aims and Results - To investigate GPR17 expression in mice hearts, before or after myocardial infarction (MI) induction, immunofluorescence was set up. In non ischemic hearts, GPR17 protein was confined into small cell groups localized between myocytes. These cells expressed the stem cell antigen-1 (Sca-1). At 24, 48 and 72 hrs post-MI, cell clusters expressing GPR17 were found to infiltrate the MI border zone and penetrate into the ischemic area. They expressed Sca-1, the myofibroblast/mesenchymal marker CD44 and the hematopoietic lineage marker CD45. Interestingly, not all cells expressing GPR17 also expressed CD45, suggesting a dual origin of GPR17 + cells recruited after MI. A flow-sorting experiment was performed to separate Sca-1 + /CD45 + from Sca-1 + /CD45 - cells at 48 hrs post-MI. RT-PCR showed that both cellular populations expressed GPR17, thus confirming their dual origin. A clonogenic Sca-1 + cell line was derived from non-ischemic hearts. In addition to CD44, these cells expressed mesenchymal markers CD29 and CD105, but not endothelial and hematopoietic markers, and showed a side population phenotype. Sca-1 + cells expressed GPR17 RNA/protein and were able to differentiate into cardiac lineage cells and myofibroblasts in culture. To investigate GPR17 functions, Sca-1 + cells were treated with receptor agonists UDP-Glucose (10nM) and LTD 4 (100nM). These ligands did not rescue cells from hypoxia-induced apoptosis. By contrast, they enhanced CSCs migratory activity (3.1±0.8 and 1.7±0.2, folds vs. control; P < .05 paired t-test). Finally, addition of GPR17 antagonists montelukast and cangrelor abolished this migratory effect. Conclusions - The present results indicate a role of dual GPR17 receptor in early homing of Sca-1 + cardiac stem cells-derived and circulatory stem cells-derived myofibroblasts into the infarcted myocardium. These findings have implications for the pharmacologic control of heart remodeling at early times after infarction.

28. Using Synchroton infrared microspectroscopy to better understand the freezing-resistance of lactic acid bacteria

Freezing is commonly applied to preserve the functionalities of concentrates of lactic acid bacteria (LAB). However, it is still a critical step in the production of LAB concentrates, as it affects both the viability and acidifying activity upon thawing. Several environmental factors influence the resistance to freezing of LAB (strain, medium composition, temperature, etc.) but the mechanisms of cell injury during freezing need to be elucidated. Cell dehydration taking place during freezing is an important event responsible for alterations of the physical state of membrane lipids and proteins, which, in turn, affect lipid organization and membrane fluidity. FTIR (Fourier Transformed InfraRed) spectroscopy and imaging technology appear to be powerful tools for investigating the biophysical response of LAB and for identifying some key issues in the understanding of the main mechanisms of bacteria degradation during freezing and thawing. In situ and in conditions close to industrial ones, FTIR spectroscopy has recently made it possible to investigate the modifications of the physical state of bacterial lipids of whole cell populations of Lactobacillus delbrueckii subsp. bulgaricus CFL1 (freezing sensitive strain) during freezing and thawing for two different physiological states, corresponding to different behaviours in terms of resistance to freezing and thawing processes. Fresh cells presenting the better resistance to freezing exhibited the lower lipid phase transition temperature, thus remaining in a liquid crystalline state for a longer time during the freezing process (Gautier et al. 2012). This study performed on bacterial suspensions and in real time during freeze–thaw processes, highlighted the difficulties for identifying and quantifying protein conformational changes because of the overlapping of the water band with the protein band. The objective of the present work was to investigate the changes in the secondary structure of proteins of some individual cells of Lb. bulgaricus CFL1 for these two extreme conditions, by using the brilliant Synchrotron infrared beamline SMIS (SOLEIL proposal number 20100789). High reflective index hemispheres (ZnSe) were used in order to get high spatial resolution (2–3 μm 2 ) making possible the quantification of the population heterogeneity and mapping of biophysical and chemical responses of small groups of cells. Concentrated suspensions of Lb. bulgaricus CFL1 were produced using standard procedure of fermentation in MRS broth or mild whey medium at 42 °C in the biology laboratory of SOLEIL Synchrotron. The bacteria were harvested at the beginning of the stationary phase growth, formulated (addition of protective medium), frozen by immersion in liquid nitrogen and stored at −20 and −80 °C. After thawing and washing, cells were dried onto ZnSe hemispheres. ATR (attenuated total reflectance) analysis on the amide I region of dehydrated bacterial suspensions was carried out to examine changes in the protein secondary structures. The impact of the physiological state (viability and acidifying activity) on cell biophysical behaviour and freezing-resistance was investigated by analysing samples before and after each storage conditions. Better resistance to freezing, characterized by a higher acidifying activity and cell survival, was observed for cells presenting a higher proportion of proteins in α-helix conformation. Furthermore, a study of the impact of freezing on the protein secondary structures is in progress.

Anisotropy of Crumbs and aPKC Drives Myosin Cable Assembly during Tube Formation

SummaryThe formation of tubular structures from epithelial sheets is a key process of organ formation in all animals, but the cytoskeletal rearrangements that cause the cell shape changes that drive tubulogenesis are not well understood. Using live imaging and super-resolution microscopy to analyze the tubulogenesis of the Drosophila salivary glands, I find that an anisotropic plasma membrane distribution of the protein Crumbs, mediated by its large extracellular domain, determines the subcellular localization of a supracellular actomyosin cable in the cells at the placode border, with myosin II accumulating at edges where Crumbs is lowest. Laser ablation shows that the cable is under increased tension, implying an active involvement in the invagination process. Crumbs anisotropy leads to anisotropic distribution of aPKC, which in turn can negatively regulate Rok, thus preventing the formation of a cable where Crumbs and aPKC are localized.

Neural coding of taste by simultaneously recorded cells in the nucleus of the solitary tract of the rat

The nucleus of the solitary tract (NTS) receives input from taste buds on the rostral tongue from the chorda tympani (CT) nerve. How this input is processed by the NTS was the subject of the present investigation. Here we used tetrodes to record from pairs or small groups of NTS cells as they responded to taste stimuli or electrical stimulation of the CT nerve in urethane-anesthetized rats. Once a pair (or small group) of NTS cells were isolated and identified as showing an evoked response to CT nerve stimulation, taste stimuli were presented in separate trials. Tastants consisted of 0.1 M NaCl, 0.01 M HCl, 0.01 M quinine HCl, and 0.5 M sucrose. Responses to various patterns of CT stimulation were then recorded. Functional connections among simultaneously recorded NTS cells were implied from analysis of cross-correlation functions of spike trains. We identified four groups of cells, not all of which responded to taste, with staggered latencies of response to CT nerve stimulation, ranging from ∼3 to 35 ms in ∼8- to 12-ms increments. Analyses of putative functional connectivity along with latencies of CT-evoked responses suggested that CT input arrives at the NTS in pulses or waves, each of which activates recurrent excitatory connections among NTS cells. These actions may amplify the incoming signal and refine its temporal pattern.

Combined SCLC Clinical and Pathologic Characteristics

IntroductionDespite the well characterized clinical course of ‘pure’ SCLC, there have not been many data on combined SCLC, ie, tumors, which contain both small-cell and non–small-cell components. Materials and MethodsWe analyzed 1628 consecutive cases of lung cancer (1200 NSCLC, 428 SCLC) at our institution over the past decade. We identified 22 patients with C-SCLC. The pathologic and clinical characteristics of these patients were reviewed. Survival analysis was performed and prognostic factors were assessed. These data were compared with the results obtained from our 406 pure SCLC patients who presented during the same time period. ResultsThe most common pathology was combined small-cell and large-cell with 16 cases followed by combined small- and squamous-cell carcinoma (3 cases), 2 cases of small-cell and nonspecified NSCLC, and 1 case of small cell and adenocarcinoma. Overall survival was significantly higher in C-SCLC patients compared with pure SCLC (median 15 vs. 10.8 months; P = .035). Surgery was significantly more common in this group of patients (45% vs. 3% in the pure small cell group; P < .0001). No difference in overall survival was observed in patients with C-SCLC and patients with pure SCLC, that did not receive surgery (P = .64). ConclusionPatients with combined SCLC carry a better prognosis than those with pure small-cell variety and are more likely to undergo surgery.

Nocturnal Hypoxemia, an Unusual Presentation of Pulmonary Endometriosis: A Case Report

Thoracic endometriosis syndrome is a rare condition with four main presentations: pneumothorax, hemothorax, hemoptysis, and lung nodules. We describe an incidental diagnosis of pulmonary endometriosis in a patient admitted with acute pyelonephritis, and developed acute hypoxemia and a productive cough of blood tinted sputum , on the third day of hospitalization. Her thoracic x-ray showed diffuse pulmonary infiltrates , and a small pleural effusion. C hest computerized tomography scan had extensive areas of ground glass opacifications scattered predominantly in the medulla of both lungs . B ronchoalveolar lavage c ytology showed small groups of cells in arrays compatible with endometrial cells, which confirmed the diagnosis of pulmonary endometriosis. On the seventh day of hospitalization, after the end of her menstrual bleeding, oxygen supplementation was discontinued, and hypoxemia did not recur. A chest x-ray at the ninth day of hospitalization was normal. Pulmonary endometriosis should be considered in a patient who has unexplained episodes of nocturnal hypoxemia associated with hemoptysis, especially if there is periodicity. doi: http://dx.doi.org/10.4021/jmc778w

Consequences of Many-Cell Correlations in Clocked Quantum-Dot Cellular Automata

Quantum-dot cellular automata (QCA) provides a basis for classical computation without transistors. Many simulations of QCA rely upon the so-called intercellular Hartree approximation (ICHA), which neglects the possibility of entanglement between cells. The ICHA was originally proposed as a solution to the problem of exponential scaling in the computational cost of fully quantum mechanical treatments. However, in some cases, the ICHA predicted errors in QCA operation, and quantum correlations were required for circuits to operate correctly. While quantum correlations can remedy certain problems that present themselves in ICHA calculations, here we present simulations that show that quantum correlations may in fact be problematic in other situations, such as clocked QCA. Small groups of QCA cells are modelled with a Hamiltonian analogous to a quantum mechanical Ising-like spin chain in a transverse field, including the effects of intercellular entanglement completely. When energy relaxation is included in the model, we find that intercellular entanglement changes the qualitative behavior of the system, and new features appear. In clocked QCA, isolated groups of active cells have a tendency to oscillate between polarization states as information propagates. Additionally, energy relaxation tends to bring groups of cells to an unpolarized steady state. This contrasts with the results of previous simulations, which employed the ICHA. The ICHA may in fact be a good approximation in the limit of very low tunneling rates, which can be realized in lithographically defined quantum dots. However, in molecular and atomic implementations of QCA, entanglement will play a greater role. The degree to which intercellular correlations pose a problem for memory, and clocking depends upon implementation-specific details of the interaction of the system with its environment, as well as the system's internal dynamics.

In This Issue

HomeCirculation ResearchVol. 110, No. 12In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessIn BriefPDF/EPUBIn This Issue Originally published8 Jun 2012https://doi.org/10.1161/RES.0b013e3182601cf2Circulation Research. 2012;110:1539Impulse Propagation of Cardiac Monolayers (p 1556)Lee et almake monolayers of iPS-derived cardiomyocytes and monitor their electrophysiology.Download figureDownload PowerPointThe derivation of human-induced pluripotent stem (iPS) cells from patients with heart disorders and the subsequent differentiation of these cells into cardiomyocytes provide an excellent renewable resource of cells for studying disease mechanisms and for testing potential therapies. To investigate disease mechanisms, researchers need accurate ways to assess the physiology, including electrophysiology, of these cells in culture. So far, such assessments have been possible in single cells or small groups of cells only. In the heart, however, cardiomyocytes beat together in unison as a syncytium. Thus, it would be desirable to study how iPS-derived cardiomyocytes behave as a tissue. Lee et al now describe a method for assessing the electrophysiology of human iPS-derived cardiomyocytes grown in large monolayers. They grew the cells on elastic membranes to allow for contractions and viewed calcium waves and voltage propagation through the monolayers simultaneously—using fluorescent reporter molecules for both. Importantly, they showed that the spontaneous beating rate of the monolayers resembled that of normal resting human hearts. The new technique will be especially helpful for studying mechanisms underlying genetic cardiomyopathies and arrhythmias, say the authors.miR-181c Regulates Mitochondrial Genome (p 1596)Das et aldiscover a microRNA that regulates a mitochondrial gene in heart cells.Download figureDownload PowerPointMicroRNAs (miRs), which are known to play important roles in cardiovascular physiology and pathogenesis, are small noncoding RNAs that bind to and suppress the expression of target mRNAs. MiRs normally suppress gene expression in the cytosol, where they and their target mRNAs associated with silencing complexes. Recently, however, miRs have also been detected in the mitochondria of a handful of cell types. Das et al now add heart cells to that list. The team isolated RNA from cardiomyocyte mitochondria and found a number of miRs that were highly expressed. Chief among them was miR-181, which was 2-fold more abundant in mitochondrial RNA than total heart RNA. MiR-181 bound to and suppressed the expression of the mitochondrial mRNA, mt-COX1, which encodes a key component of the energy-producing electron transport chain. Furthermore, overexpression of miR-181 disturbed mitochondrial function, leading to an increase in oxygen consumption and overproduction of damaging reactive oxygen species. Given the energy demands of heart muscle cells, optimal mitochondria function is essential; therefore, Das et al suggest that the action of miR-181 could have important implications for heart health.AT1 Receptors on T Cells and Hypertensive Injury (p 1604)Angiotensin II receptors on T cells play an unexpected role in hypertension, sayZhang et al.Download figureDownload PowerPointThe hormone angiotensin II promotes increases in blood pressure via interaction with its receptor in blood vessels and various organs. Drugs that block the angiotensin receptor have been shown to lower blood pressure, but they do not halt or reverse the kidney damage that is often associated with hypertension. Zhang et al have now discovered why this happens. The team was investigating the effect of angiotensin II on immune cells—namely T lymphocytes—both because these cells were found to express angiotensin II receptors and because some reports indicated T cells might be activated by the hormone. It turns out that the opposite is true, however. In hypertensive mice, a T-cell–specific knockout of the receptor prompted the cells to mount a proinflammatory response, caused more T cells to accumulate in the kidneys, and exacerbated the damage they caused there. Angiotensin, thus, appears to protect the kidneys and other organs by suppressing the inflammatory response of T cells. The authors suggest that if angiotensin II receptor blockers are used to treat hypertension, it would be worthwhile to develop a parallel strategy to prevent the blockage of the receptor in T cells and, thus, decrease the chances of kidney damage.Written by Ruth Williams. Previous Back to top Next FiguresReferencesRelatedDetails June 8, 2012Vol 110, Issue 12 Advertisement Article InformationMetrics © 2012 American Heart Association, Inc.https://doi.org/10.1161/RES.0b013e3182601cf2 Originally publishedJune 8, 2012 PDF download Advertisement

The Value of Laminin-322 Staining in Distinguishing Between Keratoacanthoma, Keratoacanthoma With Areas of Squamous Cell Carcinoma, and Crateriform Squamous Cell Carcinoma

IntroductionKeratoacanthoma is a fast-growing crateriform skin tumor. Approximately 25% of such tumors undergo malignant transformation and develop areas of squamous cell carcinoma (SCC). The presence of laminin-322 has been associated with progression to invasive forms of SCC. The aim of this study was to determine whether or not immunohistochemical staining for laminin-322 would be of value in distinguishing between keratoacanthomas, keratoacanthomas with areas of squamous cell carcinoma, and SCCs. Material and methodsSeventy-four lesions were selected from the pathology archives of our hospital and divided into 4 groups: 20 keratoacanthomas without SCC, 20 keratoacanthomas with areas of squamous cell carcinoma, 20 invasive SCCs (8 with crateriform morphology) unrelated to keratoacanthoma, and 14 problem lesions (keratoacanthomas with areas suggestive of SCC). All 74 lesions were stained for laminin-322. ResultsLaminin-322 staining was strongly positive both in areas of SCC in keratoacanthomas with malignant transformation and in invasive SCCs (mostly at the invasive front of the SCC). However, in benign keratoacanthomas, it was only weakly positive and furthermore it was confined to isolated cells or small groups of cells. The 14 problem lesions were reexamined after laminin-322 staining and 8 were diagnosed as keratoacanthomas with incipient SCC and 6 as keratoacanthomas without SCC. ConclusionsLaminin-322 staining is different in keratoacanthomas and SCCs and would thus be a useful test for differentiating keratoacanthomas from both invasive SCCs and keratoacanthomas with areas of squamous cell carcinoma. It would also be of value in diagnosing keratoacanthomas with areas suggestive of SCC or with incipient SCC.

Challenges for Engineers in Biomedical and Clinical Sciences

Challenges for Engineers in Biomedical and Clinical Sciences

An analytical spatially-based approach to study cancer cell population evolutions

Motivations. The evolution of many biological dynamics is strongly related to the spatial composition of the tissues where it takes place. It becomes of paramount importance, not only the knowledge of the type and the number of different biological entities involved, but also their position and their distribution in space. Spatial techniques are particularly useful to investigate the mechanisms affecting tumor growth and maintenance upon vaccination or drug treatment. However not many techniques have been studied to tackle the spatial definition of the environment in addition to the densities of the various elements. This is mainly due to the difficulties of modeling a spatial distributed system using conventional techniques. Methods. In this work we present a new approach, based on an evolution of the mean field analysis that exploits some of the features of the Markovian agents performance evaluation formalisms. This new technique allows to study the system evolution through a sound analytical treatment of the spatial dependency. In particular, we focus on the study of tumor progression, showing that the growth and progression of many cancers are driven by small groups of Cancer Stem Cells (CSCs). The CSC tumor model presents a hierarchically structured organization similar to that found in normal tissues: CSCs are self-renewing, capable of tissue regeneration and of giving rise to non-CSCs, the latter being more differentiated and largely lacking in tissue-regeneration ability. Considering this hierarchical structure, the response to drug treatments on the several cell populations that compose the cancer will produce different effects depending on the characteristics of the cancer subpopulation. For this reason, the CSCs are believed to be the cause of failure of conventional therapies, since effective drug treatments able to eliminate all the CSCs, hence to avoid relapses, are not easy to find. Based upon this model we study the cancer progression, the drug or DNA-vaccination effects, that locally administered, at predefined time periods, can slow down the expansion of the tumor. The considered tissue is divided in small areas, each characterized by its own parameter. The evolution in one area can affect the neighbor: this allows modeling the propagation of both cancer growth or the therapeutic effects of drugs or vaccination. Our approach will aggregate similar cellular population, using differential equations, rather than modeling all the involved entities separately, in order to reduce the model complexity. Results. We expect to model the evolution of the cancer in a volume, taking into account the total number of the different cellular population involved and their spatial distribution. The results will be compared with similar approaches in the literature based on cell automata. We show the spatial behavior of the well known therapy, and how the framework proposed could be a basic step for an optimization algorithm that will determine the best time instants in which administer the drug or vaccination, and the best locations where it should be inoculated. The solution of the model can support the in vitro/in vivo experiments for testing new biological hypothesis. Furthermore, our approach can be extended to consider the immunological tumor micro-environment by adding more details on the immunological system involved on the drug/vaccination treatments. This might be particularly interesting in the area of combined treatment development. Tumor vaccination alone is not sufficient to eradicate the disease, but combined with other immuno-pharmacological treatments, affecting the CSC differentiation rate might represent an interesting approach in the area of tertiary cancer prevention.

Two spreading states of human embryo mesenchymal cells in vitro

Spreading of mesenchymal cells of human embryo on plastic and on type I collagens (from rat, sheep, and ox) was studied. Spreading of the cells on collagens was stronger than that in control, but no differences between different collagens were revealed. The cell perimeter, the spreading coefficient, and the cell projection area on the substrate were used as morphometric parameters. The spreading of cells was monitored for 0.5–2 h after plating. During the spreading both on plastic and on collagen, groups of small cells were revealed as separate subpopulations. As a whole, such cells accounted for 9% of the cell population in control and for 2% in experiment. We assume that this cell type is associated with a special independent functional state of the cells that precedes cell spreading.

Cancer Stem Cells and Drug Resistance: The Potential of Nanomedicine

Properties of the small group of cancer cells called tumor-initiating or cancer stem cells (CSCs) involved in drug resistance, metastasis and relapse of cancers can significantly affect tumor therapy. Importantly, tumor drug resistance seems to be closely related to many intrinsic or acquired properties of CSCs, such as quiescence, specific morphology, DNA repair ability and overexpression of antiapoptotic proteins, drug efflux transporters and detoxifying enzymes. The specific microenvironment (niche) and hypoxic stability provide additional protection against anticancer therapy for CSCs. Thus, CSC-focused therapy is destined to form the core of any effective anticancer strategy. Nanomedicine has great potential in the development of CSC-targeting drugs, controlled drug delivery and release, and the design of novel gene-specific drugs and diagnostic modalities. This review is focused on tumor drug resistance-related properties of CSCs and describes current nanomedicine approaches, which could form the basis of novel combination therapies for eliminating metastatic and CSCs.

The reproductive system of Derocheilocaris typica (Crustacea, Mystacocarida)

Mystacocarids are dioecious. Their gonopores are on the medial side of the third thoracic limb. The male's paired testes lie in the thorax and abdomen. They develop from paired rows of six small follicles dorsally. In the mature animal they fill most of the abdomen. The spermatophores develop within the follicles from spermatogonia mixed with follicle cells, which support and nourish the spermatocytes and produce the seminal fluid. The short vas deferens runs along the bottom of the testes and then continues forward to the gonopore. The vas deferens has a small group of cells near the gonopore that becomes a closure mechanism. The female has reproductive cells and also support cells that provide nutrition and form the wall of the ovary and oviduct. The unpaired female ovary begins in the third thoracic segment. During maturation, the oocytes are pushed posteriorly. The enormous mature ovum extends into a caudal pocket of the ovary. Starting with its anterior end, this ovum is extruded into the short oviduct, which extends laterally and ventrally to the gonopore. During extrusion, the pocket is reabsorbed from behind. There are no accessory structures connected to the reproductive system, nor any external specializations on the third limb.

RNA Profiling and Chromatin Immunoprecipitation-Sequencing Reveal that PTF1a Stabilizes Pancreas Progenitor Identity via the Control of MNX1/HLXB9 and a Network of Other Transcription Factors

Pancreas development is initiated by the specification and expansion of a small group of endodermal cells. Several transcription factors are crucial for progenitor maintenance and expansion, but their interactions and the downstream targets mediating their activity are poorly understood. Among those factors, PTF1a, a basic helix-loop-helix (bHLH) transcription factor which controls pancreas exocrine cell differentiation, maintenance, and functionality, is also needed for the early specification of pancreas progenitors. We used RNA profiling and chromatin immunoprecipitation (ChIP) sequencing to identify a set of targets in pancreas progenitors. We demonstrate that Mnx1, a gene that is absolutely required in pancreas progenitors, is a major direct target of PTF1a and is regulated by a distant enhancer element. Pdx1, Nkx6.1, and Onecut1 are also direct PTF1a targets whose expression is promoted by PTF1a. These proteins, most of which were previously shown to be necessary for pancreas bud maintenance or formation, form a transcription factor network that allows the maintenance of pancreas progenitors. In addition, we identify Bmp7, Nr5a2, RhoV, and P2rx1 as new targets of PTF1a in pancreas progenitors.

Fine-needle aspiration cytology of eccrine hidrocystoma

Fine-needle aspiration cytology of eccrine hidrocystoma

Spatiotemporal variation of leaf epidermal cell growth: a quantitative analysis of Arabidopsis thaliana wild-type and triple cyclinD3 mutant plants.

The epidermis of an expanding dicot leaf is a mosaic of cells differing in identity, size and differentiation stage. Here hypotheses are tested that in such a cell mosaic growth is heterogeneous and changes with time, and that this heterogeneity is not dependent on the cell cycle regulation per se. Shape, size and growth of individual cells were followed with the aid of sequential replicas in expanding leaves of wild-type Arabidopsis thaliana and triple cyclinD3 mutant plants, and combined with ploidy estimation using epi-fluorescence microscopy. Relative growth rates in area of individual epidermal cells or small cell groups differ several fold from those of adjacent cells, and change in time. This spatial and temporal variation is not related to the size of either the cell or the nucleus. Shape changes and growth within an individual cell are also heterogeneous: anticlinal wall waviness appears at different times in different wall portions; portions of the cell periphery in contact with different neighbours grow with different rates. This variation is not related to cell growth anisotropy. The heterogeneity is typical for both the wild type and cycD3. Growth of leaf epidermis exhibits spatiotemporal variability.