Large Groups Of Cells Research Articles

A Comprehensive Methodology to Evaluate Losses and Process Variations in Silicon Solar Cell Manufacturing

Novel, high-throughput metrology methods are used in this paper for detailed performance loss analysis of approximately 400 industrial crystalline silicon solar cells, all coming from the same production line. The characterization sequence combines traditional global cell measurements (e.g., current–voltage, Suns- ${V}_{\text{OC}}$ ) with camera-based cell imaging of voltage distribution and power dissipation from photoluminescence and lock-in thermography, respectively. Spatial variations in current collection are visualized using a high-speed external quantum efficiency and reflectance measurement technique. A nondestructive transfer length method (TLM) measurement technique is also implemented, featuring circular TLM structures hidden within the busbars of the cells. The variance of individual loss parameters and their impact on cell performance are quantified for this large group of cells. Based on correlations performed across parameters, recombination losses in the bulk and rear surface of the cell are shown to be the primary limiting factor for the cell efficiency. The nature of these distributions and correlations provide important insights about loss mechanisms in industrial solar cells, helping to prioritize efforts for optimizing the performance of the production line. Additionally, many of the parameters extracted from these techniques can be tied back to incoming material quality issues (e.g., poor bulk carrier lifetime, nonuniform wafer doping) and to individual unit processes (e.g., texturing, phosphorus diffusion, silicon nitride deposition, metallization), allowing the data to be used directly for process control in manufacturing. All of the datasets are made available for download.

Quantifying Ca2+ signaling and contraction in vascular pericytes and smooth muscle cells

Vascular pericytes and smooth muscle cells surround many blood vessels of the body. Their primary roles include vessel stabilization and regulation of the blood flow. The high degree of heterogeneity among these cells is dictated by (1) differences in their developmental origin and (2) their location in the vascular bed. Phenotype switching contributes to this heterogeneity especially following in vitro culture. In the absence of distinguishing molecular markers, functional assays that capture their heterogeneity in vitro are needed. Spatiotemporal changes in intracellular Ca2+ levels and contraction in response to vasoconstrictors reflect the differences between vascular pericyte and smooth muscle cell. In order to capture this heterogeneity in vitro, large ensembles of cells need to be analyzed. Here we developed an automated image processing method to measure intracellular Ca2+ and contraction in large cell groups which in combination with a computational approach for integrative analysis allowed vascular pericytes and smooth muscle cells to be distinguished without knowledge of their anatomical origin.

Cytomorphological Analysis of Thyroid Nodules Diagnosed as Follicular Variant of Papillary Thyroid Carcinoma: a Fine Needle Aspiration Study of Diagnostic Clues in 42 Cases and the Impact of Using Bethesda System in Reporting-an Institutional Experience.

Follicular variant of papillary thyroid carcinoma (FVPTC) is the second most common subtype of papillary thyroid carcinoma (PTC) after classical PTC (cPTC). Follicular thyroid lesions such as follicular adenomas/carcinomas, FVPTC, and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) pose some diagnostic challenges for FNAC. In this study, we aimed to explore whether FNAC can demonstrate diagnostic clues by re-evaluating cytology slides from histopathologically diagnosed FVPTC cases. A total of 42 patients were enrolled in this study: patients were diagnosed with FVPTC via surgical resection between 2006 and 2016, and all patients were subjected to preoperative FNAC, which was conducted at either a private center or at the teaching hospital of Kocaeli University and reported by the same cytopathologist (NP). Clinical and cytomorphological characteristics were reviewed by both authors .Most cases (76.2%) are diagnosed either Bethesda IV or V. The majority of cases had a high cellularity (38/42; 90.5%), and the most frequent observations were monolayer and large syncytial groups of cells (95.2%). While microfollicular structures were observed in 30 (71.4%) cases, nuclear crowding and large naked nuclei were observed in all cases. Nuclear grooves were sparsely detected in 23 (54.8%) cases, and nuclear pseudoinclusions were detected in only six (14.3%) cases. Because thyrocytes often have a mixed architecture in FVPTC, despite a distinct follicular morphology, we believe that nuclear overcrowding, enlargement, and hyperchromasia in cases presenting with increased cellularity are notable clues for the cytodiagnosis of FVPTC. We believe that the primary aim of FNAC in such cases is to give preoperative diagnosis as either category IV or V. Nuclear crowding, monolayered clusters with large syncytial formations, nuclear enlargement, and hyperchromasia are notable cytomorphologic clues for the diagnosis of FVPTC on FNAC.

Ostreid Herpesvirus-1 Infects Specific Hemocytes in Ark Clam, Scapharca broughtonii.

High levels of ostreid herpesvirus 1 (OsHV-1) were detected in hemocytes of OsHV-1 infected mollusks. Mollusk hemocytes are comprised of different cell types with morphological and functional heterogeneity. Granular cells are considered the main immunocompetent hemocytes. This study aimed to ascertain if OsHV-1 infects specific types of hemocytes in ark clams. Types of hemocytes were first characterized through microexamination and flow cytometry. In addition to a large group of red cells, there were three types of recognizable granular cells in ark clams. Type II granular cells were mostly found with OsHV-1 infection by transmission electron microscope (TEM) examination, and represented the hemocyte type that was susceptible to OsHV-1 infection. The subcellular location of OsHV-1 particles in apoptotic type II granular cells was further analyzed. Some OsHV-1 particles were free inside the apoptotic cells, which may contribute to OsHV-1 transmission among cells in the host, some particles were also found enclosed inside apoptotic bodies. Apoptosis is an important part of the host defense system, but might also be hijacked by OsHV-1 as a strategy to escape host immune attack. Following this investigation, a primary culture of type II granular cells with OsHV-1 infection would facilitate the research on the interaction between OsHV-1 and mollusk hosts.

Spatial Proliferation of Epithelial Cells Is Regulated by E-Cadherin Force

Cell proliferation and contact inhibition play a major role in maintaining epithelial cell homeostasis. Prior experiments have shown that externally applied forces, such as stretch, result in increased proliferation in an E-cadherin force-dependent manner. In this study, the spatial regulation of cell proliferation in large epithelial colonies was examined. Surprisingly, cells at the center of the colony still had increased proliferation as compared to cells in confluent monolayers. E-cadherin forces were found to be elevated for both cells at the edge and center of these larger colonies when compared to confluent monolayers. To determine if high levels of E-cadherin force were necessary to induce proliferation at the center of the colony, a lower-force mutant of E-cadherin was developed. Cells with lower E-cadherin force had significantly reduced proliferation for cells at the center of the colony but minimal differences for cells at the edges of the colony. Similarly, increasing substrate stiffness was found to increase E-cadherin force and increase the proliferation rate across the colony. Taken together, these results show that forces through cell-cell junctions regulate proliferation across large groups of epithelial cells. In addition, an important finding of this study is that junction forces are dynamic and modulate cellular function even in the absence of externally applied loads.

Effect of Impurities on the Triple Point of Water: Experiments with Doped Cells at Different Liquid Fractions

Recent international comparisons showed that there is still room for improvement in triple point of water (TPW) realization uncertainty. Large groups of cells manufactured, maintained and measured in similar conditions still show a spread in the realized TPW temperature that is larger than the best measurement uncertainties (25 µK). One cause is the time-dependent concentration of dissolved impurities in water. The origin of such impurities is the glass/quartz envelope dissolution during a cell lifetime. The effect is a difference in the triple point temperature proportional to the impurities concentration. In order to measure this temperature difference and to investigate the effect of different types of impurities, we manufactured doped cells with different concentrations of silicon (Si), boron (B), sodium (Na) and potassium (K), the glass main chemical components. To identify any influence of the filling process, two completely independent manufacturing procedures were followed in two different laboratories, both national metrology institutes (VSL, Netherlands and UME, Turkey). Cells glass and filling water were also different while the doping materials were identical. Measuring the temperature difference as a function of the liquid fraction is a method to obtain information about impurities concentrations in TPW. Only cells doped with 1 µmol·mol−1 B, Na and K proved to be suitable for measurements at different liquid fractions. We present here the results with related uncertainties and discuss the critical points in this experimental approach.

Analysis of In Vivo Cell Migration in Mosaic Zebrafish Embryos.

Being optically clear, the zebrafish embryo is a nice model system to analyze cell migration in vivo. This chapter describes a combination of injection and cell transplant procedures that allows creation of mosaic embryos, containing a few cells labeled differently from their neighbors. Rapid 5D confocal imaging of these embryos permits to simultaneously track and quantify the movement of large cell groups, as well as analyze the cellular or subcellular dynamics of transplanted cells during their migration. In addition, expression of a candidate gene can be modified in transplanted cells. Comparing behavior of these cells to control or neighboring cells allows determination of the role of the candidate gene in cell migration. We describe the procedure, focusing on one specific cell population during gastrulation, but it can easily be adapted to other cell populations and other migration events during early embryogenesis.

Kinesin-1 promotes chondrocyte maintenance during skeletal morphogenesis.

During skeletal morphogenesis diverse mechanisms are used to support bone formation. This can be seen in the bones that require a cartilage template for their development. In mammals the cartilage template is removed, but in zebrafish the cartilage template persists and the bone mineralizes around the cartilage scaffold. Remodeling of unmineralized cartilage occurs via planar cell polarity (PCP) mediated cell rearrangements that contribute to lengthening of elements; however, the mechanisms that maintain the chondrocyte template that supports perichondral ossification remain unclear. We report double mutants disrupting two zebrafish kinesin-I genes (hereafter kif5Blof) that we generated using CRISPR/Cas9 mutagenesis. We show that zygotic Kif5Bs have a conserved function in maintaining muscle integrity, and are required for cartilage remodeling and maintenance during craniofacial morphogenesis by a PCP-distinct mechanism. Further, kif5Blof does not activate ER stress response genes, but instead disrupts lysosomal function, matrix secretion, and causes deregulated autophagic markers and eventual chondrocyte apoptosis. Ultrastructural and transplantation analysis reveal neighboring cells engulfing extruded kif5Blof chondrocytes. Initial cartilage specification is intact; however, during remodeling, kif5Blof chondrocytes die and the cartilage matrix devoid of hypertrophic chondrocytes remains and impedes normal ossification. Chimeric and mosaic analyses indicate that Kif5B functions cell-autonomously in secretion, nuclear position, cell elongation and maintenance of hypertrophic chondrocytes. Interestingly, large groups of wild-type cells can support elongation of neighboring mutant cells. Finally, mosaic expression of kif5Ba, but not kif5Aa in cartilage rescues the chondrocyte phenotype, further supporting a specific requirement for Kif5B. Cumulatively, we show essential Kif5B functions in promoting cartilage remodeling and chondrocyte maintenance during zebrafish craniofacial morphogenesis.

Generation time and fitness tradeoffs during the evolution of multicellularity

The evolution of multicellular organisms from their unicellular ancestors is an example of an evolutionary transition in individuality (ETI), i.e. a change in the units of selection and adaptation. The theory of ETIs poses particular challenges because, by definition, key theoretical constructs such as fitness are shifting during an ETI. Past work emphasized the importance of life history tradeoffs during ETIs in which lower level units form groups and become individuals at a higher level. In particular, it has been hypothesized that the convexity of the lower-level tradeoff between viability and fecundity changes with group size and determines the optimality of lower-level specialization in the fitness components of the group. This is important because lower-level specialization is a key indicator of higher-level individuality. Here we show that increasing generation time can increase the convexity of the lower-level viability-fecundity tradeoff. This effect is a novel hypothesis for the positive association between cell-group size and cellular specialization in a major model system for ETIs, the volvocine algae. The pattern in this clade is thought to be an example of a more general size-complexity rule. Our hypothesis is that larger groups have longer generation times and longer generation times lead to more convex lower-level viability-fecundity tradeoffs, which could account for specialization being optimal only in larger cell groups (colonies). We discuss the robustness of this effect to various changes in the assumptions of our model. Our work is important for the study of ETIs in general because viability and fecundity are fundamental components of fitness in all systems and because generation time is expected to be changing during many ETIs.

Epithelial stem cells are formed by small-particles released from particle-producing cells.

Recent spatiotemporal report demonstrated that epidermal stem cells have equal potential to divide or differentiate, with no asymmetric cell division observed. Therefore, how epithelial stem cells maintain lifelong stem-cell support still needs to be elucidated. In mouse blood and bone marrow, we found a group of large cells stained strongly for eosin and containing coiled-tubing-like structures. Many were tightly attached to each other to form large cellular clumps. After sectioning, these large cell-clumps were composed of not cells but numerous small particles, however with few small “naked” nuclei. The small particles were about 2 to 3 μm in diameter and stained dense red for eosin, so they may be rich in proteins. Besides the clumps composed of small particles, we identified clumps formed by fusion of the small particles and clumps of newly formed nucleated cells. These observations suggest that these small particles further fused and underwent cellularization. E-cadherin was expressed in particle-fusion areas, some “naked” nuclei and the newly formed nucleated cells, which suggests that these particles can form epithelial cells via fusion and nuclear remodeling. In addition, we observed similar-particle fusion before epithelial cellularization in mouse kidney ducts after kidney ischemia, which suggests that these particles can be released in the blood and carried to the target tissues for epithelial-cell regeneration. Oct4 and E-cadherin expressed in the cytoplasmic areas in cells that were rich in protein and mainly located in the center of the cellular clumps, suggesting that these newly formed cells have become tissue-specific epithelial stem cells. Our data provide evidence that these large particle-producing cells are the origin of epithelial stem cells. The epithelial stem cells are newly formed by particle fusion.

Live-cell super-resolution imaging of intrinsically fast moving flagellates*This article belongs to the special issue: Emerging Leaders, which features invited work from the best early-career researchers working within the scope of J Phys D. This project is part of the Journal of Physics series’ 50th anniversary celebrations in 2017. Susanne Fenz was selected by the Editorial Board of J Phys D

Recent developments in super-resolution microscopy make it possible to resolve structures in biological cells at a spatial resolution of a few nm and observe dynamical processes with a temporal resolution of ms to μs. However, the optimal structural resolution requires repeated illumination cycles and is thus limited to chemically fixed cells. For live cell applications substantial improvement over classical Abbe-limited imaging can already be obtained in adherent or slow moving cells. Nonetheless, a large group of cells are fast moving and thus could not yet be addressed with live cell super-resolution microscopy. These include flagellate pathogens like African trypanosomes, the causative agents of sleeping sickness in humans and nagana in livestock.Here, we present an embedding method based on a in situ forming cytocompatible UV-crosslinked hydrogel. The fast cross-linking hydrogel immobilizes trypanosomes efficiently to allow microscopy on the nanoscale. We characterized both the trypanosomes and the hydrogel with respect to their autofluorescence properties and found them suitable for single-molecule fluorescence microscopy (SMFM). As a proof of principle, SMFM was applied to super-resolve a structure inside the living trypanosome. We present an image of a flagellar axoneme component recorded by using the intrinsic blinking behavior of eYFP.

Gap junctional signaling in pattern regulation: Physiological network connectivity instructs growth and form.

Gap junctions (GJs) are aqueous channels that allow cells to communicate via physiological signals directly. The role of gap junctional connectivity in determining single-cell functions has long been recognized. However, GJs have another important role: the regulation of large-scale anatomical pattern. GJs are not only versatile computational elements that allow cells to control which small molecule signals they receive and emit, but also establish connectivity patterns within large groups of cells. By dynamically regulating the topology of bioelectric networks in vivo, GJs underlie the ability of many tissues to implement complex morphogenesis. Here, a review of recent data on patterning roles of GJs in growth of the zebrafish fin, the establishment of left-right patterning, the developmental dysregulation known as cancer, and the control of large-scale head-tail polarity, and head shape in planarian regeneration has been reported. A perspective in which GJs are not only molecular features functioning in single cells, but also enable global neural-like dynamics in non-neural somatic tissues has been proposed. This view suggests a rich program of future work which capitalizes on the rapid advances in the biophysics of GJs to exploit GJ-mediated global dynamics for applications in birth defects, regenerative medicine, and morphogenetic bioengineering. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 643-673, 2017.

Immunohistochemical study of ovarian psammocarcinoma: Report of a rare case

Psammocarcinoma is a rare variant of serous carcinoma of the ovaries and has a favourable prognosis resembling that of serous borderline tumors [1]. A 60-year-old woman had a pelvic mass 20weeks size. Magnetic resonance imaging (MRI) showed bilateral ovarian cysts with suspicious peritoneal deposits (Figure. 1A). Carbohydrate antigen 125 level was 1300 U/mL. Peritoneal fluid cytology showed large cell groups with high nucleocytoplasmic ratio, irregular nuclear borders, and indistinct nucleoli. A single psammoma body (PB) was detected (Figure 1B). A diagnosis of ovarian carcinoma was offered. Intraoperatively, bilateral large cystic ovarian masses were seen with thickened omentum and multiple subdiaphragmatic deposits. A biopsy of the omental deposits showed tumor composed of small cuboidal to round cells arranged in a papillary, cribriform pattern. The cells showed minimal pleomorphism and scant mitotic figures. Abundant PBs were scattered throughout the fibrous stroma and in the tips of the papillae (Figure 1C). A diagnosis of metastatic deposits of ovarian psammocarcinoma, International Federation of Gynecology and Obstetrics (FIGO) Stage IIIc was given. Cytokeratin 7 and epithelial membrane antigen showed strong immunoreactivity in tumor cells (Figure 1D and 1E) and none for cytokeratin 20, calretinin, and desmin. Immunoreactivity for estrogen receptors was seen in 75% of tumor cells (Figure 1F). The patient was given tamoxifen and chemotherapy. Patients with psammocarcinoma range in age from 36 years to 76 years (mean age 57 years) [1]. Psammocarcinoma shows: (1)

A new species of the genus Discolaimus Cobb, 1913 (Nematoda: Dorylaimida: Qudsianematidae) from Qinghai, China.

A new species of the family Qudsianematidae Jairajpuri, 1965 collected from soil from Qinghai Province, China is described as Discolaimus anemaqen n. sp. It is mainly characterized by having a disc-like lip region with six labial sectors separated by six Y-shaped radial grooves; amphid fovea an inverted-stirrup shape; odontostyle aperture 53-59% of its length; anterior part of pharynx with two swellings, basal part expanded gradually with a sheath of tissue visible ventrally and at the base; no groups of large cells observed in cardiac region; female genital system amphidelphic; tail dorsally convex, conoid, with flat ventral side and bluntly rounded terminus, and males not found. The new species is close to D. major Thorne, 1939, D. similis Thorne, 1939 and D. silvicolus Sauer & Annells, 1985 in most measurements, but can be differentiated from them by lip morphology, pharynx structure, body size, and tail shape. A key to the species of Discolaimus is also provided.

Expression of 3β-hydroxysteroid dehydrogenase in ovarian and uterine tissue during diestrus and open cervix cystic endometrial hyperplasia-pyometra in the bitch

The purpose of this study was to compare the expression of 3β-hydroxystreroid dehydrogenase (3β-HSD) in the uterus and ovary of healthy dogs and those with cystic endometrial hyperplasia and/or pyometra complex (CEH-pyometra). Eighteen female dogs were included in the study. Eleven bitches with open cervix CEH-pyometra were included in the CEH-pyometra group and seven diestrus bitches in the control group. For immunostaining a rabbit polyclonal, one raised against recombinant human type 2 (adrenal/gonadal) 3β-HSD was used. Progesterone (P4) concentrations were not statistically different between the groups. Strongly stained large interstitial cell groups in the ovarian medulla were observed particularly in CEH-pyometra group although these cells in the control group were weakly or moderately stained and existed singly or paired. The expressions of 3β-HSD in luminal epithelium (42.40 ± 22.40% vs. 18.42 ± 13.15%, P < 0.05) and glandular epithelium (32.80 ± 27.05% vs. 2.94 ± 7.79%, P < 0.01) of endometrium were significantly higher in CEH-pyometra group than those in the control group. The expression of 3β-HSD in CL was higher (29.38 ± 9.58% vs. 22.94 ± 4.97%) in CEH-pyometra group than that of control group although the differences were not significant (P > 0.05). Similarly, the significant increase in the expression of 3β-HSD in ovarian interstitial cells (33.86 ± 29.44 vs. 1.13 ± 2.97, P < 0.05) was found in CEH-pyometra group compared to the control group. The study revealed that 3β-HSD expression in the endometrium of canine CEH-pyometra was significantly high.

Interneurons Brainstem of the Human

To conduct a comparative study of the structural organization of internuclear interneurons involved in the metabolism of nitrogen monoxide, hydrogen sulphide and carbon monoxide in the caudal brain stem humans. The cross-sectional study was performed. We used histochemical and immunohistochemical methods to study the internuclear interneurons expressing neuronal nitric oxide synthase, cystathionine β-synthase and heme oxygenase-2 which are located between the giant and small cell reticular nuclei (cell group 1), small cell reticular nucleus and the nucleus of the solitary tract (cell group 2) or is surrounded by reticular lateral nucleus (cell group 3). The work was carried out on the corpses of 6 men 18-44 years old who died from causes unrelated to the damage of the central nervous system. We revealed the differences between internuclear organization and intranuclear interneurons and local structural features of internuclear interneurons that are more clearly visible between the cell group 1 including a relatively large number of large neurons and cell groups 2 and 3 (p < 0.001). In the latter two groups small cells with high concentrations of the neuronal nitric oxide synthase and heme oxygenase-2 dominated. Despite the fact that the number of internuclear interneurons significantly is less than the number of intranuclear cells, they have structural prerequisites to control integration processes in the brain. Internuclear interneurons produce gasotransmitters and classical mediators of nerve impulse, form a local chain of interneurons between vasomotor nuclei, share many links with the above and the lower parts of the brain.

Tissue patterning and cellular mechanics.

In development, cells organize into biological tissues through cell growth, migration, and differentiation. Globally, this process is dictated by a genetically encoded program in which secreted morphogens and cell–cell interactions prompt the adoption of unique cell fates. Yet, at its lowest level, development is achieved through the modification of cell–cell adhesion and actomyosin-based contractility, which set the level of tension within cells and dictate how they pack together into tissues. The regulation of tension within individual cells and across large groups of cells is a major driving force of tissue organization and the basis of all cell shape change and cell movement in development.

The Immunophenotype of Nodular Variant of Medullary Carcinoma of the Breast.

The histologic and immunohistochemical profile of typical medullary carcinomas (TMC) of the breast are well established. Among the strict histologic criteria for the diagnosis of TMC is complete circumscription of tumor with pushing borders. Those tumors that do not fulfill all morphologic requirements of TMC are designated as atypical medullary carcinomas (AMC). We herewith describe the histology and immunophenotype of a heretofore undescribed variant of TMC composed of multiple distinctly separate nodules that otherwise meet all other histologic and immunohistochemical phenotypes of TMC. Among 2952 cases of infiltrating mammary carcinomas, 111 (3.8%) met the strict criteria for TMC, including positivity for HLA-DR. Nine of these tumors were composed of multiple separate noncoalescing nodules. Immunohistochemical stains for ER, PR, HER2, and HLA-DR, as well as for p53 and Ki-67 were repeated on these nodular forms. Staining for p63 was used to identify possible intraductal components of these tumors. The age of patients ranged from 34 to 53 years. All 9 patients had negative sentinel lymph nodes. Tumors ranged in the overall size from 2.2 to 3.9 cm and were composed of 3 to 6 distinct nodules ranging in size from 0.2 to 1.1 cm surrounding a larger main tumor nodule. The nodules were composed of syncytial groups of large cells with atypical nuclei and prominent nucleoli. A lymphoplasmacytic infiltrate was present within and around each satellite nodule. Serial sections did not show coalescing of the nodules into a single tumor mass. Similarly, staining for p63 failed to support the possibility of nodules representing intraductal components of main tumor. All tumors were negative for ER, PR, and HER2, but positive for HLA-DR. Eight of 9 tumors were diffusely positive for p53 and all 9 showed a high proliferation index in >70% of tumor cells with Ki-67. We conclude that the nodular variants of medullary carcinomas (nTMC) of the breast are uncommon forms of TMC. They occur in relatively younger women and share the same immunophenotype with TMCs; they are triple negative, express HLA-DR and p53, and show a high proliferative index. As the diagnosis of TMC carries major clinical and prognostic implications, the recognition of its nodular variant becomes equally important.

A Simple Mechanism for Beyond-Pairwise Correlations in Integrate-and-Fire Neurons.

The collective dynamics of neural populations are often characterized in terms of correlations in the spike activity of different neurons. We have developed an understanding of the circuit mechanisms that lead to correlations among cell pairs, but little is known about what determines the population firing statistics among larger groups of cells. Here, we examine this question for a simple, but ubiquitous, circuit feature: common fluctuating input arriving to spiking neurons of integrate-and-fire type. We show that this leads to strong beyond-pairwise correlations—that is, correlations that cannot be captured by maximum entropy models that extrapolate from pairwise statistics—as for earlier work with discrete threshold crossing (dichotomous Gaussian) models. Moreover, we find that the same is true for another widely used, doubly stochastic model of neural spiking, the linear–nonlinear cascade. We demonstrate the strong connection between the collective dynamics produced by integrate-and-fire and dichotomous Gaussian models, and show that the latter is a surprisingly accurate model of the former. Our conclusion is that beyond-pairwise correlations can be both broadly expected and possible to describe by simplified (and tractable) statistical models.

Germ Cell Segregation from the Drosophila Soma Is Controlled by an Inhibitory Threshold Set by the Arf-GEF Steppke.

Germline cells segregate from the soma to maintain their totipotency, but the cellular mechanisms of this segregation are unclear. The Drosophila melanogaster embryo forms a posterior group of primordial germline cells (PGCs) by their division from the syncytial soma. Extended plasma membrane furrows enclose the PGCs in response to the germ plasm protein Germ cell-less (Gcl) and Rho1-actomyosin activity. Recently, we found that loss of the Arf-GEF Steppke (Step) leads to similar Rho1-dependent plasma membrane extensions but from pseudocleavage furrows of the soma. Here, we report that the loss of step also leads to premature formation of a large cell group at the anterior pole of the embryo . These anterior cells lacked germ plasm, but budded and formed at the same time as posterior PGCs, and then divided asynchronously as PGCs also do. With genetic analyses we found that Step normally activates Arf small G proteins and antagonizes Rho1-actomyosin pathways to inhibit anterior cell formation. A uniform distribution of step mRNA around the one-cell embryo cortex suggested that Step restricts cell formation through a global control mechanism. Thus, we examined the effect of Step on PGC formation at the posterior pole. Reducing Gcl or Rho1 levels decreased PGC numbers, but additional step RNAi restored their numbers. Reciprocally, GFP-Step overexpression induced dosage- and Arf-GEF-dependent loss of PGCs, an effect worsened by reducing Gcl or actomyosin pathway activity. We propose that a global distribution of Step normally sets an inhibitory threshold for Rho1 activity to restrict early cell formation to the posterior.