Effects of microRNA-mediated negative feedback on gene expression noise.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally in eukaryotes by binding with target mRNAs and preventing translation. miRNA-mediated feedback motifs are ubiquitous in various genetic networks that control cellular decision making. A key question is how such a feedback mechanism may affect gene expression noise. To answer this, we have developed a mathematical model to study the effects of a miRNA-dependent negative-feedback loop on mean expression and noise in target mRNAs. Combining analytics and simulations, we show the existence of an expression threshold demarcating repressed and expressed regimes in agreement with earlier studies. The steady-state mRNA distributions are bimodal near the threshold, where copy numbers of mRNAs and miRNAs exhibit enhanced anticorrelated fluctuations. Moreover, variation of negative-feedback strength shifts the threshold locations and modulates the noise profiles. Notably, the miRNA-mRNA binding affinity and feedback strength collectively shape the bimodality. We also compare our model with a direct auto-repression motif, where a gene produces its own repressor. Auto-repression fails to produce bimodal mRNA distributions as found in miRNA-based indirect repression, suggesting the crucial role of miRNAs in creating phenotypic diversity. Together, we demonstrate how miRNA-dependent negative feedback modifies the expression threshold and leads to a broader parameter regime of bimodality compared to the no-feedback case.

An evolutionary divergent thermodynamic brake in ZAP-70 fine-tunes the kinetic proofreading in T cells.

T cell signaling starts with assembling several tyrosine kinases and adapter proteins to the T cell receptor (TCR), following the antigen binding to the TCR. The stability of the TCR-antigen complex and the delay between the recruitment and activation of each kinase determines the T cell response. Integration of such delays constitutes a kinetic proofreading mechanism to regulate T cell response to the antigen binding. However, the mechanism of these delays is not fully understood. Combining biochemical experiments and kinetic modeling, here we report a thermodynamic brake in the regulatory module of the tyrosine kinase ZAP-70, which determines the ligand selectivity, and may delay the ZAP-70 activation upon antigen binding to TCR. The regulatory module of ZAP-70 comprises of a tandem SH2 domain that binds to its ligand, doubly-phosphorylated ITAM peptide (ITAM-Y2P), in two kinetic steps: a fast step and a slow step. We show the initial encounter complex formation between the ITAM-Y2P and tandem SH2 domain follows a fast-kinetic step, whereas the conformational transition to the holo-state follows a slow-kinetic step. We further observed a thermodynamic penalty imposed during the second phosphate-binding event reduces the rate of structural transition to the holo-state. Phylogenetic analysis revealed the evolution of the thermodynamic brake coincides with the divergence of the adaptive immune system to the cell-mediated and humoral responses. In addition, the paralogous kinase Syk expressed in B cells does not possess such a functional thermodynamic brake, which may explain the higher basal activation and lack of ligand selectivity in Syk.

Effects of random hydrolysis on biofilament length distributions in a shared subunit pool.

The sizes of filamentous structures in a cell are often regulated for many physiological processes. A key question in cell biology is how such size control is achieved. Here, we theoretically study the length distributions of multiple filaments, growing by stochastic assembly and disassembly of subunits from a limiting subunit pool. Importantly, we consider a chemical switching of subunits (hydrolysis) prevalent in many biofilaments like microtubules (MTs). We show by simulations of different models that hydrolysis leads to a skewed unimodal length distribution for a single MT. In contrast, hydrolysis can lead to bimodal distributions of individual lengths for two MTs, where individual filaments toggle stochastically between bigger and smaller sizes. For more than two MTs, length distributions are also bimodal, although the bimodality becomes less prominent. We further show that this collective phenomenon is connected with the nonequilibrium nature of hydrolysis, and the bimodality disappears for reversible dynamics. Consistent with earlier theoretical studies, a homogeneous subunit pool, without hydrolysis, cannot control filament lengths. We thus elucidate the role of hydrolysis as a control mechanism on MT length diversity.

Probing Mechanisms of Transcription Elongation Through Cell-to-Cell Variability of RNA Polymerase.

The process of transcription initiation and elongation are primary points of control in the regulation of gene expression. Although biochemical studies have uncovered the mechanisms involved in controlling transcription at each step, how these mechanisms manifest in vivo at the level of individual genes is still unclear. Recent experimental advances have enabled single-cell measurements of RNA polymerase (RNAP) molecules engaged in the process of transcribing a gene of interest. In this article, we use Gillespie simulations to show that measurements of cell-to-cell variability of RNAP numbers and interpolymerase distances can reveal the prevailing mode of regulation of a given gene. Mechanisms of regulation at each step, from initiation to elongation dynamics, produce qualitatively distinct signatures, which can further be used to discern between them. Most intriguingly, depending on the initiation kinetics, stochastic elongation can either enhance or suppress cell-to-cell variability at the RNAP level. To demonstrate the value of this framework, we analyze RNAP number distribution data for ribosomal genes in Saccharomyces cerevisiae from three previously published studies and show that this approach provides crucial mechanistic insights into the transcriptional regulation of these genes.

Broad spectral responsivity in highly photoconductive InZnO/MoS2 heterojunction phototransistor with ultrathin transparent metal electrode.

An amorphous InZnO/MoS2 heterojunction-based phototransistor with excellent photoconductive gain and responsivity over the entire visible range has been demonstrated. The photogenerated current of the InZnO phototransistor at long light wavelength (>600 nm) was significantly improved by utilizing narrow bandgap MoS2 as the capping layer (1.3 eV). At lower wavelength, photocarriers are generated due to the optical absorption of both InZnO and MoS2 layers, whereas the latter ensures significant photocarrier generation even at the higher wavelength region of the visible spectrum. The photogenerated carriers subsequently transfer to the underlying InZnO layer of superior carrier mobility that has a high channel conduction of additional electrons from the optically-induced doubly positively charged oxygen vacancies (Vo++) where the gate field is screening, thereby leading to the higher photoconductive gain of the InZnO/MoS2 phototransistors. The dynamic photosensitivity behaviour of the aforesaid phototransistor reveals the presence of persistent photoconductivity (PPC) due to the oxygen vacancy associated with InZnO which can be removed by applying a reset gate pulse from -15 to +5 V. The optical properties of these phototransistors were further enhanced by replacing the opaque Ti/Au electrode by an ultrathin transparent Ti/Au electrode. Utilization of the transparent electrode results in enhanced electron injection from source to channel due to a reduced barrier height under illumination giving rise to a ten-fold improvement in the photocurrent and responsivity of the phototransistors. A position-dependent study of the photocurrent w.r.t beam position also reveals that the enhancement in photocurrent is strongly dependent on the position and is at its maximum when the beam is placed near the source region.

Effect of transcription factor resource sharing on gene expression noise.

Gene expression is intrinsically a stochastic (noisy) process with important implications for cellular functions. Deciphering the underlying mechanisms of gene expression noise remains one of the key challenges of regulatory biology. Theoretical models of transcription often incorporate the kinetics of how transcription factors (TFs) interact with a single promoter to impact gene expression noise. However, inside single cells multiple identical gene copies as well as additional binding sites can compete for a limiting pool of TFs. Here we develop a simple kinetic model of transcription, which explicitly incorporates this interplay between TF copy number and its binding sites. We show that TF sharing enhances noise in mRNA distribution across an isogenic population of cells. Moreover, when a single gene copy shares it's TFs with multiple competitor sites, the mRNA variance as a function of the mean remains unaltered by their presence. Hence, all the data for variance as a function of mean expression collapse onto a single master curve independent of the strength and number of competitor sites. However, this result does not hold true when the competition stems from multiple copies of the same gene. Therefore, although previous studies showed that the mean expression follows a universal master curve, our findings suggest that different scenarios of competition bear distinct signatures at the level of variance. Intriguingly, the introduction of competitor sites can transform a unimodal mRNA distribution into a multimodal distribution. These results demonstrate the impact of limited availability of TF resource on the regulation of noise in gene expression.

Photosensitive organic field effect transistors: the influence of ZnPc morphology and bilayer dielectrics for achieving a low operating voltage and low bias stress effect.

Photosensitive-organic field effect transistors (PS-OFETs) based on a morphology controlled zinc phthalocyanine (ZnPc) layer, with an inorganic-organic bilayer gate dielectric system, fabricated on a glass substrate showed remarkable efficiency as light sensors at various incident optical powers. The indium tin oxide (ITO) and Si/SiO2 free low-cost OFET devices show low bias stress and a reduced operating voltage with aluminum oxide and poly(methyl methacrylate) (Al2O3/PMMA) as bilayer gate dielectrics and copper (Cu) as a top contact. They exhibit excellent p-channel behavior with a remarkable photo-responsivity of 2679.40 A W-1 and a photo-ON/OFF current ratio of 933.56 with a very low operating voltage (0 to -8 V), which have not been observed previously. The bias stress effect of the device was investigated under both light and dark conditions in a vacuum. It was observed that the effect of the stress is extremely small in the presence of light (a decay of IDS of ∼ 20% after 30 min) compared to the dark, with a characteristic carrier relaxation time τ' ∼ 104 s. This device with high electrical stability under ambient conditions and a low threshold voltage under constant electrical bias stress is expected to have potential applications in optoelectronic devices and energy efficient sensors.

White polymer light emitting diodes based on PVK: the effect of the electron injection barrier on transport properties, electroluminescence and controlling the electroplex formation.

The effects of the electron injection barrier on the charge transport, brightness and the electroluminescence (EL) properties of polymer light emitting diodes (PLEDs) with poly(9-vinylcarbazole) (PVK) as an emissive layer have been studied. By using Al and LiF/Al as the cathode in single layer PLEDs and diverse electron transporting layers (ETLs) such as 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (BCP), 4,7-diphenyl-1,10-phenanthroline (BPhen) and 2,2',2''-(1,3,5-benzinetriyl)-tris(1-phenyl-1-H-benzimidazole) (TPBi) in the case of multilayer PLEDs, the charge transport, brightness, color tuning and the EL properties of the devices were drastically modified. The energy barrier for electrons affects the electron current flowing through the device, thereby affecting the operating voltage and the brightness of the PLEDs. The PLEDs with TPBi as the ETL possess the lowest injection barrier and give the maximum brightness of 426.24 cd m-2. The electron injection barrier is also found to play a major role in defining the EL spectra of the PLEDs. A larger injection barrier gives rise to electroplex formation in the EML-ETL interface of the PLEDs and an additional peak at ∼605 nm was observed in the EL spectrum. As a result, a near white emission with CIE coordinates of (0.30, 0.30) and (0.25, 0.23) at 20 V was obtained from devices with BCP and BPhen as ETLs. Furthermore, PVK doped with 2-phenyl-5-(4-biphenylyl)-1,3,4-oxadiazole (PBD) at 10, 20 and 30 wt% ratios modified the electron transport nature of PVK and had a remarkable influence on the aforesaid properties, especially on the electroplex formation.

Efficient blue and white polymer light emitting diodes based on a well charge balanced, core modified polyfluorene derivative.

Fabrication of efficient blue and white polymer light-emitting diodes (PLEDs) using a well charge balanced, core modified polyfluorene derivative, poly[2,7-(9,9'-dioctylfluorene)-co-N-phenyl-1,8-naphthalimide (99:01)] (PFONPN01), is presented. The excellent film forming properties as observed from the morphological study and the enhanced electron transport properties due to the inclusion of the NPN unit in the PFO main chain resulted in improved device properties. Bright blue light was observed from single layer PLEDs with PFONPN01 as an emissive layer (EML) as well as from double layer PLEDs using tris-(8-hydroxyquinoline) aluminum (Alq3) as an electron transporting layer (ETL) and LiF/Al as a cathode. The effect of ETL thickness on the device performance was studied by varying the Alq3 thickness (5 nm, 10 nm and 20 nm) and the device with an ETL thickness of 20 nm was found to exhibit the maximum brightness value of 11 662 cd m(-2) with a maximum luminous efficiency of 4.87 cd A(-1). Further, by using this highly electroluminescent blue PFONPN01 as a host and a narrow band gap, yellow emitting small molecule, dithiophene benzothiadiazole (DBT), as a guest at three different concentrations (0.2%, 0.4% and 0.6%), WPLEDs with the ITO/PEDOT:PSS/emissive layer/Alq3(20 nm)/LiF/Al configuration were fabricated and maximum brightness values of 8025 cd m(-2), 9565 cd m(-2) and 10 180 cd m(-2) were achieved respectively. 0.4% DBT in PFONPN01 was found to give white light with Commission International de l'Echairage (CIE) coordinates of (0.31, 0.38), a maximum luminous efficiency of 6.54 cd A(-1) and a color-rendering index (CRI) value of 70.

Effects of bursty synthesis in organelle biogenesis.

A fundamental question of cell biology is how cells control the number of organelles. The processes of organelle biogenesis, namely de novo synthesis, fission, fusion, and decay, are inherently stochastic, producing cell-to-cell variability in organelle abundance. In addition, experiments suggest that the synthesis of some organelles can be bursty. We thus ask how bursty synthesis impacts intracellular organelle number distribution. We develop an organelle biogenesis model with bursty de novo synthesis by considering geometrically distributed burst sizes. We analytically solve the model in biologically relevant limits and provide exact expressions for the steady-state organelle number distributions and their means and variances. We also present approximate solutions for the whole model, complementing with exact stochastic simulations. We show that bursts generally increase the noise in organelle numbers, producing distinct signatures in noise profiles depending on different mechanisms of organelle biogenesis. We also find different shapes of organelle number distributions, including bimodal distributions in some parameter regimes. Notably, bursty synthesis broadens the parameter regime of observing bimodality compared to the 'non-bursty' case. Together, our framework utilizes number fluctuations to elucidate the role of bursty synthesis in producing organelle number heterogeneity in cells.

Selective depletion of Campylobacter jejuni via T6SS dependent functionality: an approach for improving chickens gut health.

The targeted depletion of potential gut pathogens is often challenging because of their intrinsic ability to thrive in harsh gut environments. Earlier, we showed that Campylobacter jejuni (C. jejuni) exclusively uses the Type-VI Secretion System (T6SS) to target its prey such as Escherichia coli (E. coli), and phenotypic differences between T6SS-negative and T6SS-positive C. jejuni isolates toward bile salt sensitivity. However, it remains unclear how the target-driven T6SS functionality prevails in a polymicrobial gut environment. Here, we investigated the fate of microbial competition in an altered gut environment via bacterial T6SS using a T6SS-negative and -positive C. jejuni or its isogenic mutant of the hemolysin-coregulated protein (hcp). We showed that in the presence of bile salt and prey bacteria (E. coli), T6SS-positive C. jejuni experiences enhanced intracellular stress leading to cell death. Intracellular tracking of fluorophore-conjugated bile salts confirmed that T6SS-mediated bile salt influx into C. jejuni can enhance intracellular oxidative stress, affecting C. jejuni viability. We further investigated whether the T6SS activity in the presence of prey (E. coli) perturbs the in vivo colonization of C. jejuni. Using chickens as primary hosts of C. jejuni and non-pathogenic E. coli as prey, we showed a marked reduction of C. jejuni load in chickens cecum when bile salt solution was administered orally. Analysis of local antibody responses and pro-inflammatory gene expression showed a reduced risk of tissue damage, indicating that T6SS activity in the complex gut environment can be exploited as a possible measure to clear the persistent colonization of C. jejuni in chickens.

Giant number fluctuations in microbial ecologies.

Statistical fluctuations in population sizes of microbes may be quite large depending on the nature of their underlying stochastic dynamics. For example, the variance of the population size of a microbe undergoing a pure birth process with unlimited resources is proportional to the square of its mean. We refer to such large fluctuations, with the variance growing as square of the mean, as giant number fluctuations (GNF). Luria and Delbrück showed that spontaneous mutation processes in microbial populations exhibit GNF. We explore whether GNF can arise in other microbial ecologies. We study certain simple ecological models evolving via stochastic processes: (i) bi-directional mutation, (ii) lysis-lysogeny of bacteria by bacteriophage, and (iii) horizontal gene transfer (HGT). For the case of bi-directional mutation process, we show analytically exactly that the GNF relationship holds at large times. For the ecological model of bacteria undergoing lysis or lysogeny under viral infection, we show that if the viral population can be experimentally manipulated to stay quasi-stationary, the process of lysogeny maps essentially to one-way mutation process and hence the GNF property of the lysogens follows. Finally, we show that even the process of HGT may map to the mutation process at large times, and thereby exhibits GNF.

Effects of length-dependent positive feedback on length distributions of microtubules undergoing hydrolysis.

Despite a rapid turnover of subunits, how cells control the lengths of cytoskeletal filaments (such as microtubules) is a fundamental question in cell biology. Here, we theoretically investigate how microscopic processes affect the length distributions of multiple microtubules growing stochastically in a shared subunit pool. In particular, we consider length-dependent positive feedback on filament growth and the chemical conversion from GTP-tubulin to GDP-tubulin (hydrolysis) inside a filament. We found different dynamical regimes for a single filament by simulating a model of microtubule kinetics, where both bimodal and unimodal (bell-shaped) length distributions emerge in the steady state. More significantly, the length distributions of multiple filaments were not unimodal, predicting a collective effect for more than one filament. Interestingly, when length distributions were bimodal, we also observed bistable toggling of individual lengths. Therefore, regulation of biophysical parameters (e.g., hydrolysis rate and feedback strength) can lead to length diversity in an ensemble of multiple microtubules.

A combined protocol for isolation of T6SS-positive Campylobacter jejuni and assessment of interspecies interaction.

The bacterial Type VI Secretion System (T6SS) functions as a nanomachine used by many gut pathogens. In the present protocol, we outlined how such molecular activities during interspecies interaction can be demonstrated at a population level. To this end, we first present a comprehensive protocol for isolation, identification, and functional characterization of T6SS-positive Campylobacter jejuni. Further, we developed straightforward techniques for unraveling how the T6SS targets prey populations and host cells when growing with or without environmental stressors. For complete details on the use and execution of this protocol, please refer to Gupta et al. (2021).

The cost of bacterial predation via type VI secretion system leads to predator extinction under environmental stress.

As a common gut pathogen, Campylobacter jejuni (C. jejuni) harbors the Type VI Secretion System (T6SS) that injects toxic effectors into neighboring cells, modulating microbial competitions in the harsh gut environment. Using bile salt as a natural stressor and T6SS-positive C. jejuni as a predator, we show that T6SS activity could entail a cost during bacterial predation under environmental stress. Our data suggest bile salt influx and subsequent DNA damage due to the prey-driven activation of the T6SS. We further combined experiments and mathematical modeling to explore how the stress-induced "predation cost" determines ecological outcomes. Consistent with a population-dynamics model, we found predator extinction above a critical bile salt concentration and prey-predator coexistence below this level. Moreover, we utilized the predation cost as an effective strategy facilitating host defense against C. jejuni infection. Together, we elucidate how predator dominance versus extinction emerges from the interplay between environmental stress and the T6SS machinery.

Fibronectin is a smart adhesive that both influences and responds to the mechanics of early spinal column development.

An extracellular matrix of Fibronectin adheres the neural tube to the two flanking columns of paraxial mesoderm and is required for normal vertebrate development. Here, we find that the bilaterally symmetric interfaces between the zebrafish neural tube and paraxial mesoderm function as optimally engineered adhesive lap joints with rounded edges, graded Fibronectin 'adhesive' and an arced adhesive spew filet. Fibronectin is a 'smart adhesive' that remodels to the lateral edges of the neural tube-paraxial mesoderm interfaces where shear stress is highest. Fibronectin remodeling is mechanically responsive to contralateral variation morphogenesis, and Fibronectin-mediated inter-tissue adhesion is required for bilaterally symmetric morphogenesis of the paraxial mesoderm. Strikingly, however, perturbation of the Fibronectin matrix rescues the neural tube convergence defect of cadherin 2 mutants. Therefore, Fibronectin-mediated inter-tissue adhesion dynamically coordinates bilaterally symmetric morphogenesis of the vertebrate trunk but predisposes the neural tube to convergence defects that lead to spina bifida.

In embryos, the spinal cord starts out as a flat sheet of cells that curls up to form a closed cylinder called the neural tube. The folding tube is attached to the surrounding tissues through an extracellular matrix of proteins and sugars. Overlapping strands of a protein from the extracellular matrix called Fibronectin connect the neural tube to adjacent tissues, like a kind of biological glue. However, it remained unclear what effect this attachment had on the embryonic development of the spinal cord. Connecting two overlapping objects with glue to form what is known as an 'adhesive lap joint' is common in fields such as woodworking and aeronautical engineering. The glue in these joints comes under shearing stress whenever the two objects it connects try to pull apart. But, thanks to work in engineering, it is possible to predict how different joints will perform under tension. Now, Guillon et al. have deployed these engineering principles to shed light on neural tube development. Using zebrafish embryos and computational models, Guillon et al. investigated what happens when the strength of the adhesive lap joints in the developing spine changes. This revealed that Fibronectin works like a smart adhesive: rather than staying in one place like a conventional glue, it moves around. As the neural tube closes, cells remodel the Fibronectin, concentrating it on the areas under the highest stress. This seemed to both help and hinder neural tube development. On the one hand, by anchoring the tube equally to the left and right sides of the embryo, the Fibronectin glue helped the spine to develop symmetrically. On the other hand, the strength of the adhesive lap joints made it harder for the neural tube to curl up and close. If the neural tube fails to close properly, it can lead to birth defects like spina bifida. One of the best-known causes of these birth defects in humans is a lack of a vitamin known as folic acid. Cell culture experiments suggest that this might have something to do with the mechanics of the cells during development. It may be that faulty neural tubes could close more easily if they were able to unglue themselves from the surrounding tissues. Further use of engineering principles could shed more light on this idea in the future.

Cell-to-cell variability in organelle abundance reveals mechanisms of organelle biogenesis.

How cells regulate the number of organelles is a fundamental question in cell biology. While decades of experimental work have uncovered four fundamental processes that regulate organelle biogenesis, namely, de novo synthesis, fission, fusion, and decay, a comprehensive understanding of how these processes together control organelle abundance remains elusive. Recent fluorescence microscopy experiments allow for the counting of organelles at the single-cell level. These measurements provide information about the cell-to-cell variability in organelle abundance in addition to the mean level. Motivated by such measurements, we build upon a recent study and analyze a general stochastic model of organelle biogenesis. We compute the exact analytical expressions for the probability distribution of organelle numbers, their mean, and variance across a population of single cells. It is shown that different mechanisms of organelle biogenesis lead to distinct signatures in the distribution of organelle numbers which allow us to discriminate between these various mechanisms. By comparing our theory against published data for peroxisome abundance measurements in yeast, we show that a widely believed model of peroxisome biogenesis that involves de novo synthesis, fission, and decay is inadequate in explaining the data. Also, our theory predicts bimodality in certain limits of the model. Overall, the framework developed here can be harnessed to gain mechanistic insights into the process of organelle biogenesis.

White light emitting diode based on purely organic fluorescent to modern thermally activated delayed fluorescence (TADF) and perovskite materials.

White organic/polymer light emitting diode (WOLED/WPLED) processed from solution has attracted significant research interest in recent years due to their low device production cost, device flexibility, easy fabrication over large area including roll to roll and ability to print in various designs and shapes providing enormous design possibilities. Although WOLEDs fabricated using solution process lack their thermally evaporated counterparts in terms of device efficiency, remarkable progress has been made in this regard in recent years by utilizing new materials and device structures. In the present review, we have summarized and extrapolated an excellent association of old and modern concept of cost-effective materials and device structure for realization of white light. In particular, this article demonstrated and focused on design, and development of novel synthesis strategy, mechanistic insights and device engineering for solution process low cost WOLEDs device. Herein, an overview of the prevailing routes towards white light emitting devices (WLEDs) and corresponding materials used, including polymer based WLED, small molecules emitters based thermally activated delayed fluorescence (TADF), perovskite light-emitting diodes (PeLEDs) and hybrid materials based LEDs, color down-converting coatings with corresponding best efficiencies ever realized. We presume that this exhaustive review on WLEDs will offer a broad overview of the latest developments on white SSL and stonework the approach en route for innovations in the immediate future.

Improved optical performance of multi-layer MoS2 phototransistor with see-through metal electrode.

In recent years, MoS2 has emerged as a prime material for photodetector as well as phototransistor applications. Usually, the higher density of state and relatively narrow bandgap of multi-layer MoS2 give it an edge over monolayer MoS2 for phototransistor applications. However, MoS2 demonstrates thickness-dependent energy bandgap properties, with multi-layer MoS2 having indirect bandgap characteristics and therefore possess inferior optical properties. Herein, we investigate the electrical as well as optical properties of single-layer and multi-layer MoS2-based phototransistors and demonstrate improved optical properties of multi-layer MoS2 phototransistor through the use of see-through metal electrode instead of the traditional global bottom gate or patterned local bottom gate structures. The see-through metal electrode utilized in this study shows transmittance of more than 70% under 532 nm visible light, thereby allowing the incident light to reach the entire active area below the source and drain electrodes. The effect of contact electrodes on the MoS2 phototransistors was investigated further by comparing the proposed electrode with conventional opaque electrodes and transparent IZO electrodes. A position-dependent photocurrent measurement was also carried out by locally illuminating the MoS2 channel at different positions in order to gain better insight into the behavior of the photocurrent mechanism of the multi-layer MoS2 phototransistor with the transparent metal. It was observed that more electrons are injected from the source when the beam is placed on the source side due to the reduced barrier height, giving rise to a significant enhancement of the photocurrent.

Organization of Embryonic Morphogenesis via Mechanical Information.

Embryonic organizers establish gradients of diffusible signaling molecules to pattern the surrounding cells. Here, we elucidate an additional mechanism of embryonic organizers that is a secondary consequence of morphogen signaling. Using pharmacological and localized transgenic perturbations, 4D imaging of the zebrafish embryo, systematic analysis of cell motion, and computational modeling, we find that the vertebrate tail organizer orchestrates morphogenesis over distances beyond the range of morphogen signaling. The organizer regulates the rate and coherence of cell motion in the elongating embryo using mechanical information that is transmitted via relay between neighboring cells. This mechanism is similar to a pressure front in granular media and other jammed systems, but in the embryo the mechanical information emerges from self-propelled cell movement and not force transfer between cells. The propagation likely relies upon local biochemical signaling that affects cell contractility, cell adhesion, and/or cell polarity but is independent of transcription and translation.