Abstract
Gene expression via transcription-translation is the most fundamental reaction to sustain biological systems, and complex reactions occur in a small compartment of living cells. There is ...increasing evidence that physical effects, such as molecular crowding or excluded volume effects of transcriptional-translational machinery, affect the yield of reaction products. On the other hand, transcriptional feedback that controls gene expression during mRNA synthesis is also a vital mechanism that regulates protein synthesis in cells. However, the excluded volume effect of spatial constraints on feedback regulation is not well understood. Here, we study the confinement effect on transcriptional autoregulatory feedbacks of gene expression reactions using a theoretical model. The excluded volume effects between molecules and the membrane interface suppress the gene expression in a small cell-sized compartment. We find that negative feedback regulation at the transcription step mitigates this size-induced gene repression and alters the scaling relation of gene expression level on compartment volume, approaching the regular scaling relation without the steric effect. This recovery of regular size-scaling of gene expression does not appear in positive feedback regulation, suggesting that negative autoregulatory feedback is crucial for maintaining reaction products constant regardless of compartment size in heterogeneous cell populations.
This article describes the state and the development of an artificial cell project. We discuss the experimental constraints to synthesize the most elementary cell-sized compartment that can ...self-reproduce using synthetic genetic information. The original idea was to program a phospholipid vesicle with DNA. Based on this idea, it was shown that in vitro gene expression could be carried out inside cell-sized synthetic vesicles. It was also shown that a couple of genes could be expressed for a few days inside the vesicles once the exchanges of nutrients with the outside environment were adequately introduced. The development of a cell-free transcription/translation toolbox allows the expression of a large number of genes with multiple transcription factors. As a result, the development of a synthetic DNA program is becoming one of the main hurdles. We discuss the various possibilities to enrich and to replicate this program. Defining a program for self-reproduction remains a difficult question as nongenetic processes, such as molecular self-organization, play an essential and complementary role. The synthesis of a stable compartment with an active interface, one of the critical bottlenecks in the synthesis of artificial cell, depends on the properties of phospholipid membranes. The problem of a self-replicating artificial cell is a long-lasting goal that might imply evolution experiments.
Topological defects in nematically aligned cell populations play a critical role in modulating collective motion, ranging from microbial colonies to epithelial tissues. Despite the potential of ...manipulating such topological defects to control diverse self-organized structures and collective dynamics, controlling the position of defects in active matter remains a challenging area of research. In this study, we investigated the geometry-guided control of defect positioning and alignment in a nematic cell population by imposing spatial constraints consisting of two or three overlapping circular boundaries. The confined cell population exhibited a paired and ordered distribution of half-integer topological defects that remained stable even when the size of the spatial constraint was altered using geometric parameters. These defects direct the inward flow of cells, induced by the curved boundary shape, towards the geometric center of the confined space. This inward flow contributes to an increase in a local cell density, and furthermore the geometry-induced nematic order provides mechanical stimulation to confined cells, as indicated by the elongated cell nucleus. Our geometry-based approach sets the foundation for controlling defect pairing and provides insights into the interplay among geometry, topology, and collective dynamics.
Bacterial suspensions show turbulence-like spatiotemporal dynamics and vortices moving irregularly inside the suspensions. Understanding these ordered vortices is an ongoing challenge in active ...matter physics, and their application to the control of autonomous material transport will provide significant development in microfluidics. Despite the extensive studies, one of the key aspects of bacterial propulsion has remained elusive: The motion of bacteria is chiral, i.e., it breaks mirror symmetry. Therefore, the mechanism of control of macroscopic active turbulence by microscopic chirality is still poorly understood. Here, we report the selective stabilization of chiral rotational direction of bacterial vortices in achiral circular microwells sealed by an oil/water interface. The intrinsic chirality of bacterial swimming near the top and bottom interfaces generates chiral collective motions of bacteria at the lateral boundary of the microwell that are opposite in directions. These edge currents grow stronger as bacterial density increases, and, within different top and bottom interfaces, their competition leads to a global rotation of the bacterial suspension in a favored direction, breaking the mirror symmetry of the system. We further demonstrate that chiral edge current favors corotational configurations of interacting vortices, enhancing their ordering. The intrinsic chirality of bacteria is a key feature of the pairing order transition from active turbulence, and the geometric rule of pairing order transition may shed light on the strategy for designing chiral active matter.
We studied the features of CuSbS2 (CAS) and CuSbSe2 (CASe), two proposed photovoltaic compounds, and clarified their electronic structures by first-principles calculations and compared them to the ...chalcopyrite-type CuInSe2 results. For both CAS and CASe, the calculated enthalpies of formation of the chalcostibite phases were considerably lower than those of the chalcopyrite phases. Therefore, we considered that the chalcostibite phase is more stable for CAS and CASe. In their band structure calculated with the HSE06 hybrid functional, the valence band maxima of CAS and CASe were located at the Γ-point, and the conduction band minima were located at the R-point. Their second lowest conduction band was located at the Γ-point, whose energy level nearly equaled the R-point. For CAS (CASe), the partial density of the states shows the character of the Cu 3d and S 3p (Se 4p) orbitals at the top of the valence bands and the Sb 5p and S 3p (Se 4p) orbitals at the bottom of the conduction bands. The conduction bands of CAS and CASe have a p-orbital character (Sb 5p) that differs from the s-orbital character (In 5s) of CuInSe2. It is for the reason that CAS and CASe do not have a chalcopyrite structure but a chalcostibite-type structure. The calculated absorption coefficient of CuSbS2 (104–105cm−1) is comparable to that of CuInSe2.
•We studied the features of CuSbS2 and CuSbSe2, newly proposed photovoltaic compounds.•Chalcostibite phase is more stable in CuSbS2 and CuSbSe2.•Band structures of CuSbS2 and CuSbS2 were calculated with HSE06 hybrid functional.•Absorption coefficient of chalcostibite-type CuSbS2 is comparable to that of CuInSe2.
Cellular surface breaks the symmetry of molecular diffusion across membrane. Here, we study how steric interactions between the surface and the bulk of cell-sized emulsion droplets alters gene ...expression emulated by a cell-free transcription/translation (TXTL) system. The concentration of synthesized reporter proteins in droplets of radius R shows an anomalous geometric scaling of R
different from the expected size-dependence of R
. Given that TXTL becomes less efficient at thin surface layer, a mathematical model explains the anomalous size-dependence found in experiment. The surface of cell-sized compartment can thus play a regulatory role for cell-free gene expression.
Preventing dystocia can stabilise beef cattle management. This study aimed to investigate the relationship between serum pregnancy-associated glycoproteins (PAGs) S-N values and estrone sulphate ...(E1S) concentrations during pregnancy and the calf birth weight in beef cattle and to evaluate their usefulness as new predictive parameters for dystocia due to foetal overgrowth. Thirty-eight pregnant Japanese Black cattle were used. Blood samples were collected at 40, 70, 100, 150, 200, 250, 280, and 285 days after artificial insemination (AI), and birth weight of the offspring was measured. Serum PAGs S-N values and E1S concentrations were measured, and the area under the curve (AUC) and the ratio of change based on 70 days after AI were calculated, followed by calculation of the correlation coefficient with the birth weight of the offspring and comparison between the eutocia (n = 32) and dystocia (n = 6) groups. The birth weight of the offspring was moderately positively correlated with the AUC of serum PAGs S-N values and E1S concentrations in the second (r = 0.425, P < 0.01) and third (r = 0.595, P < 0.01) trimesters, respectively. The ratio of change in serum E1S concentrations between 70 and 280 days after AI was greater (P < 0.05) in the dystocia group (1276.6 ± 229.1 %) than in the eutocia group (852.6 ± 69.6 %). These results suggest that blood PAGs S-N values at mid-pregnancy (100–199 days after AI) and the ratio of changes in blood E1S concentrations between 70 and 280 days after AI may be new parameters for predicting dystocia.
Display omitted
•Pregnancy-associated glycoproteins’ profile in beef cattle was clarified.•Estrone sulphate (E1S) concentration significantly increased in third trimester.•Serum PAGs in second trimester was positively correlated with calf birth weight.•Serum E1S in third trimester was positively correlated with calf birth weight.•Change in E1S from 70 to 280 days of pregnancy was greater in the dystocia group than eutocia group.
Thermal therapy is used to manage various psychological diseases, such as depression. We investigated the relationship between hot spring bathing and depression in older adults using questionnaire ...responses.
We comprehensively evaluated the preventive effects of long-term hot spring bathing in 10429 adults aged ≥ 65 years in Beppu, Japan, by conducting a questionnaire study on the prevalence of depression (n = 219).
Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a multivariable logistic regression model for history of depression.
A separate multivariable logistic regression model for inference showed that female sex (OR, 1.56; 95 % CI, 1.17–2.08; p = 0.002), arrhythmia (OR, 1.73; 95 % CI, 1.18–2.52; p = 0.004), hyperlipidemia (OR, 1.63; 95 % CI, 1.14–2.32; p = 0.006), renal disease (OR, 2.26; 95 % CI, 1.36–3.75; p = 0.001), collagen disease (OR, 2.72; 95 % CI, 1.48–5.02; p = 0.001), allergy (OR, 1.97; 95 % CI, 1.27–3.04; p = 0.002), and habitual daily hot spring bathing (OR, 0.63; 95 % CI, 0.41–0.94; p = 0.027) were independently significantly associated with a history of depression.
We found an inverse relationship between habitual daily hot spring bathing and history of depression. Prospective randomized controlled trials on habitual daily hot spring bathing as a treatment for depression are warranted to investigate whether the use of hot springs can provide relief to those with psychiatric and mental health disorders.
•Hot spring bathing was correlated with a history of depression (odds ratio 0.63).•Having history of depression was associated with a habitual daily hot spring bathing (odds ratio 0.65).•Randomized control trials on the effects of hot spring bathing are warranted.
Controlling the phases of matter is a challenge that spans from condensed materials to biological systems. Here, by imposing a geometric boundary condition, we study the controlled collective motion ...of Escherichia coli bacteria. A circular microwell isolates a rectified vortex from disordered vortices masked in the bulk. For a doublet of microwells, two vortices emerge but their spinning directions show transition from parallel to anti-parallel. A Vicsek-like model for confined self-propelled particles gives the point where the two spinning patterns occur in equal probability and one geometric quantity governs the transition as seen in experiments. This mechanism shapes rich patterns including chiral configurations in a quadruplet of microwells, thus revealing a design principle of active vortices.
In thermophoresis, with the fluid at rest, suspensions move along a gradient of temperature. In an aqueous solution, a PEG polymer suspension is depleted from the hot region and builds a ...concentration gradient. In this gradient, DNA polymers of different sizes can be separated. In this work the effect of the polymer structure for genomic DNA and small RNA is studied. For genome-size DNA, individual single T4 DNA is visualized and tracked in a PEG solution under a temperature gradient built by infrared laser focusing. We find that T4 DNA follows steps of depletion, ring-like localization, and accumulation patterns as the PEG volume fraction is increased. Furthermore, a coil–globule transition for DNA is observed for a large enough PEG volume fraction. This drastically affects the localization position of T4 DNA. In a similar experiment, with small RNA such as ribozymes we find that the stem–loop folding of such polymers has important consequences. The RNA polymers having a long and rigid stem accumulate, whereas a polymer with stem length less than 4 base pairs shows depletion. Such measurements emphasize the crucial contribution of the double-stranded parts of RNA for thermal separation and selection under a temperature gradient. Because huge temperature gradients are present around hydrothermal vents in the deep ocean seafloor, this process might be relevant, at the origin of life, in an RNA world hypothesis. Ribozymes could be selected from a pool of random sequences depending on the length of their stems.
PDF
