Cortical tension drug screen links mitotic spindle integrity to Rho pathway.

Mechanical force generation plays an essential role in many cellular functions, including mitosis. Actomyosin contractile forces mediate changes in cell shape in mitosis and are implicated in mitotic spindle integrity via cortical tension. An unbiased screen of 150 small molecules that impact actin organization and 32 anti-mitotic drugs identified two molecular targets, Rho kinase (ROCK) and tropomyosin 3.1/2 (Tpm3.1/2), whose inhibition has the greatest impact on mitotic cortical tension. The converse was found for compounds that depolymerize microtubules. Tpm3.1/2 forms a co-polymer with mitotic cortical actin filaments, and its inhibition prevents rescue of multipolar spindles induced by anti-microtubule chemotherapeutics. We examined the role of mitotic cortical tension in this rescue mechanism. Inhibition of ROCK and Tpm3.1/2 and knockdown (KD) of cortical nonmuscle myosin 2A (NM2A), all of which reduce cortical tension, inhibited rescue of multipolar mitotic spindles, further implicating cortical tension in the rescue mechanism. GEF-H1 released from microtubules by depolymerization increased cortical tension through the RhoA pathway, and its KD also inhibited rescue of multipolar mitotic spindles. We conclude that microtubule depolymerization by anti-cancer drugs induces cortical-tension-based rescue to ensure integrity of the mitotic bipolar spindle mediated via the RhoA pathway. Central to this mechanism is the dependence of NM2A on Tpm3.1/2 to produce the functional engagement of actin filaments responsible for cortical tension.

Image Stitching Based on Color Difference and KAZE with a Fast Guided Filter.

Image stitching is of great importance for multiple fields such as moving object detection and tracking, ground reconnaissance and augmented reality. To ameliorate the stitching effect and alleviate the mismatch rate, an effective image stitching algorithm based on color difference and an improved KAZE with a fast guided filter is proposed. Firstly, the fast guided filter is introduced to reduce the mismatch rate before feature matching. Secondly, the KAZE algorithm based on improved random sample consensus is used for feature matching. Then, the color difference and brightness difference of the overlapping area are calculated to make an overall adjustment to the original images so as to improve the nonuniformity of the splicing result. Finally, the warped images with color difference compensation are fused to obtain the stitched image. The proposed method is evaluated by both visual effect mapping and quantitative values. In addition, the proposed algorithm is compared with other current popular stitching algorithms. The results show that the proposed algorithm is superior to other algorithms in terms of the quantity of feature point pairs, the matching accuracy, the root mean square error and the mean absolute error.

Modified Two-Point Correction Method for Wide-Spectrum LWIR Detection System.

Non-uniformity commonly exists in the infrared focal plane, which behaves as the fixed-pattern noise (FPN) and seriously affects the image quality of long-wave infrared (LWIR) detection systems. The two-point correction (TPC) method is commonly used to reduce image FPN in engineering. However, when a wide-spectrum LWIR detection system calibrated with a black body is used to detect weak and small targets in the sky, FPN still appears in the image, affecting its uniformity. The effects of atmospheric transmittance characteristics of long-range paths on the non-uniformity of wide-spectrum long-wave infrared systems have not been studied. This paper proposes a modified TPC model based on spectral subdivision that introduces atmospheric transmittance. Additionally, the effects of atmospheric transmittance characteristics on the long-wave infrared non-uniform correction coefficient are analyzed. The experimental results for a black body scene and sky scene using a weak and small target detection system with a long-wave Sofradir FPA demonstrate that the wide-spectrum LWIR detection system fully considers atmospheric transmittance when performing calibration based on the TPC method, which can reduce the non-uniformity of the image.

Spatiotemporally mapping temperature dynamics of lysosomes and mitochondria using cascade organelle-targeting upconversion nanoparticles.

The intracellular metabolism of organelles, like lysosomes and mitochondria, is highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of adenosine triphosphate (ATP) generation during active metabolism. Here, we developed temperature-sensitive LysoDots and MitoDots to monitor the in situ thermal dynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K-1 and low uncertainty of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the ion concentrations and pH values. With Ca2+ ion shock, the temperatures of both lysosomes and mitochondria increased by ∼2 to 4 °C. Intriguingly, with chloroquine (CQ) treatment, the lysosomal temperature was observed to decrease by up to ∼3 °C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed an ∼3 to 7 °C temperature increase and a thermal transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multimodality functional imaging of subcellular organelles and interactions with high spatial, temporal, and thermal dynamics resolutions.

Lanthanide Ion Resonance-Driven Rayleigh Scattering of Nanoparticles for Dual-Modality Interferometric Scattering Microscopy.

Light scattering from nanoparticles is significant in nanoscale imaging, photon confinement. and biosensing. However, engineering the scattering spectrum, traditionally by modifying the geometric feature of particles, requires synthesis and fabrication with nanometre accuracy. Here it is reported that doping lanthanide ions can engineer the scattering properties of low-refractive-index nanoparticles. When the excitation wavelength matches the ion resonance frequency of lanthanide ions, the polarizability and the resulted scattering cross-section of nanoparticles are dramatically enhanced. It is demonstrated that these purposely engineered nanoparticles can be used for interferometric scattering (iSCAT) microscopy. Conceptually, a dual-modality iSCAT microscopy is further developed to identify different nanoparticle types in living HeLa cells. The work provides insight into engineering the scattering features by doping elements in nanomaterials, further inspiring exploration of the geometry-independent scattering modulation strategy.

Single Small Extracellular Vesicle (sEV) Quantification by Upconversion Nanoparticles.

Cancer-derived small extracellular vesicles (sEVs) are potential circulating biomarkers in liquid biopsies. However, their small sizes, low abundance, and heterogeneity in molecular makeups pose major technical challenges for detecting and characterizing them quantitatively. Here, we demonstrate a single-sEV enumeration platform using lanthanide-doped upconversion nanoparticles (UCNPs). Taking advantage of the unique optical properties of UCNPs and the background-eliminating property of total internal reflection fluorescence (TIRF) imaging technique, a single-sEV assay recorded a limit of detection 1.8 × 106 EVs/mL, which was nearly 3 orders of magnitude lower than the standard enzyme-linked immunosorbent assay (ELISA). Its specificity was validated by the difference between EpCAM-positive and EpCAM-negative sEVs. The accuracy of the UCNP-based single-sEV assay was benchmarked with immunomagnetic-beads flow cytometry, showing a high correlation (R2> 0.99). The platform is suitable for evaluating the heterogeneous antigen expression of sEV and can be easily adapted for biomarker discoveries and disease diagnosis.

miR-340-5p Mediates Cardiomyocyte Oxidative Stress in Diabetes-Induced Cardiac Dysfunction by Targeting Mcl-1.

Diabetic cardiomyopathy (DCM) is initially characterized by early diastolic dysfunction, left ventricular remodeling, hypertrophy, and myocardial fibrosis, and it is eventually characterized by clinical heart failure. MicroRNAs (miRNAs), endogenous small noncoding RNAs, play significant roles in diabetes mellitus (DM). However, it is still largely unknown about the mechanism that links miRNAs and the development of DCM. Here, we aimed to elucidate the mechanism underlying the potential role of microRNA-340-5p in DCM in db/db mouse, which is a commonly used model of type 2 DM and diabetic complications that lead to heart failure. We first demonstrated that miR-340-5p expression was dramatically increased in heart tissues of mice and cardiomyocytes under diabetic conditions. Overexpression of miR-340-5p exacerbated DCM, which was reflected by extensive myocardial fibrosis and more serious dysfunction in db/db mice as represented by increased apoptotic cardiomyocytes, elevated ROS production, and impaired mitochondrial function. Inhibition of miR-340-5p by a tough decoy (TUD) vector was beneficial for preventing ROS production and apoptosis, thus rescuing diabetic cardiomyopathy. We identified myeloid cell leukemia 1 (Mcl-1) as a major target gene for miR-340-5p and showed that the inhibition of Mcl-1 was responsible for increased functional loss of mitochondria, oxidative stress, and cardiomyocyte apoptosis, thereby caused cardiac dysfunction in diabetic mice. In conclusion, our results showed that miR-340-5p plays a crucial role in the development of DCM and can be targeted for therapeutic intervention.

Design and Optimization for Mounting Primary Mirror with Reduced Sensitivity to Temperature Change in an Aerial Optoelectronic Sensor.

In order to improve the image quality of the aerial optoelectronic sensor over a wide range of temperature changes, high thermal adaptability of the primary mirror as the critical components is considered. Integrated optomechanical analysis and optimization for mounting primary mirrors are carried out. The mirror surface shape error caused by uniform temperature decrease was treated as the objective function, and the fundamental frequency of the mirror assembly and the surface shape error caused by gravity parallel or vertical to the optical axis are taken as the constraints. A detailed size optimization is conducted to optimize its dimension parameters. Sensitivities of the optical system performance with respect to the size parameters are further evaluated. The configuration of the primary mirror and the flexure are obtained. The simulated optimization results show that the size parameters differently affect the optical performance and which factors are the key. The mirror surface shape error under 30 °C uniform temperature decrease effectively decreased from 26.5 nm to 11.6 nm, despite the weight of the primary mirror assembly increases by 0.3 kg. Compared to the initial design, the value of the system's modulation transfer function (0° field angle) is improved from 0.15 to 0.21. Namely, the optical performance of the camera under thermal load has been enhanced and thermal adaptability of the primary mirror has been obviously reinforced after optimization. Based on the optimized results, a prototype of the primary mirror assembly is manufactured and assembled. A ground thermal test was conducted to verify difference in imaging quality at room and low temperature, respectively. The image quality of the camera meets the requirements of the index despite degrading.

Stratified Disk Microrobots with Dynamic Maneuverability and Proton-Activatable Luminescence for in Vivo Imaging.

Microrobots can expand our abilities to access remote, confined, and enclosed spaces. Their potential applications inside our body are obvious, e.g., to diagnose diseases, deliver medicine, and monitor treatment efficacy. However, critical requirements exist in relation to their operations in gastrointestinal environments, including resistance to strong gastric acid, responsivity to a narrow proton variation window, and locomotion in confined cavities with hierarchical terrains. Here, we report a proton-activatable microrobot to enable real-time, repeated, and site-selective pH sensing and monitoring in physiological relevant environments. This is achieved by stratifying a hydrogel disk to combine a range of functional nanomaterials, including proton-responsive molecular switches, upconversion nanoparticles, and near-infrared (NIR) emitters. By leveraging the 3D magnetic gradient fields and the anisotropic composition, the microrobot can be steered to locomote as a gyrating "Euler's disk", i.e., aslant relative to the surface and along its low-friction outer circumference, exhibiting a high motility of up to 60 body lengths/s. The enhanced magnetomotility can boost the pH-sensing kinetics by 2-fold. The fluorescence of the molecular switch can respond to pH variations with over 600-fold enhancement when the pH decreases from 8 to 1, and the integration of upconversion nanoparticles further allows both the efficient sensitization of NIR light through deep tissue and energy transfer to activate the pH probes. Moreover, the embedded down-shifting NIR emitters provide sufficient contrast for imaging of a single microrobot inside a live mouse. This work suggests great potential in developing multifunctional microrobots to perform generic site-selective tasks in vivo.

Metformin Suppresses the Progress of Diabetes-Accelerated Atherosclerosis by Inhibition of Vascular Smooth Muscle Cell Migration Through AMPK-Pdlim5 Pathway.

Backgrounds: Our previous work revealed that AMP-activated protein kinase (AMPK) activation inhibits vascular smooth muscle cell migration in vitro by phosphorylating PDZ and LIM domain 5 (Pdlim5). As metformin is an AMPK activator, we used a mouse vascular smooth muscle cell (VSMC) line and a Myh11-cre-EGFP mice to investigate whether metformin could inhibit the migration of VSMCs in vitro and in a wire-injury model in vivo. It is recognized that VSMCs contribute to the major composition of atherosclerotic plaques. In order to investigate whether the AMPK-Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, we utilized ApoE-/- male mice to investigate whether metformin could suppress diabetes-accelerated atherosclerosis by inhibition of VSMC migration via the AMPK-Pdlim5 pathway. Methods: The mouse VSMC cell line was exogenously transfected wild type, phosphomimetic, or unphosphorylatable Pdlim5 mutant before metformin exposure. Myh11-cre-EGFP mice were treated with saline solution or metformin after these were subjected to wire injury in the carotid artery to study whether metformin could inhibit the migration of medial VSMCs into the neo-intima. In order to investigate whether the AMPK-Pdlim5 pathway is involved in the protective function of metformin against atherosclerosis, ApoE-/- male mice were divided randomly into control, streptozocin (STZ), and high-fat diet (HFD)-induced diabetes mellitus; STZ+HFD together with metformin or Pdlim5 mutant carried the adenovirus treatment groups. Results: It was found that metformin could induce the phosphorylation of Pdlim5 and inhibit cell migration as a result. The exogenous expression of phosphomimetic S177D-Pdlim5 inhibits lamellipodia formation and migration in VSMCs. It was also demonstrated that VSMCs contribute to the major composition of injury-induced neointimal lesions, while metformin could alleviate the occlusion of the carotid artery. The data of ApoE-/- mice showed that increased plasma lipids and aggravated vascular smooth muscle cell infiltration into the atherosclerotic lesion in diabetic mice were observed Metformin alleviated diabetes-induced metabolic disorders and atherosclerosis and also reduced VSMC infiltration in atherosclerotic plaques, while the Pdlim5 phospho-abolished mutant that carried adenovirus S177A-Pdlim5 undermines the protective function of metformin. Conclusions: The activation of the AMPK-Pdlim5 pathway by metformin could interrupt the migratory machine of VSMCs and inhibit cell migration in vitro and in vivo. The maintenance of AMPK activity by metformin is beneficial for suppressing diabetes-accelerated atherosclerosis.

Quantitatively Monitoring In Situ Mitochondrial Thermal Dynamics by Upconversion Nanoparticles.

Temperature dynamics reflect the physiological conditions of cells and organisms. Mitochondria regulate the temperature dynamics in living cells as they oxidize the respiratory substrates and synthesize ATP, with heat being released as a byproduct of active metabolism. Here, we report an upconversion nanoparticle-based thermometer that allows the in situ thermal dynamics monitoring of mitochondria in living cells. We demonstrate that the upconversion nanothermometers can efficiently target mitochondria, and the temperature-responsive feature is independent of probe concentration and medium conditions. The relative sensing sensitivity of 3.2% K-1 in HeLa cells allows us to measure the mitochondrial temperature difference through the stimulations of high glucose, lipid, Ca2+ shock, and the inhibitor of oxidative phosphorylation. Moreover, cells display distinct response time and thermodynamic profiles under different stimulations, which highlight the potential applications of this thermometer to study in situ vital processes related to mitochondrial metabolism pathways and interactions between organelles.

Optical tweezers beyond refractive index mismatch using highly doped upconversion nanoparticles.

Optical tweezers are widely used in materials assembly1, characterization2, biomechanical force sensing3,4 and the in vivo manipulation of cells5 and organs6. The trapping force has primarily been generated through the refractive index mismatch between a trapped object and its surrounding medium. This poses a fundamental challenge for the optical trapping of low-refractive-index nanoscale objects, including nanoparticles and intracellular organelles. Here, we report a technology that employs a resonance effect to enhance the permittivity and polarizability of nanocrystals, leading to enhanced optical trapping forces by orders of magnitude. This effectively bypasses the requirement of refractive index mismatch at the nanoscale. We show that under resonance conditions, highly doping lanthanide ions in NaYF4 nanocrystals makes the real part of the Clausius-Mossotti factor approach its asymptotic limit, thereby achieving a maximum optical trap stiffness of 0.086 pN µm-1 mW-1 for 23.3-nm-radius low-refractive-index (1.46) nanoparticles, that is, more than 30 times stronger than the reported value for gold nanoparticles of the same size. Our results suggest a new potential of lanthanide doping for the optical control of the refractive index of nanomaterials, developing the optical force tag for the intracellular manipulation of organelles and integrating optical tweezers with temperature sensing and laser cooling7 capabilities.

Unidirectional intercellular communication on a microfluidic chip.

Cell co-culture serves as a standard method to study intercellular communication. However, random diffusion of signal molecules during co-culture may arouse crosstalk among different types of cells and hide directive signal-target responses. Here, a microfluidic chip is proposed to study unidirectional intercellular communication by spatially controlling the flow of the signal molecules. The chip contains two separated chambers connected by two channels where the culture media flows oppositely. A zigzag signal-blocking channel is designed to study the function of a specific signal. The chip is applied to study the unidirectional communication between tumor cells and stromal cells. It shows that the expression of α-smooth muscle actin (a marker of cancer-associated fibroblast (CAF)) of both MRC-5 fibroblasts and mesenchymal stem cells can be up-regulated only by the secreta from invasive MDA-MB-231 cells, but not from non-invasive MCF-7 cells. The proliferation of the tumor cells can be improved by the stromal cells. Moreover, transforming growth factor beta 1 is found as one of the main factors for CAF transformation via the signal-blocking function. The chip achieves unidirectional cell communication along X-axis, signal concentration gradient along Y-axis and 3D cell culture along Z-axis, which provides a useful tool for cell communication studies.

Clinical characteristics and surgical outcomes of ependymomas in the upper cervical spinal cord: a single-center experience of 155 consecutive patients.

Ependymomas occurring in the upper cervical spinal cord (above the level of the C4 segment) are rare entities with great therapeutic challenges. This study was aimed to investigate the clinicoradiological characteristics and the prognosis in a large cohort of upper cervical ependymomas from a single institution. This retrospective study enrolled 155 patients with primary ependymomas in the upper cervical spinal cord. The pre- and post-operative clinical and magnetic resonance imaging profiles were collected. The neurological outcomes and survival events were evaluated, and potential independent risk factors were analyzed. There were 82 females and 73 males, with an average age of 43.1 ± 11.3 years. Immediately post-operatively, 118 (76.1%) patients experienced neurological deterioration and 32 (20.7%) patients remained unchanged. Three months after surgery, 61 (39.4%) patients showed deteriorated neurological functions compared to the pre-operative baseline levels. After an average follow-up period of 56.0 ± 24.7 months, the neurological functions were worse than the baseline status in 37 (23.9%) patients and improved in 33 (21.3%) patients, respectively. Logistic regression analysis identified that lower age (≤ 42 years) and lower pre-operative MMS (I-II) were independent protective factors for predicting favorable neurological functions. Multivariate Cox regression analysis revealed that incomplete resection was the only independent risk factor associated with a shorter progression-free survival. Age and pre-operative functional status affect the long-term neurological outcomes, and incomplete resection was associated with a shorter survival. Our findings indicate that gross total resection should be the goal of surgical treatment of upper cervical ependymomas.

A Median-Ratio Scene-Based Non-Uniformity Correction Method for Airborne Infrared Point Target Detection System.

Infrared detectors suffer from severe non-uniform noise which highly reduces image resolution and point target signal-to-noise ratio. This is the restriction for airborne point target detection systems in reaching the background limit. The existing methods are either not accurate enough, or too complex to be applied to engineering. To improve the precision and reduce the algorithm complexity of scene-based Non-Uniformity Correction (NUC) for an airborne point target detection system, a Median-Ratio Scene-based NUC (MRSBNUC) method is proposed. The method is based on the assumption that the median value of neighboring pixels is approximately constant. The NUC coefficients are calculated recursively by selecting the median ratio of adjacent pixels. Several experiments were designed and conducted. For both the clear sky scene and scene with clouds, the non-uniformity is effectively reduced. Furthermore, targets were detected in outfield experiments. For Target 1 48.36 km away and Target 2 50.53 km away, employing MRSBNUC the SNR of the target increased 2.09 and 1.73 times respectively compared to Two-Point NUC. It was concluded that the MRSBNUC method can reduce the non-uniformity of the detector effectively which leads to a longer detection distance and fewer false alarms of the airborne point target detection system.

Extinction ratio and image accuracy of relayed-microgrid polarimetric imaging systems: theory and experiment.

Herein we propose a polarimetric imaging system that uses a microgrid polarizer placed on the conjugate point of two telecentric optical paths, matching large polarizers with small sensors and thus effectively decreasing optical crosstalk and increasing imaging accuracy. We define a new parameter used to construct the high-precision polarization vector transfer model under crosstalk. Using the equivalent surface of the detector, we establish the relationship between focal shift and crosstalk ratio and obtain a multi-physical coupling mathematical model that accounts for the crosstalk ratio, extinction ratio, sensor error, target vector, and imaging accuracy of the system. The relayed-microgrid polarimetric imaging system is anticipated to be able to help identify objects of interest for remote sensing and military applications.

Subependymoma of the Conus Medullaris with Cystic Formation: Case Report and a Literature Review.

BACKGROUND: Subependymoma in the spinal cord is very rare and usually occurs in the cervical cord. We report an exceptional case of subependymoma that occurred at the conus medullaris with cystic formation. This article reviews the literature on subependymoma in the conus medullaris; discusses its clinical manifestations, imaging findings, and differential diagnoses; and offers an opinion about the cystic formation of the subependymoma. CASE DESCRIPTION: A 69-year-old woman experienced progressive limb weakness with a somatosensory abnormality for 3 months. Preoperative magnetic resonance imaging showed a cystic intramedullary lesion at the conus medullaris with a well-defined margin. A preliminary diagnosis of epidermoid cyst was made based on the imaging findings. During the operation, cystic formation of the tumor was found, and the tumor was completely removed. Pathology showed an uneven proliferation of glial cells, consistent with subependymal morphology, and the tumor was confirmed as subependymoma. CONCLUSIONS: We present an extremely rare case of cystic formation in subependymoma at the conus medullaris. Subependymoma should be included in the differential diagnosis of intramedullary cystic lesions. The breakdown of the blood-brain barrier and excessive extravasation may be potential mechanisms of cystic formation.

[Metformin inhibits aortic atherosclerosis in mice by regulating actin skeleton in vascular smooth muscle cells].

ObjectiveInvestigate the effect and mechanism of metformin on the development of metabolic syndrome related atherosclerosis.MethodTransfecting EGFP-CLIP170 or EGFP-Pdlim5 plasmid to the mouse aortic smooth muscle cell line, to test the expression of p-AMPK, pCLIP-170 and pPdlim5, and observe the microtubule or the actin skeleton system by immunofluorescence staining. Scratch the cells to perform wound healing experiment, stimulating the cells with gradient metformin (0, 0.5, 1 mmol/L) for 8 h, and observe the change of the scratch size and the dynamic change of cell skeleton and migration in vitro. ApoE-/- mice were injected with streptozotocin and followed by 8 weeks of high fat diet to induce metabolic syndrome model. In the therapeutic group, mice were treated metformin (Met) instead of saline in control group (Control, CTL group). In the end, the whole aorta and its root were isolated and performed oil red O staining and immol/Lunostaining of α-SMA to evaluate the migration of smooth muscle cells and the accumulation of lipids in the aorta.ResultsMouse aortic smooth muscle cells showed an enhanced stress fiber and focal adhesion which representing the dynamic change of actin skeleton after Met stimulation, while the tubulin system rarely showed any change to Met. In animal model, The staining of α-SMA showed smooth muscle cells migrated to the intima or even to the lipid area from the media of aorta in CTL group compared to the Met group. Oil red O staining showed a reduced accumulation of lipids in the Met group than the controls (P < 0.05).ConclusionMetformin reduces the formation of atherosclerosis by inhibiting the migration of smooth muscle cells through modulating cellular actin skeleton system in mice.

Effect of sensor SNR and extinction ratio on polarimetric imaging error for nanowire-based systems.

High-sensor SNR and high extinction ratio (ER), which are often contradictory requirements for nanowire-filter-based polarimetric imaging systems, aid in attenuating polarimetric imaging system errors. Expressions were derived to analyze their attenuation effects and then simplified using photoelectronic numbers received by superpixels (PNRS). The first-derivative ratios of PNRS and ER were calculated to compare their attenuation effects. Mathematical models and experiments conducted using polarimetric imaging systems with various ERs and PNRSs indicate that systems with low PNRS and high ER exhibit a polarization error affected more by the attenuation effect of the PNRS than that of the ER. When the system ER is higher than 28, the attenuation effect of the PNRS is higher than that of the ER. Thus, system error attenuation is a trade-off between sensor SNR and ER.

Increased Formation of Follicular Antrum in Aquaporin-8-Deficient Mice Is Due to Defective Proliferation and Migration, and Not Steroidogenesis of Granulosa Cells.

Aquaporin-8 (AQP8) is a water channel protein expressed exclusively in granulosa cells (GCs) in mouse ovary. Our previous studies of AQP8-deficient (AQP8-/-) mice demonstrated that AQP8 participates in folliculogenesis, including in the formation of follicles, ovulation, and atresia. However, its physiological function in formation of the antral follicle is still largely unknown. In the present study, we observed significantly increased numbers of antral follicles in AQP8-/- ovaries as well as significantly increased follicular antrum formation in in vitro 3D culture of AQP8-/- follicles. Functional detection of AQP8-/- GCs indicated that cell proliferation is impaired with FSH treatment, and wound healing and Transwell migration are also impaired with or without FSH treatment, compared with that in WT. However, the biosynthesis of estradiol and progesterone as well as the mRNA levels of key steroidogenic enzyme genes (CYP19A1 and StAR) in AQP8-/- GCs did not change, even with addition of FSH and/or testosterone. In order to estimate the influence of the impaired proliferation and migration on the density of GC mass, preantral follicles were injected with FITC-dextran, which distributes only in the intercellular space, and analyzed by confocal microscopy. The micrographs showed significantly higher transmission of fluorescence in AQP8-/- follicles, suggesting increased intercellular space of GCs. Based on this evidence, we concluded that AQP8 deficiency leads to increased formation of follicular antra in vivo and in vitro, and the mechanism may be associated with increased intercellular space of GCs, which may be caused by defective proliferation and migration of GCs. This study may offer new insight into the molecular mechanisms of the formation of follicular antrum.