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Nonsense-mediated mRNA decay (NMD) represents a highly conserved RNA surveillance mechanism through which mRNA transcripts bearing premature termination codons (PTCs) are selectively degraded to maintain transcriptomic fidelity in the cell. Numerous in vitro studies have demonstrated the importance of the NMD pathway; however, evidence supporting its physiological necessity has only just started to emerge. Here, we report that ablation of Upf2, which encodes a core NMD factor, in murine embryonic Sertoli cells (SCs) leads to severe testicular atrophy and male sterility owing to rapid depletion of both SCs and germ cells during prepubertal testicular development. RNA-Seq and bioinformatic analyses revealed impaired transcriptomic homeostasis in SC-specific Upf2 knockout testes, characterized by an accumulation of PTC-containing transcripts and the transcriptomewide dysregulation of genes encoding splicing factors and key proteins essential for SC fate control. Our data demonstrate an essential role of UPF2-mediated NMDin prepubertal SC development and male fertility. [ABSTRACT FROM AUTHOR]

Cyclic nucleotide-gated channels (CNGCs) have been implicated in diverse aspects of plant growth and development, including responses to biotic and abiotic stress, as well as pollen tube growth and fertility. Here, genetic evidence identifies CNGC16 in Arabidopsis (Arabidopsis thaliana) as critical for pollen fertility under conditions of heat stress and drought. Two independent transfer DNA disruptions of cngc16 resulted in a greater than 10-fold stress-dependent reduction in pollen fitness and seed set. This phenotype was fully rescued through pollen expression of a CNGC16 transgene, indicating that cngc16-1 and 16-2 were both loss-of-function null alleles. The most stress-sensitive period for cngc16 pollen was during germination and the initiation of pollen tube tip growth. Pollen viability assays indicate that mutant pollen are also hypersensitive to external calcium chloride, a phenomenon analogous to calcium chloride hypersensitivities observed in other cngc mutants. A heat stress was found to increase concentrations of 3',5'-cyclic guanyl monophosphate in both pollen and leaves, as detected using an antibody-binding assay. A quantitative PCR analysis indicates that cngc16 mutant pollen have attenuated expression of several heat-stress response genes, including two heat shock transcription factor genes, HsfA2 and HsfB1. Together, these results provide evidence for a heat stress response pathway in pollen that connects a cyclic nucleotide signal, a Ca2+-permeable ion channel, and a signaling network that activates a downstream transcriptional heat shock response. [ABSTRACT FROM AUTHOR]

Background: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection. Methodology/Principal Findings: We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8- week-old mice) to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection. Conclusions/Significance: Using the established, very susceptible 2009 Pandemic Influenza A (H1N1) mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1pandemics. [ABSTRACT FROM AUTHOR]

Background: The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model. Methodology/Principal Findings: Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 μg HA per dose) included rg-A/Vietnam/1203/ 2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 μg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60% in single A/Anhui/1/2005 vaccine group. Conclusion/Significance: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination against unknown pandemic virus. [ABSTRACT FROM AUTHOR]

Copper sulfate pentahydrate is investigated by terahertz time-domain spectroscopy. It is shown that the terahertz absorption coefficients are correlated with the particle size of the samples, as well as the heating rates of the ambient temperature. Furthermore, the water molecules of copper sulfate pentahydrate can be quantitatively characterized due to the high sensitivity of the terahertz wave to water molecules. Based on such results, the status of water incorporated in mineral opal is also characterized using terahertz time-domain spectroscopy. It indicates that terahertz technology can be considered as an efficient method to detect the dehydration of minerals. [ABSTRACT FROM AUTHOR]

As the genome is organized into a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, most epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the horizontal dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to resolve the genome conformation by capturing the epigenetic information in single-molecular resolution while simultaneously resolving the genome conformation. Using SCA-seq, we are able to examine the spatial interaction of chromatin accessibility (e.g. enhancer–promoter contacts), CpG island methylation, and spatial insulating functions of the CCCTC-binding factor. We demonstrate that SCA-seq paves the way to explore the mechanism of epigenetic interactions and extends our knowledge in 3D packaging of DNA in the nucleus. [ABSTRACT FROM AUTHOR]

A solid-like propellant of carbon-doped glycerol ablated by a nanosecond pulsed laser is investigated. The results show that the specific impulse increases with increasing carbon content, and a maximum value of 228 s is obtained. The high specific impulse is attributed to the low ablated mass loss that occurs at high carbon content. More importantly, with increasing carbon content, the properties of the doped glycerol approach to those of a solid. These results indicate that propulsion at the required coupling coefficient and specific impulse can be realized by doping a liquid propellant with an absorber. [ABSTRACT FROM AUTHOR]

Disruptions in glucose metabolism are frequently observed among patients undergoing peritoneal dialysis (PD) who utilize glucose-containing dialysis solutions. We aimed to investigate the relationship between glucometabolic indices, including fasting glucose, insulin resistance, advanced glycation end products (AGEs), PD-related glucose load, and icodextrin usage, and aortic stiffness in PD patients with and without diabetic mellitus (DM). This study involved 172 PD patients (mean age 58.3 ± 13.5 years), consisting of 110 patients without DM and 62 patients with DM. Aortic stiffness was assessed using the carotid-femoral pulse wave velocity (cfPWV). Impaired fasting glucose was defined as a fasting glucose level ≥ 100 mg/dL. Homeostatic model assessment for insulin resistance (HOMA-IR) scores, serum AGEs, dialysate glucose load, and icodextrin usage were assessed. Patients with DM exhibited the highest cfPWV (9.9 ± 1.9 m/s), followed by those with impaired fasting glucose (9.1 ± 1.4 m/s), whereas patients with normal fasting glucose had the lowest cfPWV (8.3 ± 1.3 m/s), which demonstrated a significant trend. In non-DM patients, impaired fasting glucose (β = 0.52, 95% confidence interval [CI] = 0.01–1.03, p = 0.046), high HOMA-IR (β = 0.60, 95% CI = 0.12–1.08, p = 0.015), and a high PD glucose load (β = 0.58, 95% CI = 0.08–1.08, p = 0.023) were independently associated with increased cfPWV. In contrast, none of the glucometabolic factors contributed to differences in cfPWV in DM patients. In conclusion, among PD patients without DM, impaired fasting glucose, insulin resistance, and PD glucose load were closely associated with aortic stiffness.

Robot arms used for service applications require safe human−machine interactions; therefore, the control gain of such robot arms must be minimized to limit the force output during operation, which slows the response of the control system. To improve cost efficiency, low-resolution sensors can be used to reduce cost because the robot arms do not require high precision of position sensing. However, low-resolution sensors slow the response of closed-loop control systems, leading to low accuracy. Focusing on safety and cost reduction, this study proposed a low-gain, sensorless Brushless DC motor control architecture, which performed position and torque control using only Hall-effect sensors and a current sensor. Low-pass filters were added in servo controllers to solve the sensing problems of undersampling and noise. To improve the control system’s excessively slow response, we added a dynamic force compensator in the current controllers, simplified the system model, and conducted tuning experiments to expedite the calculation of dynamic force. These approaches achieved real-time current compensation, and accelerated control response and accuracy. Finally, a seven-axis robot arm was used in our experiments and analyses to verify the effectiveness of the simplified dynamic force compensators. Specifically, these experiments examined whether the sensorless drivers and compensators could achieve the required response and accuracy while reducing the control system’s cost.

To protect operators and conform to safety standards for human−machine interactions, the design of collaborative robot arms often incorporates flexible mechanisms and force sensors to detect and absorb external impact forces. However, this approach increases production costs, making the introduction of such robot arms into low-cost service applications difficult. This study proposes a low-cost, sensorless rigid robot arm design that employs a virtual force sensor and stiffness control to enable the safety collision detection and low-precision force control of robot arms. In this design, when a robot arm is subjected to an external force while in motion, the contact force observer estimates the external torques on each joint according to the motor electric current and calculation errors of the system model, which are then used to estimate the external contact force exerted on the robot arm’s end-effector. Additionally, a torque saturation limiter is added to the servo drive for each axis to enable the real-time adjustment of joint torque output according to the estimated external force, regulation of system stiffness, and achievement of impedance control that can be applied in safety measures and force control. The design this study developed is a departure from the conventional multisensor flexible mechanism approach. Moreover, it is a low-cost and sensorless design that relies on model-based control for stiffness regulation, thereby improving the safety and force control in robot arm applications.