Abnormal spindle-like microcephaly associated (ASPM) is a causative gene of primary autosomal recessive microcephaly. Microcephaly is considered to be a consequence of a small brain, but the ...associated molecular mechanisms are not fully understood. In this study, we generated brain-specific Aspm knockout mice to evaluate the fetal brain phenotype and observed cortical reduction in the late stage of murine cortical development. It has been reported that the total number of neurons is regulated by the number of neural stem and progenitor cells. In the Aspm knockout mice, no apparent change was shown in the neural progenitor cell proliferation and there was no obvious effect on the number of newly generated neurons in the developing cortex. On the other hand, the knockout mice showed a constant increase in apoptosis in the cerebral cortex from the early through the late stages of cortical development. Furthermore, apoptosis occurred in the neural progenitor cells associated with DNA damage. Overall, these results suggest that apoptosis of the neural progenitor cells is involved in the thinning of the mouse cerebral cortex, due to the loss of the Aspm gene in neocortical development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The filamentous fungus
is one of the main contaminants of the International Space Station (ISS). It forms highly pigmented, airborne spores that have thick cell walls and low metabolic activity, ...enabling them to withstand harsh conditions and colonize spacecraft surfaces. Whether
r spores are resistant to space radiation, and to what extent, is not yet known. In this study, spore suspensions of a wild-type and three mutant strains (with defects in pigmentation, DNA repair, and polar growth control) were exposed to X-rays, cosmic radiation (helium- and iron-ions) and UV-C (254 nm). To assess the level of resistance and survival limits of fungal spores in a long-term interplanetary mission scenario, we tested radiation doses up to 1000 Gy and 4000 J/m
. For comparison, a 360-day round-trip to Mars yields a dose of 0.66 ± 0.12 Gy. Overall, wild-type spores of
were able to withstand high doses of X-ray (LD
= 360 Gy) and cosmic radiation (helium-ion LD
= 500 Gy; and iron-ion LD
= 100 Gy). Drying the spores before irradiation made them more susceptible toward X-ray radiation. Notably,
spores are highly resistant to UV-C radiation (LD
= 1038 J/m
), which is significantly higher than that of other radiation-resistant microorganisms (e.g.,
). In all strains, UV-C treated spores (1000 J/m
) were shown to have decreased biofilm formation (81% reduction in wild-type spores). This study suggests that
spores might not be easily inactivated by exposure to space radiation alone and that current planetary protection guidelines should be revisited, considering the high resistance of fungal spores.
Purpose
Laparoscopic liver resection is increasingly used to treat patients with hepatic tumor. However, during laparoscopic resection, information obtained by palpation using laparoscopic forceps or ...from intraoperative ultrasonography is extremely limited, which may pose a risk for positive surgical margins. This study aimed to investigate the feasibility and clinical application of near-infrared (NIR) fluorescence imaging to guide laparoscopic liver resection of a liver tumor and secure the surgical margins.
Methods
A preliminary study in 25 patients was conducted. NIR imaging was used intraoperatively during laparoscopic liver resection. The liver tumors were preoperatively labeled by intravenously injecting the patients with indocyanine green dye (0.5 mg/kg), an NIR fluorescence agent. During the surgical procedure, the PINPOINT Endoscopic Fluorescence Imaging System was used to assess the surgical margin by using real-time endoscopic high-definition visible and NIR fluorescence imaging.
Results
All tumors were identified and resected laparoscopically by using the PINPOINT system, and all resections successfully secured the surgical margin. The pathological findings of all tumors indicated negative margins, defined as R0.
Conclusions
This technique showed the potential to improve the intraoperative identification and demarcation of tumors. Its use could potentially reduce the number of positive resection margins.
Among the celestial bodies in the Solar System, Mars currently represents the main target for the search for life beyond Earth. However, its surface is constantly exposed to high doses of cosmic rays ...(CRs) that may pose a threat to any biological system. For this reason, investigations into the limits of resistance of life to space relevant radiation is fundamental to speculate on the chance of finding extraterrestrial organisms on Mars. In the present work, as part of the STARLIFE project, the responses of dried colonies of the black fungus
Culture Collection of Fungi from Extreme Environments (CCFEE) 515 to the exposure to accelerated iron (LET: 200 keV/μm) ions, which mimic part of CRs spectrum, were investigated. Samples were exposed to the iron ions up to 1000 Gy in the presence of Martian regolith analogues. Our results showed an extraordinary resistance of the fungus in terms of survival, recovery of metabolic activity and DNA integrity. These experiments give new insights into the survival probability of possible terrestrial-like life forms on the present or past Martian surface and shallow subsurface environments.
Recent progress in the fields of tissue engineering, micro-electro mechanical systems, and materials science have greatly improved cell culture systems, which were traditionally performed in a static ...two-dimensional manner. This progress has led to a number of new cell culture concepts represented by organ-on-a-chip, three dimensional (3D)-tissues, and microphysiological systems, among others. In this review, these culture models are categorized as reconstituted human organ models, which recapitulate human organ-like structure, function, and responses with physiological relevance. In addition, we also describe the expectations of reconstituted organ models from the viewpoint of a pharmaceutical company based on recent concerns expressed in drug discovery and development. These models can be used to assess the pharmacokinetics, safety and efficacy of new molecular entities (NMEs) prior to clinical trials. They can also be used to conduct mechanistic investigations of events that arise due to administration of NMEs in humans. In addition, monitoring biomarkers of organ function in these models will aid in the translation of their changes in humans. As the majority of reconstituted human organ models show improved functional characteristics and long-term maintenance in culture, they are valuable for modeling human events. An example is described using the three-dimensional bioprinted human liver tissue model in this article. Implementation of reconstituted human organ models in drug discovery and development can be accelerated by encouraging collaboration between developers and users. Such efforts will provide significant benefits for delivering new and improved medicines to patients.
The sharp high dose Bragg peak of a carbon-ion beam helps it to deliver the highest dosage to the malignant cells while leaving the normal cells relatively unharmed. However, the precise range in ...which it distributes dosages that significantly induce cell death or genotoxicity surrounding its Bragg peak remains unclear. To evaluate biological effects of carbon-ion radiation through entrance to post Bragg peak in a single biological system, CHO and xrs5 cells were cultured in T-175 cell culture flasks and irradiated with 290 MeV/n monoenergetic carbon-ions with initial dosages upon entrance to the flask of 1, 2, or 3 Gy for cell survival assays or 1 Gy for cytokinesis block micronuclei assays. Under all initial dosages, the biological Bragg peak and the highest micronuclei formation was observed at the depth of 14.5 cm. Moreover, as the initial dosage increased the range displaying a significant decrease in survival fraction increased as well (P < 0.0001). Intriguingly from 1 Gy to 3 Gy, we observed a significant increase in reappearance of colony formation depth (P < 0.05), possibly indicating the nuclear fragmentation lethality potential of the carbon-ion. By means of our single system approach, we can achieve a more comprehensive understanding of biological effects surrounding of carbon-ions Bragg peak.
Previous work pointed to a critical role of excessive production of reactive oxygen species (ROS) in increased radiation hematopoietic death in GFP mice. Meanwhile, enhanced antioxidant capability ...was not demonstrated in the mouse model of radio-induced adaptive response (RAR) using rescue of radiation hematopoietic death as the endpoint. ROS induction by ex vivo X-irradiation at a dose ranging from 0.1 to 7.5 Gy in the nucleated bone marrow cells was comparatively studied using GFP and wild type (WT) mice. ROS induction was also investigated in the cells collected from mice receiving a priming dose (0.5 Gy) efficient for RAR induction in WT mice. Significantly elevated background and increased induction of ROS in the cells from GFP mice were observed compared to those from WT mice. Markedly lower background and decreased induction of ROS were observed in the cells collected from WT mice but not GFP mice, both receiving the priming dose. GFP overexpression could alter background and induction of ROS by X-irradiation in hematopoietic cells. The results provide a reasonable explanation to the previous study on the fate of cells and mice after X-irradiation and confirm enhanced antioxidant capability in RAR. Investigations involving GFP overexpression should be carefully interpreted.
Abstract
The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was sent to 4458 dialysis facilities at the end of 2018; among these facilities, 4402 facilities ...(98.7%) responded to the facility questionnaire, and 4222 (94.7%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year; as of the end of 2018, it had reached 339,841 patients, representing 2688 patients per million population. Among the prevalent dialysis patients, the mean age was 68.75 years, and diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (26.8%) and nephrosclerosis (10.8%). The number of incident dialysis patients was 40,468, and a reduction by 491 from 2017. The mean age of the incident dialysis patients was 69.99 years old. Diabetic nephropathy was also the most common primary disease (42.3%), representing a 0.2 percent point reduction from 2017. The distribution of diabetic nephropathy appears to have reached a plateau. The number of deceased patients during 2018 was 33,863, and the crude annual death rate was 10.0%. Heart failure was the most common cause of death (23.5%), followed by infection (21.3%) and malignant tumor (8.4%); these causes were similar to those for 2017. The number of patients receiving hemodiafiltration has been increasing since 2012, reaching 125,793 or 37.0% of all dialysis patients at the end of 2018. The number of patients receiving peritoneal dialysis has been gradually increasing since 2017, reaching 9445, and 19.7% of these patients were treated using a combination of peritoneal dialysis and hemodialysis or hemodiafiltration. The proportion of patients receiving combination therapy has remained at around 20% of all peritoneal dialysis patients. The number of patients undergoing home hemodialysis was 720, representing an increase of 36 patients from 2017. The 2018 JRDR survey included several topics such as the present status of the patient kinetics of chronic dialysis patients at the end of 2018, water treatment and hemodiafiltration, peritoneal dialysis, treatments for diabetes, mental and physical conditions, and the present status of viral hepatitis. In this paper, we describe the patient and facility kinetics.
Trial registration
The JRDR was approved by the ethics committee of the JSDT (approval number 1-3) and was registered in the “University hospital Medical Information Network (UMIN) Clinical Trials Registry” under the clinical trial ID of
UMIN000018641
on August 8, 2015: (Accessed June 2, 2020)
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