Lokiarchaeota archaeon schizorhodopsin-2 (LaSzR2) is an inward proton pump displaying a characteristic feature of acid-induced spectral blue-shift

The photoreactive protein rhodopsin is widespread in microorganisms and has a variety of photobiological functions. Recently, a novel phylogenetically distinctive group named 'schizorhodopsin (SzR)' has been identified as an inward proton pump. We performed functional and spectroscopic studies on an uncharacterised schizorhodopsin from the phylum Lokiarchaeota archaeon. The protein, LaSzR2, having an all-trans-retinal chromophore, showed inward proton pump activity with an absorption maximum at 549 nm. The pH titration experiments revealed that the protonated Schiff base of the retinal chromophore (Lys188, pK(a)=12.3) is stabilised by the deprotonated counterion (presumably Asp184, pK(a)=3.7). The flash-photolysis experiments revealed the presence of two photointermediates, K and M. A proton was released and uptaken from bulk solution upon the formation and decay of the M intermediate. During the M-decay, the Schiff base was reprotonated by the proton from a proton donating residue (presumably Asp172). These properties were compared with other inward (SzRs and xenorhodopsins, XeRs) and outward proton pumps. Notably, LaSzR2 showed acid-induced spectral 'blue-shift' due to the protonation of the counterion, whereas outward proton pumps showed opposite shifts (red-shifts). Thus, we can distinguish between inward and outward proton pumps by the direction of the acid-induced spectral shift

Oncofertility care in young women and the outcomes of pregnancy over the last 5 years

Aim: To ascertain the actual outcomes of oncofertility care in young women to provide more appropriate care. Materials & methods: We analyzed the data of 67 female patients under 43 years of age who underwent oncofertility care between January 2015 and September 2019. Results: There were 28 patients with breast cancer, 19 patients with hematologic cancer and 20 patients with other cancer diagnoses. Breast cancer patients tended to take longer than hematologic cancer patients to initiate oncofertility treatment. Despite undergoing oncofertility care, seven of nine pregnant patients did not choose assisted reproductive technology (ART). Conclusion: As spontaneous pregnancies were more common than ART pregnancies in our study, pregnancy by not only ART but also non-ART method is a viable option for young cancer survivors

Resuscitation of Preterm Infants with Reduced Oxygen Results in Less Oxidative Stress than Resuscitation with 100% Oxygen

The objective of this study was to determine the effects of the level of inhaled oxygen during resuscitation on the levels of free radicals and anti-oxidative capacity in the heparinized venous blood of preterm infants. Forty four preterm infants <35 weeks of gestation with mild to moderate neonatal asphyxia were randomized into two groups. The first group of infants were resuscitated with 100% oxygen (100% O2 group), while in the other group (reduced O2 group), the oxygen concentration was titrated according to pulse oximeter readings. We measured total hydroperoxide (TH) and redox potential (RP) in the plasma within 60 min of birth. The integrated excessive oxygen (∑(FiO2-0.21) × Time(min)) was higher in the 100% O2 group than in the reduced O2 group (p<0.0001). TH was higher in the 100% O2 group than in the reduced O2 group (p<0.0001). RP was not different between the 100% O2 and reduced O2 groups (p = 0.399). RP/TH ratio was lower in the 100% O2 group than in the reduced O2 group (p<0.01). We conclude that in the resuscitation of preterm infants with mild to moderate asphyxia, oxidative stress can be reduced by lowering the inspired oxygen concentration using a pulse oximeter

14-3-3 proteins stabilize LGI1-ADAM22 levels to regulate seizure thresholds in mice

新たなてんかん治療戦略を提案 --脳の過剰興奮を阻止するタンパク質ADAM22の量が鍵--. 京都大学プレスリリース. 2021-12-15.What percentage of the protein function is required to prevent disease symptoms is a fundamental question in genetic disorders. Decreased transsynaptic LGI1-ADAM22 protein complexes, because of their mutations or autoantibodies, cause epilepsy and amnesia. However, it remains unclear how LGI1-ADAM22 levels are regulated and how much LGI1-ADAM22 function is required. Here, by genetic and structural analysis, we demonstrate that quantitative dual phosphorylation of ADAM22 by protein kinase A (PKA) mediates high-affinity binding of ADAM22 to dimerized 14-3-3. This interaction protects LGI1-ADAM22 from endocytosis-dependent degradation. Accordingly, forskolin-induced PKA activation increases ADAM22 levels. Leveraging a series of ADAM22 and LGI1 hypomorphic mice, we find that ∼50% of LGI1 and ∼10% of ADAM22 levels are sufficient to prevent lethal epilepsy. Furthermore, ADAM22 function is required in excitatory and inhibitory neurons. These results suggest strategies to increase LGI1-ADAM22 complexes over the required levels by targeting PKA or 14-3-3 for epilepsy treatment

Oligodendrocyte-derived LGI3 and its receptor ADAM23 organize juxtaparanodal Kv1 channel clustering for short-term synaptic plasticity

Neurodevelopmental disorders, such as intellectual disability (ID), epilepsy, and autism, involve altered synaptic transmission and plasticity. Functional characterization of their associated genes is vital for understanding physio-pathological brain functions. LGI3 is a recently recognized ID-associated gene encoding a secretory protein related to an epilepsy-gene product, LGI1. Here, we find that LGI3 is uniquely secreted from oligodendrocytes in the brain and enriched at juxtaparanodes of myelinated axons, forming nanoscale subclusters. Proteomic analysis using epitope-tagged Lgi3 knockin mice shows that LGI3 uses ADAM23 as a receptor and selectively co-assembles with Kv1 channels. A lack of Lgi3 in mice disrupts juxtaparanodal clustering of ADAM23 and Kv1 channels and suppresses Kv1-channel-mediated short-term synaptic plasticity. Collectively, this study identifies an extracellular organizer of juxtaparanodal Kv1 channel clustering for finely tuned synaptic transmission. Given the defective secretion of the LGI3 missense variant, we propose a molecular pathway, the juxtaparanodal LGI3-ADAM23-Kv1 channel, for understanding neurodevelopmental disorders.<br/

Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams

Yagi M., Shimizu S., Hamatani N., et al. Development and characterization of a dedicated dose monitor for ultrahigh-dose-rate scanned carbon-ion beams. Scientific Reports 14, 11574 (2024); https://doi.org/10.1038/s41598-024-62148-2.The current monochromatic beam mode (i.e., uHDR irradiation mode) of the scanned carbon-ion beam lacks a dedicated dose monitor, making the beam control challenging. We developed and characterized a dedicated dose monitor for uHDR-scanned carbon-ion beams. Furthermore, a simple measurable dose rate (dose rate per spot (DRspot)) was suggested by using the developed dose monitor and experimentally validating quantities relevant to the uHDR scanned carbon-ion beam. A large plane-parallel ionization chamber (IC) with a smaller electrode spacing was used to reduce uHDR recombination effects, and a dedicated operational amplifier was manufactured for the uHDR-scanned carbon-ion beam. The dose linearity of the IC was within ± 1% in the range of 1.8–12.3 Gy. The spatial inhomogeneity of the dose response of the IC was ± 0.38% inside the ± 40-mm detector area, and a systematic deviation of approximately 2% was measured at the edge of the detector. uHDR irradiation with beam scanning was tested and verified for different doses at the corresponding dose rates (in terms of both the average dose rate and DRspot). We confirmed that the dose monitor can highlight the characteristics (i.e., dose, dose rate, and dose profile) of uHDR-scanned carbon-ion beams at several dose levels in the monochromatic beam mode

Superficial Depressed Type (IIc) Early Cancer of the Colon : Report of Two Cases

Two cases of superficial depressed type (IIc) early cancer of the colon are reported. Case 1 was a 65-year-old male and case 2 a 69-year old male. The lesion was located in the descending colon in both cases, and was removed by strip biopsy endoscopically in the former and surgically in the latter. The size of the lesion after resection was 6 mm in case 1 and 5 mm in case 2. Histopathologically, both cases were well differentiated adenocarcinoma without adenomatous components, and carcinoma developed de novo by submucosal (sm) invasion. As to the immunohistochemical staining of the cancer tissue by tumor associated antigen, case 1 showed a strong expression of carcinoembrionic antigen (CEA) and partial expression of sialyl Lewisx, and case 2 showed expressions of both CEA and sialyl Lewisx . The nuclear DNA content by flow cytometry was aneuploid only in case 1. Thus, although the two cases were morphologically the same IIc type cancer, the process of carcinogenesis and secondary phenomena varied

Diversity of Antarctic lakes from the perspective of nutrients in gap water of lake sediments and lake water

第2回極域科学シンポジウム/第33回極域生物シンポジウム 11月18日（金） 統計数理研究所 3階リフレッシュフロ