Broad-Band Activatable White-Opsin

The authors would like to thank C. Cote and K. Dhakal (UTA) for help during initiation of the project. SM would like to thank K. Deisseroth (Stanford University) for ChR2 and C1V1 plasmids, and J. Lin (UCSD) for the ReaChR construct.Currently, the use of optogenetic sensitization of retinal cells combined with activation/inhibition has the potential to be an alternative to retinal implants that would require electrodes inside every single neuron for high visual resolution. However, clinical translation of optogenetic activation for restoration of vision suffers from the drawback that the narrow spectral sensitivity of an opsin requires active stimulation by a blue laser or a light emitting diode with much higher intensities than ambient light. In order to allow an ambient light-based stimulation paradigm, we report the development of a ‘white-opsin’ that has broad spectral excitability in the visible spectrum. The cells sensitized with white-opsin showed excitability at an order of magnitude higher with white light compared to using only narrow-band light components. Further, cells sensitized with white-opsin produced a photocurrent that was five times higher than Channelrhodopsin-2 under similar photo-excitation conditions. The use of fast white-opsin may allow opsin-sensitized neurons in a degenerated retina to exhibit a higher sensitivity to ambient white light. This property, therefore, significantly lowers the activation threshold in contrast to conventional approaches that use intense narrow-band opsins and light to activate cellular stimulation.Yeshttp://www.plosone.org/static/editorial#pee

Repair of Uterine Rupture during Second Trimester Leading to Successful Pregnancy Outcome: Case Study and Literature's Review

Abstract It was thought to be impossible to prolong the pregnancy in a case of uterine rupture in the second trimester. We encountered a case of rupture of the pregnant uterus in early mid-trimester, which we repaired with suture and overlapping of collagen fleece coated with fibrin glue, resulting in pregnancy prolongation until the 34th week. Our case and five previously reported cases were reviewed. Pregnant uterine rupture in mid-trimester could be repaired with suture and overlapping of collagen fleece in the absence of placenta percreta

An extragonadal yolk sac tumor presumed to be of postmeiotic germ cell origin by genetic zygosity analysis via single nucleotide polymorphism array

金沢大学医薬保健研究域医学系An extragonadal yolk sac tumor (YST) is a rare malignant germ cell tumor that usually occurs in childhood. The pathogenesis of extragonadal YST remains largely unknown, especially with regards to its cell of origin. Herein, we report a case of extragonadal YST arising in the uterine round ligament. A 31-year-old Japanese woman, para 2, underwent partial resection of a left-sided, 5-cm, solid inguinal mass. Intraoperative findings showed enlargement of the uterine round ligament in the inguinal canal. Pathological evaluation diagnosed the mass as YST with a mature teratoma (MT) component. The preoperative α-fetoprotein level was markedly elevated, at 24 790 ng/mL. Postoperative magnetic resonance imaging revealed a right ovarian MT and a 3-cm mass remaining in the left lower abdominal wall. The patient underwent total abdominal hysterectomy, bilateral adnexectomy, and left inguinal mass resection. We sampled three frozen tissues (YST, right ovarian MT, and left normal ovary) and performed a single nucleotide polymorphism (SNP) array. Pathological evaluation revealed remnant extragonadal YST in the left inguinal region. The SNP array demonstrated a completely homozygous YST genotype. Copy number variations were gains of 1p, 1q, 2p, 3p, 7p, 8p, 10q, 14q, 18p, 20q, Xp, and Xq and losses of 12q, 20p, and Xq. The right ovarian MT and left normal ovary were partially homozygous and heterozygous, respectively. The evidence suggests that this neoplasm is presumed to be a postmeiotic germ cell origin. © 2019 Wiley Periodicals, Inc

Isolated loss of PMS2 immunohistochemical expression is frequently caused by heterogeneous MLH1 promoter hypermethylation in Lynch syndrome screening for endometrial cancer patients

Lynch syndrome (LS) is an autosomal dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2) and is associated with increased risk of various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2–6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation (PMS2-LS) is the rarest contribution to LS etiology among the four LS- associated MMR germline mutations, and its detection is complicated. Therefore, prudent screening for PMS2-LS is important as it leads to an efficient LS-identification strategy. Immunohistochemistry (IHC) is recommended as a screening method for LS in EC. Isolated loss of PMS2 expression (IL- PMS2) is caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter hypermethylation (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2 to avoid inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2 germline mutation testing for the IL-PMS2 cases. By performing MMR-IHC for 360 unselected ECs, we selected eight (2.2%) cases as IL-PMS2. Heterogeneous MLH1 staining and MLH1-PHM were detected in 4/8 (50%) IL-PMS2 tumors. Out of five IL-PMS2 patients who underwent genetic analysis, one had PMS2 germline mutation with normal MLH1 expression (without MLH1-PHM) and no MLH1 germline mutation was detected. We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed to exclude sporadic cases prior to further PMS2 genetic testing