The randomized study of enteral nutrition with rapid versus conventional administration in acute stroke patients; the protocol of rapid EN trial.

Rationale: Enteral nutrition is beneficial for stroke patients with oral intake difficulties. However, it is time consuming and may interfere with routine medical care. Therefore, there is a clinical benefit if enteral nutrition can be safely administered in a short time. Although our retrospective study showed the safety of rapid administration, it remains unclear whether rapid administration of enteral nutrition is as safe as conventional administration. Aim: The randomized study of Enteral Nutrition with Rapid versus conventional administration in acute stroke patients (Rapid EN trial) aims to clarify the safety of rapid feeding of enteral nutrition compared with conventional feeding. Methods and design: This is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded end-point clinical trial. Eligible criteria include acute stroke patients who have difficulty with oral intake defined as severe altered consciousness (Japan Coma Scale 10-300) or modified water swallowing test <4. The target enrollment is 700 patients, with 350 patients receiving rapid enteral nutrition at a rate of 100 mL in 5 min (Rapid EN group) and 350 patients receiving conventional enteral nutrition at a rate of 100 mL in 30 min (Conventional EN group). Study outcome: The primary outcome is the incidence of one or more complications of vomiting or diarrhea or pneumonia within 7 days would be non-inferior in the rapid EN group compared to the conventional EN group. Secondary outcomes were total time spent on enteral nutrition within 7 days from enteral nutrition, the incidence of vomiting, diarrhea and pneumonia within 3 or 7 days, and the rate of favorable clinical outcome. Discussion: Since no previous reports have focused on the speed of administration, we felt it was necessary to prove the safety of rapid administration. If this study shows positive results, it will not only benefit patients, but also reduce the burden of medical care. We believe this study is novel and will be useful in clinical practice. Clinical trial registration: https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000046610 Identifier UMIN000046610.

The safety of rapid administration of enteral nutrition in acute stroke patients.

BACKGROUND/AIMS: Early initiation of enteral nutrition (EN) is recommended for acute stroke patients, but it is time-consuming. Reducing EN administration time without increasing the frequency of complications is a worthwhile goal. We aimed to determine whether this goal was feasible. METHODS: Consecutive acute stroke patients with severe dysphagia within 72 h of hospital admission who received EN were retrospectively enrolled. Patients were classified into two groups (Rapid administration group: 100 mL/5 min on days 1-3 after stroke onset and 200 mL/30 min on days 4-7, Conventional administration group: 100 mL/h on days 1-3 and 200 mL/h on days 4-7). RESULTS: Among 118 consecutive acute stroke patients, 71 patients [median age, 77 (68-82) years; 37 (52%) males] were enrolled. The baseline clinical characteristics of the rapid administration group (45 patients) and the conventional administration group (26 patients) did not differ. The total duration of EN administration in the first week after stroke onset was significantly longer in the conventional vs. rapid administration group [21 (15-21) h vs. 6 (2-8) h, p < 0.01]. There were no significant differences in the frequency of diarrhea (42% vs. 42%, p = 1.00), vomiting (0% vs. 7%, p = 0.29), or pneumonia (15% vs. 7%, p = 0.41). There was also no difference in the percentage of patients with one or more complications (54% vs. 49%, p = 0.81). CONCLUSIONS: Rapid administration of EN is safe and has the potential to decrease the time required for EN feeding.

Analysis of the therapeutic effects of hysteroscopic polypectomy with and without doxycycline treatment on chronic endometritis with endometrial polyps.

PROBLEM: We aimed to compare the therapeutic effects of hysteroscopic polypectomy with and without doxycycline treatment on chronic endometritis (CE) with endometrial polyps. METHOD OF STUDY: DESIGN: A cross-sectional study was conducted on 267 infertile patients, of whom 243 were recruited, who underwent hysteroscopic polypectomy between March 2019 and March 2020. During surgery, the endometrial specimens for the immunohistochemistry analysis of the plasma cell marker CD138 and for the intrauterine bacterial culture were obtained to diagnose CE, and the prevalence of CE was analyzed. Of the 222 women who were diagnosed with CE after polypectomy, we treated 62 women with doxycycline (antibiotic group) and did not provide antibiotics in 160 women (non-antibiotic group). RESULTS: Most of the infertile patients with endometrial polyps had CE (92.6%). The recovery rate from CE by hysteroscopic polypectomy was significantly higher in the non-antibiotic group than in the antibiotic group (88.8% and 58.1%, respectively, p < 0.0001). The duration of recovery from CE in the non-antibiotic group was shorter than that in the antibiotic group (42.6 ± 41.0 and 56.5 ± 32.3 days, respectively, p < 0.0001). The clinical pregnancy rate within 6 months in non-antibiotic group was higher than that in the antibiotic group (63.2% and 43.8%, respectively, p = 0.034). CONCLUSION: Endometrial polyps are significantly associated with CE. Most CE patients with endometrial polyps had been cured by polypectomy without doxycycline. Inappropriate antibiotic therapy may delay recovery from CE and decrease the efficacy of polypectomy on CE and pregnancy rates.

The Endometriosis Fertility Index Is Useful for Predicting the Ability to Conceive without Assisted Reproductive Technology Treatment after Laparoscopic Surgery, Regardless of Endometriosis.

OBJECTIVE: The endometriosis fertility index (EFI) is a novel index for predicting pregnancy after surgery. We investigated the utility of the EFI for predicting the ability to conceive without assisted reproductive technology (ART) treatment after laparoscopic surgery. METHODS: From July 2011 through December 2012, we recruited 133 infertile patients who underwent laparoscopy, and the EFI was calculated. After surgery, 55 of 133 achieved pregnancy without ART treatment. We evaluated the factors that predicted a naturally successful pregnancy and compared them between the pregnant and non-pregnant subjects. RESULTS: On a univariate linear regression analysis, we found that a younger age, shorter duration of infertility, and higher EFI were positively associated with a successful pregnancy without ART after laparoscopic surgery (p < 0.05). According to 50th percentile EFI, the cutoff EFI predicting a successful pregnancy without ART was 7, the pregnancy rate in the high-EFI group (EFI; 8-10) was significantly higher than that in the low-EFI group (EFI ≤7; p < 0.05), but the duration to natural conception after surgery was similar between the 2 groups. CONCLUSION: The EFI possesses greater predictive power for a successful pregnancy with natural intercourse or intrauterine insemination in infertile patients, regardless of endometriosis, than the Revised-American Society of Reproductive Medicine classification.

Frequency of endometrial cancer and atypical hyperplasia in infertile women undergoing hysteroscopic polypectomy.

AIM: We aimed to determine the frequency of endometrial cancer in infertile women undergoing hysteroscopic endometrial polypectomy for endometrial polyps. METHODS: A total of 1035 infertile patients who underwent office-based hysteroscopic polypectomy at Sugiyama Clinic Marunouchi between July 2011 and October 2015 were eligible for this retrospective study. All patients had been diagnosed with endometrial polyps via hysterofiberscopy prior to operation, and they underwent hysteroscopic endometrial polypectomy using a resectoscope with monopolar resection. Surgical specimens were examined histopathologically. Characteristics of patients diagnosed with endometrial cancer on histopathological examination were evaluated retrospectively. RESULTS: The median age of patients was 32 years (range, 19-44 years). On histopathological examination, endometrial cancer was found in 10 patients (0.97%). Each histological type of endometrial cancer was represented as follows: three cases of endometrioid adenocarcinoma G1; one of endometrioid adenocarcinoma G2; two of endometrioid adenocarcinoma G3; and four of atypical endometrial hyperplasia. The median age of endometrial cancer patients was 34 years (range, 28-41 years), and the median body mass index was 21.2 kg/m2 (range, 16.7-29.9 kg/m2 ). Nine endometrial cancer patients were nulliparous, and all had undergone infertility treatment, with only one woman having delivered a healthy baby. An ovulation disorder was noted in four patients, with obesity (body mass index > 25 kg/m2 ) in just two. Polycystic ovary syndrome was concomitantly observed in one patient. However, abnormal vaginal bleeding was not noted in any of these patients. CONCLUSION: Hysteroscopic polypectomy should be performed when endometrial polyps are detected on investigational screening, and surgical specimens should be checked for the presence of malignancy.

Perinatal outcomes of patients who achieved pregnancy with a morphologically poor embryo via assisted reproductive technology.

PURPOSE: To learn more about the perinatal outcomes of conception via the use of low-grade embryos, we evaluated the relationship between the status of transferred embryos and the resultant perinatal outcomes. METHODS: A total of 340 patients who achieved pregnancy via ART treatment and consequently delivered in our clinic between April 2009 and March 2014 were recruited for this study. Patients were divided into two groups according to a morphological assessment of the transferred embryos, which relegated 79 patients into a poor-embryo group with the remainders (n = 261) placed into a good-embryo group. RESULTS: The mean maternal age for the poor-embryo group was 36.0 years, which was similar to the good-embryo group (36.8). In both groups, the percentages of fresh ET cycles were similar. The values for the mean birth weight and birth height of infants in the poor-embryo group were 3055 g and 50.3 cm, respectively, and there were no significant differences with the good-embryo group. The umbilical blood gas analysis in the poor-quality group was similar to that in the good-embryo group. There were no obvious major anomalies among the infants of either group. CONCLUSIONS: The perinatal outcomes of the poor-embryo group were comparable to those of the good-embryo group. Based on these results, we can provide qualified assurance for a normal perinatal outcome to patients who had no choice but to undergo embryo transfer with a poor-quality embryo.

The fission yeast MTREC complex targets CUTs and unspliced pre-mRNAs to the nuclear exosome.

Cryptic unstable transcripts (CUTs) are rapidly degraded by the nuclear exosome. However, the mechanism by which they are recognized and targeted to the exosome is not fully understood. Here we report that the MTREC complex, which has recently been shown to promote degradation of meiotic mRNAs and regulatory ncRNAs, is also the major nuclear exosome targeting complex for CUTs and unspliced pre-mRNAs in Schizosaccharomyces pombe. The MTREC complex specifically binds to CUTs, meiotic mRNAs and unspliced pre-mRNA transcripts and targets these RNAs for degradation by the nuclear exosome, while the TRAMP complex has only a minor role in this process. The MTREC complex physically interacts with the nuclear exosome and with various RNA-binding and RNA-processing complexes, coupling RNA processing to the RNA degradation machinery. Our study reveals the central role of the evolutionarily conserved MTREC complex in RNA quality control, and in the recognition and elimination of CUTs.

The Effect of a Newly Designed Needle on the Pain and Bleeding of Patients During Oocyte Retrieval of a Single Follicle.

BACKGROUND: The purpose of this study was to evaluate the effect of needle type on pain and bleeding during oocyte pick-up (OPU). METHODS: From May through November 2013, patients undergoing OPU from a single follicle without any analgesic treatment were including this study. Eligible patients (n=75) were randomized 1:1 to undergo the procedure with either a reduced needle (17 gauge body, 20 gauge tip; RN group) or a standard needle (19 gauge; SN group). Overall pain was assessed by patients using a visual analogue scale (VAS), and vaginal bleeding after the procedure was recorded. Fisher exact, t-test or Wilcoxon test were used, and p<0.05 was considered to be statistically significant. RESULTS: The percentage of mature oocytes was 86.5% in the RN group and 91.7% in the SN group. Pain during OPU was significantly lower in the RN group than in the SN group (mean VAS score±SD: 3.2±2.0 cm vs. 4.9±2.2 cm, p<0.01; mean±SD). The frequency of vaginal bleeding was also significantly lower in the SN group (26.3% vs. 48.6%; p<0.05). The frequency of bleeding in the RN group was also significantly lower than that in the SN group (26.3% vs. 48.6%; p<0.05). No significant differences were found between the two groups with regard to fertilization and pregnancy rates. CONCLUSION: The newly designed needle significantly reduced pain and vaginal bleeding associated with single-follicle OPU in patients receiving no analgesic treatment, in comparison with a standard needle. The RN had no adverse effect on the quality of retrieved oocytes.

Clomiphene citrate affects the receptivity of the uterine endometrium.

Purpose: To investigate whether clomiphene citrate (CC) affects uterine receptivity or not, we evaluated pregnancy rates (PR) during the hormone replacement cycle (HRC) according to the period between the last day of CC administration and the day of embryo transfer (ET). Methods: From March 2008 through March 2010, a total of 378 treatment cycles among 378 patients who received CC and had to avoid fresh ET due to a thin uterine endometrium were recruited. All patients underwent thawed ET using HRC. PRs were evaluated according to the period between the last CC treatment and the day of ET. Results: PR for the groups in which the period between the last CC treatment and the day of ET increased to more than 91 days were significantly higher than that for group in which the period was less than 90 days (p < 0.05). Conclusions: A lower PR was shown by the patients who underwent thawed ET in the HRC within 90 days after their last CC treatment, which shows that CC affects the receptivity of the uterine endometrium.

Advanced scheduling for zygote intrafallopian transfer is possible via the use of a hormone replacement cycle for patients who have experienced repeated implantation failures.

PURPOSE: Zygote intrafallopian transfer (ZIFT) is an effective option for patients who have experienced repeated implantation failures (RIF) in assisted reproductive technology (ART) treatment. However, advance planning for the day of the operation can be problematic. Using a hormone replacement cycle (HRC) makes it possible to plan for the day of ZIFT. In the present study, we evaluated whether HRC-ZIFT is useful for RIF patients who have experienced difficulties obtaining morphologically good embryos in vitro. METHODS: A total of 55 patients with a history of five or more unsuccessful transfers received HRC-ZIFT between June 2008 and June 2013. The oocyte pick-ups were performed and the oocytes showing two pronuclei (2PN) were cryopreserved. After receiving more than five 2PN oocytes, the operation day was scheduled in advance, and as a consequence, a HRC was started and ZIFT was performed. The clinical outcomes were evaluated. RESULTS: The average age of the patients was 39.3 years, and the previous OPU and ET attempts numbered 7.5 and 6.9, respectively. The number of previously transferred embryos was 11.8, and the number of morphologically good embryos (MGEs) was only 1.2. The number of transferred 2PN oocytes was 6.7, and the subsequent pregnancy rate was 23.6 %. No ectopic or multiple pregnancies were observed, but there were 6 cases of miscarriage. CONCLUSION: Among RIF patients, in particular those who have difficulty obtaining MGEs in vitro, ZIFT might be a useful option. The HRC allows patients and medical staff to plan for the operation day in advance.

Prostaglandin therapy during the proliferative phase improves pregnancy rates following frozen embryo transfer in a hormone replacement cycle.

AIM: To determine the efficacy of prostaglandin administration during the proliferative phase in order to improve pregnancy rates following frozen embryo transfer during a hormone replacement cycle (HRC). METHODS: From September 2010 through March 2012, patients (n = 135) were recruited who had undergone oocyte retrieval during a stimulation cycle with clomiphene and had deferred fresh embryo transfer (ET) due to a thin uterine endometrium. All patients were less than 40 years of age and underwent thawed ET following all embryo cryopreservation, and were randomly divided into two groups for thawed ET using a conventional hormone replacement cycle with or without prostaglandin derivatives (prostaglandin or conventional group). Prostaglandin derivatives were administrated during the proliferative phase. Pregnancy and implantation rates following frozen ET were compared between the two groups. RESULTS: Although the endometrial thickness on the day of ET was similar for the prostaglandin and conventional groups, the pregnancy and implantation rates for the prostaglandin group were 40.0% and 22.0%, respectively, which was significantly higher than the rates for the conventional group (P < 0.01). CONCLUSION: Among patients who avoided fresh ET due to a thin endometrium, the pregnancy rate following a thawed cycle was low. However, it was improved when prostaglandin derivatives were used during the proliferative phase.

Red5 and three nuclear pore components are essential for efficient suppression of specific mRNAs during vegetative growth of fission yeast.

Zinc-finger domains are found in many nucleic acid-binding proteins in both prokaryotes and eukaryotes. Proteins carrying zinc-finger domains have important roles in various nuclear transactions, including transcription, mRNA processing and mRNA export; however, for many individual zinc-finger proteins in eukaryotes, the exact function of the protein is not fully understood. Here, we report that Red5 is involved in efficient suppression of specific mRNAs during vegetative growth of Schizosaccharomyces pombe. Red5, which contains five C3H1-type zinc-finger domains, localizes to the nucleus where it forms discrete dots. A red5 point mutation, red5-2, results in the upregulation of specific meiotic mRNAs in vegetative mutant red5-2 cells; northern blot data indicated that these meiotic mRNAs in red5-2 cells have elongated poly(A) tails. RNA-fluorescence in situ hybridization results demonstrate that poly(A)(+) RNA species accumulate in the nucleolar regions of red5-deficient cells. Moreover, Red5 genetically interacts with several mRNA export factors. Unexpectedly, three components of the nuclear pore complex also suppress a specific set of meiotic mRNAs. These results indicate that Red5 function is important to meiotic mRNA degradation; they also suggest possible connections among selective mRNA decay, mRNA export and the nuclear pore complex in vegetative fission yeast.

Role of salpingoscopy in assessing the inner fallopian tubes of infertility patients with ovarian endometriomas.

AIM: The aim of this study was to observe the insides of the fallopian tubes of patients with unilateral or bilateral endometriomas by using salpingoscopy and evaluate the inner cavity of the fallopian tubes according to our original scoring system. MATERIAL AND METHODS: From April 2008 through December 2010, patients with unilateral or bilateral endometriomas were recruited (n = 157, endometrioma group). All patients underwent laparoscopic ovarian cystectomy and salpingoscopy. Using salpingoscopy, we observed the tubal lumen and calculated a fallopian tube score (F score) paying attention to the following six results: adhesions, loss of mucosal folds, rounded edges of mucosal folds, debris, foreign bodies, and abnormal vessels. The F scores were compared with those of the unexplained infertility patients who received those same procedures during the same period (n = 235; control group). RESULTS: Slightly more than three-quarters (75.9%) of the patients in the endometrioma group received F scores of 0, and this percentage was significantly higher than that for the control group (139/235 = 59.1%, P < 0.05). The pregnancy rate after conventional treatment for the endometrioma group was 21.7%, and all pregnant patients had achieved an F score of less than 2. CONCLUSION: It is highly possible that infertility patients with ovarian endometriomas are more likely to have intact fallopian tubes, by comparison with infertility patients who do not have ovarian endometriomas.

Using a mild stimulation protocol combined with clomiphene citrate and recombinant follicle-stimulating hormone to determine the optimal number of oocytes needed to achieve pregnancy and reduce the concerns of patients.

PURPOSE: The purpose of this study was to investigate how many oocytes are needed to achieve an adequate pregnancy rate per 1 oocyte retrieval cycle in mild ovarian stimulation. METHODS: This protocol consisted of clomiphene citrate and recombinant-follicle-stimulating hormone injection without a gonadotropin-releasing hormone-antagonist. From January 2009 through December 2010, there were 1,227 women who underwent assisted reproductive technologies treatment with mild stimulation at the Sugiyama Clinic. The overall pregnancy rate per single oocyte retrieval cycle was evaluated using both fresh and cryopreserved-and-thawed embryos according to the retrieved oocyte number. RESULTS: According to the retrieved oocyte number, a total of 1,227 cycles were divided into 4 groups: group A (the oocyte number <4; 433 cycles), group B (the oocyte number = 4, 5; 317 cycles), group C (the oocyte number = 6, 7; 206 cycles), and group D (the oocyte number ≥8; 271 cycles). The overall pregnancy rates for groups A, B, C, and D were 22.2, 42.9, 52.4, and 56.0 %, respectively, the rates for groups C and D were significantly higher than that for group A (p < 0.01). CONCLUSIONS: The optimal number of retrieved oocytes proved to be between 6 and 7 for the patients who received our milder stimulation protocol and experienced no reduction in their overall pregnancy rate.

Rhn1, a nuclear protein, is required for suppression of meiotic mRNAs in mitotically dividing fission yeast.

In the fission yeast Schizosaccharomyces pombe, many meiotic mRNAs are transcribed during mitosis and meiosis and selectively eliminated in mitotic cells. However, this pathway for mRNA decay, called the determinant of selective removal (DSR)-Mmi1 system, targets only some of the numerous meiotic mRNAs that are transcribed in mitotic cells. Here we describe Rhn1, a nuclear protein involved in meiotic mRNA suppression in vegetative fission yeast. Rhn1 is homologous to budding yeast Rtt103 and localizes to one or a few discrete nuclear dots in growing vegetative cells. Rhn1 colocalizes with a pre-mRNA 3'-end processing factor, Pcf11, and with the 5'-3' exoribonuclease, Dhp1; moreover, Rhn1 coimmunoprecipitates with Pcf11. Loss of rhn1 results in elevated sensitivity to high temperature, to thiabendazole (TBZ), and to UV. Interestingly, meiotic mRNAs--including moa1(+), mcp5(+), and mug96(+)--accumulate in mitotic rhn1Δ cells. Accumulation of meiotic mRNAs also occurs in strains lacking Lsk1, a kinase that phosphorylates serine 2 (Ser-2) in the C-terminal domain (CTD) of RNA polymerase II (Pol II), and in strains lacking Sen1, an ATP-dependent 5'-3' RNA/DNA helicase: notably, both Lsk1 and Sen1 have been implicated in termination of Pol II-dependent transcription. Furthermore, RNAi knockdown of cids-2, a Caenorhabditis elegans ortholog of rhn1(+), leads to elevated expression of a germline-specific gene, pgl-1, in somatic cells. These results indicate that Rhn1 contributes to the suppression of meiotic mRNAs in vegetative fission yeast and that the mechanism by which Rhn1 downregulates germline-specific transcripts may be conserved in unicellular and multicellular organisms.

Hyaluronan-enriched transfer medium improves outcome in patients with multiple embryo transfer failures.

PURPOSE: To ascertain whether the use of hyaluronan-enriched transfer medium (HETM) improves pregnancy and implantation rates among embryo transfer patients with a history of multiple implantation failures. METHODS: Patients (n = 314) under the age of 40 and with a history of multiple unsuccessful embryo transfers were enrolled. There were three groups of patients: those undergoing fresh embryo transfer (fresh ET [n = 111]), those undergoing vitrified-warmed ET in the natural cycle (WET-N [n = 101]) and those undergoing WET in a hormone replacement cycle (WET-H [n = 102]). On the day of ET, patients were randomized to HETM (0.5 mg/ml hyaluronan) or control medium containing no hyaluronan. Only patients with good quality embryos on day 3 were included. RESULTS: For all three patients groups (fresh ET, WET-N and WET-H) pregnancy rates (37.5 %, 31.4 % and 41.2 %, respectively) were significantly higher when using HETM compared with control medium (10.9 %, 10.0 % and 15.7 %, respectively; p < 0.05), and implantation rates when using HETM were also significantly higher compared with control medium (p < 0.05). Miscarriage rates were similar in both groups. CONCLUSION: HETM significantly increased pregnancy and implantation rates among embryo transfer patients with a history of multiple unsuccessful implantations-regardless of method used to prepare the endometrium.

A programmed schedule of oocyte retrieval using mild ovarian stimulation (clomiphene citrate and recombinant follicle-stimulating hormone).

PURPOSE: The purpose was to establish a mild ovarian stimulation protocol that would help assisted reproductive technology (ART) units to avoid scheduling on weekends. METHODS: This protocol directed patients to take 50 mg/day of clomiphene citrate between days 3 and 7 of the menstrual cycle: 225 IU of recombinant follicle-stimulating hormone (rec-FSH) were administered on days 3, 5 and 7; human chorionic gonadotropin (hCG) was administered on day 9; and, oocyte pick-up (OPU) was planned for day 11. From October 2008 through October 2009, 514 women underwent ART treatment with mild stimulation at the Sugiyama Clinic, and we evaluated whether OPU was accomplished on the planned day. RESULTS: Of all the treatment cycles, 419 (81.5%) underwent OPU on day 11 (scheduled group). Additional rec-FSH administration was needed in 83 cycles, in which case OPU was performed on day 12 or later. In 12 cycles, OPU was canceled. The unscheduled group (n = 95) consisted of delayed OPU cycles and canceled cycles. Of all treatment cycles, 332 cycles in the scheduled group and 68 cycles in the unscheduled group underwent embryo transfer, with 81 and 16, respectively, resulting in pregnancies. CONCLUSIONS: Using this protocol, OPU was performed on the scheduled day in about 80% of the cycles. Most weekend scheduling of OPU can be avoided using this mild stimulation.

A homolog of male sex-determining factor SRY cooperates with a transposon-derived CENP-B protein to control sex-specific directed recombination.

Schizosaccharomyces pombe cells switch mating type by replacing genetic information at the expressed mat1 locus with sequences copied from mat2-P or mat3-M silent donor loci. The choice of donor locus is dictated by cell type, such that mat2 is the preferred donor in M cells and mat3 is the preferred donor in P cells. Donor choice involves a recombination-promoting complex (RPC) containing Swi2 and Swi5. In P cells, the RPC localizes to a specific DNA element located adjacent to mat3, but in M cells it spreads across the silent mating-type region, including mat2-P. This differential distribution of the RPC regulates nonrandom choice of donors. However, cell-type-specific differences in RPC localization are not understood. Here we show that the mat1-M-encoded factor Mc, which shares structural and functional similarities with the male sex-determining factor SRY, is highly enriched at the swi2 and swi5 loci and promotes elevated levels of RPC components. Loss of Mc reduces Swi2 and Swi5 to levels comparable to those in P cells and disrupts RPC spreading across the mat2/3 region. Mc also localizes to loci expressed preferentially in M cells and to retrotransposon LTRs. We demonstrate that Mc localization at LTRs and at swi2 requires Abp1, a homolog of transposon-derived CENP-B protein and that loss of Abp1 impairs Swi2 protein expression and the donor choice mechanism. These results suggest that Mc modulates levels of recombination factors, which is important for mating-type donor selection and for the biased gene conversion observed during meiosis, where M cells serve as preferential donors of genetic information.

Sde2: a novel nuclear protein essential for telomeric silencing and genomic stability in Schizosaccharomyces pombe.

Telomeres, specialized domains assembled at the ends of linear chromosomes, are essential for genomic stability in eukaryotes. The formation and maintenance of telomeres are governed by numerous factors such as telomeric repeats, telomere-binding proteins, heterochromatin proteins, and telomerase. Here, we report Sde2, a novel nuclear protein essential for telomeric silencing and genomic stability in the fission yeast Schizosaccharomyces pombe. A deficiency in sde2 results in the derepression of the ura4(+) gene inserted near telomeric repeats, and the noncoding transcripts from telomeric regions accumulate in sde2Δ cells. The loss of Sde2 function compromises transcriptional silencing at telomeres, and this silencing defect is accompanied by increased levels of acetylated histone H3K14 and RNA polymerase II occupancy at telomeres as well as reduced recruitment of the SNF2 ATPase/histone deacetylase-containing complex SHREC to telomeres. Deletion of sde2 also leads to a higher frequency of mitotic minichromosome loss, and sde2Δ cells often form asci that contain spores in abnormal numbers, shapes, or both. In addition, sde2Δ cells are highly sensitive to several stresses, including high/low temperatures, bleomycin, which induces DNA damage, and thiabendazole, a microtubule-destabilizing agent. Furthermore, Sde2 genetically interacts with the telomere regulators Taz1, Pof3, and Ccq1. These findings demonstrate that Sde2 cooperates with other telomere regulators to maintain functional telomeres, thereby preventing genomic instability.

Red1 promotes the elimination of meiosis-specific mRNAs in vegetatively growing fission yeast.

Meiosis-specific mRNAs are transcribed in vegetative fission yeast, and these meiotic mRNAs are selectively removed from mitotic cells to suppress meiosis. This RNA elimination system requires degradation signal sequences called determinant of selective removal (DSR), an RNA-binding protein Mmi1, polyadenylation factors, and the nuclear exosome. However, the detailed mechanism by which meiotic mRNAs are selectively degraded in mitosis but not meiosis is not understood fully. Here we report that Red1, a novel protein, is essential for elimination of meiotic mRNAs from mitotic cells. A red1 deletion results in the accumulation of a large number of meiotic mRNAs in mitotic cells. Red1 interacts with Mmi1, Pla1, the canonical poly(A) polymerase, and Rrp6, a subunit of the nuclear exosome, and promotes the destabilization of DSR-containing mRNAs. Moreover, Red1 forms nuclear bodies in mitotic cells, and these foci are disassembled during meiosis. These results demonstrate that Red1 is involved in DSR-directed RNA decay to prevent ectopic expression of meiotic mRNAs in vegetative cells.