Dysmorphic megakaryocytes in TAFRO syndrome: A case series from a single institute.

TAFRO syndrome is a rare systemic inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. The diagnosis of TAFRO syndrome can be challenging; however, prompt diagnosis is vital because TAFRO syndrome is a progressive and life-threatening disease. We have showcased five patients with TAFRO syndrome who had similar bone marrow (BM) findings that could be considered the findings that characterize TAFRO syndrome. All patients were treated with corticosteroids and tocilizumab; three of the five patients (60 %) responded positively to the treatment. The unique BM findings observed in this study were megakaryocytes with distinct multinuclei and three-dimensional and indistinct bizarre nuclei ("dysmorphic megakaryocyte"), similar to the megakaryocyte morphology observed in myeloproliferative neoplasms (MPNs). Notably, dysmorphic megakaryocytes were observed in all five cases, whereas only two of the five patients tested positive for reticulin myelofibrosis, and three of the five patients had megakaryocytic hyperplasia, which are considered typical findings of TAFRO syndrome. Thus, the BM findings of dysmorphic megakaryocytes could help in the correct and immediate diagnosis of TAFRO syndrome.

Exercise, Dietary Habits, and Defecatory Dysfunction in Patients Living with Colorectal Cancer: A Preliminary Quantitative Study.

This study investigated the association of exercise and dietary habits with defecatory dysfunction in patients living with colorectal cancer. We recruited 61 adult patients who had undergone surgery within the past 20 years and attended outpatient clinics at designated cancer hospitals in Japan. Defecatory dysfunction was defined as any symptom caused by issues with colon and anal function, including fecal incontinence, evacuation difficulties, frequent stools, diarrhea, and constipation. Exercise and dietary habits were assessed via a quantitative questionnaire survey. Postoperative defecatory dysfunction occurred in all the patients. Multivariate analysis revealed no association between exercise habits and defecatory dysfunction; however, dietary fiber intake ≥4 times a week was associated with frequent stools (adjusted odds ratio, 5.11; 95% confidence interval, 1.10, 23.70). These findings suggest a need to alleviate defecatory dysfunction by improving one's dietary habits. Interventions aimed at alleviating defecatory dysfunction by improving the dietary habits in patients living with colorectal cancer are needed.

Performance evaluation and user experience of BT-50 transportation unit with automated and scheduled quality control measurements.

OBJECTIVES: Even in the current era of hematology analyzer automation and peripheral equipment, quality control sample measurement remains a manual task, leading to variability in quality control data and increased workload. In this study, we evaluated the performance of quality control measurement using the BT-50 Transportation Unit (BT-50, Sysmex, Kobe, Japan), equipped with a scheduled automatic quality control function, to ensure measurement accuracy and streamline the workflow of hematology testing. METHODS: We evaluated the automatic measurement performance of quality control samples using the BT-50 for six representative blood test parameters: WBC (white blood cell), RBC (red blood cell), HGB (hemoglobin), HCT (hematocrit), PLT (platelet), and RET% (reticulocyte percent). We evaluated the equivalence and compared measurement accuracy between the BT-50 and the manual method. We then compared the variability to other laboratories and confirmed the stability of quality control samples. We also evaluated changes in workflow and staff resources before and after the introduction of the BT-50. RESULTS: The quality control measurement results for the BT-50 and the manual method were found to be equivalent for all six parameters. The variability measured by the BT-50 was lower for some parameters compared to the manual method. Furthermore, the workflow was streamlined by reducing manual processes, resulting in increased efficiency. CONCLUSIONS: We confirmed the performance of quality control measurements using the schedule function of the BT-50. Introducing the BT-50 reduced the operator's workload, improved operational efficiency, and promoted the standardization of quality control measurements.

The chromatin remodeler RSC prevents ectopic CENP-A propagation into pericentromeric heterochromatin at the chromatin boundary.

Centromeres of most eukaryotes consist of two distinct chromatin domains: a kinetochore domain, identified by the histone H3 variant, CENP-A, and a heterochromatic domain. How these two domains are separated is unclear. Here, we show that, in Schizosaccharomyces pombe, mutation of the chromatin remodeler RSC induced CENP-ACnp1 misloading at pericentromeric heterochromatin, resulting in the mis-assembly of kinetochore proteins and a defect in chromosome segregation. We find that RSC functions at the kinetochore boundary to prevent CENP-ACnp1 from spreading into neighbouring heterochromatin, where deacetylated histones provide an ideal environment for the spread of CENP-ACnp1. In addition, we show that RSC decompacts the chromatin structure at this boundary, and propose that this RSC-directed chromatin decompaction prevents mis-propagation of CENP-ACnp1 into pericentromeric heterochromatin. Our study provides an insight into how the distribution of distinct chromatin domains is established and maintained.

Defecation Dysfunction and Exercise Habits among Survivors of Rectal Cancer: A Pilot Qualitative Study.

This pilot qualitative study aimed to investigate exercise habits and assess defecatory dysfunction among adult survivors of rectal cancer with and without stomas. Patients were eligible for the study if they had stage I-IV rectal cancer, and less than 5 years had elapsed since surgery. We conducted semi-structured interviews with outpatients visiting two general hospitals in Japan and inquired about their diets, defecation, and exercise habits. The interview data were transcribed verbatim, interpreted, and abstracted to generate coding units; we divided the responses into categories and subcategories. Eleven patients had stomas inserted after surgery while six did not. Content analysis identified four categories common to patients with and without stomas: [diet control], [coping with defecation dysfunction], [compromising with defecation dysfunctions], and [maintenance of exercise habits]. Our results suggest the need for intervening among rectal cancer survivors to address eating habits to alleviate defecation dysfunction and exercise habits to maintain physical function. In clinical practice, symptom relief and exercise instruction may improve the well-being of cancer survivors with bowel dysfunction.

Effects of eicosapentaenoic acid on serum levels of selenoprotein P and organ-specific insulin sensitivity in humans with dyslipidemia and type 2 diabetes.

AIM: Selenoprotein P (SeP, encoded by SELENOP in humans) is a hepatokine that causes insulin resistance in the liver and skeletal muscle. It was found that polyunsaturated fatty acid eicosapentaenoic acid (EPA) downregulates Selenop expression by inactivating SREBP-1c. The present study aimed to examine the effect of EPA for 12 weeks on circulating SeP levels and insulin sensitivity in humans with type 2 diabetes. METHODS: A total of 20 participants with dyslipidemia and type 2 diabetes were randomly assigned to an EPA (900 mg, twice daily) group and a control group. The primary endpoint was a change in serum SeP levels. Organ-specific insulin sensitivity in the liver (HGP and %HGP), skeletal muscle (Rd), and adipose tissue (FFA and %FFA) were assessed using a hyperinsulinemic-euglycemic clamp study with stable isotope-labeled glucose infusion. RESULTS: Serum SeP levels were not changed in either group at the end of the study. In the EPA group, the changes in SeP levels were positively correlated with the change in serum EPA levels (r = 0.709, P = 0.022). Treatment with EPA significantly enhanced %FFA but not %HGP and Rd. The change in serum EPA levels was significantly positively correlated with the change in %HGP, and negatively correlated with changes in Rd. CONCLUSIONS: The change in serum EPA levels was positively correlated with serum SeP levels, hepatic insulin sensitivity, and negatively with skeletal muscle insulin sensitivity in humans with type 2 diabetes. The EPA-induced enhancement of hepatic insulin sensitivity might be associated with a mechanism independent of serum SeP levels.

Nursing Students' Practicums during the COVID-19 Crisis and the Effect on Infection-Prevention Behavior in Students: A Mixed-Method Approach.

Background and Objectives: The coronavirus disease pandemic is ongoing. Infection-prevention measures in nursing education (practicum) are essential. However, there are few studies on infection-prevention behaviors among nursing students participating in practicums. We aimed to clarify the effect of practicums during the coronavirus disease crisis on infection-prevention behavior in Japanese nursing students. Materials and Methods: We conducted semi-structured interviews with 13 third-year nursing students in Osaka City within one week of their clinical placement training. From the results of the interview analysis, we compiled a questionnaire and surveyed 90 third-year students. We conducted qualitative and quantitative analyses. We used descriptive statistics for the quantitative analysis and the chi-squared test for binary variables. Results: From the qualitative analysis, we identified five categories regarding the awareness of infection-prevention measures: , , , , and . In the quantitative analysis, the practicum students who attended at least three pre-practicum orientations continued wearing masks during lunch breaks and avoided the three Cs. Conclusions: Students could recall the knowledge and experiences gained from pre-practicum orientations/practicums. This experience created a new awareness of infection-prevention and change of infection-prevention behavior. Infection-prevention education using practicums is important for infection-prevention behavior during this pandemic. However, there should be a much larger-scale study to support these findings in the future.

Physical Fitness Levels among Colon Cancer Survivors with a Stoma: A Preliminary Study.

Background and Objectives: Stoma surgery is linked to reduced physical activity in colon cancer survivors and leads to decreased physical fitness, activity of daily living dysfunction, and poorer quality of life. However, few studies have investigated the physical fitness levels of colon cancer survivors living with stomas. This study aimed to compare the physical fitness levels of colon cancer survivors with stomas and healthy adults, assessing them in a variety of dimensions (e.g., strength and flexibility) and in terms of physical fitness age (PFA), an integrated index of overall fitness. Materials and Methods: The study population consisted of 17 colon cancer survivors with (stoma group) and 20 healthy adults without (control group) a stoma. Physical fitness was assessed using a battery of five tests: repeated back-and-forth steps, 30-s chair stand, chair sit-and-reach, grip strength, and single-leg balance with eyes closed. Respective performance values were converted into PFA, which was compared between the stoma and control groups. Fitness indicators were compared between groups by analysis of covariance, and PFA and chronological age (CA) by paired t-tests. Results: The mean ages (±standard deviation) of the stoma and control groups were 74.1 ± 7.9 and 73.5 ± 7.1 years, respectively. Colon cancer survivors with stomas had poorer lower limb muscular strength, endurance, and flexibility than controls. In the stoma group, the marginal mean (±standard error) PFA was calculated to be 82.5 ± 3.7 years, significantly higher than the CA and PFA of the control group (69.6 ± 3.9 years). Conclusions: Colon cancer survivors with stomas have lower physical fitness levels than healthy adults, with apparent deficits in lower limb flexibility, muscular strength, and endurance. Our findings demonstrated the need for exercise interventions in this population, focusing on these dimensions of fitness. However, our results should be corroborated by means of a larger-scale comparison in future studies.

Providing Weight Loss Support to Patients Who Are Obese in Preparation for Colorectal Cancer Surgery to Reduce Surgical Site Infection Risk: A Mixed-methods Study.

Obesity increases the risk of surgical site infections (SSIs) after colorectal cancer surgery, but strategies to support weight loss in obese patients who have colorectal cancer have not been established. PURPOSE: This mixed-methods study, using retrospective and prospective data, aimed to explore inhibitors and facilitators of preoperative weight loss in obese patients with colorectal cancer and the potential impact of preoperative weight loss support on SSIs. METHODS: Patients with a body mass index (BMI) of ≥ 25 kg/m2 were eligible to participate in the weight loss support program. Patient demographic, history, surgical, and outcomes variables were abstracted from the records. Five (5) nurses who provided weight loss support participated in a focus group interview method to explore weight loss inhibitory and promotional factors. Descriptive statistics and qualitative analysis methods were used to examine the data. RESULTS: Twenty-six (26) patients participated in the program for a mean of 45.5 days (SD ± 25.3). Body weight decreased from 79.8 kg (SD ± 15.6) to 75.7 kg (SD ± 14.3), and BMI decreased from 30.4 kg/m² (SD ± 4.7) to 29.4 kg/m² (SD ± 5.0) (P < .05). The average weight loss percentage was 4.9% (SD ± 3.4). In 14 patients, the weight loss percentage was 5% or more. SSIs occurred in 5 of 26 patients (19.2%). Additionally, 4 of 26 patients (15.4%) who had 8.8% or more weight loss did not manifest SSIs. Previous weight loss before the preoperative surgery visits, lack of motivation for weight loss, and time and duration required for weight loss were identified as inhibitory factors, whereas history of successful weight loss experience, knowledge acquisition, family support, and reduced knee and lower back pain were identified as promotional factors for weight loss. CONCLUSION: Patients in this program lost weight prior to colorectal surgery. Research to further explore the safety and effects of preoperative weight loss in obese patients with colorectal cancer as well as inhibitory and promotional factors for participation and success is needed.

The clinical course and potential underlying mechanisms of everolimus-induced hyperglycemia.

The mechanistic target of rapamycin (mTOR) inhibitor everolimus is an antitumor agent known to cause hyperglycemia. However, the clinical course of everolimus-induced hyperglycemia, its pathophysiological basis, and the treatment strategy are not clear. In this case series report, we present the clinical course of everolimus-induced hyperglycemia in four patients. Hyperglycemia occurred 3-8 weeks after the administration of everolimus irrespective of the body mass index (range, 21.3-29.1 kg/m2) or pre-existing diabetes. Insulin or insulin secretagogues were required for glycemic control in most of the patients. Of note, the hyperglycemia was reversible in all patients, and none of the patients required anti-diabetic agents to achieve adequate glycemic control after cessation of everolimus therapy. To investigate the underlying mechanism of everolimus-induced hyperglycemia, we assessed insulin secretion and sensitivity by 75 g oral glucose tolerance test, arginine challenge test, and/or hyperinsulinemic-euglycemic clamp study using stable isotope-labeled glucose tracer in two patients. Everolimus did not affect insulin sensitivity in the liver, skeletal muscle, or the adipose tissue. In contrast, everolimus impaired insulin secretion and thereby increased basal hepatic glucose production. These findings further our understanding of the role of mTOR in glucose homeostasis in humans and provide insights for treatment strategies against everolimus-induced hyperglycemia.

Sfh1, an essential component of the RSC chromatin remodeling complex, maintains genome integrity in fission yeast.

Abp1 is a fission yeast CENP-B homologue that contributes to centromere function, silencing at pericentromeric heterochromatin and silencing of retrotransposons. We identified the sfh1 gene, encoding a core subunit of the fission yeast chromatin remodeling complex RSC as an Abp1-interacting protein. Because sfh1 is essential for growth, we isolated temperature-sensitive sfh1 mutants. These mutants showed defects in centromere functions, reflected by sensitivity to an inhibitor of spindle formation and minichromosome instability. Sfh1 localized at both kinetochore and pericentromeric heterochromatin regions. Although sfh1 mutations had minor effect on silencing at these regions, they decreased the levels of cohesin on centromeric heterochromatin. Sfh1 also localized at a retrotransposon, Tf2, in a partly Abp1-dependent manner, and assisted in silencing of Tf2 by Abp1 probably in the same pathway as a histone chaperon, HIRA, which is also known to involve in Tf2 repression. Furthermore, sfh1 mutants were sensitive to several DNA-damaging treatments (HU, MMS, UV and X-ray). Increase in spontaneous foci of Rad22, a recombination Mediator protein Rad52 homologue, in sfh1 mutant suggests that RSC functions in homologous recombination repair of double-stranded break downstream of the Rad22 recruitment. These results indicate that RSC plays multiple roles in the maintenance of genome integrity.

The Effect of Preoperative Subcutaneous Fat Thickness on Surgical Site Infection Risk in Patients Undergoing Colorectal Surgery: Results of a Multisite, Prospective Cohort Study.

Surgical site infection (SSI) is one of the most frequent postoperative complications among patients undergoing elective colorectal surgery. A multisite, prospective cohort study was conducted to investigate whether the thickness of subcutaneous fat (TSF) influences the occurrence of SSI in patients undergoing colorectal surgery. Participants included patients scheduled to receive colorectal laparotomy for colorectal cancer and who were under the care of a wound ostomy continence nurse at 17 participating general hospitals in Japan. Patients were not eligible to participate if they had undergone emergency surgery, reoperation, or laparoscopic surgery. Demographic, wound, and surgical data and American Society of Anesthesiologists (ASA) scale scores were collected and assessed, along with nutritional status, TSF, body mass index, and risk factors for SSI (ie, length of surgery and wound classification). The incidence of SSI and nutritional conditions was assessed weekly for 30 days after surgery. Of the 155 participants (mean age 68.9 ± 10.8 years, 53 [34.2%] of whom were women), 90 (58.1%) underwent rectal surgery, and the remaining 65 underwent colon surgery. Seventy-two (72, 46.5%) of the 155 patients underwent colostomy surgery; 24 (15.5%) developed a SSI. The mean onset of SSI was 7.3 ± 2.9 days after surgery and commonly observed in the stoma group when the ASA score was 3 or higher (P = 0.02). Patients who developed SSI resumed oral dietary intake later than those without SSI (7.4 days versus 4.6 days, P = 0.02). Multivariate analysis indicated TSF >15 mm (P = 0.01), Alb level <3.5 g/dL at postoperative days 14 (P = 0.03) and 21 (P = 0.02), and total protein level <6.8 g/dL at postoperative day 7 (P = 0.02) were statistically significantly correlated with SSI occurrence. These results suggest preoperative TSF and preoperative and postoperative serum albumin levels are independent risk factors for SSI in patients undergoing colorectal surgery, confirming current recommendations to maximize the preoperative nutritional status of patients in order to prevent major complications. The results also confirm obesity/TSF should be assessed preoperatively to ascertain the risk of SSI in patients undergoing colorectal surgery.

[Positive Effect of an Anesthesia Preoperative Evaluation Clinic in a Small Hospital].

BACKGROUND: We investigated the effect of an anesthetic clinic in a small hospital, with only two anesthesiologists, on operation unit activities and labor burden of the anesthesiologists. METHODS: The number of outpatients visiting the anesthetic clinic during the six month after opening of the clinic was evaluated. The doctor's fee and the number of operations under our anesthetic management were also analyzed. The total time of anesthesiologist's overtime work was compared with that of the corresponding period of the past year. RESULTS: 241 cases (48%) among 502 elective anesthesia cases were examined at the clinic, and 65% of them visited before admission for the surgery and paid for doctor's examination. Although the number of anesthesiologists working at operating rooms decreased 8% after opening of the clinic, the number of operations under the anesthetic management increased 6% compared to the corresponding period of the past year. The overtime work of anesthesiologists decreased drastically probably due to increased efficiency of the operative anesthetic labor resulting from the reduction of anesthesiologist's preoperative duties at bedside. CONCLUSIONS: Establishment of an anesthetic clinic had a positive effect on both hospital-management and anesthesiologist-labor even in a small hospital with a few anesthesiologists.

Effect of stoma location on the incidence of surgical site infections in colorectal surgery patients.

PURPOSE: The purpose of this study was to investigate the association between ostomy location and the incidence of surgical site infections (SSIs) in colorectal surgery patients. DESIGN: Prospective comparison cohort study. SUBJECTS AND SETTING: The study sample comprised 25 adult inpatients with colorectal cancer managed surgically. All participants underwent stoma site marking before surgery. Persons undergoing emergency stoma creation and those requiring reconstruction of stomas were excluded. Subjects were recruited by WOC nurses at 6 facilities with outpatient clinics operated by WOC nurses and infection control nurses. All facilities were located in Japan. METHODS: Six WOC nurses and 6 infection control nurses collected data including participant demographics, types of surgery, and occurrence of SSIs. Participants were prospectively observed for 30 days following surgery. RESULTS: Surgical site infections occurred in 9 out of 25 study participants (36%). Specifically, infections were reported at a rate of 43.8% (n = 7) and 36% (n = 2) with colon and rectal surgery, respectively. Inferential statistical analysis revealed no association between the likelihood of SSI and the distance between abdominal incision and the newly created intestinal ostomy. CONCLUSION: Based on these findings, we concluded that the distance between the location of stoma and the abdominal midline incision is not a significant risk factor for development of an SSI among postcolorectal surgery patients.

[How to improve positioning of the head--the sniffing position, considered to be suitable for endotracheal intubation].

BACKGROUND: The sniffing position, a combination of flexion of the neck and extension of the head, is considered to be suitable for the performance of endotracheal intubation. To place a patient in this position, anesthesiologists usually put a pillow under a patient's occiput. However, with a regular pillow, the resulting extension of the head tends to be suboptimal. METHODS: In an attempt to improve positioning of the head, we started using "a triangular pillow". The name of this pillow comes from its shape in the sagittal section. A patient's head rests on a slope of the pillow so that it assumes an extended position. RESULTS: In this retrospective study, we compared the triangular pillow and the regular pillow employing the laryngoscopic view grade (Cormack grade) and times for tracheal intubation trial. We found that the triangular pillow group showed lower Cormack grades, compared with the regular pillow group. And in the first attempt, the success rate of the triangular pillow group was higher than that of the regular pillow group. CONCLUSIONS: The triangular pillow improves the laryngoscopic view and facilitates endotracheal intubation by optimizing a patient's head position.

[Landiolol prevented myocardial ischemia in a patient with severe aortic stenosis undergoing total gastrectomy].

Gastric cancer was detected in a 71-year-old man with severe aortic stenosis. According to ACC/AHA guidelines, aortic stenosis in the patient was so severe that noncardiac surgery was considered appropriate only after aortic valve replacement. However, due to uncontrollable hemorrhage from gastric cancer, total gastrectomy was urgently required. Surgery was performed under epidural and general anesthesia. Blood pressure and heart rate were stable during anesthetic induction, tracheal intubation and skin incision. Just after peritoneal incision, however, ST decreased significantly following hypertension and sinus tachycardia, which were controllable by deepening of the anesthetic level. This ST depression was dependent on heart rate but not blood pressure. Therefore, in order to control the heart rate and prevent myocardial ischemia, low dose landiolol was infused prophylactically. This agent regulated the heart rate below 85 beats per minute without inducing hypotension and prevented myocardial ischemia during the remaining anesthetic course including extubation and recovery from anesthesia. Although beta blocker is not generally recommended in patients with aortic stenosis, present case suggests that landiolol is effective and useful to prevent cardiac ischemia even in a patient with severe aortic stenosis.

Optimal preparation of immobilized liposome-bound cellulase for hydrolysis of insoluble cellulose in an external loop airlift bioreactor.

Immobilized liposome-bound cellulase (ILC) was optimally prepared for the ILC-catalyzed hydrolysis of insoluble cellulose in an external loop airlift bioreactor. The liposomes with mean diameters of 200, 100, and 50 nm were used to prepare three kinds of ILCs, i.e., ILC(200), ILC(100) and ILC(50), respectively. The activity and stability of ILC(100) were examined with soluble cellulose (CMC) in addition to the insoluble substrate of cellulose powder (CC31) in a shaking flask as well as the airlift bioreactors. The experiments were carried out with 45 degrees C and pH 4.8 being found to be optimal for the activity. The activity of ILC(100) was stable in either airlift or shaking flask bioreactor during the five times repeated hydrolyses of CC31 corresponding to a total reaction time of 240 h. This confirmed that the cellulase molecules were covalently bonded to the liposomes covalently bound to the chitosan gel beads. Nevertheless, the activity of ILC(100) with CMC steadily decreased throughout the repeated reactions, suggesting an adverse effect of CMC on the ILC(100) activity. Among the three ILCs, ILC(50) was found to be the most stable and productive biocatalyst during the repeated hydrolyses of insoluble CC31 in the airlift bioreactor. More than 70% of the initial activity of ILC(50) was retained even after the six times repeated reactions for 288 h. Conversely, the ILC(200) was found to be the most unstable catalyst. Such a difference in stability among these ILCs was suggested to be caused by the difference in physical stability of their liposome membranes to the liquid shear stress due to the rising bubbles and circulating liquid as well as that in the amount of the cellulase molecules unstably incorporated in the membranes. ILC(50) was thus shown to have the most potential for an efficient hydrolysis of insoluble cellulose in a practical airlift bioreactor.

Fission yeast CENP-B homologs nucleate centromeric heterochromatin by promoting heterochromatin-specific histone tail modifications.

Heterochromatin is a functionally important chromosomal component, especially at centromeres. In fission yeast, conserved heterochromatin-specific modifications of the histone H3 tail, involving deacetylation of Lys 9 and Lys 14 and subsequent methylation of Lys 9, promote the recruitment of a heterochromatin protein, Swi6, a homolog of the Drosophila heterochromatin protein 1. However, the primary determinants of the positioning of heterochromatin are still unclear. The fission yeast proteins Abp1, Cbh1, and Cbh2 are homologs of the human protein CENP-B that bind to centromeric alpha-satellite DNA and associate with centromeric heterochromatin. We show that the CENP-B homologs are functionally redundant at centromeres, and that Abp1 binds specifically to centromeric heterochromatin. In the absence of Abp1 or Cbh1, the centromeric association of Swi6 is diminished, resulting in a decrease in silencing of the region. CENP-B-homolog double disruptants show a synergistic reduction of Swi6 at centromeric heterochromatin, indicating that the three proteins are functionally redundant in the recruitment of Swi6. Furthermore, using chromatin immunoprecipitation assays, we show that disruption of CENP-B homologs causes a decrease in heterochromatin-specific modifications of histone H3. These results indicate that the CENP-B homologs act as site-specific nucleation factors for the formation of centromeric heterochromatin by heterochromatin-specific modifications of histone tails.