Centromeres are essential chromosomal structures that mediate accurate chromosome segregation during cell division. Centromeres are specified epigenetically by the heritable incorporation of the ...centromeric histone H3 variant CENP-A. While many of the primary factors that mediate centromeric deposition of CENP-A are known, the chromatin and DNA requirements of this process have remained elusive. Here, we uncover a role for transcription in Drosophila CENP-A deposition. Using an inducible ectopic centromere system that uncouples CENP-A deposition from endogenous centromere function and cell-cycle progression, we demonstrate that CENP-A assembly by its loading factor, CAL1, requires RNAPII-mediated transcription of the underlying DNA. This transcription depends on the CAL1 binding partner FACT, but not on CENP-A incorporation. Our work establishes RNAPII passage as a key step in chaperone-mediated CENP-A chromatin establishment and propagation.
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•CENP-A deposition is coupled with transcription•CAL1 recruits RNAPII onto DNA during CENP-A deposition•CAL1 interacts directly with the histone chaperone FACT•FACT depletion causes loss of transcription and defective CENP-A deposition
Centromeres are specified epigenetically by chromatin containing the histone H3 variant CENP-A. Chen et al. shed light on CENP-A deposition mechanisms, showing that the CENP-A chaperone CAL1 recruits FACT and RNAPII to CENP-A assembly sites, where they trigger transcription. In the absence of FACT, transcription ceases and CENP-A deposition is defective.
The role of the difference and ratio of albuminuria (urine albumin-to-creatinine ratio, uACR) and proteinuria (urine protein-to-creatinine ratio, uPCR) has not been systematically evaluated with ...all-cause mortality. We retrospectively analyzed 2904 patients with concurrently measured uACR and uPCR from the same urine specimen in a tertiary hospital in Taiwan. The urinary albumin-to-protein ratio (uAPR) was derived by dividing uACR by uPCR, whereas urinary non-albumin protein (uNAP) was calculated by subtracting uACR from uPCR. Conventional severity categories of uACR and uPCR were also used to establish a concordance matrix and develop a corresponding risk matrix. The median age at enrollment was 58.6 years (interquartile range 45.4-70.8). During the 12,391 person-years of follow-up, 657 deaths occurred. For each doubling increase in uPCR, uACR, and uNAP, the adjusted hazard ratios (aHRs) of all-cause mortality were 1.29 (95% confidence interval CI 1.24-1.35), 1.12 (1.09-1.16), and 1.41 (1.34-1.49), respectively. For each 10% increase in uAPR, it was 1.02 (95% CI 0.98-1.06). The linear dose-response association with all-cause mortality was only observed with uPCR and uNAP. The 3 × 3 risk matrices revealed that patients with severe proteinuria and normal albuminuria had the highest risk of all-cause mortality (aHR 5.25, 95% CI 1.88, 14.63). uNAP significantly improved the discriminative performance compared to that of uPCR (c statistics: 0.834 vs. 0.828, p-value = 0.032). Our study findings advocate for simultaneous measurements of uPCR and uACR in daily practice to derive uAPR and uNAP, which can provide a better mortality prognostic assessment.
Angiotensin II receptor blockers (ARBs) improve the survival rates of patients with various cancers. However, it remains unclear whether ARBs confer a survival benefit on patients with oral squamous ...cell carcinoma (OSCC). Here, we assessed the associations between ARB use and survival in patients with OSCC of different stages.
This was a 10-year retrospective cohort study of OSCC patients. We enrolled 7,558 patients diagnosed with oral cancer between January 2007 and December 2017 whose details had been entered into the Chang Gung Research Database. Seven hundred and fourteen patients were recruited from the Chang Gung Research Database after performing 1:1 propensity score-matching between ARB users and non-users. Cox's regression models with adjusted covariates were employed to detect factors influencing the survival rates of patients with OSCC.
Kaplan-Meier analysis revealed that the overall survival (OS) rate of 180-day ARB users increased (p = 0.038). Cox's regression models indicated that ARB use, younger patients, early-stage OSCC, and patients without diabetes mellitus were independently prognostic of improved OS. Increased OS was more prominent in 180-day ARB users in stage III, Iva, and IVb categories.
ARB use for more than 180 days is associated with an increased survival rate and is a positive, independent prognostic factor in patients with OSCC. A further two-arm study should be conducted to confirm the clinical usefulness of ARBs in OSCC patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim was to assess the protective effect of pioglitazone (PGZ) on retinal ganglion cells (RGCs) after anterior ischemic optic neuropathy (AION) in diabetic and non-diabetic mice. Adult C57BL/6 ...mice with induced diabetes were divided into three groups: group 1: oral PGZ (20 mg/kg) in 0.1% dimethyl sulfoxide (DMSO) for 4 weeks; group 2: oral PGZ (10 mg/kg) in 0.1% DMSO for 4 weeks; and group 3: oral DMSO only for 4 weeks (control group). Two weeks after treatment, AION was induced through photochemical thrombosis. For non-diabetic mice, adult C57BL/6 mice were divided into four groups after AION was induced: group 1: oral DMSO for 4 weeks; group 2: oral PGZ (20 mg/kg) in 0.1% DMSO for 4 weeks; group 3: oral PGZ (20 mg/kg) in 0.1% DMSO + peritoneal injection of GW9662 (one kind of PPAR-γ inhibitor) (1 mg/kg) for 4 weeks; group 4: peritoneal injection of GW9662 (1 mg/kg) for 4 weeks; One week after the induction of AION in diabetic mice, apoptosis in RGCs was much lower in group 1 (8.0 ± 4.9 cells/field) than in group 2 (24.0 ± 11.5 cells/field) and 3 (25.0 ± 7.7 cells/field). Furthermore, microglial cell infiltration in the retina (group 1: 2.0 ± 2.6 cells/field; group 2: 15.6 ± 3.5 cells/field; and group 3: 14.8 ± 7.5 cells/field) and retinal thinning (group 1: 6.7 ± 5.7 μm; group 2: 12.8 ± 6.1 μm; and group 3: 15.8 ± 5.8 μm) were also lower in group 1 than in the other two groups. In non-diabetic mice, preserved Brn3A
cells were significantly greater in group 2 (2382 ± 140 Brn3A+ cells/mm
,
= 7) than in group 1 (1920 ± 228 Brn3A+ cells/mm
;
= 0.03,
= 4), group 3 (1938 ± 213 Brn3A+ cells/mm
;
= 0.002,
= 4), and group 4 (2138 ± 126 Brn3A+ cells/mm
;
= 0.03,
= 4), respectively; PGZ confers protection to RGCs from damage caused by ischemic optic neuropathy in diabetic and non-diabetic mice.
is known to cause severe acute endophthalmitis and often leads to poor visual outcomes in most ophthalmic infections. This retrospective study is to report the clinical settings, antimicrobial ...susceptibility patterns, and visual outcome of
endophthalmitis at a tertiary referral institution in Taoyuan, Taiwan.
endophthalmitis was diagnosed in 37 eyes of 37 patients. Post-cataract surgery was the most common cause (
= 27, 73%), followed by bleb-associated (
= 3, 8%), endogenous (
= 2, 5%), corneal ulcer-related (
= 2, 5%), post-vitrectomy (
= 1, 3%), post-pterygium excision (
= 1, 3%), and trauma (
= 1, 3%). Visual acuities upon presentation ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics were performed in 23 eyes (76%) as primary or secondary treatment. All isolates (37/37, 100%) were sensitive to vancomycin, penicillin, ampicillin, and teicoplanin. Six of 22 eyes (27%) were resistant to high-level gentamicin (minimum inhibitory concentration > 500 mg/L). Final visual acuities were better than 20/400 in 11 eyes (30%), 5/200 to hand motions in 4 eyes (11%), and light perception to no light perception in 22 eyes (59%). Three eyes were treated with evisceration. Compared with non-cataract subgroups, the post-cataract subgroup showed a significant difference of better visual prognosis (
= 0.016).
The air-conditioning systems have become an indispensable part of our daily life for keeping the quality of life. However, to improve the thermal comfort and reduce energy consumption is crucial to ...use the air conditioners effectively with rapid development of artificial intelligence technology. This study explored the correlation between the response of human physiological parameters and thermal sensation voting (TSV) to evaluate the comfort level among various cold and hot stimulations. The variations of the three physiological parameters, which were body surface temperature, skin blood flow (SBF), and sweat area on the skin surface, and TSV values were all positively correlated with the stimulation amount under the stimulation of cold wind, hot wind, and heat radiation, but the relationship was not completely linear. Among the three physiological parameters, the forehead skin temperature has the closest relationship with TSV, followed by the SBF and sweat. Among three stimulations, the cold wind stimulation causes the closest relationship between TSV and forehead temperature, followed by the radiation and hot wind stimulations. Through three different machine learning models, namely, random forest (RF) model, support vector machine (SVM) model, and neural network (NN) model, the stimulation of cold wind, hot wind, and heat radiation was applied to investigate the variation of the three physiological parameters as the input of the models. Moreover, the models were evaluated and verified by TSV. The results revealed that among the three different machine learning methods, RF had the best accuracy. The established thermal comfort models can predict the real-time user’s thermal comfort feeling, so that air-conditioning equipment’s performance can be optimized to create a healthy and energy-saving comfortable environment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Arsenic is a well-established human carcinogen and is considered a health risk worldwide, especially where groundwater is consumed as drinking water. In 2018, bladder and kidney cancers were the 14th ...and 17th leading causes of global cancer mortality, respectively. Our aim was to investigate the association between arsenic exposure, DNA damage, and the incidence of bladder and kidney cancers. A total of 788 participants aged ≥40 years were enrolled in a prospective cohort study in Taiwan between 1991 and 1994, with follow-up between 2011 and 2014. Well-water and first-morning spot urine samples were collected between 1991 and 1994 to estimate arsenic exposure, and the baseline urinary levels of 8-Oxo-2′-deoxyguanosine (8-OHdG) and N7-methylguanine (N7-MeG) were quantified to assess DNA lesions. The Cox proportional hazard model was used to estimate the effects of arsenic exposure and DNA adduct levels on the risk of bladder or kidney cancer. Urinary arsenic species were associated with significantly increased 8-OHdG and N7-MeG after adjusting for age, sex, and cigarette smoking. Only non-statistically significant mediation effects of 8-OHdG were observed. In a fully adjusted Cox model, participants with arsenic exposure and urinary 8-OHdG levels higher than the median had a higher risk of bladder cancer (HR = 4.60, confidence interval: 1.43–14.85). Overall, the combined effects of high cumulative arsenic exposure from artesian well-water and advanced DNA damage predicted the risk of bladder cancer.
•The subjects were followed for two decades in an arseniasis endemic area of northeastern Taiwan.•The urinary 8-OHdG and N7-MeG positively associated with cumulative well arsenic exposure.•Arsenic exposure and 8-OHdG have joint effects on risk of kidney/bladder cancer.
Environmental factors contribute significantly to the pathogenesis of chronic kidney disease. However, these factors, and particularly the toxic effects of heavy metals, have not been completely ...evaluated. Chromium is a widespread industrial contaminant that has been linked to nephrotoxicity in animal and occupational population studies. Nevertheless, its role in population renal health and its potential interactions with other nephrotoxic metals, such as lead and cadmium, remain unknown. We assessed the association between exposure to chromium, lead, and cadmium with renal function using estimated glomerular filtration rate (eGFR) in an analysis of 360 Taiwanese adults aged 19–84 years from the National Nutrition and Health Survey in Taiwan (2005–2008). Doubling of urinary chromium or lead decreased the eGFR by -5.99 mL/min/1.73 m2 (95% confidence interval -9.70, -2.27) and -6.61 (-9.71, -3.51), respectively, after adjusting for age, sex, body mass index, hypertension, diabetes, cigarette smoking, sodium intake, education, urinary volume, and other metals. For those in the highest tertile of cadmium exposure, the eGFR decreased by -12.68 mL/min/1.73 m2 (95% confidence interval -20.44, -4.93) and -11.22 mL/min/1.73 m2 (-17.01, -5.44), as urinary chromium or lead levels doubled, respectively. Thus, there is a significant and independent association between chromium exposure and decreased renal function. Furthermore, co-exposure to chromium with lead and cadmium is potentially associated with additional decline in the glomerular filtration rate in Taiwanese adults.
To determine the correlation between higher-order aberrations (HOAs) and best-corrected visual acuity (BCVA) recovery speed after spectacles treatment using iDesign measurements in refractive ...amblyopic children.
This is a prospective case series. Children aged from 3 to 7 years with refractive amblyopia (Landolt C equivalent < 0.8) were recruited. All participants were followed for at least 6 months after full correction of the refraction error by spectacles. The HOAs were measured using iDesign before and after cycloplegia at first visit and at 3-month intervals. Then correlation between BCVA recovery after treatment for 6 months and HOAs was determined.
We analyzed 24 eyes of 12 children (mean age, 4.5 years). Baseline mean BCVA was logarithm of minimal angle of resolution (logMAR) 0.335 (Landolt C equivalent 0.46), which improved to logMAR 0.193 (Landolt C equivalent 0.64) after treatment with full-correction spectacles for 6 months. The amblyopic eye BCVA recovery was negatively correlated with tetrafoil with/without cycloplegia (P = 0.006 and 0.022, respectively) and trefoil with cycloplegia (P = 0.049).
trefoil and tetrafoil measured with iDesign negatively correlates with the BCVA recovery speed of refractive amblyopic eyes after spectacles treatment in this pilot study. The current study results may aid in further investigation for diagnosis and treatment of refractory refractive and idiopathic amblyopia.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetes has become a chronic metabolic disorder, and the growing diabetes population makes medical care more important. We investigated using a portable and noninvasive contact lens as an ideal ...sensor for diabetes patients whose tear fluid contains glucose. The key feature is the reversible covalent interaction between boronic acid and glucose, which can provide a noninvasive glucose sensor for diabetes patients. We present a phenylboronic acid (PBA)-based HEMA contact lens that exhibits a reversible swelling/shrinking effect to change its thickness. The difference in thickness can be detected in a picture taken with a smartphone and analyzed using software. Our novel technique offers the following capabilities: (i) non-enzymatic and continuous glucose detection with the contact lens; (ii) no need for an embedded circuit and power source for the glucose sensor; and (iii) the use of a smartphone to detect the change in thickness of the contact lens with no need for additional photo-sensors. This technique is promising for a noninvasive measurement of the glucose level and simple implementation of glucose sensing with a smartphone.
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