Although hormonal regulation of ovarian follicle development has been extensively investigated, most studies concentrate on the development of early antral follicles to the preovulatory stage, ...leading to the successful use of exogenous FSH for infertility treatment. Accumulating data indicate that preantral follicles are under stringent regulation by FSH and local intraovarian factors, thus providing the possibility to develop new therapeutic approaches. Granulosa cell-derived C-type natriuretic factor not only suppresses the final maturation of oocytes to undergo germinal vesicle breakdown before ovulation but also promotes preantral and antral follicle growth. In addition, several oocyte- and granulosa cell-derived factors stimulate preantral follicle growth by acting through wingless, receptor tyrosine kinase, receptor serine kinase, and other signaling pathways. In contrast, the ovarian Hippo signaling pathway constrains follicle growth and disruption of Hippo signaling promotes the secretion of downstream CCN growth factors capable of promoting follicle growth. Although the exact hormonal factors involved in primordial follicle activation has yet to be elucidated, the protein kinase B (AKT) and mammalian target of rapamycin signaling pathways are important for the activation of dormant primordial follicles. Hippo signaling disruption after ovarian fragmentation, combined with treating ovarian fragments with phosphatase and tensin homolog (PTEN) inhibitors and phosphoinositide-3-kinase stimulators to augment AKT signaling, promote the growth of preantral follicles in patients with primary ovarian insufficiency, leading to a new infertility intervention for such patients. Elucidation of intraovarian mechanisms underlying early folliculogenesis may allow the development of novel therapeutic strategies for patients diagnosed with primary ovarian insufficiency, polycystic ovary syndrome, and poor ovarian response to FSH stimulation, as well as for infertile women of advanced reproductive age.
Effective toughness of heterogeneous media Hossain, M.Z.; Hsueh, C.-J.; Bourdin, B. ...
Journal of the mechanics and physics of solids,
11/2014, Letnik:
71
Journal Article
Recenzirano
We propose a versatile approach to computing the effective toughness of heterogeneous media. This approach focusses on the material property independent of the details of the boundary condition. The ...key idea is what we call a surfing boundary condition, where a steadily propagating crack opening displacement is applied as a boundary condition to a large domain while the crack set is allowed to evolve as it chooses. The approach is verified and used to study examples in brittle fracture. We demonstrate that effective toughness is different from effective or weighted surface area of the crack set. Furthermore, we demonstrate that elastic heterogeneity can have a profound effect on fracture toughness: it can be a significant toughening mechanism and it can lead to toughness asymmetry wherein the toughness depends not only on the direction but also on the sense of propagation. The role of length-scale is also discussed.
A total of 118 patients with
Elizabethkingia meningoseptica
bacteremia at a medical center in Taiwan from 1999 to 2006 were studied. Minimum inhibitory concentrations (MICs) of 99 preserved isolates ...were determined. The incidence (per 100,000 admissions) of
E. meningoseptica
bacteremia increased from 7.5 in 1996 to 35.6 in 2006 (
p
= 0.006). Among them, 84% presented with fever, 86% had nosocomial infections, and 60% had acquired the infection in intensive care units (ICUs). The most common underlying diseases were malignancy (36%) and diabetes mellitus (25%). Seventy-eight percent of patients had primary bacteremia, followed by pneumonia (9%), soft tissue infection, and catheter-related bacteremia (6%). Forty-five patients (38%) had polymicrobial bacteremia. Overall, the 14-day mortality was 23.4%. Multivariate analysis revealed
E. meningoseptica
bacteremia acquired in an ICU (
p
= 0.048, odds ratio OR 4.23) and presence of effective antibiotic treatment after the availability of culture results (
p
= 0.049, OR 0.31) were independent predictors of 14-day mortality. The 14-day mortality was higher among patients receiving carbapenems (
p
= 0.046) than fluoroquinolones or other antimicrobial agents. More than 80% of the isolates tested were susceptible to trimethoprim-sulfamethoxzole, moxifloxacin, and levofloxacin. The MIC
50
and MIC
90
of the isolates to tigecycline and doxycycline were both 4 μg/mL and 8 μg/ml, respectively.
It has been established that contrast in the elastic properties can lead to enhancement of fracture toughness in heterogeneous materials. Focussing on layered materials as a model system, we show ...that this enhancement is a result of two distinct phenomena – first, fluctuations in stress leading to regions where the stress intensity at the crack is considerably smaller than that of the macroscopically applied value; and second, the lack of stress intensity when a crack is at a compliant to stiff interface thereby requiring renucleation. Using theoretical, computational and experimental methods, we study two geometries – a layered material and a layered material with a narrow channel – to separate the two phenomena. The stress fluctuation is present in both, but renucleation is present only in the layered medium. We provide quantitative estimates for the enhanced toughness.
A front-end adaptive folder with a filter is presented to instantaneously push jammers to higher frequencies while preserving the integrity of small signals of interest. A programmable filter is ...utilised to further suppress folded jammers for achieving a widely scalable dynamic range over a large frequency range. To achieve maximum programmability with a minimal increase of power and area, combinatorial intrinsic device characteristics are exploited to tune folding points for rapid adaptation to a changing electromagnetic environment.
MicroRNAs (miRNAs) play important roles in tumorigenesis by regulating oncogenes and tumor-suppressor genes. In this study, miR-187 and miR-200a were found to be expressed at higher levels in ovarian ...cancers than in benign tumors. In patients with ovarian cancer, however, higher levels of miR-187 and miR-200a expression were paradoxically associated with better OS and recurrence-free survival. Further, multivariate analysis showed that miR-187 served as an independent prognostic factor for patients with ovarian cancer (n=176). Computational prediction and microarray results indicated that miR-187 directly targeted Disabled homolog-2 (Dab2), and luciferase reporter assays confirmed that the target site of miR-187 was located at the 3'-UTR of the Dab2 gene. Generally considered as a tumor-suppressor gene, Dab2 may actually promote tumor progression in advanced cancers through epithelial-to-mesenchymal transition (EMT). Ectopic expression of miR-187 in cancer cells promoted cell proliferation, but continued overexpression of miR-187 suppressed Dab2 and inhibited migration. Suppression of miR-187 upregulated Dab2, which, by inhibiting E-cadherin levels while stimulating vimentin and phospho-FAK levels, promoted EMT. Reduced ovarian cancer Dab2 histoscores correlated with high miR-187 levels and improved outcomes of patients. Collectively, these results demonstrate distinct dual roles of Dab2 in cell proliferation and tumor progression. In the initial steps of tumorigenesis, upregulated miR-187 suppresses Dab2, promoting cell proliferation. During the later stages, however, continued increased levels of miR-187 inhibits the Dab2-dependent EMT that is associated with tumor invasiveness, which is presumed to be the reason why cancers with high miR-187 levels were associated with better survivals.
Objectives
This study aimed to investigate whether accelerometer-measured light physical activity (LPA) is associated with cognitive function and whether engaging in ≥3 h/day of LPA can reduce the ...chance of cognitive impairment among a sample of older adults in Taiwan.
Design
Cross-sectional study.
Setting
An outpatient department in a medical center.
Participants
Participants were community-dwelling older adults aged 65 years and older who were able to walk independently from September 2020 to March 2021.
Measurements
A tri-axial accelerometer was used to measure LPA for 7 consecutive days, and the Mini-Mental State Examination (MMSE) scale was used to assess the chance of cognitive impairment. Multiple linear regression model and binary logistic regression model were performed to examine the association between LPA and MMSE scores.
Results
145 older Taiwanese adults (51.7% men; 81.2±6.8 years; 6.9% at chance of cognitive impairment) were included. After adjusting for moderate-to-vigorous physical activity (MVPA) and wear time, we found that there was a significant association between LPA and cognitive function (95% confidence interval CI: 0.64–1.65; P<0.001), and further found that those who engaged in LPA ≥3 h/ day were at reduced chance of cognitive impairment compared with people who engaged in LPA <3 h/day (odds ratio OR: 0.16; 95% CI: 0.03–0.80; P=0.025).
Conclusion
This study demonstrated that engaging in LPA ≥3 h/day could be viewed as a protective factor for maintaining cognitive function in older adults. We recommend further longitudinal research to elucidate the association between intensity-specific LPA and cognitive function.
CD5L is a canonical component of circulatory IgM Oskam, Nienke; den Boer, Maurits A; Lukassen, Marie V ...
Proceedings of the National Academy of Sciences - PNAS,
12/2023, Letnik:
120, Številka:
50
Journal Article
Recenzirano
Odprti dostop
Immunoglobulin M (IgM) is an evolutionary conserved key component of humoral immunity, and the first antibody isotype to emerge during an immune response. IgM is a large (1 MDa), multimeric protein, ...for which both hexameric and pentameric structures have been described, the latter additionally containing a joining (J) chain. Using a combination of single-particle mass spectrometry and mass photometry, proteomics, and immunochemical assays, we here demonstrate that circulatory (serum) IgM exclusively exists as a complex of J-chain-containing pentamers covalently bound to the small (36 kDa) protein CD5 antigen-like (CD5L, also called apoptosis inhibitor of macrophage). In sharp contrast, secretory IgM in saliva and milk is principally devoid of CD5L. Unlike IgM itself, CD5L is not produced by B cells, implying that it associates with IgM in the extracellular space. We demonstrate that CD5L integration has functional implications, i.e., it diminishes IgM binding to two of its receptors, the FcαµR and the polymeric Immunoglobulin receptor. On the other hand, binding to FcµR as well as complement activation via C1q seem unaffected by CD5L integration. Taken together, we redefine the composition of circulatory IgM as a J-chain containing pentamer, always in complex with CD5L.
Long-term exposure to ingested inorganic arsenic is associated with peripheral vascular disease (PVD) in the blackfoot disease (BFD)-hyperendemic area in Taiwan. This study further examined the ...interaction between arsenic exposure and urinary arsenic speciation on the risk of PVD. A total of 479 (220 men and 259 women) adults residing in the BFD-hyperendemic area were studied. Doppler ultrasound was used to diagnose PVD. Arsenic exposure was estimated by an index of cumulative arsenic exposure (CAE). Urinary levels of total arsenic, inorganic arsenite (As
III) and arsenate (As
V), monomethylarsonic acid (MMA
V), and dimethylarsinic acid (DMA
V) were determined. Primary methylation index PMI = MMA
V/(As
III + As
V) and secondary methylation index (SMI = DMA
V/MMA
V) were calculated. The association between PVD and urinary arsenic parameters was evaluated with consideration of the interaction with CAE and the confounding effects of age, sex, body mass index, total cholesterol, triglycerides, cigarette smoking, and alcohol consumption. Results showed that aging was associated with a diminishing capacity to methylate inorganic arsenic and women possessed a more efficient arsenic methylation capacity than men did. PVD risk increased with a higher CAE and a lower capacity to methylate arsenic to DMA
V. The multivariate-adjusted odds ratios for CAE of 0, 0.1–15.4, and >15.4 mg/L × year were 1.00, 3.41 (0.74–15.78), and 4.62 (0.96–22.21), respectively (
P < 0.05, trend test); and for PMI ≤ 1.77 and SMI > 6.93, PMI > 1.77 and SMI > 6.93, PMI > 1.77 and SMI ≤ 6.93, and PMI ≤ 1.77 and SMI ≤ 6.93 were 1.00, 2.93 (0.90–9.52), 2.85 (1.05–7.73), and 3.60 (1.12–11.56), respectively (
P < 0.05, trend test). It was concluded that individuals with a higher arsenic exposure and a lower capacity to methylate inorganic arsenic to DMA
V have a higher risk of developing PVD in the BFD-hyperendemic area in Taiwan.
Stenotrophomonas maltophilia
can cause various clinical diseases; however, pleural infections due to
S. maltophilia
are rare. We evaluated the clinical characteristics and outcomes of patients with ...pleural infections (complicated parapneumonic effusion or empyema) due to
S. maltophilia
who were treated at a medical center in Taiwan from 2004 to 2012. During the study period, 40 patients were treated for pleural infections due to
S. maltophilia
. The incidence of
S. maltophilia
pleural infections ranged from 2.66 per 1,000,000 patient-days in 2009 to 12.44 per 1,000,000 patient-days in 2011. Most of the patients with
S. maltophilia
pleural infections were immunocompromised male adults and all of the infections were acquired in healthcare settings. The majority of patients had polymicrobial pleural infections (
n
= 31, 77.5 %) and the most common pathogen was
Pseudomonas aeruginosa
(
n
= 12). The causes of pleural infections due to
S. maltophilia
were pneumonia due to
S. maltophilia
in two patients (5 %), post-surgical/tube thoracostomy in 26 (65 %) patients, and fistula (bronchopleural, esophagopleural and biliopleural) in 12 (30 %) patients. The 14-day and 30-day mortality rates were 32.5 % and 42.5 %, respectively. Pleural infections due to
S. maltophilia
are most commonly the result of surgical procedures, thoracostomy, and underlying fistulas. These infections are associated with a high mortality rate, especially among immunocompromised patients.
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