| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Salvo, Gloria, et al.
(författare)
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Open vs minimally invasive radical trachelectomy in early-stage cervical cancer : International Radical Trachelectomy Assessment Study
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 226:1, s. 1-97
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Tidskriftsartikel (refereegranskat)abstract
- Background: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer. Objective: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy. Study Design: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005–2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental. Results: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20–42) years for open surgery vs 31 (18–45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0–31) mm for open surgery and 12 (0.8–40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20–16.70) years for open surgery and 3.1 years (0.02–11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6–97.0) for open surgery and 91.5% (95% confidence interval, 87.6–95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6–99.7) for open surgery and 99.0% (95% confidence interval, 79.0–99.8) for minimally invasive surgery. Conclusion: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management.
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| 3. |
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| 4. |
- Chen, Si, et al.
(författare)
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A graphene field-effect capacitor sensor in electrolyte
- 2012
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 101:15, s. 154106-
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Tidskriftsartikel (refereegranskat)abstract
- The unique electronic properties of graphene are exploited for field-effect sensing in both capacitor and transistor modes when operating the sensor device in electrolyte. The device is fabricated using large-area graphene thin films prepared by means of layer-by-layer stacking. Although essentially the same device, its operation in the capacitor mode is found to yield more information than in the transistor mode. The capacitor sensor can simultaneously detect the variations of surface potential and electrical-double-layer capacitance at the graphene/electrolyte interface when altering the ion concentration. The capacitor-mode operation further facilitates studies of the molecular binding-adsorption kinetics by monitoring the capacitance transient
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| 5. |
- Fang, Xin, et al.
(författare)
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Sex Hormones, Gonadotropins, and Sex Hormone-binding Globulin in Infants Fed Breast Milk, Cow Milk Formula, or Soy Formula
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Measurement of endogenous hormones in early life is important to investigate the effects of hormonally active environmental compounds. To assess the possible hormonal effects of different feeding regimens in different sample matrices of infants, 166 infants were enrolled from two U.S hospitals between 2006 and 2009. The children were classified into exclusive soy formula, cow milk formula or breast milk regimens. Urine, saliva and blood samples were collected over the first 12 months of life. Estradiol, estrone, testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) levels were measured in the three matrices. Lower estradiol and LH levels were found in urine and saliva samples of soy formula-fed boys compared to cow formula-fed boys. Higher LH level was found in urine samples of soy formula-fed girls compared to cow formula-fed girls. However, we found neither a neonatal testosterone rise in the boys nor a gender-specific difference in testosterone levels, which suggests that urinary testosterone levels may not accurately reflect blood levels during mini-puberty. Nevertheless, our study shows that blood, urine and saliva samples are readily collectible and suitable for multi-hormone analyses in children and allow examination of hypotheses concerning endocrine effects from dietary compounds.
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| 6. |
- Gao, Jiacheng, et al.
(författare)
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Irvsp : To obtain irreducible representations of electronic states in the VASP
- 2021
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Ingår i: Computer Physics Communications. - : ELSEVIER. - 0010-4655 .- 1879-2944. ; 261
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Tidskriftsartikel (refereegranskat)abstract
- We present an open-source program irvsp, to compute irreducible representations of electronic states for all 230 space groups with an interface to the Vienna ab-initio Simulation Package. This code is fed with plane-wave-based wavefunctions (e.g. WAVECAR) and space group operators (listed in OUTCAR), which are generated by the VASP package. This program computes the traces of matrix presentations and determines the corresponding irreducible representations for all energy bands and all the k-points in the three-dimensional Brillouin zone. It also works with spin-orbit coupling (SOC), i.e., for double groups. It is in particular useful to analyze energy bands, their connectivities, and band topology, after the establishment of the theory of topological quantum chemistry. Accordingly, the associated library -irrep_bcs.a - is developed, which can be easily linked to by other ab-initio packages. In addition, the program has been extended to orthogonal tight-binding (TB) Hamiltonians, e.g. electronic or phononic TB Hamiltonians. A sister program is presented as well. Program summary Program title: irvsp CPC Library link to program files: http://doi.org/10.1763/y9ds5nnm2f.1 Licensing provisions: GNU Lesser General Public License Programming language: Fortran 90/77 Nature of problem: Determining irreducible representations for all energy bands and all the k-points in 230 space groups. It is in particular useful to analyze energy bands, their connectivities, and band topology. Solution method: By computing the traces of matrix presentations of space group operators for the eigen-wavefunctions at a certain k-point in a given space group, one can determine irreducible representations for them.
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| 7. |
- Guo, Jianqiu, et al.
(författare)
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Anthropometric measures at age 3 years in associations with prenatal and postnatal exposures to chlorophenols
- 2019
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Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 228, s. 204-211
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chlorophenols (CPs), suspected as endocrine disrupting chemicals, exposure during early life may contribute to body size. However, limited human data with inconsistent findings have examined the developmental effects of CPs exposure.Objective: To explore associations between prenatal and postnatal CPs exposure and anthropometric parameters in children aged 3 years.Methods: A subset of 377 mother-child pairs with urinary five CP concentrations were enrolled from a prospective birth cohort. Generalized linear models were conducted to evaluate associations of CPs exposure with children's anthropometric measures.Results: Maternal urinary 2,4,6-trichlorophenol (2,4,6-TCP) concentrations were significantly negatively associated with weight z scores [regression coefficient (beta)=-0.51, 95% confidence interval (Cl): -0.96, -0.05; p = 0.01], weight for height z scores (beta = -0.54, 95% Cl:-1.02, -0.06; p= 0.01) and body mass index (BMI) z scores (beta = -0.53, 95% CI;-1.03, 0.03; p = 0.01) of children aged 3 years, after adjustment for potential confounders and postnatal CPs exposure. In the sex-stratified analyses, these inverse associations remained among boys, while in girls, positive associations of prenatal 2,4,6-TCP exposure with weight for height z scores and BMI z scores were observed. Postnatal exposure to 2,5-diclorophenol (2,5-DCP) was positively associated with weight z scores (beta = 0.26, 95% CI: 0.02, 0.50; p = 0.04), after controlling for possible confounders and maternal CPs exposure during pregnancy. Considering potential sex-specific effects, these associations were only observed in girls.Conclusions: Our findings indicate that prenatal 2,4,6-TCP exposure and postnatal 2,5-DCP exposure may have adverse and sex-specific effects on children's physical development.
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| 8. |
- Guo, Jianqiu, et al.
(författare)
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Associations of melamine and cyanuric acid exposure with markers of kidney function in adults : Results from NHANES 2003-2004
- 2020
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Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Higher melamine exposure may increase the risk of kidney stone formation and kidney injury in infants, but little is known about the potential nephrotoxic effects of environmental low-dose melamine and its derivative exposure on kidney function of adults in the general population. Our objective was to assess associations between urinary concentrations of melamine and its derivative, cyanuric acid, and kidney function through analyzing the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. Information on 298 participants aged ≥20 years was utilized. Urinary melamine and cyanuric acid levels were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were calculated to reflect kidney function. Covariate-adjusted creatinine standardization concentrations accounting for sex, race, age, race/ethically, and body mass index, was employed to control potential confounding of kidney function. Multivariable linear regression models were conducted to estimate associations of covariate-adjusted creatinine standardization urinary melamine and cyanuric acid concentrations with eGFR and UACR. Log-binomial regression models were performed to estimate risks of impaired kidney function and hypertension associated with urinary melamine and cyanuric acid levels. The geometric mean values of urinary melamine and cyanuric acid concentrations were 1.51 μg/L [95% confidence interval (CI): 1.21 μg/L, 1.89 μg/L] and 5.86 μg/L (95% CI: 5.34 μg/L, 6.44 μg/L), respectively. The median value of estimated daily intake (EDI) for melamine was 0.06 (ranging from undetectable to 1.11) μg/kg body weight/day calculated by urinary concentration and creatinine excretion accounting for sex and body weight. Adults in the fourth quartile of melamine and cyanuric acid exposure had 0.142 mL/min/1.73 m2 (95% CI: -0.271, -0.014) and 0.106 mL/min/1.73 m2 (95% CI: -0.020, 0.006) lower eGFR for melamine and cyanuric acid, respectively, compared to participants in the first quartile of exposure with adjustment for potential confounders. To our best knowledge, this is the first study to report associations between melamine and its derivative and kidney function of the U.S. adults from NHANES 2003-2004. The suggestive evidence revealed that individuals with high melamine exposure had lower eGFR than those with low melamine exposure, although no significant association between melamine and cyanuric acid exposure and markers of kidney function was observed. These findings should be interpreted with caution regarding the possible reverse causality.
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| 9. |
- Guo, Jianqiu, et al.
(författare)
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Associations of prenatal and childhood chlorpyrifos exposure with Neurodevelopment of 3-year-old children
- 2019
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Ingår i: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 251, s. 538-546
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Tidskriftsartikel (refereegranskat)abstract
- Chlorpyrifos (CPF), an organophosphate insecticide, has been linked to adverse neurodevelopmental effects in animal studies. However, little is known about long-term neurotoxicity of early-life CPF exposure in humans. We aimed to evaluate the associations of both prenatal and early childhood CPF exposure with neurodevelopment of children. In this observational study based on Sheyang Mini Birth Cohort, pregnant women were recruited from an agricultural region between June 2009 and January 2010, and their children were followed up from birth to age three. Urinary 3,5,6-Trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, was quantified using large-volume-injection gas chromatography tandem mass spectrometry. Developmental quotients (DQs) of children in motor, adaptive, language, and social areas were assessed by trained pediatricians. Data from 377 mother-child pairs were used in the current study. Associations between CPF exposure and neurodevelopmental indicators were estimated using generalized linear models with adjustment for potential confounders. The median concentrations of TCPy in maternal and children's urine were 5.39 mu g/L and 5.34 mu g/L, respectively. No statistically significant association was found between maternal urinary TCPy concentrations and children neurodevelopment. While for postnatal exposure, we found lower motor area DQ score 0.61 [95% confidence interval (CI): -1.13, -0.09; p = 0.02] and social area DQ score 0.55 (95% CI: -1.07, -0.03; p = 0.04) per one-unit increase in the In-transformed childhood urinary TCPy concentrations. Further stratification by sex indicated that the inverse associations were only observed in boys, but not in girls. Our findings suggest that adverse neurodevelopmental effects were associated with early childhood CPF exposure, but not prenatal exposure. Additional longitudinal studies are needed to replicate these results and to further understand the toxicological mechanisms of CPF.
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| 10. |
- Guo, Jianqiu, et al.
(författare)
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Early life triclosan exposure and neurodevelopment of children at 3 years in a prospective birth cohort
- 2020
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Ingår i: International journal of hygiene and environmental health. - : Urban & Fischer. - 1438-4639 .- 1618-131X. ; 224
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early life exposure to triclosan, an emerging endocrine disrupting chemical, may adversely impact childhood neurodevelopment, but limited epidemiologic studies have examined the associations.OBJECTIVE: We evaluated the associations between prenatal and postnatal triclosan exposure and child neurodevelopment at 3 years.METHODS: The study included 377 mother-child pairs who participated in Sheyang Mini Birth Cohort Study (SMBCS), a longitudinal birth cohort in China. Triclosan concentrations in maternal and 3-year-old child urine samples were quantified using gas chromatography-tandem mass spectrometry (GC-MS/MS). Gesell Developmental Schedules (GDS) were used to assess child neurodevelopment at 3 years of age. Multivariate linear regression models were applied to estimate associations of prenatal and postnatal urinary triclosan concentrations with children's developmental quotients (DQs).RESULTS: Detection frequencies of triclosan in maternal and childhood urine samples were 100% and 99.5%, respectively. The median values of prenatal and postnatal urinary triclosan levels were 0.65 and 0.44 μg/L, respectively. One ln-unit increase of maternal urinary triclosan concentration was associated with increase of DQ scores in motor area of children (regression coefficient, β = 0.28, 95% confidence interval, CI: 0.03, 0.54; p = 0.03). In sex-stratified analyses, maternal urinary triclosan levels were significantly related to increases in DQ scores in motor area among boys (β = 0.25, 95%CI: 0.01, 0.50; p = 0.04), while postnatal urinary triclosan concentrations were inversely associated with DQ scores in social area in boys (β = -0.37, 95%CI: -0.72, -0.03; p = 0.03).CONCLUSIONS: The findings suggested that prenatal triclosan exposure predicted increases in motor scores, while postnatal triclosan exposure was related to reductions in social scores of 3-year-old children. These associations were only observed in boys. The biological mechanisms linking triclosan exposure to neurodevelopment await further studies.
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