Potterlindahl0544
Naive flies preferentially self-administer food with methamphetamine over plain food. Exposing flies to volatilized methamphetamine after voluntary self-administration abolishes locomotor sensitization. We tested period null (per01 ) mutant flies and showed that they do not develop locomotor sensitization, nor do they show preferential self-administration of methamphetamine. Our results suggest that there may be partially overlapping neural circuitry that regulates the expression of locomotor sensitization and preferential self-administration to methamphetamine and that this circuitry requires a functional per gene.The Pd-catalyzed directed thiocyanation reaction of arenes and heteroarenes by C-H bond activation was achieved. In the presence of an electrophilic SCN source, this original methodology offered an efficient tool to access a panel of functionalized thiocyanated compounds (21 examples, up to 78 % yield). Post-functionalization reactions further demonstrated the synthetic utility of the approach by converting the SCN-containing molecules into value-added scaffolds.Conditional control of CRISPR/Cas9 has been developed by using a variety of different approaches, many focusing on manipulation of the Cas9 protein itself. However, more recent strategies for governing CRISPR/Cas9 function are based on guide RNA (gRNA) modifications. They include control of gRNAs by light, small molecules, proteins, and oligonucleotides. These designs have unique advantages compared to other approaches and have allowed precise regulation of gene editing and transcription. Here, we discuss strategies for conditional control of gRNA function and compare effectiveness of these methods.
We aimed to determine the indication of fine-needle aspiration (FNA) for parathyroid adenoma (PA)-suspected nodules and the cytological features of PA, and to discuss the ancillary techniques for diagnostic confirmation.
Clinical, cytological, and histological examinations of 15 PA patients (4.0% of all PA resected patients) were conducted through FNA on 16 nodules. We also examined the cytological preparations of 10 follicular neoplasms (FNs) and 10 poorly differentiated thyroid carcinomas (PDTCs).
FNA was performed to detect PA in nine (56.3%) nodules. The remaining seven (43.8%) nodules underwent FNA for lesions considered as thyroid nodules or lymph nodes. The levels of parathyroid hormone (PTH) in the aspiration needle washout fluid were observably high, except for that from one nodule with unsatisfactory FNA. Cytologically, the incidences of wedge pattern (86.7%) and salt and pepper chromatin (86.7%) in PAs were significantly higher than in FNs and PDTCs. In contrast, the appearance of colloid gloTH measurements using needle washout fluid for PA-suspected nodules, and immunocytochemistry with the GATA-3 antibody for cytologically PA-suspected nodules.The Polycomb Repressive complex 2 (PRC2) maintains a repressive chromatin state and silences many genes, acting as methylase on histone tails. This enzyme was found overexpressed in many types of cancer. In this work, we have set up a Computer-Aided Drug Design approach based on the allosteric modulation of PRC2. In order to minimize the possible bias derived from using a single set of coordinates within the protein-ligand complex, a dynamic workflow was developed. In details, molecular dynamic was used as tool to identify the most significant ligand-protein interactions from several crystallized protein structures. The identified features were used for the creation of dynamic pharmacophore models and docking grid constraints for the design of new PRC2 allosteric modulators. Our protocol was retrospectively validated using a dataset of active and inactive compounds, and the results were compared to the classic approaches, through ROC curves and enrichment factor. Our approach suggested some important interaction features to be adopted for virtual screening performance improvement.
This study aimed to investigate the molecular mechanisms involved in the onset of the white striping (WS) myopathy with particular attention to the role of oxidative stress and protein oxidation in the loss of meat quality.
It was found that WS-M (moderate degree; white stripes <1 mm thickness) and WS-S (severe degree; white stripes >1 mm thickness) breast presented higher pH, hardness, redness, lipid, and collagen content, and lower lightness than normal breast. Compared with the latter, WS-S had a more severe loss of protein thiols (70.7% less thiols than in N), reduced activity of antioxidant enzymes such as catalase (23 versus 40 U g
), glutathione peroxidase (0.21 versus 0.54 U g
), and superoxide dismutase (56 versus 73 U g
), and consequently, had greater accretion of thiobarbituric acid reactive substances (0.64 versus 0.22 mg MDAkg
muscle), allysine (3.1 versus 1.9 nmol mg
protein) and Schiff base structures (645 versus 258 fluorescent units). The analysis of sarcoplasmic proteins revealed that muscles severely affected by the myopathy suffered a chronic impairment of physiological (upregulation of sarcoplasmic reticulum Ca2+ ATPase, sarcalumenin and calsequestrin-2) and metabolic processes (downregulation of pyruvate kinase, creatine kinase, and l-lactate dehydrogenase).
The overexpression of ribonuclease / angiogenin inhibitor 1 and Kelch-like proteins in WS chicken breasts indicates altered protein turnover plausibly mediated by oxidative stress and accumulation of oxidized proteins. © 2020 Society of Chemical Industry.
The overexpression of ribonuclease / angiogenin inhibitor 1 and Kelch-like proteins in WS chicken breasts indicates altered protein turnover plausibly mediated by oxidative stress and accumulation of oxidized proteins. © 2020 Society of Chemical Industry.The assembly of complex molecules, such as organic cages, can be achieved through supramolecular and dynamic covalent strategies. Their use in a range of applications has been demonstrated, including gas uptake, molecular separations, and in catalysis. However, the targeted design and synthesis of new species for particular applications is challenging, particularly as the systems become more complex. High-throughput computation-only and experiment-only approaches have been developed to streamline the discovery process, although are still not widely implemented. Additionally, combined hybrid workflows can dramatically accelerate the discovery process and lead to the serendipitous discovery and rationalisation of new supramolecular assemblies that would not have been designed based on intuition alone. This Minireview focuses on the advances in high-throughput approaches that have been developed and applied in the discovery of supramolecular organic cages.
Age-related macular degeneration (AMD) is generally considered a disease of the macula. However, recent studies show peripheral retinal lesions are prevalent in patients with AMD, indicative of a disease process that is more widespread. Full-field electroretinography (ffERG) measures an electrical response, not only from the macula, but from the entire retina. We wanted to study the ffERG response in eyes with AMD.
We performed full-field electroretinography (RETI-port/scan 21, Roland, Berlin) in 13 patients with early AMD, 25 patients with late AMD and 24 individuals without vitreoretinal disease as a control group. Dawson-Trick-Litzkow fibre electrodes were used. Statistical analysis was performed and a p-value <0.05 was considered significant.
After adjusting for multiple comparisons, both the light-adapted 3.0 a-wave implicit time (p<0.001) and 30-Hertz flicker peak time (p=0.012) showed significant difference between patients with late AMD and individuals without vitreoretinal disease. There was a significant difference in the light-adapted 3.0 a-wave implicit time (p=0.011) between patients with early AMD and the control group, but the difference in 30Hz flicker peak time was not significant (p=0.256).
The difference in cone function measured by light-adapted 3.0 a-wave implicit time and 30-Hertz flicker peak time in early and late AMD when compared to healthy controls suggests a more diminished overall response when AMD has reached later stages.
The difference in cone function measured by light-adapted 3.0 a-wave implicit time and 30-Hertz flicker peak time in early and late AMD when compared to healthy controls suggests a more diminished overall response when AMD has reached later stages.
To assess correlation between results from both eyes of the same patient after implantation of intrastromal corneal ring segments (ICRS) and define whether they can be used together in clinical studies.
A review of medical records of 74 patients with keratoconus implanted with bilateral Ferrara ICRS at Centro de Oftalmología Barraquer from January 2005 until December 2014. Data were collected on uncorrected visual acuity, best-corrected visual acuity and subjective refractive values (sphere, cylinder and axis).
A total of 39 patients were male (53%), and 35 were female (47%). Mean age at the time of implantation was 32.5±10years. No major complications occurred. A significant correlation between the results from right and left eyes was found (p<0.0043), indicating that both eyes significantly resembled each other. No significant interaction in the magnitude of change between eye and surgery was observed under classic and mixed models.
Based on our data, whenever application is not possible under mixed-model analyses, we recommend the use of a first eye operated only, either right or left, in order to avoid bias and errors derived from autocorrelation and guarantee the independence of the registered observations.
Based on our data, whenever application is not possible under mixed-model analyses, we recommend the use of a first eye operated only, either right or left, in order to avoid bias and errors derived from autocorrelation and guarantee the independence of the registered observations.
To characterize pharyngocutaneous fistula (PCF) rates and functional outcomes following microvascular free tissue transfer (MVFTT) reconstruction of salvage total laryngectomy (STL) with a review of two different flap inset techniques and a review of the literature.
Retrospective review.
Review of the literature revealed 887 patients who underwent STL MVFTT from 14 references. Ninety-six STL MVFTTs were performed by the authors, with 36 (38%) patients undergoing multilayer fascial underlay (MLFU) closure and 60 (62%) a standard single layer closure (SLC). One (3%) PCF occurred in the MLFU group compared to 12 (20%) in the SLC cohort (P = .03). Postoperative gastrostomy (G)-tube dependence was lower following MLFU closure compared to SLC (25% vs. 57%, P < .01), whereas pharyngoesophageal stricture (PES) (28% vs. 38%), tracheoesophageal puncture (TEP) placement (42% vs. 42%), and TEP usage (87% vs. 88%) did not significantly differ (P > .05). Compared to pooled rates from the literature, patients who underwent a MLFU MVFTT inset technique demonstrated significantly lower PCF incidence (3% vs. 23%, P < .01) without significant differences in PES (28% vs 23%, P = .55), G-tube dependence (25% vs. 23%, P = .25), or TEP placement (42% vs. 59%, P = .09).
Despite MVFTT reconstruction after STL, G-tube dependence, PCF formation, and limitations of speaking rehabilitation (TEP) remain a significant issue. Modification of MVFTT inset may provide an opportunity to reduce PCF incidence without affecting other functional outcomes.
4 Laryngoscope, 131E875-E881, 2021.
4 Laryngoscope, 131E875-E881, 2021.
