220 research outputs found
Detection of horizontal transfer of individual genes by anomalous oligomer frequencies
Background
Understanding the history of life requires that we understand the transfer of genetic material across phylogenetic boundaries. Detecting genes that were acquired by means other than vertical descent is a basic step in that process. Detection by discordant phylogenies is computationally expensive and not always definitive. Many have used easily computed compositional features as an alternative procedure. However, different compositional methods produce different predictions, and the effectiveness of any method is not well established. Results
The ability of octamer frequency comparisons to detect genes artificially seeded in cyanobacterial genomes was markedly increased by using as a training set those genes that are highly conserved over all bacteria. Using a subset of octamer frequencies in such tests also increased effectiveness, but this depended on the specific target genome and the source of the contaminating genes. The presence of high frequency octamers and the GC content of the contaminating genes were important considerations. A method comprising best practices from these tests was devised, the Core Gene Similarity (CGS) method, and it performed better than simple octamer frequency analysis, codon bias, or GC contrasts in detecting seeded genes or naturally occurring transposons. From a comparison of predictions with phylogenetic trees, it appears that the effectiveness of the method is confined to horizontal transfer events that have occurred recently in evolutionary time. Conclusions
The CGS method may be an improvement over existing surrogate methods to detect genes of foreign origin
Fatty Acid Synthase, a Novel Target for the Treatment of Drug Resistant Breast Cancers
Indiana University-Purdue University Indianapolis (IUPUI)Many cancers, including breast cancer, often develop resistance to chemotherapeutic drugs over a course of treatment. Many factors, including ABC transporter-mediated drug efflux, have been shown to play a role in acquired drug resistance. Fatty acid synthase (FASN), the key enzyme of lipid synthesis pathway, was found to be over-produced in an Adiamycin resistant breast cancer cell line MCF7/AdrVp3000, compared to its parental drug sensitive MCF7 cell line. Inhibition of FASN expression increased the drug sensitivity in breast cancer cells (MCF7/AdrVp3000 and MDA-MB-468), but not in the normal breast epithelia cell line MCF10A1. Enforced overexpression of FASN in MCF7 breast cancer cells decreased its drug sensitivity. These results indicated that FASN overexpression can induce drug resistance in breast cancers.
Ectopic overexpression of FASN in MCF7 cells did not affect cell membrane permeability, transporter activity, nor did it affect cell proliferation rate. However, FASN overexpression protects cancer cells from drug-induced apoptosis by decreasing caspase-8 activation. In FASN over-expressing MCF7 cells, I discovered the positive feedback relationship between FASN and activation of Akt as previously reported. However, activation of Akt did not mediate FASN-induced drug resistance.
Together with the findings that FASN expression associates with poor prognosis in several types of cancers, my investigations suggest that FASN overexpression is a novel mechanism of drug resistance in breast cancer chemotherapy. Inhibitors of FASN can be used as sensitizing agents in breast cancer chemotherapy
Maintenance of Circulation Anomalies during the 1988 Drought and 1993 Floods over the United States
The large-scale circulation anomalies associated with the 1988 drought and the 1993 floods are investigated with the National Centers for Environmental Prediction Reanalysis data and a linear stationary wave model. The transient vorticity and thermal forcings are explicitly calculated and the diabatic heating is derived as a residual in the thermodynamic energy equation. Using the April–June (AMJ) data for 1988, and June–August (JJA) data for 1993, the linear stationary wave model is able to reproduce the main features of the geopotential height anomaly for the two seasons when all forcings are included. This provides a basis for further investigation of stationary wave response to different forcing mechanisms using the linear model. Within the linear model framework, the linear model responses to different forcings are examined separately. The results indicate that the 1988 anomaly over the United States is a result of both the diabatic heating and the transient vorticity and thermal forcings. The large anticyclonic anomalies over the North Pacific and Canada are forced mainly by the diabatic heating. The 1993 anomaly, however, is dominated by the response to transient vorticity forcing. By further separating the linear model responses to regional diabatic heating anomalies in 1988, the results indicate that the western North Pacific heating is entirely responsible for the anticyclonic center over the North Pacific, which causes the northward shift and intensification of the Pacific jet stream. The eastern North Pacific heating/cooling couplet is the most important for maintaining the North American circulation anomaly. The tropical eastern Pacific cooling/heating anomalies associated with the La Nina condition have negligible influence on the North American circulation. In 1993, the strong diabatic heating over the North American continent largely compensates the effect of the cooling over the North Pacific. The dynamics of the AMJ and JJA climate is further explored by calculating its Green’s function for both diabatic heating and vorticity forcing. The results again show negligible influence from the equatorial Pacific. The most effective location for diabatic heating to generate a North American circulation anomaly is along the west coast of North America, where the zonal wind is relatively weak. There is little sensitivity in the Green’s function solution to the different basic states
Leptin signaling and its central role in energy homeostasis
Leptin plays a critical role in regulating appetite, energy expenditure and body weight, making it a key factor in maintaining a healthy balance. Despite numerous efforts to develop therapeutic interventions targeting leptin signaling, their effectiveness has been limited, underscoring the importance of gaining a better understanding of the mechanisms through which leptin exerts its functions. While the hypothalamus is widely recognized as the primary site responsible for the appetite-suppressing and weight-reducing effects of leptin, other brain regions have also been increasingly investigated for their involvement in mediating leptin’s action. In this review, we summarize leptin signaling pathways and the neural networks that mediate the effects of leptin, with a specific emphasis on energy homeostasis
Impact of high standard farmland construction policy on chemical fertilizer reduction: a case study of China
Promoting chemical fertilizer (CF) reduction is an inevitable requirement for achieving high-quality agricultural development, and high standard farmland construction (HSFC) provides a new path for promoting CF reduction. Takes the implementation of HSFC policy as the starting point, this paper uses the provincial panel data of China from 2005 to 2017 to analyze the impact of HSFC policy on CF reduction and its mechanism of action by using the continuous difference-in-difference (DID) model and mediating model. The baseline regression results show that implementing the HSFC policy has reduced the amount of CF per unit area by 8.9 % on average, which has a significant policy effect. The mechanism analysis shows that the HSFC policy can promote CF reduction by improving the agricultural mechanization level and expanding the scale of operations in agriculture. The results of heterogeneity analysis show that in the natural geographical location dimension, the effect of HSFC policy on CF reduction in the eastern and central regions is more obvious; In the dimension of functional areas of grain production, the impact of HSFC policy on CF reduction in major grain-producing regions is more obvious. Therefore, in the future, it is necessary to continue to vigorously promote the HSFC and give full play to the effective role of HSFC in CF reduction. China should vigorously promote the development level of agricultural mechanization and the large-scale operation of agriculture and further strengthen the HSFC in the western region and non-major grain-producing areas
Biomineralization stimulated peri-titanium implants prepared by selective laser melting
AbstractTitanium implants prepared by selective laser melting (SLM), a method of additive manufacturing, were subjected to implantation in beagle dogs for two and four weeks. Argon ion beam-polished cross sections of the implants after in vivo tests were characterized by scanning electron microscope (SEM) to evaluate the bone–implant interface and the early peri-implant biomineralization with sufficiently improved resolution. Two bone mineralization mechanisms were disclosed. As early as two weeks after implantation, a layer of new bone was found to form directly on the implant surface and bone in-growth was also observed. Osseointegration was found to establish partly at the tip of the implants. After healing for four weeks it was found that osseointegration was established around the entire tip of the implants, whereas only partly at the third thread region of the implants. The experimental evidences observed reveal that an inherent highly porous surface of the titanium implants generated by selective laser melting is favorable for new bone apposition
Dual-attention Focused Module for Weakly Supervised Object Localization
The research on recognizing the most discriminative regions provides
referential information for weakly supervised object localization with only
image-level annotations. However, the most discriminative regions usually
conceal the other parts of the object, thereby impeding entire object
recognition and localization. To tackle this problem, the Dual-attention
Focused Module (DFM) is proposed to enhance object localization performance.
Specifically, we present a dual attention module for information fusion,
consisting of a position branch and a channel one. In each branch, the input
feature map is deduced into an enhancement map and a mask map, thereby
highlighting the most discriminative parts or hiding them. For the position
mask map, we introduce a focused matrix to enhance it, which utilizes the
principle that the pixels of an object are continuous. Between these two
branches, the enhancement map is integrated with the mask map, aiming at
partially compensating the lost information and diversifies the features. With
the dual-attention module and focused matrix, the entire object region could be
precisely recognized with implicit information. We demonstrate outperforming
results of DFM in experiments. In particular, DFM achieves state-of-the-art
performance in localization accuracy in ILSVRC 2016 and CUB-200-2011.Comment: 8 pages, 6 figures and 4 table
Construction of Trust Relationship between Doctors and Patients: A Social Psychological Analysis
Doctor-patient trust is the basis of harmonious doctor-patient relationship. Social psychology plays a unique role in interpreting the connotation and construction of doctor-patient trust relationship. From the two levels of doctor-patient interpersonal trust and intergroup trust, this paper summarizes the relevant theoretical viewpoints of social psychology on the construction of doctor-patient trust relationship, and analyzes the key factors affecting doctor-patient interpersonal trust and intergroup trust. On this basis, this paper puts forward the construction path of doctor-patient trust of “interpersonal interaction-emotional communication-interpersonal trust” and “intergroup interaction-social knowledge-intergroup trust”, reveals the interaction mechanism of interpersonal trust and intergroup trust and the circular feedback mechanism between them to promote the formation of doctor-patient trust relationship, and establishes a social psychology model of the formation mechanism of doctor-patient trust relationship
Alteration of Metabolite Profiling by Cold Atmospheric Plasma Treatment in Human Myeloma Cells
BACKGROUND: Despite new progress of chemotherapy in multiple myeloma (MM) clinical treatment, MM is still a refractory disease and new technology is needed to improve the outcomes and prolong the survival. Cold atmospheric plasma is a rapidly developed technology in recent years, which has been widely applied in biomedicine. Although plasma could efficiently inactivate various tumor cells, the effects of plasma on tumor cell metabolism have not been studied yet.
METHODS: In this study, we investigated the metabolite profiling of He plasma treatment on myeloma tumor cells by gas-chromatography time-of-flight (GC-TOF) mass-spectrometry. Meanwhile, by bioinformatic analysis such as GO and KEGG analysis we try to figure out the metabolism pathway that was significantly affected by gas plasma treatment.
RESULTS: By GC-TOF mass-spectrometry, 573 signals were detected and evaluated using PCA and OPLS-DA. By KEGG analysis we listed all the differential metabolites and further classified into different metabolic pathways. The results showed that beta-alanine metabolism pathway was the most significant change after He gas plasma treatment in myeloma cells. Besides, propanoate metabolism and linoleic acid metabolism should also be concerned during gas plasma treatment of cancer cells.
CONCLUSIONS: Cold atmospheric plasma treatment could significantly alter the metabolite profiling of myeloma tumor cells, among which, the beta-alanine metabolism pathway is the most susceptible to He gas plasma treatment. © The Author(s) 2018
Mechanism of Virus Inactivation by Cold Atmospheric-Pressure Plasma and Plasma-Activated Water
ABSTRACT Viruses cause serious pathogenic contamination that severely affects the environment and human health. Cold atmospheric-pressure plasma efficiently inactivates pathogenic bacteria; however, the mechanism of virus inactivation by plasma is not fully understood. In this study, surface plasma in argon mixed with 1% air and plasma-activated water was used to treat water containing bacteriophages. Both agents efficiently inactivated bacteriophages T4, Ď•174, and MS2 in a time-dependent manner. Prolonged storage had marginal effects on the antiviral activity of plasma-activated water. DNA and protein analysis revealed that the reactive species generated by plasma damaged both nucleic acids and proteins, consistent with the morphological examination showing that plasma treatment caused the aggregation of bacteriophages. The inactivation of bacteriophages was alleviated by the singlet oxygen scavengers, demonstrating that singlet oxygen played a primary role in this process. Our findings provide a potentially effective disinfecting strategy to combat the environmental viruses using cold atmospheric-pressure plasma and plasma-activated water. IMPORTANCE Contamination with pathogenic and infectious viruses severely threatens human health and animal husbandry. Current methods for disinfection have different disadvantages, such as inconvenience and contamination of disinfection by-products (e.g., chlorine disinfection). In this study, atmospheric surface plasma in argon mixed with air and plasma-activated water was found to efficiently inactivate bacteriophages, and plasma-activated water still had strong antiviral activity after prolonged storage. Furthermore, it was shown that bacteriophage inactivation was associated with damage to nucleic acids and proteins by singlet oxygen. An understanding of the biological effects of plasma-based treatment is useful to inform the development of plasma into a novel disinfecting strategy with convenience and no by-product
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