Modeling premalignant lung squamous carcinoma via gene expression changes associated with EP300 knockout

Lung cancer is the third most common type of cancer and the leading cause of cancer death, in both men and women, and prognosis for lung carcinoma remains poor due to late diagnosis. While lung squamous cell carcinoma (LUSC) makes up 20-30% of all lung cancer cases, identification of genetic signatures and successful targeted therapies remain limited. An ongoing effort is being made to create an in vitro system for modeling the early stages of lung squamous carcinoma and premalignancy, which will ultimately serve as a model for drug discovery. A previous effort performed whole exome and targeted DNA sequencing to reveal the somatic mutations in endobronchial biopsies that harbored lung squamous premalignant histology. EP300 was identified as a candidate gene which may act as a driver for carcinogenesis, but remains understudied when compared to prominent oncogenic driver genes such TP53, NOTCH1, or NFE2L2 in LUSC. The p300 protein is a histone acetyltransferase that regulates gene expression by means of chromatin remodeling and has been implicated in various diseases, including cancer. My objective as part of my thesis was to first generate stable EP300 knockout (KO) clones from the NL20 bronchial epithelial cell line utilizing the CRISPR/Cas gene editing system. Using the NL20 clones and EP300 KO clones in the HBEC-3KT cell line generated in a previous effort, I then validated the knockouts at the DNA, RNA, and protein levels. Literature review was also conducted to identify possible cellular pathways that EP300 participates in and validate its role in those pathways by observing changes in downstream protein targets. Finally, I generated RNA sequencing data from the functionally validated clones to identify differentially expressed genes and cellular pathways perturbed by EP300 knockout. Through these efforts, I developed sets of gene signatures unique to each cell line and found that EP300 is associated with bronchial carcinogenesis progression and likely functions as an oncogene in LUSC

Wind power in China - Dream or reality?

After tremendous growth of wind power generation capacity in recent years, China now has 44.7 GW of wind-derived power. Despite the recent growth rates and promises of a bright future, two important issues - the capability of the grid infrastructure and the availability of backup systems - must be critically discussed and tackled in the medium term. The study shows that only a relatively small share of investment goes towards improving and extending the electricity infrastructure which is a precondition for transmitting clean wind energy to the end users. In addition, the backup systems are either geographically too remote from the potential wind power sites or currently financially infeasible. Finally, the introduction of wind power to the coal-dominated energy production system is not problem-free. Frequent ramp ups and downs of coal-fired plants lead to lower energy efficiency and higher emissions, which are likely to negate some of the emission savings from wind power. The current power system is heavily reliant on independently acting but state-owned energy companies optimizing their part of the system, and this is partly incompatible with building a robust system supporting renewable energy technologies. Hence, strategic, top-down co-ordination and incentives to improve the overall electricity infrastructure is recommended

Buildout and integration of an automated high-throughput CLIA laboratory for SARS-CoV-2 testing on a large urban campus

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.Boston UniversityPublished versio

Simultaneous Reduction of Co³⁺ and Mn⁴⁺ in P2-Na_2/3Co_2/3Mn_1/3O₂ As Evidenced by X‑ray Absorption Spectroscopy during Electrochemical Sodium Intercalation

Sodium intercalation in P2-Na_2/3Co_2/3Mn_1/3O₂ (obtained by a coprecipitation method) was investigated by ex situ and in situ X-ray absorption spectroscopy. The electronic transitions at the O K-edge and the charge compensation mechanism, during the sodium intercalation process, were elucidated by combining Density Function Theory (DFT) calculations and X-ray absorption spectroscopy (XAS) data. The pre-edge of the oxygen K-edge moves to higher energy while the integrated intensity dramatically decreases, indicating that the population of holes in O 2p states is reduced with increasing numbers of sodium ions. From the K-edge and L-edge observations, the oxidation states of pristine Co and Mn were determined to be +III and +IV, respectively. The absorption energy shifts to lower positions during the discharging process for both the Co and the Mn edges, suggesting that the redox pairs, that is, Co³⁺/Co²⁺ and Mn⁴⁺/Mn³⁺, are both involved in the reaction

Complement C3a and C5a receptors promote GVHD by suppressing mitophagy in recipient dendritic cells

Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT). DCs play critical roles in GVHD induction. Modulating autophagy represents a promising therapeutic strategy for the treatment of immunological diseases. Complement receptors C3aR/C5aR expressed on DCs regulate immune responses by translating extracellular signals into intracellular activity. In the current study, we found that C3aR/C5aR deficiency enhanced ceramide-dependent lethal mitophagy (CDLM) in DCs. Cotransfer of host-type C3aR-/-/C5aR-/- DCs in the recipients significantly improved GVHD outcome after allogeneic HCT, primarily through enhancing CDLM in DCs. C3aR/C5aR deficiency in the host hematopoietic compartment significantly reduced GVHD severity via impairing Th1 differentiation and donor T cell glycolytic activity while enhancing Treg generation. Prophylactic treatment with C3aR/C5aR antagonists effectively alleviated GVHD while maintaining the graft-versus-leukemia (GVL) effect. Altogether, we demonstrate that inhibiting C3aR/C5aR induces lethal mitophagy in DCs, which represents a potential therapeutic approach to control GVHD while preserving the GVL effect

Impact of the synthesis parameters on the microstructure of nano-structured LTO prepared by glycothermal routes and 7Li NMR structural investigations

The efficient materials for Li-ion battery electrodes require suitable composition, high-crystallinity and appropriate structuration. The last one is important to assure an efficient exchange of Li ions between the anode and electrolyte, thus enhancing the kinetics of electrochemical reactions. Therefore, the synthesis of well-crystallized nano-sized electrode materials exhibiting high surface area is of great interest. Herein, we explore the influence of the glycothermal synthesis variations on the structure and porosity of Li4Ti5O12. The utilized precursors and their concentration have a minor influence on crystallites size, but they could be used to control the porosity of assembled particles. The prepared Li-ion battery anode could be charged at low and high rate reaching the theoretical capacity of Li4Ti5O12. The material retains its peculiar porous structuration even after 1000 cycles at charging/discharging rate of 50C which contributes to the lack of capacity fading. Additionally, 7Li NMR is performed on one of synthesized nano-structured Li4Ti5O12 and compared with commercially available nanosized Li4Ti5O12 to understand the excellent electrochemical performance. Open image in new window Glycothermal synthesis of lithium titanate, in 1,4-butanediol leads to crystalline NPs of 4-5 nm assembled into highly porous microstructures. Such structuration assures well-developed contact area between the electrode and an electrolyte in Li-ion batteries, which facilitates exchange of Li-ions. Therefore, the material shows excellent electrochemical performances. LTO characterized by different nanostructuration is obtained by varying the synthesis conditions (precursors type and concentration, temperature and co-solvent). , Highlights Pure nanostructure Li4Ti5O12 was synthesized in varying glycothermal conditions using 1,4-butanediol as the solvent. Simple adjustment of precursors and their concentration tuned the microstructure of the material without affecting the size of crystallites which oscillated around 4 nm. Nano-scaling and proper microstructuration is an effective way to improve kinetics of electrochemical reactions due to the efficient exchange of Li ions between electrodes and electrolytes. 7Li NMR was performed on synthesized material and commercial one in order to understand the peculiar electrochemical properties of the material