The nexus between agroforestry landscapes and dietary diversity: insights from Myanmar’s Central Dry Zone

Gefördert durch den Publikationsfonds der Universität Kasse

Structural Basis for Polθ-Helicase DNA Binding and Microhomology-Mediated End-Joining

DNA double-strand breaks (DSBs) present a critical threat to genomic integrity, often precipitating genomic instability and oncogenesis. Repair of DSBs predominantly occurs through homologous recombination (HR) and non-homologous end joining (NHEJ). In HR-deficient cells, DNA polymerase theta (Polθ) becomes critical for DSB repair via microhomology-mediated end joining (MMEJ), also termed theta-mediated end joining (TMEJ). Thus, Polθ is synthetically lethal with BRCA1/2 and other HR factors, underscoring its potential as a therapeutic target in HR-deficient cancers. However, the molecular mechanisms governing Polθ-mediated MMEJ remain poorly understood. Here we present a series of cryo-electron microscopy structures of the Polθ helicase domain (Polθ-hel) in complex with DNA containing different 3\u27-ssDNA overhangs. The structures reveal the sequential conformations adopted by Polθ-hel during the critical phases of DNA binding, microhomology searching, and microhomology annealing. The stepwise conformational changes within the Polθ-hel subdomains and its functional dimeric state are pivotal for aligning the 3\u27-ssDNA overhangs, facilitating the microhomology search and subsequent annealing necessary for DSB repair via MMEJ. Our findings illustrate the essential molecular switches within Polθ-hel that orchestrate the MMEJ process in DSB repair, laying the groundwork for the development of targeted therapies against the Polθ-hel

Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses

available in PMC 2011 September 1Vaccines based on recombinant proteins avoid the toxicity and antivector immunity associated with live vaccine (for example, viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8+ T-cell responses comparable to those for live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. Interbilayer-crosslinked vesicles stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying vesicles form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to those for the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for therapeutic protein delivery.Ragon Institute of MGH, MIT and HarvardBill & Melinda Gates FoundationUnited States. Dept. of Defense (contract W911NF-07-D-0004)National Institutes of Health (U.S.) (P41RR002250)National Institutes of Health (U.S.) (RC2GM092599

Enhancing Oral Delivery of Plant-Derived Vesicles for Colitis

Plant-derived vesicles (PDVs) are attractive for therapeutic applications, including as potential nanocarriers. However, a concern with oral delivery of PDVs is whether they would remain intact in the gastrointestinal tract. We found that 82% of cabbage PDVs were destroyed under conditions mimicking the upper digestive tract. To overcome this limitation, we developed a delivery method whereby lyophilized Eudragit S100-coated cabbage PDVs were packaged into a capsule (Cap-cPDVs). Lyophilization and suspension of PDVs did not have an appreciable impact on PDV structure, number, or therapeutic effect. Additionally, packaging the lyophilized Eudragit S100-coated PDVs into capsules allowed them to pass through the upper gastrointestinal tract for delivery into the colon better than did suspension of PDVs in phosphate-buffered saline. Cap-cPDVs showed robust therapeutic effect in a dextran sulfate sodium-induced colitis mouse model. These findings could have broad implications for the use of PDVs as orally delivered nanocarriers of natural therapeutic plant compounds or other therapeutics

A nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID‐19

AimsTo investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission.Materials and methodsRetrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression.ResultsIn total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment.ConclusionsHospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA

Assessment of level and differences among Vicia faba L. genotypes for their degree of cross-fertilization and for their paternal mating success, based on a polycross field experiment.

Faba bean (Vicia faba L) is an important food legume all over the world since it is useful for both human consumption and animal feeding and can be adaptable to many regions. A higher degree of cross fertilization is leading to higher heterozygosity and hence to a higher amount of heterosis and that kind of genotypes might have a higher yield stability. Therefore, hybrid breeding and synthetic breeding are major faba bean breeding categories for yield and yield stability now a day. In this research, we employed a new allele-specific SNP based on a PCR genotyping system developed at KBiosciences. A “complete neighbor balance” design (Morgan, 1987) was used for sowing the polycross with two factors, mother plant or pollen acceptor and father plant or pollen distributor for polycross. To analyze the degree of cross-fertilization and paternal mating success, eight different genotypes with the contribution of six different lines and two F1s were used for a polycross. The six inbred lines had achieved the higher degree of cross-fertilization and the lower paternal mating success. The higher paternal mating success with lower degree of cross fertilization was observed in F1 genotypes. A negative correlation of these two variables and no correlation between paternal mating success and neighborhood proximity of father genotypes were observed in this polycross. A higher negative correlation between degree of cross-fertilization and paternal mating success was occurred at the more heterozygous genotypes

Location tracking using IMU and UWB

This report includes research, development and testing of indoor positioning system using Inertial Measurement Unit (IMU) and Ultra-wideband (UWB). UWB can receive its location from fixed UWB anchors placed in the environment. However, it performs poorly in NLOS condition. On the other hand, IMU can measure its location without relying on external sensors. The drawback is that IMU sensors are prone to noises and biases, and they are not reliable for long-term use. Therefore, localization systems using IMU and UWB have become very popular. In this report, Mahony Filter is applied to IMU outputs to get the heading of the system. Calibrated accelerometer data from IMU is integrated twice to get displacement measurement, which is fused with position data from UWB using Extended Kalman Filter. Fused position data is then transferred to back-end computer via User Datagram Protocol (UDP) for data recording and visualization. The accuracy of positioning is tested by varying the update rate of UWB from 1 Hz to 10 Hz, and changing the way the device is carried during the tests. It was found that the system with UWB alone is accurate to minimum ±20cm when it is within the UWB anchor cluster. If it is away from the cluster more than 2m, the tag does not receive the position from anchors, and the accuracy drops drastically. However, positioning system using IMU and UWB can maintain the position error at ± 40-80cm at 10Hz. At 1Hz, the latency in getting estimate position increases due to UWB signal path obstruction, and accuracy drops to ± 1.5 m. More improvements are to be done to IMU to reduce the drift without affecting the double integral results when UWB cannot give its position.Bachelor of Engineering (Electrical and Electronic Engineering

Wind Load Design of a Triangular Shaped Building Using finite Element Analysis

This major qualifying project investigates wind loading and structural design of a triangular-shaped 5-story building in San Francisco. Finite Element Method (FEM) software, ANSYS 19.1 is adopted to create a virtual wind tunnel test in accordance with ASCE 7-16 and ASCE 49-12. This project focuses on simulating two types of wind-tunnel test, Rigid Pressure Model Technique and High-Frequency Base-Balance (Time-Domain Analysis) Technique. Of those two techniques, the final structural design in based on the Rigid Pressure Model Technique

Scope 3 Greenhouse Gas Emission

This study determined an initial estimate of the Scope 3 greenhouse gas emissions caused by the travel of WPI faculty, staff, and students. The collection of data on transportation-related Scope 3 carbon emissions of Worcester Polytechnic Institute’s students, faculty, and staff, in order to calculate WPI’s carbon footprint, is important to making the university sustainable. We estimated and recorded WPI’s Scope 3 emissions for the first time in WPI’s sustainability projects.Using the results of this paper which is 26,500 tonnes of CO2 and comparing it with other emission sources, WPI will be able to set reduction goals on its greenhouse gas emissions and become a more sustainable institution

The nexus between agroforestry landscapes and dietary diversity: insights from Myanmar’s Central Dry Zone

Abstract Context Agroforestry plays a crucial role in increasing tree-based food production for healthy and sustainable food systems. However, the potential of farm trees to contribute to farmers' dietary diversity along multiple paths remains under-researched. Objectives This study aimed to fill existing knowledge gaps by investigating the role of native trees (toddy palm, jujube, and thanakha) in increasing dietary diversity within dryland agroforestry systems. Methods We conducted face-to-face qualitative interviews with 47 farmers from the Central Dry Zone of Myanmar (i) to appraise the multiple roles of native tree species in agroforestry landscapes, (ii) to unravel their contributions to four dietary diversity paths, and (iii) to elucidate factors driving the stability of or changes in these pathways. Results We found that native trees provide food directly and through interaction with crop production and livestock farming, leading to dietary diversification. Agroforestry byproducts are used as fuel and manure, and income from trading agroforestry products provides access to additional food sources. Farmers emphasized the ease of tree management and the roles they play in providing passive income and enhancing resilience to climate stressors as stabilizing factors. However, social-cultural changes, lack of extension services, the unsustainable use of tree products, and market instability were identified as destabilizing factors. Conclusions This study advances knowledge about the holistic contribution of agroforestry landscapes to dietary diversity by presenting evidence from dryland agroforestry systems in Myanmar. Our findings suggest a need for enhanced understanding of social and ecological changes and cultural factors in agroforestry landscapes to maintain the role of native trees in strengthening dietary diversity