Spaceflight modulates gene expression in the whole blood of astronauts

Astronauts are exposed to a unique combination of stressors during spaceflight, which leads to alterations in their physiology and potentially increases their susceptibility to disease, including infectious diseases. To evaluate the potential impact of the spaceflight environment on the regulation of molecular pathways mediating cellular stress responses, we performed a first-of-its-kind pilot study to assess spaceflight-related gene-expression changes in the whole blood of astronauts. Using an array comprised of 234 well-characterized stress-response genes, we profiled transcriptomic changes in six astronauts (four men and two women) from blood preserved before and immediately following the spaceflight. Differentially regulated transcripts included those important for DNA repair, oxidative stress, and protein folding/degradation, including HSP90AB1, HSP27, GPX1, XRCC1, BAG-1, HHR23A, FAP48, and C-FOS. No gender-specific differences or relationship to number of missions flown was observed. This study provides a first assessment of transcriptomic changes occurring in the whole blood of astronauts in response to spaceflight

Entrepreneurship in American Higher Education

Presents recommendations by the Kauffman Panel on Entrepreneurship Curriculum in Higher Education on making entrepreneurship a key element in the curriculum, co-curriculum activities, and university management. Includes profiles of innovative programs

Biomimetic and Biophysical Approach to Profile Metastatic Cancer Cell Migration

Honors Research ScholarshipCancer metastasis is a complex process by which cells in a primary tumor acquire an aggressive phenotype, and travel to distant, secondary sites in the body. One aspect of cancer metastasis is cell migration toward the vascular system, called invasion. Multiple modalities of single cell invasion exist, including amoeboid migration and mesenchymal migration. Amoeboid migration is less well understood, and in particular, the forces involved in amoeboid migration have yet to be fully elucidated at a subcellular scale. Cellular traction force microscopy, or CTFM, is one method used to probe migration forces. However, this approach is largely limited to two dimensions, and is limited by the size of the pillars on the substrate. To address these limitations, we developed a system using microfluidics and DNA origami capable of real-time force measurement of cell migration on a subcellular scale with a 10 pN resolution. Microfluidic devices were made using soft lithography and replica molding in our laboratory. DNA origami were made using protocols developed by Michael Hudoba and Dr. Carlos Castro in the Nanoengineering and Biodesign Laboratory. The devices were imaged using TIRF microscopy to study dwell times of the sensors in the open and closed states, and the devices were analyzed with an AFM to determine that they are best suited for measuring shear forces. Further, the presence of streptavidin protein was found to have a significant effect on DOFS binding with a p-value less than 0.05. DOFS concentrations around 1 nM were found to provide the most coverage while minimizing structure aggregation. Thus, our microfluidic devices are able to be functionalized with DNA origami force sensors with a high degree of attachment. This platform is thus capable of measuring cell migration and adhesion forces, and future work should harness this system to create 3D maps of cell migration to gain insight into invasion.Institute for Materials ResearchSecond-Year Transformational Experience Program (STEP)A one-year embargo was granted for this item.Academic Major: Biomedical Engineerin

Hubungan Positif antara Ulkus Kaki Diabetik dengan Persentase Sel Bermarkah Cd4+ Pembawa Malondialdehid

Tingginya angka kejadian ulkus kaki diabetik (UKD) dan luka di kaki yangsulit sembuh memberi petunjuk kemungkinan ada proses kematian sel imun yangsangat banyak dan belum jelas mekanismenya secara molekuler pada jaringan UKD.Telah diteliti hubungan antara derajat UKD dengan persentase sel bermarkahCD4+ pembawa malondialdehid (MDA). Penelitian ini adalah penelitianobservasional dengan rancangan cross sectional analytic study yang dilakukan diRumah Sakit pemerintah dan swasta di Denpasar, Badung, Tabanan, dan Gianyar.Parameter yang diukur dari bahan darah adalah kadar gula darah memakai metodeenzimatik (heksokinase), dan dari bahan jaringan kaki, dihitung sel bermarkah CD4+pembawa MDA memakai metode imunohistokimia (reagen dari Biodesign danAbcam ). Dari 80 sampel UKD didapatkan 49 (61,2%) penderita laki-laki dan 31(38.8%) penderita wanita, berdasarkan tingkat keparahan UKD, sampel dipilah lagimenjadi: 29 (31,9%) derajat 2; 20 (21,9%) derajat 3; 13 (14,3%) derjat 4; dan18(19,8%) derajat 5, rata-rata persentase sel bermarkah CD4+MDA adalah 75,0 ±20,5 %, Didapatkan korelasi positif kuat antara persentase sel bermarkah CD4+pembawa malondialdehid dengan derajat UKD (r = 0,71; p < 0,01). Pada penelitianini membuktikan ada mekanisme kematian sel imun dan sekaligus menjawabpermasalahan bahwa pada penderita UKD mudah terkena infeksi dan sulit untukdisembuhkan, dengan dibuktikan bahwa ada korelasi positif kuat antara derajat UKDdengan persentase pembentukan MDA dari sel bermarkah CD4+, ini menyatakanbahwa semakin berat derajat UKD semakin banyak mengalami kematian sel imun.

Three-dimensional organotypic co-culture model of intestinal epithelial cells and macrophages to study Salmonella enterica colonization patterns

Three-dimensional models of human intestinal epithelium mimic the differentiated form and function of parental tissues often not exhibited by two-dimensional monolayers and respond to Salmonella in key ways that reflect in vivo infections. To further enhance the physiological relevance of three-dimensional models to more closely approximate in vivo intestinal microenvironments encountered by Salmonella, we developed and validated a novel three-dimensional co-culture infection model of colonic epithelial cells and macrophages using the NASA Rotating Wall Vessel bioreactor. First, U937 cells were activated upon collagen-coated scaffolds. HT-29 epithelial cells were then added and the three-dimensional model was cultured in the bioreactor until optimal differentiation was reached, as assessed by immunohistochemical profiling and bead uptake assays. The new co-culture model exhibited in vivo-like structural and phenotypic characteristics, including three-dimensional architecture, apical-basolateral polarity, well-formed tight/adherens junctions, mucin, multiple epithelial cell types, and functional macrophages. Phagocytic activity of macrophages was confirmed by uptake of inert, bacteria-sized beads. Contribution of macrophages to infection was assessed by colonization studies of Salmonella pathovars with different host adaptations and disease phenotypes (Typhimurium ST19 strain SL1344 and ST313 strain D23580; Typhi Ty2). In addition, Salmonella were cultured aerobically or microaerobically, recapitulating environments encountered prior to and during intestinal infection, respectively. All Salmonella strains exhibited decreased colonization in co-culture (HT-29-U937) relative to epithelial (HT-29) models, indicating antimicrobial function of macrophages. Interestingly, D23580 exhibited enhanced replication/survival in both models following invasion. Pathovar-specific differences in colonization and intracellular co-localization patterns were observed. These findings emphasize the power of incorporating a series of related three-dimensional models within a study to identify microenvironmental factors important for regulating infection

Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56Fe or sham (n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56Fe exposure resulted in 65-78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values

Interplay of space radiation and microgravity in DNA damage and DNA damage response

In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the DNA integrity of living organisms. Specifically, space radiation can cause damage to DNA directly, through the interaction of charged particles with the DNA molecules themselves, or indirectly through the production of free radicals. Although organisms have evolved strategies on Earth to confront such damage, space environmental conditions, especially microgravity, can impact DNA repair resulting in accumulation of severe DNA lesions. Ultimately these lesions, namely double strand breaks, chromosome aberrations, micronucleus formation, or mutations, can increase the risk for adverse health effects, such as cancer. How spaceflight factors affect DNA damage and the DNA damage response has been investigated since the early days of the human space program. Over the years, these experiments have been conducted either in space or using ground-based analogs. This review summarizes the evidence for DNA damage induction by space radiation and/or microgravity as well as spaceflight-related impacts on the DNA damage response. The review also discusses the conflicting results from studies aimed at addressing the question of potential synergies between microgravity and radiation with regard to DNA damage and cellular repair processes. We conclude that further experiments need to be performed in the true space environment in order to address this critical question.publishe

Algae Biofuel Triacylglyceride Transesterification Optimization

Algae biofuels may hold the key to solving the problem of fossil fuel consumption by being comparable in content, renewable, and carbon-neutral. Many biofuel researchers and corporations have undertaken to increase the production rate or capacity of triacylglycerides (TAG), the fat precursor to biodiesel fuel produced by algae, in algae cultures and published articles documenting their findings. This research is devoted to evaluating the effect of water that may be present in samples on the conversion efficiency of TAG into fatty acid methyl esters (FAME), commonly referred to as biodiesel. Therefore, that efficiency was studied to find the water content which optimizes the yield and determine if further drying of algae was necessary as an additional step in sample preparation. The results showed that the water content typically present in lyophilized algae samples is not sufficient to appreciably inhibit the reaction efficiency and necessitate extensive drying as a sample preparation step prior to transesterification

Grow-Made Textiles

This paper explores the emergent notion of the ‘grow-made’ by evaluating current work produced for Mycelium Textiles, a design research project that investigates the potential for co-making and co-designing with mycelium. Inscribed within an exploration of alternative sustainable fabrication models, this design research investigates expanded design toolkits and methods for co-making with living systems. Augmented by husbandry techniques, traditional and contemporary textile craft can inform the cultivation of living mycelium for patterning and surface embellishments. Whilst textiles are profoundly anchored in the history of humanity as material and cultural artifacts, they have so far allowed us to navigate both the hand-made and the man-made paradigms. With emergent practices in biodesign, the notion of the ‘grow-made’ is now also possible