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Spaceflight and terrestrial spaceflight analogs can alter immune phenotypes. Macrophages are important immune cells that bridge the innate and adaptive immune systems and participate in immunoregulatory processes of homeostasis. Furthermore, macrophages are critically involved in initiating immunity, defending against injury and infection, and are also involved in immune resolution and wound healing. Heterogeneous populations of macrophage-type cells reside in many tissues and cause a variety of tissue-specific effects through direct or indirect interactions with other physiological systems, including the nervous and endocrine systems. It is vital to understand how macrophages respond to the unique environment of space to safeguard crew members with appropriate countermeasures for future missions in low Earth orbit and beyond. This review highlights current literature on macrophage responses to spaceflight and spaceflight analogs., (© 2024. The Author(s).)

Differences in chromatin state inherited from the parental gametes influence the regulation of maternal and paternal alleles in offspring. This phenomenon, known as genomic imprinting, results in genes preferentially transcribed from one parental allele. While local epigenetic factors such as DNA methylation are known to be important for the establishment of imprinted gene expression, less is known about the mechanisms by which differentially methylated regions (DMRs) lead to differences in allelic expression across broad stretches of chromatin. Allele-specific higher-order chromatin structure has been observed at multiple imprinted loci, consistent with the observation of allelic binding of the chromatin-organizing factor CTCF at multiple DMRs. However, whether allelic chromatin structure impacts allelic gene expression is not known for most imprinted loci. Here we characterize the mechanisms underlying brain-specific imprinted expression of the Peg13-Kcnk9 locus, an imprinted region associated with intellectual disability. We performed region capture Hi-C on mouse brains from reciprocal hybrid crosses and found imprinted higher-order chromatin structure caused by the allelic binding of CTCF to the Peg13 DMR. Using an in vitro neuron differentiation system, we showed that imprinted chromatin structure precedes imprinted expression at the locus. Additionally, activation of a distal enhancer induced imprinted expression of Kcnk9 in an allelic chromatin structure-dependent manner. This work provides a high-resolution map of imprinted chromatin structure and demonstrates that chromatin state established in early development can promote imprinted expression upon differentiation., (© 2023 Loftus et al.; Published by Cold Spring Harbor Laboratory Press.)

The survival of patients undergoing hematopoietic cell transplantation (HCT) from unrelated donors for acute leukemia exhibits considerable variation, even after stringent genetic matching. To improve the donor selection process, we attempted to create an algorithm to quantify the likelihood of survival to 5 years after unrelated donor HCT for acute leukemia, based on the clinical characteristics of the donor selected. All standard clinical variables were included in the model, which also included average leukocyte telomere length of the donor based on its association with recipient survival in severe aplastic anemia, and links to multiple malignancies. We developed a multivariate classifier that assigned a Preferred or NotPreferred label to each prospective donor based on the survival of the recipient. In a previous analysis using a resampling method, recipients with donors labeled Preferred experienced clinically compelling better survival compared with those labeled NotPreferred by the test. However, in a pivotal validation study in an independent cohort of 522 patients, the overall survival of the Preferred and NotPreferred donor groups was not significantly different. Although machine learning approaches have successfully modeled other biological phenomena and have led to accurate predictive models, our attempt to predict HCT outcomes after unrelated donor transplantation was not successful., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Recent studies suggest improved survival in patients with severe aplastic anemia receiving hematopoietic cell transplant (HCT) from unrelated donors with longer telomeres. Here, we tested whether this effect is generalizable to patients with acute leukemia. From the Center for International Blood and Marrow Transplant Research (CIBMTR ® ) database, we identified 1097 patients who received 8/8 HLA-matched unrelated HCT for acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) between 2004 and 2012 with myeloablative conditioning, and had pre-HCT blood sample from the donor in CIBMTR repository. The median age at HCT for recipients was 40 years (range ≤1-68), and 32 years for donors (range = 18-61). We used qPCR for relative telomere length (RTL) measurement, and Cox proportional hazard models for statistical analyses. In a discovery cohort of 300 patients, longer donor RTL (>25th percentile) was associated with reduced risks of relapse (HR = 0.62, p = 0.05) and acute graft-versus-host disease II-IV (HR = 0.68, p = 0.05), and possibly with a higher probability of neutrophil engraftment (HR = 1.3, p = 0.06). However, these results did not replicate in two validation cohorts of 297 and 488 recipients. There was one exception; a higher probability of neutrophil engraftment was observed in one validation cohort (HR = 1.24, p = 0.05). In a combined analysis of the three cohorts, no statistically significant associations (all p > 0.1) were found between donor RTL and any outcomes.

This study presents the morphological and chemical modification of the cell structure of aerosolized Escherichia coli treated with a dielectric barrier discharge (DBD). Exposure to DBD results in severe oxidation of the bacteria, leading to the formation of hydroxyl groups and carbonyl groups and a significant reduction in amine functionalities and phosphate groups. Near edge x-ray absorption fine structure (NEXAFS) measurements confirm the presence of additional oxide bonds upon DBD treatment, suggesting oxidation of the outer layer of the cell wall. Electron microscopy images show that the bacteria undergo physical distortion to varying degrees, resulting in deformation of the bacterial structure. The electromagnetic field around the DBD coil causes severe damage to the cell structure, possibly resulting in leakage of vital cellular materials. The oxidation and chemical modification of the bacterial components are evident from the Fourier transform infrared spectroscopy and NEXAFS results. The bacterial reculture experiments confirm inactivation of airborne E. coli upon treating with DBD.

Glioblastoma presents a formidable clinical challenge because of its complex microenvironment. Here, we characterized tumor-associated foam cells (TAFs), a type of lipid droplet--loaded macrophage, in human glioblastoma. Through extensive analyses of patient tumors, together with in vitro and in vivo investigations, we found that TAFs exhibit distinct protumorigenic characteristics related to hypoxia, mesenchymal transition, angiogenesis, and impaired phagocytosis, and their presence correlates with worse outcomes for patients with glioma. We further demonstrated that TAF formation is facilitated by lipid scavenging from extracellular vesicles released by glioblastoma cells. We found that targeting key enzymes involved in lipid droplet formation, such as diacylglycerol O-acyltransferase or long- chain acyl- CoA synthetase, effectively disrupted TAF functionality. Together, these data highlight TAFs as a prominent immune cell population in glioblastoma and provide insights into their contribution to the tumor microenvironment. Disrupting lipid droplet formation to target TAFs may represent an avenue for future therapeutic development for glioblastoma. [ABSTRACT FROM AUTHOR]

Multiple cancers, including colorectal cancer (CRC), are more frequent and often more aggressive in individuals with obesity. Here, we showed that macrophages accumulated within tumors of patients with obesity and CRC and in obese CRC mice and that they promoted accelerated tumor growth. These changes were initiated by oleic acid accumulation and subsequent tumor cell–derived acid production and were driven by macrophage signaling through the acid-sensing receptor GPR65. We found a similar role for GPR65 in hepatocellular carcinoma (HCC) in obese mice. Tumors in patients with obesity and CRC or HCC also exhibited increased GPR65 expression, suggesting that the mechanism revealed here may contribute to tumor growth in a range of obesity-associated cancers and represent a potential therapeutic target. Editor's summary: Obesity is a risk factor for the development of several types of cancer, but how obesity contributes to tumorigenesis remains incompletely understood. Using a mouse model of colon cancer, Bagchi et al. found that tumor-associated macrophages (TAMs) accumulate and drive tumor growth in obese mice. Obesity-associated accumulation of oleic acid enhanced tumor acidity and suppressed TAM inflammatory responses. During obesity, TAMs up-regulated the acid-sensing receptor GPR65, which promoted growth of both colon and liver tumors. Together, these findings identify tumor acidity and GPR65-mediated TAM adaptations as drivers of tumor growth in obesity-associated cancers. —Claire Olingy [ABSTRACT FROM AUTHOR]

Communication has been limited to shortwave radio broadcasts, telephone connections to some communities, and some local TV stations. The Anik satellite, launched in 1972, will allow areas previously unserved to receive TV and telephone service. 2 maps.

A major scientific objective of cognitive neuroscience is to define cortico-cortical functional connections supporting cognitive functions. Here, we use an original approach combining frequency-tagging and direct electrical stimulation (DES) to test for bidirectional and cross-hemispheric category-specific modulations within the human cortical face network. A unique patient bilaterally implanted with depth electrodes in multiple face-selective cortical regions of the ventral occipito-temporal cortex (VOTC) was shown 70 s sequences of variable natural object images at a 6 Hz rate, objectively identifying deviant face-selective neural activity at 1.2 Hz (i.e., every five images). Concurrent electrical stimulation was separately applied for 10 seconds on four independently defined face-selective sites in the right and left VOTC. Upon stimulation, we observed reduced or even abolished face-selective neural activity locally and, most interestingly, at distant VOTC recording sites. Remote DES effects were found up to the anterior temporal lobe (ATL) in both forward and backward directions along the VOTC, as well as across the two hemispheres. This reduction was specific to face-selective neural activity, with the general 6 Hz visual response being mostly unaffected. Overall, these results shed light on the functional connectivity of the cortical face-selective network, supporting its non-hierarchical organization as well as bidirectional effective category-selective connections between posterior 'core' regions and the ATL. They also pave the way for widespread and systematic development of this approach to better understand the functional and effective connectivity of human brain networks. [ABSTRACT FROM AUTHOR]

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex–mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD. Editor's summary: Vision loss in the late stages of neovascular age-related macular degeneration (nvAMD) is mainly caused by the formation of new blood vessels in the choroid layer of the eye. Current therapeutic strategies to inhibit choroidal neovascularization (CNV) are only partially effective. Dong et al. used a CNV mouse model and tissue samples from patients with nvAMD to show that natural killer cells accumulated in the choroid layer of the diseased eye. Depletion of NK cells prevented NETosis, a process known to regulate vascular remodeling, and aggravated pathology in CNV mice. IL-2–mediated NK cell expansion curbed the development of CNV in mice, highlighting the protective effects of NK cells. —Daniela Neuhofer [ABSTRACT FROM AUTHOR]

Light interacts with every matter according to the entity's shape, size, and scattering properties. It employs the study of the intensity of scattered light as a function of angular distribution and conveys information regarding the morphology of the particles. The particles may range from nano to micrometer scale. We outline a method which uses static light scattering method to study the properties of antibacterial action of Black turmeric (Curcuma caesia) against bacterial cells, i.e., E. coli-ATCC 9637. The identification of Black turmeric (BT) with and without the inoculation of bacterial cells was performed by means of a He–Ne laser-based static light scattering (SLS) instrument which operated at incident probe wavelength of 632.8 nm. The samples displayed distinct angular behaviors for the d11 normalized scattering parameters of the Mueller matrix depending on the unaided BT sample and that inoculated with E. coli. The sample of Black turmeric (Curcuma caesia) was chosen for our subject of investigation to study its antibacterial properties by both biochemical and light scattering methods. BT is a perennial herb with a bluish–black rhizome. It is a miracle herb with the highest curcumin content and has high medicinal value. The antibacterial activity of Black turmeric on the growth of E. coli-ATCC 9637 was carried out by using a biochemical method, namely, Agar well diffusion method. BT inhibited bacterial growth on the agar plate, leading to a noticeable inhibition zone, which confirmed the antibacterial action of BT. Investigation of the same samples was done by using SLS technique. The antibacterial activity was subsequently validated by the light scattering signals. This was undertaken to ascertain the scattering profile of the BT after the inoculation of BT with E. coli. The scattered light intensity was obtained for different angles over an angular range of 10°–170°. The changes in morphology of E. coli cells as a result of antibacterial action were recorded by light scattering investigations. The scattering signals of unaided BT and BT inoculated with E. coli displayed a similar trend line of scattering profiles; however, both the profiles significantly varied in their intensities. The scattering profiles of the BT samples have revealed their uniqueness in the unaided and inoculated forms with the bacterial strain. The samples displayed distinct scattering behaviors for the d11 normalized scattering parameter of the Mueller matrix depending on the sizes of unaided BT and BT inoculated with E. coli. This ensured the use of a light scattering tool as an alternate means of studying the antimicrobial activity of BT without involving any invasive method. In this paper, we report the antimicrobial activity and health importance of BT by SLS for the first time. The experiments point out the possibility of achieving real-time identification of antibacterial action of BT against the selected microorganism by SLS. [ABSTRACT FROM AUTHOR]

The main objective of this work is to characterize the stress–strain relationship of cross-laminated timber (CLT) wall panels when loaded in compression and how different confinement mechanisms provide compression reinforcement for the CLT panels. CLT crushing tests were performed to define the behavior of CLT under compression up to the failure point, defined here as the strain at which the gross stress falls by 20% from the peak value. Testing included monotonic uniform compression experiments of five-ply CLT with specimens that were 0.457 m wide by 1.52 m long. The motion of the specimens perpendicular to loading direction was restrained at midlength to prevent buckling. Twelve specimens were tested, including six bare CLT specimens and six reinforced specimens of CLT—three with self-tapping screws while the other three with self-tapping screws and an additional U-shape steel plate at the bottom of the specimens. Various damage points were observed during the tests, including (1) point at the onset of damage (through visual observation and instrumental observation) (2) point of initiation of strength degradation, (3) point at which buckling occurs, (4) point at which 25.4 mm delamination was observed, and (5) failure point. Three axial compression stress–strain models were adopted, calibrated, and compared. Results indicate that a stress–strain model combining linear and cubic functions for the elastic and softening responses, respectively, captures well the CLT inelastic behavior under compression. [ABSTRACT FROM AUTHOR]