Cultural Survival Research Articles

Enhancing Reproductive Performance of Freshwater Finfish Species through Dietary Lipids.

Dietary lipid manipulation in the feed of commercially cultured finfish is used not only to improve production and culture but also to enhance their reproductive performances. The inclusion of lipid in broodstock diet positively affects growth, immunological responses, gonadogenesis, and larval survival. In this review, existing literature on the importance of freshwater finfish species to aquaculture and the inclusion of dietary lipid compounds in freshwater fish feed to accelerate the reproduction rate is being summarized and discussed. Although lipid compounds have been confirmed to improve reproductive performance, only a few members of the most economically important species have reaped benefits from quantitative and qualitative lipid studies. There is a knowledge gap on the effective inclusion and utilization of dietary lipids on gonad maturation, fecundity, fertilization, egg morphology, hatching rate, and consequently, larval quality contributing to the survival and good performance of freshwater fish culture. This review provides a baseline for potential future research for optimizing dietary lipid inclusion in freshwater broodstock diets.

Evaluation of Unrestricted Somatic Stem Cells Therapy in an Ex-Vivo and in-Vivo Acquired Severe Aplastic Anemia Model

Background: In acquired severe aplastic anemia (aSAA), oligoclonal expansion of dysregulated CD8+ cytotoxic T cells, abnormal function of CD4+ T helper cells, along with elevated production of IFN-γ and TNF-α have been associated with the apoptosis of hematopoietic stem and progenitor cells (HSPC) (Young, N Engl J Med, 2018). Liao and Cairo et al (Cell Transplantation, 2014) have demonstrated that cord blood-derived unrestricted somatic stem cells (USSCs) could significantly reverse the abnormal/inverted ratio of CD4:CD8 T cells, increases the number of FOXP3A positive Treg cells and decrease the level of IFN-γ in an animal model of recessive dystrophic epidermolysis bullosa (RDEB). Alternative therapies are in great need for patients with aSAA as immunosuppressive therapy (IST) overall responses are sub-optimal. Objectives:To determine the effect of USSCs on HSPC survival, differentiation and phosphorylation pathways in an ex-vivo culture of aSAA with human CD34+ cells.To determine the effect of USSCs administration on blood cell count recovery, bone marrow (BM) cellularity and survival in an in-vivo inflammatory cytokine mediated mice model of aSAA. Design/Methods: Human HSPC were cultured with SCF, FLT3 and human TPO. HSPCs alone, with and without IFN-γ and TNF-α served as controls. USSCs (transwell and direct) were added to the culture. HSPC were harvested and assayed for their survival at day 7 and 14. Annexin-V+/PI+ were referred to as late apoptotic cells. Each experimental condition was set up in triplicate. The cells were cultured at 37°C with 5% CO2. Multi-lineage differentiation capacity was assessed with a selective colony forming units (CFU) assay and compared between experimental groups. Signaling pathways were determined using phosphor-flow cytometric analysis of pSTAT1. For the immune mediated mouse model of aSAA, 8-week-old C57BL/6 mice were irradiated with 6.5Gy TBI. Spleen lymphocytes were collected from FVB donors, and injected 4 hours post-radiation into B6 recipient mice via the retro-orbital vein, at 1-1.5 × 106 cells/recipient in 100μL PBS. Each experimental group (PBS control and USSCs) included 20 mice per group. Mice were continuously monitored for their survival. Peripheral blood (PB) was analyzed using a VETSCAN® HM5 Analyzer. Mean ± SEM of the blood counts was compared between experimental groups. Mice femur bones were extracted and cleaned of soft tissue, fixed and sectioned. Paraffin sections were stained with Hematoxylin and Eosin (H&E) to assess morphology. Results: The myelosuppressive effect of IFN-γ and TNF-α was significantly rescued (4-fold increase) by the addition of USSCs (transwell) at day 7. After 28 days direct co-culture with USSCs increased CD34+ survival as well (p<0.001) from 5 to 35 cells/µl. A significantly higher percent of viable cells (73% versus 63%) was observed among the USSCs treated cells (P<0.05). Phosphor-flow cytometric analysis demonstrated an almost 50% decrease in pSTAT1 in the presence of USSCs (p<0.05). Based on CFU analysis, CD34+ cells cultured in the presence of USSCs were able to produce more CFU (52, SD±3.7) at day 7 (p<0.01) compared to IFN-γ and TNF-α treated cells (16, SD±2.8). Also, USSCs were associated with more BFU (p<0.05) at day 14. In our immune mediated aplastic anemia mice model, treatment with USSCs was associated with substantial prolonged mice survival (p=0.02) (Figure 1a). Evaluation of PB counts demonstrated increased hemoglobin levels at day 14 in the USSCs treated mice (p<0.05) 5.6g/dL (SD±0.6), compared to PBS treated mice 2.1g/dL (SD±0.1). BM evaluation of USSCs treated mice versus PBS control displayed higher cellularity in the USSCs treated sections (Figure 1b). Conclusions: Cellular therapy, such as USSCs, may be instrumental in the treatment of aSAA, specifically by increasing BFU-E and eventually hemoglobin levels. Future studies will need to be done to investigate the exact mechanisms of action and the clinical efficacy of this novel cellular therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Effect of Traditional and Online Learning Approaches on the Survival and Transmission of the Oral Culture, Students' Attitude and National Values

This study examines the effects of providing students with the literature-related foundations of knowledge revealed in the works of the famous Zhyrau who lived in the in the city of Aktau, Mangistau region of Kazakhstan, through online and traditional teaching. For this purpose, pretest-posttest model with study control group was applied. The study was conducted on the subject of "The Zhyrau and Their Place in Kazakh Language Literature" at the Department of Kazakh Philology in the 2022 academic year and lasted 6 weeks. According to the research findings, it has been seen that online supported blended teaching has a positive effect on the success of the course and the retention of what has been learned in the subject of "The Zhyrau and Their Place in Kazakh Language Literature" compared to traditional teaching. In another finding of the study, there was no significant difference in the attitudes and perceptions of national values of the participant student groups on the subject of "The Zhyrau and Their Place in Kazakh Language Literature". In both groups, students in the experimental group with online supported blended teaching and the control group students in the traditional teaching achieved very high posttest course attitude and national value perception scores. Online, blended and traditional activities on "The Zhyrau and Their Place in Kazakh Language Literature" have positively and highly affected students' attitudes and perceptions of national values.

The Impact of Contact and Colonization on Indigenous Worldviews, Rock Art, and the History of Southern Africa

The archaeological record undergoes a dramatic shift in appearance whenever indigenous peoples encounter incoming populations—whether in the form of economy, politics, or identity. Rock art in southern Africa testifies to successive interactions among hunter-gatherers, incoming African herders, African farmers, and, later, European settlers. New subject matter, however, is not simply incorporated into the preexisting tradition. Without exception, the many rock arts that depict novel motifs are made differently from the “traditional corpus,” usually rougher in appearance (in both paintings and engravings), more dynamic, or made with vivid and chalky paints. The drop in pigment quality is likely owing to the disruption and ultimate decimation of indigenous groups and the subsequent breakdown in trade and social communications—the Disconnect. The shifts in manners of depiction and the ways in which motifs are treated owe more, it seems, to the increasingly heterogeneous and creolizing membership of the art-producing people and the mixing of their cosmologies, albeit with specific cultural survivals. Precolonial contact images speak to a multitude of interactions and entanglements in ways that can inform the archaeological record, and colonial-era rock art constitutes a major component of the historical archive, an emic, agentive artifact that offers a reverse gaze from an indigenous perspective.

Hypoxic preconditioning promotes survival of human adipose derived mesenchymal stem cell via expression of prosurvival and proangiogenic biomarkers

Background: Contributing factors for improved survival of human adipose derived mesenchymal stem cells (h-AMSCs) cultured through hypoxia preconditioning, in example apoptosis inhibition involving BCL2 and HSP27 expression, trigger signal expression (VEGF), SCF expression, OCT-4 expression, and CD44+ expression. The objective if this study was to explain the mechanism and role of hypoxic preconditioning and the optimal duration of hypoxic preconditioning exposure to improve survival of h-AMSCs. Methods: An experimental laboratory explorative study (in vitro) with hypoxic preconditioning in h-AMSCs cultures. This research was conducted through four stages. First, isolation of h-AMSCs culture from adipose tissue of patients. Second, the characterization of h-AMSCs from adipose tissue by phenotype (flowcytometry) through CD44+, CD90+ and CD45-expression before being pre-conditioned for hypoxic treatment. Third, the hypoxic preconditioning in h-AMSCs culture (in vitro) was performed with an oxygen concentration of 1% for 24, 48 and 72 hours. Fourth, observation of survival from h-AMSCs culture was tested on the role of CD44+, VEGF, SCF, OCT-4, BCL2, HSP27 with Flowcytometry and apoptotic inhibition by Tunnel Assay method. Results: The result of regression test showed that time difference had an effect on VEGF expression (p&lt;0.001;β=-0.482) and hypoxia condition also influenced VEGF expression (p&lt;0.001;β=0.774). The result of path analysis showed that SCF had effect on OCT-4 expression (p&lt;0.001; β=0.985). The regression test results showed that time effects on HSP27 expression (p&lt;0.001; β=0.398) and hypoxia precondition also affects HSP27 expression (p&lt;0.001; β=0.847). Pathway analysis showed that BCL2 expression inhibited apoptosis (p=0.030; β=-0.442) and HSP27 expression also inhibited apoptosis (p&lt;0,001;β=-0.487). Conclusion: Hypoxic preconditioning of h-AMSC culture has proven to increase the expression of VEGF, SCF, OCT-4, and BCL2 and HSP27. This study demonstrated and explained the existence of a new mechanism of increased h-AMSC survival in cultures with hypoxic preconditioning (O2 1%) via VEGF, SCF, OCT-4, BCL2, and HSP 27.

Specifics of Algorithmization in Data Culture

Abstract Information societies effectively transform existing cultures. New cultures are variously defined, but because of the fact that they are dominated by information, the term “data cultures” seems to be the most relevant name for them. Although, it is possible to create a single global data culture in the future and such predictions prevail in academic and non-academic reflections on this subject, so far in addition to global trends there occur local data cultures, what also dynamizes and enriches both individual and collective identities. As Kazimierz Krzysztofek aptly notes, in this situation: "The greatest contradiction of the civilization of the 21st century is drawn. On the one hand, a continuous imperative: be creative and innovative, on the other hand, an increasing pressure on prediction of people’s behaviour, because unpredictability causes chaos, which cannot be managed". In other words, one of the most important social issues today is to create some order in data culture / cultures (often pictured by columnists and researchers as a "magnetic storm"), to reduce its / their infinite complexity, i.e. simply the algorithmization process. With regard to culture, it is not possible to use unequivocally a mathematical algorithm that is the most precise, or a genetic or hormonal algorithm that functions in nature, because accustoming cultural chaos is always strongly ideologized. The algorithm should be treated as a metaphor used to explain cultural phenomena, especially their developmental tendencies. For the researcher of contemporary societies, it is very important to answer the question: what proportions of structure and network are the most beneficial for the survival of data culture / cultures? This answer also directs reflection on the quality of life of individuals and societies, limiting or promoting individualism and collective intelligence in the era of hyper-digitization. These considerations are limited to the initial characterization and evaluation of the information algorithmization of man. The author of the study refers to the concepts of researchers from different countries, highlighting the specificity of today's algorithmization, among others the model of ambient perception, which facilitates participation in the networked information environment, scope and reach of the big data phenomenon, forms of data visualization, personalization of content, Isotype visual language, network custody, data journalism and others. In conclusion, it is pointed out that the information algorithmization of man is constantly growing, which proves that data management strategies weaken the phenomenon of information overload through the logic of numerical civilization, which limits diversity, seeking to count, record and globalize everything.

Effect of Different Stocking Density on Growth and Survival of Monosex Tilapia Cage Culture in Perumpallam Reservoir, Tamil Nadu

Effect of Different Stocking Density on Growth and Survival of Monosex Tilapia Cage Culture in Perumpallam Reservoir, Tamil Nadu

Targeting Microtubule-Associated Protein Tau in Chemotherapy-Resistant Models of High-Grade Serous Ovarian Carcinoma.

Simple SummaryResistance to chemotherapy in patients with high-grade serous ovarian carcinoma is a clinically relevant problem, and it results in high mortality. The aim of the study was to determine whether targeting microtubule-associated protein tau could reduce cell proliferation and tumor burden in cell culture and mouse models of chemotherapy-resistant high-grade serous ovarian carcinoma. To achieve this aim, I tested an inhibitor of tau, leucomethylene blue, which was originally developed against neurodegenerative diseases, and found that it efficiently reduced cell and tumor growth. Additionally, paclitaxel and leucomethylene blue synergized in reducing cell growth and tumor burden. Altogether, the data demonstrate that tau could be considered a new target for treatment of chemotherapy-resistant high-grade serous ovarian carcinoma, and leucomethylene blue could potentially add to the arsenal of drugs to treat the terminal stage of this deadly malignancy.Relapsed, recurrent, chemotherapy-resistant high-grade serous ovarian carcinoma is the deadliest stage of this disease. Expression of microtubule-associated protein tau (tau) has been linked to resistance to paclitaxel treatment. Here, I used models of platinum-resistant and created models of platinum/paclitaxel-resistant high-grade serous ovarian carcinoma to examine the impact of reducing tau expression on cell survival and tumor burden in cell culture and xenograft and syngeneic models of the disease. Tau was overexpressed in platinum/paclitaxel-resistant models; expression of phosphoSer396 and phosphoThr181 species was also found. A treatment with leucomethylene blue reduced the levels of tau in treated cells, was cytotoxic in cell cultures, and efficiently reduced the tumor burden in xenograft models. Furthermore, a combination of leucomethylene blue and paclitaxel synergized in eliminating cancer cells in cell culture and xenograft models. These findings underscore the feasibility of targeting tau as a treatment option in terminal-stage high-grade serous ovarian cancer.

AP39, a Mitochondrial-Targeted H2S Donor, Improves Porcine Islet Survival in Culture.

The rapid deterioration of transplanted islets in culture is a well-established phenomenon. We recently reported that pancreas preservation with AP39 reduces reactive oxygen species (ROS) production and improves islet graft function. In this study, we investigated whether the addition of AP39 to the culture medium could reduce isolated islet deterioration and improve islet function. Isolated islets from porcine pancreata were cultured with 400 nM AP39 or without AP39 at 37 °C. After culturing for 6–72 h, the islet equivalents of porcine islets in the AP39(+) group were significantly higher than those in the AP39(−) group. The islets in the AP39(+) group exhibited significantly decreased levels of ROS production compared to the islets in the AP39(−) group. The islets in the AP39(+) group exhibited significantly increased mitochondrial membrane potential compared to the islets in the AP39(−) group. A marginal number (1500 IEs) of cultured islets from each group was then transplanted into streptozotocin-induced diabetic mice. Culturing isolated islets with AP39 improved islet transplantation outcomes in streptozotocin-induced diabetic mice. The addition of AP39 in culture medium reduces islet deterioration and furthers the advancements in β-cell replacement therapy.

The Quest for the Survival of African Culture and Tradition: A Structuralist Reading of Ayi Kwei Armah’s Fragments

Using reader-response literary criticism and structuralism, this paper has evaluated and examined the necessity of preserving and revitalising African culture and tradition. It has also shown the intrinsic relation between the ancestors and the living people as featured by Ayi Kwei Armah in Fragments. Ancestors are revered and worshipped because of their importance in the lives of African people. Ancestors protect people who are still living and they also punish people who disobey the norms of society. The study revealed that western culture and the excessive love of materialism threaten African culture and prevent it from thriving socio-culturally. African people should undertake serious actions which will contribute to the rebirth and the restoration of African tradition. The contact between Africa and the West has negatively influenced the leadership of Africa. Corruption and bad governance have been embraced and introduced into the system of governance by new African leaders who took over. Nepotism, theft, bribery, and their likes have become cherished values in post-colonial Africa. The study recommends that African people should go back to their sources in order to build a solid foundation in Africa

Yaşar Kemal'in "Bir Ada Hikâyesi" Dörtlemesinde Kültürlerarası İletişim Engelleri

The relationship between the concepts of language, communication, culture and text is discussed in the sociocultural context through literary texts. Literary texts are accepted as communication forms/tools and language/literary text ensures the survival, maintenance and transmission of culture. Language/communication based on cultural difference in Yashar Kemal's novels- Tetralogy of “An Island Story”- have been analyzed in a sociocultural context based on Raymond Williams' concept of "structure of feeling”. It has been researched how the forms of collective experience shaped by the whole lifestyle -culture- are reflected in the context of the communication established between the subcultures of the Anatolian geography in the novels and how they affect/prevent communication. As a result of the research, stereotypes, prejudices, ethnocentrism and discrimination, which are conceptualized as barriers to intercultural communication and are the analysis themes of this study, were revealed by analyzing the narrative of the literary text and the conversations/dialogues of the novel characters. In the study, it is explained by questioning how and with which values Yashar Kemal, as an intellectual created a "new language/communication" between cultures at the point of positive change/transformation of structure of feeling and therefore collective experiences in order to eliminate barriers to intercultural communication.

Situating Music and Solidarity Within the Yoeme Water Struggle

The role of music as a tool for promoting political and community solidarity is determined, at least in part, by the stakes. For Indigenous communities facing state repression, cultural survival goes hand in hand with physical survival. How might attitudes toward the role of music have an effect on the Yoemem’s water struggle? Acueducto Independencia is a 155 kilometer long aqueduct which began transporting 75 million cubic meters of water per year from the Rio Yaqui to the city of Hermosillo in 2013. The aqueduct breaks a 1937 treaty guaranteeing the Indigenous Yoeme (Yaqui) 50% of the Rio Yaqui’s water. The fact that many Yoemem do not have access to sufficient amounts of non-pesticide laced water for drinking, agriculture, or other everyday needs affects health and way of life and is tantamount to an ongoing structural genocide. Many perceive this ongoing threat to their livelihood as a form of low-intensity warfare considering the violent history between the Yoeme, Mexican government and state officials (Personal communication, April 7, 2021). The Yoemem have called upon others to support their fight for basic human rights, cultural and political sovereignty, and environmental justice. This call-to-action has resulted in music becoming a space for promoting Indigenous solidarity–in part. Indeed, the use of music has arguably become widespread recently in environmental justice movements around the globe. This article will explore how music is posed as a form of Indigenous solidarity within the context of the environmental justice movement.

Biosorption of heavy metals by microorganisms: Evaluation of different underlying mechanisms

Globally, ecotoxicologists, environmental biologists, biochemists, pathologists, and other experts are concerned about environmental contamination. Numerous pollutants, such as harmful heavy metals and emerging hazardous chemicals, are pervasive sources of water pollution. Water pollution and sustainable development have several eradication strategies proposed and used. Biosorption is a low-cost, easy-to-use, profitable, and efficient method of removing pollutants from water resources. Microorganisms are effective biosorbents, and their biosorption efficacy varies based on several aspects, such as ambient factors, sorbing materials, and metals to be removed. Microbial culture survival is also important. Biofilm agglomerates play an important function in metal uptake by extracellular polymeric molecules from water resources. This study investigates the occurrence of heavy metals, their removal by biosorption techniques, and the influence of variables such as those indicated above on biosorption performance. Ion exchange, complexation, precipitation, and physical adsorption are all components of biosorption. Between 20 and 35 °C is the optimal temperature range for biosorption efficiency from water resources. Utilizing living microorganisms that interact with the active functional groups found in the water contaminants might increase biosorption efficiency. This article discusses the negative impacts of microorganisms on living things and provides an outline of how they affect the elimination of heavy metals.

Selective Survival of Protective Cultures during High-Pressure Processing by Leveraging Freeze-Drying and Encapsulation.

High-Pressure Processing’s (HPP) non-thermal inactivation of cells has been largely incompatible with food products in which the activity of selected cultures is intended (e.g., bio-preservation). This work aims to overcome this limitation using a cocoa butter encapsulation system for freeze-dried cultures that can be integrated with HPP technology with minimal detrimental effects on cell viability or activity capabilities. Using commercially available freeze-dried protective cultures, the desiccated cells survived HPP (600 MPa, 5 °C, 3 min) and subsequently experienced a 0.66-log increase in cell counts during 2 h of incubation. When the same culture was rehydrated prior to HPP, it underwent a >6.07-log decrease. Phosphate-buffered saline or skim milk inoculated with cocoa butter-encapsulated culture up to 24 h before HPP displayed robust cell counts after HPP and subsequent plating (8.37–9.16 CFU/mL). In addition to assessing viability following HPP, the study sought to test the applicability in a product in which post-HPP fermentation is desired While HPP-treated encapsulated cultures initially exhibited significantly delayed fermentative processes compared to the positive controls, by 48 h following inoculation, the HPP samples’ pH values bore no significant difference from those of the positive controls (encapsulated samples: pH 3.83 to 3.92; positive controls: pH 3.81 to 3.85). The HPP encapsulated cultures also maintained high cell counts throughout the fermentation (≥8.95 log CFU/mL).

Optimization of spray‐dried probiotic buttermilk powder using response surface methodology and evaluation of its shelf stability

In the present study, double-toned milk was inoculated with Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus, and Bifidobacterium bifidum, to result in a curd which was further subjected to homogenization and spray drying. Various process parameters like inlet temperature (140–160°C), the flow rate of feed (10–20 ml/min), and compressed air (2–4 kg/cm2) were varied to obtain the best-operating conditions for the maximum viable count in the probiotic cultured buttermilk powder. The yields of the powder ranged between 58.4% and 71.5%. An inlet temperature of 150°C, feed flow rate of 15 ml/min and compressed air of 3 kg/cm2 were the optimum process parameters obtained by response surface methodology for maximum survival of starter culture and probiotic bacteria Bifidobacterium bifidum. The powder stored at 4 ± 1°C showed superior qualities to that stored at 27 ± 1°C. While moisture content, aw, solubility and density showed an increase, hygroscopicity exhibited a decline during storage. The final moisture content, hygroscopicity, aw, solubility index, and bulk density of buttermilk powder stored at 4 ± 1°C and 27 ± 1°C were 5.93, 13.73, 0.293, 59.78, 0.71, and 6.27, 12.31, 0.301, 60.12, 0.93 respectively. The viable counts of Streptococcus thermophilus, Lactobacillus delbrueckii subsp. bulgaricus and Bifidobacterium bifidum in BMP were 8.07 ± 0.21, 7.68 ± 0.17, 6.01 ± 0.18 at 4 ± 1°C and 5.73 ± 0.17, 5.57 ± 0.14, 4.14 ± 0.20 at 27 ± 1°C after 4 weeks of storage. Practical applications Probiotics have gained tremendous attention in recent times. However, the viability of probiotics during rigorous food processing and handling steps remains a matter of concern. Spray drying results in a powder that can be easily handled, stored, and reconstituted in beverages. A probiotic cultured buttermilk powder was obtained by optimizing the inlet temperature, feed flow rate, and compressed air while spray drying. Buttermilk is a valuable by-product usually lost in waste streams during the manufacturing of butter. This study attempts to valorize buttermilk by developing a spray dried probiotic buttermilk powder and evaluate its shelf-life under refrigerated storage and ambient conditions, which would be of great help to the industry.

State of Nationalism (SoN): Ethics of Nationalism

Is nationalism morally defensible, or is it a destructive holdover from our primitive past? Are certain forms of nationalism normatively preferable to others? To what extent are liberals ethically entitled to accommodate the demands and concerns of nationalists? Do the claims of nationality entail a right to independence or autonomy? Can the ‘politics of cultural survival’ justify the state’s protection and promotion of particular national identities? This article will provide an overview of how thinkers have dealt with such problems in the different eras of the study of nationalism.

WINIKO: Life of an Object, First Americans Museum, Oklahoma City, Oklahoma

<i>WINIKO: Life of an Object</i>, First Americans Museum, Oklahoma City, Oklahoma

Myocyte Culture with Decellularized Skeletal Muscle Sheet with Observable Interaction with the Extracellular Matrix.

In skeletal muscles, muscle fibers are highly organized and bundled within the basement membrane. Several microfabricated substrate models have failed to mimic the macrostructure of native muscle, including various extracellular matrix (ECM) proteins. Therefore, we developed and evaluated a system using decellularized muscle tissue and mouse myoblasts C2C12 to analyze the interaction between native ECM and myocytes. Chicken skeletal muscle was sliced into sheets and decellularized to prepare decellularized skeletal muscle sheets (DSMS). C2C12 was then seeded and differentiated on DSMS. Immunostaining for ECM molecules was performed to examine the relationship between myoblast adhesion status, myotube orientation, and collagen IV orientation. Myotube survival in long-term culture was confirmed by calcein staining. C2C12 myoblasts adhered to scaffolds in DSMS and developed adhesion plaques and filopodia. Furthermore, C2C12 myotubes showed orientation along the ECM orientation within DSMS. Compared to plastic dishes, detachment was less likely to occur on DSMS, and long-term incubation was possible. This culture technique reproduces a cell culture environment reflecting the properties of living skeletal muscle, thereby allowing studies on the interaction between the ECM and myocytes.

In This Issue

Current murine models of myeloproliferative neoplasms (MPN) cannot address how MPN can invade hematopoietic organs from a defined single anatomical origin as observed in patients. Murakami et al. developed an immunocompetent wild-type mouse model of Polycythemia Vera (PV) spreading from a single bone marrow site. PV development was abrogated in mice with splenectomy or lacking carbonic anhydrase 1 (CA1) in mutant hematopoietic progenitors. Increased expression of CA1 was found in CD34+ cells from PV patients, and its pharmacologic inhibition decreased variant allele frequency in colony-forming assays, suggesting CA1 as a potential therapeutic target for PV.See article, p. 285.Approximately every fifth patient with myeloproliferative neoplasms (MPN) harbors a CALR mutation of either type I or type II, which differ in clinical features and outcomes. Ibarra et al. show that type I, but not type II, mutant CALR proteins lose Ca2+ binding, causing Ca2+ depletion from the endoplasmic reticulum and activation of the IRE1α/XBP1 pathway. IRE1α inhibition prevented type I-mutant CALR cell survival in culture and thrombocythemia development in mice. These results identify IRE1α/XBP1 as a potentially targetable dependency specific to type I CALR-mutated MPNs.See article, p. 298.By single-cell DNA, RNA and proteogenomic sequencing of matched patient samples, Guess et al. uncovered three clonal evolution patterns associated with clinical progression from myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (sAML). The Static pattern, characterized by minimal clonal change, had founding clones with mutations in DNA methylation genes and transitioned to sAML in the absence of further genomic aberrations, suggesting nongenetic evolution. Clonal architecture changed dramatically in Dynamic groups, often involving acquisition of mutations in signaling pathways (Dynamic-S) or progressive structural aberrations along with TP53 mutations (Dynamic-C). Collectively, these findings elucidate the interplay of genetic and nongenetic factors in leukemic transformation.See article, p. 316.To investigate patterns of subclone evolution during progression from myelodysplastic syndrome (MDS) to secondary acute myeloid leukemia (sAML), Menssen et al. sequenced paired MDS and sAML samples from a cohort of patients. Signaling gene mutations were found to occur universally in subclones and undergo complex patterns of clonal evolution, including acquisition, expansion, persistence, and contraction of mutations during progression, with multiple patterns often coexisting in the same patient. The presence of at least one signaling gene mutation at MDS was associated with future progression to sAML in patients with lower risk MDS.See article, p. 330.Nakauchi et al. report the genome-wide landscape of DNA hydroxymethylation (5hmC) in human hematopoietic lineages. The authors map TET2-dependent 5hmC, epigenetic and transcriptional programs matched to competitive advantage, myeloid skewing, and reduced erythroid output in TET2-deficient hematopoietic stem and progenitor cells (HSPC). Vitamin C and azacitidine restore the 5hmC landscape and phenotypes in TET2-mutant HSPCs. These findings offer a comprehensive resource for TET-dependent transcriptional regulation of human hematopoiesis and shed light on the potential mechanisms by which TET deficiency contributes to clonal hematopoiesis and malignancies.See article, p. 346.

Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes.

SLC26A4/Pendrin is the major electroneutral Cl−/HCO3 − exchanger of the apical membrane of the Type B intercalated cell (IC) of the connecting segment (CNT) and cortical collecting duct (CCD). Pendrin mediates both base secretion in response to systemic base load and Cl− reabsorption in response to systemic volume depletion, manifested as decreased nephron salt and water delivery to the distal nephron. Pendrin‐mediated Cl−/HCO3 − exchange in the apical membrane is upregulated through stimulation of the β‐IC apical membrane G protein‐coupled receptor, 2‐oxoglutarate receptor 1 (OXGR1/GPR99), by its ligand α‐ketoglutarate (αKG). αKG is both filtered by the glomerulus and lumenally secreted by proximal tubule apical membrane organic anion transporters (OATs). OXGR1‐mediated regulation of Pendrin by αKG has been documented in transgenic mice and in isolated perfused CCD. However, aspects of the OXGR1 signaling pathway have remained little investigated since its original discovery in lymphocytes. Moreover, no ex vivo cellular system has been reported in which to study the OXGR1 signaling pathway of Type B‐IC, a cell type refractory to survival in culture in its differentiated state. As Xenopus oocytes express robust heterologous Pendrin activity, we investigated OXGR1 regulation of Pendrin in oocytes. Despite functional expression of OXGR1 in oocytes, co‐expression of Pendrin and OXGR1 failed to exhibit αKG‐sensitive stimulation of Pendrin‐mediated Cl−/anion exchange under a wide range of conditions. We conclude that Xenopus oocytes lack one or more essential molecular components or physical conditions required for OXGR1 to regulate Pendrin activity.