Long-term Deprivation Research Articles

Deprivation-Induced Plasticity in the Early Central Circuits of the Rodent Visual, Auditory, and Olfactory Systems.

Activity-dependent neuronal plasticity is crucial for animals to adapt to dynamic sensory environments. Traditionally, it has been investigated using deprivation approaches in animal models primarily in sensory cortices. Nevertheless, emerging evidence emphasizes its significance in sensory organs and in subcortical regions where cranial nerves relay information to the brain. Additionally, critical questions started to arise. Do different sensory modalities share common cellular mechanisms for deprivation-induced plasticity at these central entry points? Does the deprivation duration correlate with specific plasticity mechanisms? This study systematically reviews and meta-analyzes research papers that investigated visual, auditory, or olfactory deprivation in rodents of both sexes. It examines the consequences of sensory deprivation in homologous regions at the first central synapse following cranial nerve transmission (vision - lateral geniculate nucleus and superior colliculus; audition - ventral and dorsal cochlear nucleus; olfaction - olfactory bulb). The systematic search yielded 91 papers (39 vision, 22 audition, 30 olfaction), revealing substantial heterogeneity in publication trends, experimental methods, measures of plasticity, and reporting across the sensory modalities. Despite these differences, commonalities emerged when correlating plasticity mechanisms with the duration of sensory deprivation. Short-term deprivation (up to 1 d) reduced activity and increased disinhibition, medium-term deprivation (1 d to a week) involved glial changes and synaptic remodeling, and long-term deprivation (over a week) primarily led to structural alterations. These findings underscore the importance of standardizing methodologies and reporting practices. Additionally, they highlight the value of cross-modal synthesis for understanding how the nervous system, including peripheral, precortical, and cortical areas, respond to and compensate for sensory inputs loss.

Violation of food taboos by peasant women of Kyiv region and political use of accusations of anthropophagy: the case of Hanna Bilorus

The article analyzes the emergence of psychopathological changes in peasant women resulting from long-term deprivation, using the examples of the archival and criminal case of Hanna Bilorus, oral historical testimonies, and official sources. These changes affected the deformation of women’s behavior and led to the spread of its extreme manifestations — violations of food taboos, an increase in cases of anthropophagy and necrophagy since the beginning of 1933. However, they were perceived by the peasants in different ways: from a sympathetic attitude to condemnation and lynchings. We discovered the long-term impact of the consequences of cannibalism on rural communities and the psyche of eyewitnesses to the tragedy. Additionally, it investigates the representation of cannibalism cases by the authorities, which often carry political undertones. Anthropophages were represented in official sources as marginal non-working elements (“ledar”), representatives of hostile social groups (“kurkuli”, “odnoosibnyky”), and spies. Using the archive-criminal case of Hanna Bilorus, the article demonstrates the correlation between accusations of espionage for Poland and the suspicion of cannibalism with the broader political context of 1932–1933. This context emphasized the “Polish threat” and the alleged dismantling of the DPU «counter-revolutionary network» associated with the Polish General Staff.

How does Information Manipulation Interfere with Normal Brain Function? The Disruption of Neuroethics in War-Time Mass Media

The article describes massive changes in the brain function of mass-media recipients. It is written within the relevant neuro social state of the Ukrainian mass media society in the conditions of undeclared military censorship and counter-propaganda. The material for analysis was two groups of data: content analysis of news media and a sociological survey of citizens for the presence of cognitive dissonance and lies that can violate neuroethics, namely, forming a distorted picture of the world, creating long-term deprivation and inadequate neural connections. The purpose of such research was to find out the regular influence of affective and defamatory infospace on the brains of people whose countries are at war. We clarified the nature of the newest manipulations in the media and around ethical issues, the state of research on the neuroethics of manipulations, comparing the nature of war journalistic manipulations in Russian and Ukrainian media and the objectification and explanation of neuroethical violations in Ukrainian media through the techniques of lying, silencing, avoidance, analysis, self-counting, etc. The authors used methods of theoretical, statistical, comparative and systemic analysis, content analysis, sociological methods of collecting background data and neuro interpretive methods for the received input data. The result of the article was a systematization of the manipulation of the brain in a state of permanent tension; in particular, we identified ways of institutional avoidance or deception and diagnosis of specific neuroethical threats and consequences among the population (emotional dependency, deprivation, emotional-cognitive dissonance, lack of entitlement to accurate truth, the difference between the content of the national and local media, etc.)

Spatial trends and projections of chronic malnutrition among children under 5 years of age in Ethiopia from 2011 to 2019: a geographically weighted regression analysis

IntroductionUndernutrition is a serious global health issue, and stunting is a key indicator of children's nutritional status which results from long-term deprivation of basic needs. Ethiopia, the largest and most populous country in Sub-Saharan Africa, has the greatest rate of stunting among children under the age of five, yet the problem is unevenly distributed across the country. Thus, we investigate spatial heterogeneity and explore spatial projection of stunting among under-five children. Further, spatial predictors of stunting were assessed using geospatial regression models.MethodsThe Ethiopia Demographic and Health Surveys (EDHS) data from 2011, 2016, and 2019 were examined using a geostatistical technique that took into account spatial autocorrelation. Ordinary kriging was used to interpolate stunting data, and Kulldorff spatial scan statistics were used to identify spatial clusters with high and low stunting prevalence. In spatial regression modeling, the ordinary least square (OLS) model was employed to investigate spatial predictors of stunting and to examine local spatial variations geographically weighted regression (GWR) and multiscale geographically weighted regression (MGWR) models were employed.ResultsOverall, stunting prevalence was decreased from 44.42% [95%, CI: 0.425–0.444] in 2011 to 36.77% [95%, CI: 0.349–0.375] in 2019. Across three waves of EDHS, clusters with a high prevalence of stunting in children under 5 years were consistently observed in northern Ethiopia stretching in Tigray, Amhara, Afar, and Benishangul-Gumuz. Another area of very high stunting incidence was observed in the Southern parts of Ethiopia and the Somali region of Ethiopia. Our spatial regression analysis revealed that the observed geographical variation of under-five stunting significantly correlated with poor sanitation, poor wealth index, inadequate diet, residency, and mothers' education.ConclusionsIn Ethiopia, substantial progress has been made in decreasing stunting among children under the age of 5 years; although disparities varied in some areas and districts between surveys, the pattern generally remained constant over time. These findings suggest a need for region and district-specific policies where priority should be given to children in areas where most likely to exhibit high-risk stunting.

Exploring the need for external input through the prism of social, material and sensation seeking input.

External input is any kind of physical stimulation created by an individual's surroundings that can be detected by the senses. The present research established a novel conceptualization of this construct by investigating it in relation to the needs for material, social and sensation seeking input, and by testing whether these needs predict psychological functioning during long- and short-term input deprivation. It was established that the three needs constitute different dimensions of an overarching construct (i.e. need for external input). The research also suggested that the needs for social and sensation seeking input are negatively linked to people's experiences of long-term input deprivation (i.e. COVID-19 restrictions), and that the need for material input may negatively predict the experiences of short-term input deprivation (i.e. sitting in a chair without doing anything else but thinking). Overall, this research indicates that the needs for social, material and sensation seeking input may have fundamental implications for experiences and actions in a range of different contexts.

Mechanistic Effects of Estrogens on Breast Cancer.

Current concepts regarding estrogen and its mechanistic effects on breast cancer in women are evolving. This article reviews studies that address estrogen-mediated breast cancer development, the prevalence of occult tumors at autopsy, and the natural history of breast cancer as predicted by a newly developed tumor kinetic model. This article reviews previously published studies from the authors and articles pertinent to the data presented. We discuss the concepts of adaptive hypersensitivity that develops in response to long-term deprivation of estrogen and results in both increased cell proliferation and apoptosis. The effects of menopausal hormonal therapy on breast cancer in postmenopausal women are interpreted based on the tumor kinetic model. Studies of the administration of a tissue selective estrogen complex in vitro, in vivo, and in patients are described. We review the various clinical studies of breast cancer prevention with selective estrogen receptor modulators and aromatase inhibitors. Finally, the effects of the underlying risk of breast cancer on the effects of menopausal hormone therapy are outlined. The overall intent of this review is to present data supporting recent concepts, discuss pertinent literature, and critically examine areas of controversy.

Loss of p19Arf promotes fibroblast survival during leucine deprivation

ABSTRACTFibroblasts are quiescent and tumor suppressive in nature but become activated in wound healing and cancer. The response of fibroblasts to cellular stress has not been extensively investigated, however the p53 tumor suppressor has been shown to be activated in fibroblasts during nutrient deprivation. Since the p19 Alternative reading frame (p19Arf) tumor suppressor is a key regulator of p53 activation during oncogenic stress, we investigated the role of p19Arf in fibroblasts during nutrient deprivation. Here, we show that prolonged leucine deprivation results in increased expression and nuclear localization of p19Arf, triggering apoptosis in primary murine adult lung fibroblasts (ALFs). In contrast, the absence of p19Arf during long-term leucine deprivation resulted in increased ALF proliferation, migration and survival through upregulation of the Integrated Stress Response pathway and increased autophagic flux. Our data implicates a new role for p19Arf in response to nutrient deprivation. This article has an associated First Person interview with the first author of the paper.

CORRELATIONS BETWEEN CD68 RECEPTOR EXPRESSION AND ACTIVITY OF MACROPHAGE POLARIZATION MARKER ENZYMES IN RAT TESTES DURING PROLONGED BLOCKADE OF LUTEINIZING HORMONE SYNTHESIS BY TRIPTORELIN

Luteinizing hormone and testosterone have a significant effect on the polarization of macrophages. Changing the polarization of macrophages can cause morphological and metabolic changes in various organs and tissues. The CD68 receptor is associated with proinflammatory polarization of macrophages. Currently, the scientific literature provides limited data on the relationship between the expression of the CD68 receptor on testicular macrophages and the activity of markers of macrophage polarization enzymes during long-term deprivation of luteinizing hormone synthesis. The aim of this study was to establish correlations between the number of CD68+ cells in the interstitial space and testicular vessels and the activity of inducible NO synthase, arginase and superoxide anion radical production after 270 and 365 days of central blockade of luteinizing hormone synthesis by triptorelin. Materials and methods. The study was performed on 15 adult male Wistar rats. Animals were randomly divided into 2 groups: control (5 animals) and experimental (10 animals). Animals of the experimental group were injected with a solution of triptorelin acetate at the rate of 0.3 mg of active substance per kg of animal weight to model the central derivation of luteinizing hormone synthesis. Animals from the experimental group were removed from the experiment on days 270 and 365 of the simulation of central derivation of luteinizing hormone synthesis. Histological examination of the testes was performed after preparation of paraffin sections. To perform immunohistochemical study of testicular macrophages for the presence of CD68 receptors we performed, after the manufacture of paraffin blocks, deparaffinization of sections was with subsequent unmasking of antigens. Inducible NO synthase activity, arginase and superoxide anion radical production were determined in 10% of testicular homogenates. Quantitative distribution of the CD68 receptor in the interstitium and testicular blood vessels was also determined. After determining the distribution of the studied parameters, a correlation analysis was performed by the Spearman method and the correlation of the ranks of the studied parameters and its statistical significance were determined. Results. The production of superoxide anion radical is directly proportionally strongly correlated with the expression of CD68 on interstitial and vascular macrophages. There were no statistically significant correlations between the prevalence of CD68 receptor in the interstitium and vascular vessels and the activity of inducible NO synthase and arginase on day 270 of central deprivation of luteinizing hormone synthesis by triptorelin. The production of superoxide anion radical, inducible NO synthase and arginase activity, and the prevalence of the CD68 receptor in the interstitium and blood vessels of testes on day 365 of central deprivation of luteinizing hormone synthesis do not have statistically significant correlations. Conclusions. Expression of the CD68 receptor on interstitial and parietal testicular macrophages leads to hyperproduction of superoxide anion radical on day 270 of central deprivation of luteinizing hormone synthesis by triptorelin. The prevalence of CD68 on day 360 of central deprivation of luteinizing hormone synthesis by triptorelin does not affect the activity of macrophage polarization marker enzymes.

Homeostatic Regulation of Astrocytes by Visual Experience in the Developing Primary Visual Cortex.

During postnatal development, sensory experience shapes the organization and function of cortical circuits. Previous studies focusing on experience-dependent plasticity of neurons have revealed a variety of mechanisms underlying cortical circuit rewiring. Emerging evidence shows that astrocytes play important roles in shaping cortical circuits through extensive interactions with different types of neurons and other glia cells. However, it remains unclear how astrocytes respond to sensory experience during postnatal development. In the present study, we profiled the maturation of astrocytes in the primary visual cortex (V1) at different postnatal stages. We then investigated the anatomical and physiological changes of astrocytes in V1 induced by multiple types of visual experience within 4 postnatal weeks. Compared with monocular deprivation during the critical period, binocular deprivation showed stronger impact on reactive astrocytes in V1. Moreover, long-term binocular deprivation significantly reduced the density of reactive astrocytes in layer 2/3 of V1 while strengthening gap junction couplings between astrocytes at the same time. Therefore, our data demonstrated that cortical astrocytes could undergo homeostatic plasticity in response to long-term changes of sensory inputs. The plasticity of astrocytes may interact with the plasticity of neurons to cooperatively shape cortical circuit refinement during postnatal development.

Nutrient removal and phosphorus recovery performance of an anaerobic side-stream extraction based enhanced biological phosphorus removal subjected to low dissolved oxygen

An enhanced biological phosphorus removal (EBPR) system based on anaerobic side-stream phosphorus recovery was operated to investigate the nutrient removal performance of the mainstream system under low dissolved oxygen (DO = 1.0, 0.6, 0.2 mg L−1) and the corresponding phosphorus recovery efficiency with different extracting ratio (m = 0, 1/4, 1/3, 1/2) of anaerobic supernatant within 310 days. The results showed that the nutrient removal efficiency remained stable even though DO was extremely low. Nevertheless, phosphorus removal performance was found to deteriorate as side-stream ratio increased to 1/3 at DO = 0.2 mg L−1, suggesting that extracting a higher ratio of supernatant was not favorable for phosphorus removal in the mainstream process at ultra-low DO. The stoichiometric ratios of Prelease/HAcuptake during anaerobic phase which decreased from 0.125 to 0.020 P-mol/C-mol as DO decreased with increasing side-stream ratio were lower than that of typical PAO metabolism. It was very likely that the metabolic mode of PAOs changed due to long-term deprivation of phosphate. Consequently, the mainstream EBPR system failed to remove phosphorus efficiently. It was also observed that phosphorus recovery efficiency was considerable at DO ≥ 0.6 mg L−1 coupled with high side-stream ratio. Therefore, it was feasible and energy-saving to extract appropriate ratio of anaerobic supernatant for recovering phosphorus and removing nutrient efficiently in an EBPR process under low DO.

Plant inputs mediate the linkage between soil carbon and net nitrogen mineralization

Plant residue inputs play a crucial role in regulating soil carbon (C) stock and nitrogen (N) availability in cropland. However, little is known regarding how plant inputs mediate the relationships between soil C and net N mineralization, causing additional uncertainty in predicting ecosystem C and N dynamics. This study investigated the influences of long-term deprivation of plant inputs, short-term addition of maize straw and experimental warming on soil C and net N mineralization and their relationships. We conducted an 815-day laboratory incubation experiment under 10 and 20 °C using soils from a long-term bare fallow plot (without plant inputs for 23 years) and its adjacent old field plot (with continuous plant inputs). Our results showed that long-term deprivation of plant inputs decreased soil net N mineralization (per unit total N or TN) by 56% on average, but had minor effect on soil C mineralization (per unit soil organic C). Soil C and net N mineralization rates were positively correlated in the old field soil under 20 °C. However, soil C and net N mineralization rates were not correlated in the bare fallow soil, mainly due to the low level of net N mineralization. Moreover, soil C and net N mineralization rates were significantly increased by the addition of maize straw in both land-use types. When net N mineralization was <162 (or 159) μg N g−1 TN d−1, soil C and net N mineralization rates were negatively correlated due to an increase of microbial N demand during plant litter mineralization. When net N mineralization was >162 (or 159) μg N g−1 TN d−1, soil C and net N mineralization rates were positively correlated owing to a greater microbial mining of N from soil organic matter (SOM). Further, elevated temperature increased soil C and net N mineralization rates, and changed the relationships between soil C and net N mineralization. Taken together, this study provides evidence that plant inputs mediate the relationships between soil C and net N mineralization, and is thus critical in controlling ecosystem C and N cycling.

Влияние мелатонина и льняного масла на состояние липидного обмена крыс при десинхронозе

The purpose of this study was to substantiate the possibility of correcting lipid metabolism changes at dark deprivation using linseed oil, melatonin, and their combination. Materials and methods. The experiment involved 130 white outbred male rats with a body weight of 170–220 g. The animals were divided into 5 groups: rats under standard fixed lighting conditions (12 hours light/12 hours dark); rats under modelled dark deprivation with round-the-clock lighting (24 hours light); rats under modelled dark deprivation with round-the-clock lighting (24 hours light) receiving intragastric injections of linseed oil, melatonin or their combination from day 1 of the experiment. Serum concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total phospholipids (TPL) and atherogenic index (AI) were determined. Results. Long-term dark deprivation led to dyslipoproteinemia, which consists in an increase in serum concentrations of TC by a factor of 1.33 (p = 0.0009), TG by a factor of 1.62 (p = 0.013), LDL-C by a factor of 1.2 (p = 0.026) and TPL by a factor of 1.15 (p = 0.0082). The severity of changes in TC, TG, LDL-C, HDL-C and TPL concentrations varied depending on the duration of the experiment. During the use of linseed oil, melatonin or their combination under dark deprivation, the severity of disorders caused by desynchronosis decreased and lipid metabolism in rat serum normalized, especially at the initial stages of the research. Conclusion. Changes in lipid metabolism due to desynchronosis in rats injected with the substances under study were significantly smaller compared with animals that did not receive them. The most pronounced effects of administering these substances were observed in the group of rats treated with linseed oil and melatonin at the same time.

Deficit of female sex hormones desensitizes rat cardiac mitophagy.

Long-term deprivation of female sex hormones has been shown to mediate accumulation of damaged mitochondria in ventricular muscle leading to cardiovascular dysfunction. Therefore, the roles of female sex hormones in mitochondrial quality control are closely focused. In the present study, depletion of female sex hormones impairing mitochondrial autophagy in the heart was hypothesized. Cardiac mitophagy was therefore investigated in the heart of 10-week ovariectomized (OVX) and sham-operated (SHAM) rats. By using isolated mitochondria preparation, results demonstrated an increase in mitochondrial PTEN-induced kinase 1 accumulation in the sample of OVX rats indicating mitochondrial outer membrane dysfunction. However, no change in p62 and LC3-II translocation to mitochondria was observed between two groups indicating unresponsiveness of mitophagosome formation in the OVX rat heart. This loss might be resulted from significant decreases in Parkin and Bcl2l13 expression, but not Bnip3 activation. In summary, results suggest that mitochondrial abnormality in the heart after deprivation of female sex hormones could consequently be due to desensitization of mitophagy process.

Land use systems and livelihoods in demographically heterogeneous frontier stages in the amazon

We investigate how Amazonian smallholders' land use systems coevolve with household-level demographic factors associated with changing livelihood strategies over the different stages of frontier development. Few micro-level studies have investigated this association, particularly due to the paucity of longitudinal data on cohorts of farm colonist households and plots. Cohort analysis is the only way to depict how the structural conditions affecting individual and household livelihood decisions differ from earlier to later stages of frontier development. Our methodological approach involves a unique dataset, based on a micro-level panel of farm households depicting 25 years of settlement in the municipality of Machadinho, in the Brazilian Amazon. We use descriptive statistics with paired t-tests, land use classification analysis, latent transition analysis, and longitudinal multinomial regressions to understand which cohorts of households thrived or failed and, most importantly, why and when. Splitting the data into panels of settlement cohorts helped us understand the effect of demographic life cycle markers on land use choices over the different stages of frontier development and the ability of farm households to adapt their livelihoods at the frontier over time. We found that, as the colonization frontier integrated into markets, the most successful original settlers were those who diversified their portfolio of capitals and livelihood strategies as a response to new local and regional market conditions. We also found a progressive change from land use systems based on subsistence agriculture to diversified land use systems that combine on- and off-farm activities. Livelihood diversification is key to preventing households from becoming trapped in a long-term deprivation trajectory, particularly when the frontier becomes more urban and market-oriented. This explains why land use has become progressively independent of household demographic dynamics in advanced stages. We contend that, as frontiers integrate into markets, diversification should not only be incentivized, but should also be used as a technical strategy to enhance access to subsidized rural credit, as it seems to increase farmers’ likelihood to thrive and improve their resilience against shocks.

Impact of Acculturation on Dental Attendance of Preschoolers Among Filipino Immigrants in Edmonton, Canada

To explore how acculturation influences preventive dental care-seeking behavior for children among Filipino newcomers. We conducted a qualitative focused ethnographic research using semi-structured interviews and focus groups. Participants were a purposive sample of English-speaking, self-identified members of Filipino community in Edmonton who had lived in Canada for less than 10 years and had children aged 2–6 years. Concurrent thematic analysis was used. Six interviews and two focus groups were conducted with 18 participants. Three main themes identified from our inductive analysis were emergency pain-driven concept for children’s dental visit before migration, migration challenges and low priority for preventive dental visits, and acculturation and new perceptions of preventive dental care utilization. Long-term socioeconomic deprivation in home country, challenges for survival in host country, and dental care-seeking behaviors influenced by acculturation process were psychosocially conceptualized within the three identified themes. Exposure to the new culture of dental care in Canada caused a shift from an aggressive treatment-oriented to a more conservative preventive-oriented approach among Filipino immigrants in our study.

Effects of longstanding degraded auditory signal on visuospatial, visuomotor, and visual attention skills in adults with hearing loss

Objective This study examined the consequences of long-term auditory deprivation on visuospatial functions, visuomotor functions, and visual attention skills in adults with early-onset hearing loss. Methods Fifteen adults with bilateral, early-onset (before age 3), severe-to-profound hearing loss who used spoken language participated in this study. Visuospatial (figure ground, form constancy, visual perception) and visuomotor functions (visuomotor integration, visual search) were examined using norm-referenced tests. Visual attention scales were examined using a computerized program, IVA plus continuous performance test. Results As a group, participants performed in the average range on visuospatial and visuomotor functions when compared to normative data presented in the test instruments. However, participants demonstrated below average performance on sustained visual attention. Duration of cochlear implant use positively correlated with one of the visual attention scales, namely visual speed. Conclusions The findings of the current study suggest that adults with early-onset hearing loss may demonstrate difficulties in sustaining attention to visual information. Data also suggest that increased experience with cochlear implant may ameliorate deficits associated with visual attention. Future studies should explore challenges experienced by adults with early-onset hearing loss in their daily activities that may result from this deficit and intervention programs that may enhance visual attention skills.

ROLE OF THE REACTIVE OXYGEN AND NITROGEN SPECIES IN THE DEVELOPMENT OF FIBROSIS IN THE TESTES OF RATS WITH PROLONGED CENTRAL DEPRIVATION OF TESTOSTERONE SYNTHESIS

Prostate cancer is the second most common diagnosis in oncology and ranks the fifth among the causes of mortality in men around the world. 1,276,106 cases of newly diagnosed prostate cancer were recorded in 2018. Androgens play a large role in the development of prostate cancer. Elimination of androgens and blockade of their synthesis are key pathogenetic steps in the treatment of prostate cancer. Metabolic and morphological changes in the testes under prolonged central deprivation of testosterone synthesis are currently not well understood. The aim of this study was to establish the role of reactive oxygen and nitrogen species in the development of morphological changes in the testes of rats under prolonged central deprivation of testosterone synthesis. Materials and methods. The experiments were conducted on 20 sexually mature male Wistar rats. Animals were divided into 4 groups of 5 animals in each. The first group (control) received a subcutaneous injection of 0.9% sodium chloride for 180 days. The second group received a subcutaneous injection of diphereline (triptoreline) in a dose of 0.3 mg/kg of active agent for 30 days in order to simulate the central deprivation of testosterone synthesis. In the third group, diphereline was administered in a dose of 0.3 mg/kg of the active agent for 90 days. The fourth group received a subcutaneous injection of diphereline in a dose of 0.3 mg/kg of the active agent for 180 days. Small pieces of testes were fixed and enclosed in paraffin blocks; then 4-μm thick sections were made and stained with hematoxylin and eosin. Histological preparations were studied using an optical microscope with a digital microphotographic nozzle Olympus C 3040-ADU with programs adapted for these studies. The total activity of NO synthases (gNOS), the activity of the inducible isoform of NO synthase (iNOS) and constitutive isoforms (cNOS), as well as the production of superoxide anion radical (O2•-) were determined in 10% homogenate of testes. Results. Long-term central deprivation of testosterone synthesis leads to an increase in the interstitial space volume with the development of fibrotic changes in the testes on the 180th day of the experiment. The wall of seminiferous tubules was compacted, swollen, there were a large number of parietal macrophages from the outside compared to previous periods of the experiment. In the structure of some convoluted seminiferous tubules, first there was discompletion and disorientation, and then desquamation of spermatids. The number of spermatogonia type A and B decreased. Hypochromia and pycnosis were noted in the nuclei. The activities of gNOS and iNOS increased until the 90th day and decreased by 180th when compared with 90th day, remaining higher than the activities of the control group. Activity of cNOS was reduced in all experimental groups. O2•- production increased in all experimental groups. Conclusion: an increase in the production of nitric oxide by the inducible isoform of NO synthase leads to destructive changes in the testes of rats with the subsequent development of fibrotic changes on the 180th day of central deprivation of testosterone synthesis by enhancing the production of superoxide anion radical.

Glutamine Cooperatively Upregulates Lipopolysaccharide-Induced Nitric Oxide Production in BV2 Microglial Cells through the ERK and Nrf-2/HO-1 Signaling Pathway

Glutamine (Gln) is a nonessential α-amino acid for protein biosynthesis. However, the mechanism through which Gln regulates NO production in microglial cells is still unclear. In this study, we investigated whether the presence or absence of Gln affects NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Our data revealed that Gln depletion decreased cell viability accompanied by mild cytotoxicity, and blocked LPS-induced NO production concomitant with a significant decrease in inducible NO synthase (iNOS) expression. Additionally, Gln depletion for 24 h blocked the restoration of LPS-mediated NO production in the presence of Gln, suggesting that Gln depletion caused long-term immune deprivation. In particular, sodium-coupled amino acid transporter 1 and 2 (SNAT1 and SNAT2), which are the main Gln transporters, were highly upregulated in LPS-stimulated BV2 microglial cells, in the presence of Gln accompanied by NO production. Regardless of the presence of Gln, LPS positively stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression, and transient Nrf2 knockdown and HO-1 inhibition stimulated LPS-induced NO production and iNOS expression; however, transient Nrf2 knockdown did not affect SNAT1 and SNAT2 expression, indicating that Gln transporters, SNAT1 and SNAT2, were not regulated by Nrf2, which downregulated the HO-1-mediated NO production. Moreover, Gln depletion significantly reduced LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation; furthermore, a specific ERK inhibitor, PD98059, and transient ERK knockdown attenuated LPS-stimulated NO production and iNOS expression, in the presence of Gln, accompanied by downregulation of SNAT1 and SNAT2, suggesting that the ERK signaling pathway was related to LPS-mediated NO production via SNAT1 and SNAT2. Altogether, our data indicated that extracellular Gln is vital for NO production from microglia in inflammatory conditions.

Effects of a temporary period on pasture on the welfare state of horses housed in individual boxes

Domesticated horses mainly live in individual boxes, a housing system reported as compromising animal welfare. A common practice in riding schools involves offering a temporary period on pasture with conspecifics to alleviate the impact of long-term deprivation triggered by boxes. The aim of this study was to assess the influence of this practice using four behavioural indicators reflecting a compromised welfare state: stereotypies; aggressive behaviours towards humans; the “withdrawn posture” reflecting unresponsiveness to the environment; and the “alert posture” indicating hypervigilance. A group of 31 horses was monitored before, during and after a period of 1.5 months on pasture (intra-group comparisons) and their behaviours were compared to those of 29 horses kept in individual boxes during the study (inter-group comparisons). On pasture, no stereotypies and aggressive behaviours towards humans were observed, and the occurrence of the “alert posture” decreased, although the results were not significant. An increase in the expression of natural behaviours such as locomotion, exploration and social behaviours was observed. However, the expression of the “withdrawn posture” increased during the first five days on pasture (Friedman: P < 0.001; Wilcoxon signed-rank: P < 0.001) before a decrease was observed after 20 days, returning to the level previously observed when horses were in boxes (Wilcoxon signed-rank: P < 0.01). These results suggest that going out to pasture can positively influence the welfare state of horses, but also that several days of adaptation are needed, probably due to the novelty of the environmental and social conditions. The most noticeable result occurred when horses returned to individual boxes. A sharp increase in the occurrence of stereotypies (Cochran test: P < 0.001; Chi² of homogeneity: P = 0.05), of the “withdrawn” (Friedman: P < 0.001; Wilcoxon rank-sum: P < 0.05) and the “alert” postures (Friedman: P < 0.01; Wilcoxon rank-sum: P < 0.001) was observed during the first five days of returning to confinement. The expression of the majority of natural behaviours immediately returned to the level observed during the pre-pasture period. After three months, the expression of the four welfare indicators was not different from that in the pre-pasture period. These results demonstrate that the beneficial effects likely to be induced by the pasture do not last when horses return to individual boxes and that the environmental change causes deleterious short-term effects on the animals’ welfare state. It would thus be recommended to keep domestic horses permanently on pasture when possible.

Abstract P2-11-20: Endocrine resistance in breast cancer: A dynamic gene expression analysis approach reveals potential new responsible genes

Abstract While ER-targeted endocrine therapies are the most successful therapies for ER-positive breast cancer, tumor recurrence and endocrine-resistance happens in many of the cases. Despite efforts, the underlying genes and mechanisms of this acquired resistance remain largely unknown. Here, we utilized a recently developed pipeline for dynamic gene regulatory network analysis1to re-analyze the publically available datasets related to endocrine resistance in breast cancer in order to find new target genes related to endocrine resistance. The pipeline exploits the time-resolved expression pattern of genes to identify dynamic responsive genes (DRG) and group them into multiple modules based on the similarity in their dynamic activities, which leads us to identify more significant genes compared with previous gene expression analysis models that solely focus on expression value of the genes. Here, we analyzed a dataset of time-resolved gene expression during MCF-7 cell transition to endocrine-resistant cells by long-term deprivation of estrogen, which is an accepted model of endocrine resistance2. The dataset is publically available as GES20361 in the Gene Expression Omnibus (GEO) database. Based on their dynamic expression pattern over time, our method of analysis grouped genes into three main modules. Interestingly, the majority of well-studied genes in the literature related to endocrine resistance are part of one of these modules, while there are many genes such as GABPA, TFDP1, MCM7, MDC1, and FOXC1 that are potential novel targets for treatments against endocrine resistance. Module One included genes related to endocrine resistance, mainly those related to cell cycle, such as CCNA1, CCNA2, CCND1, and CDK family, and DNA replication and repair, such as MDC1 and PARP1, as well as EGFR. Consistent with the previous literature on endocrine resistant breast cancer cells, these genes all showed similar up-regulated expression patterns over time. Furthermore, our model confirmed the identified genes shown in the previous paper2 (POLD1, TERF1, RAF1, and E2F1) as part of Module One and as important genes in endocrine resistance regulation. Module Two was enriched for genes related to PI3K/AKT/mTOR signaling pathway, while Module Three mostly contained tyrosine kinase related genes, which not only confirms the previous findings related to the importance of these genes in acquiring endocrine resistance, but also indicates the difference between the expression patterns of these genes compare to cell cycle genes and those in Module One. Our analysis revealed that the genes in Module One continued their up-regulating trend beyond day 90, when the marked transition toward resistance happens and resistance phenotype starts to arise, while genes in Module Two got up-regulated before the 90 days and down-regulated afterward, suggesting different roles from the genes in Module One. Lastly, we studied the gene regulatory networks, transcription factors, and miRNAs upstream of the identified genes, and discovered several interesting targets, such as MiR-193b and MiR-16, which have integral parts in the regulation of our identified genes and thus can be of great importance toward endocrine resistance.