Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These ...three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro‐survival or pro‐death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti‐cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis‐related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment.
Population viability might become compromised by the loss of genetic diversity and the accumulation of inbreeding resulting from population decline and fragmentation. The Iberian lynx (Lynx pardinus) ...provides a paradigmatic example of a species at the verge of extinction, and because of the well‐documented and different demographic histories of the two remaining populations (Doñana and Andújar), it provides the opportunity to evaluate the performance of analytical methods commonly applied to recently declined populations. We used mitochondrial sequences and 36 microsatellite markers to evaluate the current genetic status of the species and to assess the genetic signatures of its past history. Mitochondrial diversity was extremely low with only two haplotypes, alternatively fixed in each population. Both remnant populations have low levels of genetic diversity at microsatellite markers, particularly the population from Doñana, and genetic differentiation between the two populations is high. Bayesian coalescent‐based methods suggest an earlier decline starting hundreds of years ago, while heterozygosity excess and M‐ratio tests did not provide conclusive and consistent evidence for recent bottlenecks. Also, a model of gene flow received overwhelming support over a model of pure drift. Results that are in conflict with the known recent demography of the species call for caution in the use of these methods, especially when no information on previous demographic history is available. Overall, our results suggest that current genetic patterns in the Iberian lynx are mainly the result of its recent decline and fragmentation and alerts on possible genetic risks for its persistence. Conservation strategies should explicitly consider this threat and incorporate an integrated genetic management of wild, captive and re‐introduced populations, including genetic restoration through translocations.
Iran lies at the southernmost range limit of brown bears globally. Therefore, understanding the habitat associations and patterns of population connectivity for brown bears in Iran is relevant for ...the species' conservation. We applied species distribution modeling to predict habitat suitability and connectivity modeling to identify population core areas and corridors. Our results showed that forest density, topographical roughness, NDVI and human footprint were the most influential variables in predicting brown bear distribution. The most crucial core areas and corridor networks for brown bear are concentrated in the Alborz and Zagros Mountains. These two core areas were predicted to be fragmented into a total of fifteen isolated patches if dispersal of brown bear across the landscape is limited to 50,000 cost units, and aggregates into two isolated habitat patches if the species is capable of dispersing 400,000 cost units. We found low overlap between corridors, and core habitats with protected areas, suggesting that the existing protected area network may not be adequate for the conservation of brown bear in Iran. Our results suggest that effective conservation of brown bears in Iran requires protection of both core habitats and the corridors between them, especially outside Iran's network of protected areas.
The two-time correlation functions of the coordinate and velocity of a non-Markovian harmonic particle are derived analytically. They are decomposed into the components of differences between the ...initial variances and the equilibrium of the particle; in particular, the dependence of a random force on the initial preparation of the system is included. Using those expressions, we simultaneously investigate nonstationary, nonergodic, and nonequilibrium features of a forced system. It is demonstrated that the result of combining the oscillating relaxation and the initial preparation-dependent noise leads to breakdown of both ergodicity and equilibration of a forced system. The finite-size effect of a coupled-oscillator-chain heat bath is also discussed.
Abstract
Three bulk microphysics schemes with different complexities in the Weather Research and Forecasting Model are compared in terms of the individual microphysical process terms of the ...hydrometeor mass and number mixing ratio tendency equations in an idealized 2D squall-line case. Through evaluation of these process terms and of hydrometeor size distributions, it is shown that the differences in the simulated population characteristics of snow, graupel, and rainwater are the prominent factors contributing to the differences in the development of the simulated squall lines using these schemes. In this particular case, the gust front propagation speed produced by the Thompson scheme is faster than in the other two schemes during the first 2 h of the simulation because it has a larger dominant graupel size. After 2 h into the simulation, the initially less intense squall lines in the runs using the WSM6 and Morrison schemes start to catch up in intensity and development to the run using the Thompson scheme. Because the dominant size of graupel particles in the runs using the WSM6 and Morrison schemes is smaller, these particles take more time to fall below the freezing level and enhance the rainwater production and its evaporative cooling. In the run using the Thompson scheme, the graupel production slows down at later times while the snow particle growth increases, leading to more snow falling below the freezing level to melt and surpass graupel particle melting in the production of rainwater.
Mounting evidence has shown that periodontitis is associated with diabetes. However, a causal relationship remains to be determined. Recent studies reported that periodontitis may be associated with ...gut microbiota, which plays an important role in the development of diabetes. Therefore, we hypothesized that gut microbiota might mediate the link between periodontitis and diabetes. Periodontitis was induced by ligatures. Glycemic homeostasis was evaluated through fasting blood glucose (FBG), serum glycosylated hemoglobin (HbA1c), and intraperitoneal glucose tolerance test. Micro–computed tomography and hematoxylin and eosin staining were used to evaluate periodontal destruction. The gut microbiota was analyzed using 16S ribosomal RNA gene sequencing and bioinformatics. Serum endotoxin, interleukin (IL) 6, tumor necrosis factor α (TNF-α), and IL-1β were measured to evaluate the systemic inflammation burden. We found that the levels of FBG, HbA1c, and glucose intolerance were higher in the periodontitis (PD) group than in the control (Con) group (P < 0.05). When periodontitis was eliminated, the FBG significantly decreased (P < 0.05). Several butyrate-producing bacteria were decreased in the gut microbiota of the PD group, including Lachnospiraceae_NK4A136_group, Eubacterium_fissicatena_group, Eubacterium_coprostanoligenes_group, and Ruminococcaceae_UCG-014 (P < 0.05), which were negatively correlated with serum HbA1c (P < 0.05). Subsequently, the gut microbiota was depleted using antibiotics or transplanted through cohousing. Compared with the PD group, the levels of HbA1c and glucose intolerance were decreased in the gut microbiota-depleted mice with periodontitis (PD + Abx) (P < 0.05), as well as the serum levels of endotoxin and IL-6 (P < 0.05). The serum levels of IL-6, TNF-α, and IL-1β in the PD + Abx group were higher than those of the Con group (P < 0.05). Antibiotics exerted a limited impact on the periodontal microbiota. When the PD mice were cohoused with healthy ones, the elevated FBG and HbA1c significantly recovered (P < 0.05), as well as the aforementioned butyrate producers (P < 0.05). Thus, within the limitations of this study, our data indicated that the gut microbiota may mediate the influence of periodontitis on prediabetes.
Abstract
This paper focuses on parameterizing the effect of sea spray at hurricane-strength winds on the momentum and heat fluxes in weather prediction models using the Monin–Obukhov similarity ...theory (a common framework for the parameterizations of air–sea fluxes). In this scheme, the mass-density effect of sea spray is considered as an additional modification to the stratification of the near-surface profiles of wind, temperature, and moisture in the marine surface boundary layer (MSBL). The overall impact of sea-spray droplets on the mean profiles of wind, temperature, and moisture depends on the wind speed at the level of sea-spray generation. As the wind speed increases, the mean droplet size and the mass flux of sea-spray increase, rendering an increase of stability in the MSBL and the leveling-off of the surface drag. Sea spray also tends to increase the total air–sea sensible and latent heat fluxes at high winds. Results from sensitivity testing of the scheme in a numerical weather prediction model for an idealized case of hurricane intensification are presented along with a dynamical interpretation of the impact of the parameterized sea-spray physics on the structure of the hurricane boundary layer.
Decision-makers in wildlife policy require reliable population size estimates to justify interventions, to build acceptance and support in their decisions and, ultimately, to build trust in managing ...authorities. Traditional capture-recapture approaches present two main shortcomings, namely, the uncertainty in defining the effective sampling area, and the spatially-induced heterogeneity in encounter probabilities. These limitations are overcome using spatially explicit capture-recapture approaches (SCR). Using wolves as case study, and non-invasive DNA monitoring (faeces), we implemented a SCR with a Poisson observation model in a single survey to estimate wolf density and population size, and identify the locations of individual activity centres, in NW Iberia over 4,378 km
. During the breeding period, posterior mean wolf density was 2.55 wolves/100 km
(95%BCI = 1.87-3.51), and the posterior mean population size was 111.6 ± 18.8 wolves (95%BCI = 81.8-153.6). From simulation studies, addressing different scenarios of non-independence and spatial aggregation of individuals, we only found a slight underestimation in population size estimates, supporting the reliability of SCR for social species. The strategy used here (DNA monitoring combined with SCR) may be a cost-effective way to generate reliable population estimates for large carnivores at regional scales, especially for endangered species or populations under game management.
Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
Evidence suggests that periodontitis contributes to the pathogenesis of inflammatory bowel disease, including Crohn’s disease and ulcerative colitis. However, few studies have examined the role of ...swallowing and saliva in the pathogenesis of gastrointestinal diseases. Saliva contains an enormous number of oral bacteria and is swallowed directly into the intestine. Here, we explored the influence of periodontitis salivary microbiota on colonic inflammation and possible mechanisms in dextran sulfate sodium (DSS)–induced colitis. The salivary microbiota was collected from healthy individuals and those with periodontitis and gavaged to C57BL/6 mice. Periodontitis colitis was induced by DSS for 5 d and ligature for 1 wk. The degree of colon inflammation was evaluated through hematoxylin and eosin staining, ELISA, and quantitative real-time polymerase chain reaction. Immune parameters were measured with quantitative real-time polymerase chain reaction, flow cytometry, and immunofluorescence. The gut microbiota and metabolome analyses were performed via 16S rRNA gene sequencing and liquid chromatography–mass spectrometry. Although no significant colitis-associated phenotypic changes were found under physiologic conditions, periodontitis salivary microbiota exacerbated colitis in a periodontitis colitis model after DSS induction. The immune response more closely resembled the pathology of ulcerative colitis, including aggravated macrophage M2 polarization and Th2 cell induction (T helper 2). Inflammatory bowel disease–associated microbiota, such as Blautia, Helicobacter, and Ruminococcus, were changed in DSS-induced colitis after periodontitis salivary microbiota gavage. Periodontitis salivary microbiota decreased unsaturated fatty acid levels and increased arachidonic acid metabolism in DSS-induced colitis, which was positively correlated with Aerococcus and Ruminococcus, suggesting the key role of these metabolic events and microbes in the exacerbating effect of periodontitis salivary microbiota on experimental colitis. Our study demonstrated that periodontitis contributes to the pathogenesis of colitis through the swallowing of salivary microbiota, confirming the role of periodontitis in systemic disease and providing new insights into the etiology of gastrointestinal inflammatory diseases.
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