Longevity-relevant regulation of autophagy at the level of the acetylproteome

The acetylase inhibitor, spermidine and the deacetylase activator, resveratrol, both induce autophagy and prolong life span of the model organism Caenorhabditis elegans in an autophagydependent fashion. Based on these premises, we investigated the differences and similarities in spermidine and resveratrol-induced autophagy. The deacetylase sirtuin 1 (SIRT1) and its orthologs are required for the autophagy induction by resveratrol but dispensable for autophagy stimulation by spermidine in human cells, Saccharomyces cerevisiae and C. elegans. SIRT1 is also dispensable for life-span extension by spermidine. Mass spectrometry analysis of the human acetylproteome revealed that resveratrol and/or spermidine induce changes in the acetylation of 560 peptides corresponding to 375 different proteins. Among these, 170 proteins are part of the recently elucidated human autophagy protein network. Importantly, spermidine and resveratrol frequently affect the acetylation pattern in a similar fashion. In the cytoplasm, spermidine and resveratrol induce convergent protein de-acetylation more frequently than convergent acetylation, while in the nucleus, acetylation is dominantly triggered by both agents. We surmise that subtle and concerted alterations in the acetylproteome regulate autophagy at multiple levels.     

DNA flow cytometry in metastases and a recurrency of malignant melanomas. A comparison of results from fresh and paraffin embedded material

Single cell suspensions from 16 biopsies from 15 patients with metastatic or recurrent malignant melanoma were prepared according to the method described by Vindel?v (1977) and the nuclear DNA content was measured by a laboratory-built flow cytometer. The DNA histograms thus obtained were compared with those obtained from suspensions of single nuclei from the same biopsies after formalin fixation and paraffin embedding, according to the method of Hedley et al. (1983). Linear regression analysis of ploidy values from fresh material compared with those from paraffin blocks showed a strong correlation (R2 = 0.85), while that of the S-phase fraction was somewhat weaker (R2 = 0.66). It is concluded that archival wax preparations of malignant melanoma cell populations are suitable for FCM analysis of ploidy, and to a lesser extent for analysis of fraction of cells in various cell cycle phases.     

On the snow leopard Trails: Occupancy pattern and implications for management in the Pamir

The snow leopard (Panthera uncia) inhabits one of the most challenging environments on Earth, referred to as the ‘third pole’. Only a fraction of its vast range has been explored thus far, owing to myriad of barriers inflicted by the remote terrain and socio-ecological realities of the landscapes. Understanding distribution patterns of species is essential to devise practical management measures. This study aimed to understand the distribution pattern and factors influencing occupancy of snow leopard in the Pamir Mountain range through sign-based occupancy modelling. Our study confirmed that the Pamir range is a snow leopard stronghold, with occupancy estimated at 0.57 ± 0.02. The topographic features positively influenced the detection probability (p = 0.37 ± 0.005) of snow leopards. Occupancy was influenced by mean annual precipitation (β = -6.12 ± 1.8), density of roads (β = -1.61 ± 0.6) and water sources (β = 0.74 ± 0.4). Our findings underpin that sign-based distribution surveys provide vigorous scientific knowledge about elusive species and merit replication being used for other species. We propose to redefine the protected area boundaries based on ecological knowledge and encourage transboundary cooperation to safeguard snow leopards at a landscape scale.     

Integrative analysis reveals methylenetetrahydrofolate dehydrogenase 1-like as an independent shared diagnostic and prognostic biomarker in five different human cancers

Background: Defects in methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression have earlier been examined in only a few human cancers. Objectives: Multi-omics profiling of MTHFD1L as a shared biomarker in distinct subtypes of human cancers. Methods: In the current study, for the multi-omics analysis of MTHFD1L in 24 major subtypes of human cancers, a comprehensive in silico approach was adopted to mine different open access online databases including UALCAN, Kaplan–Meier (KM) plotter, LOGpc, GEPIA, Human Protein Atlas (HPA), Gene Expression across Normal and Tumor tissue (GENT2), MEXPRESS, cBioportal, STRING, DAVID, TIMER, and Comparative Toxicogenomics Database (CTD). Results: We noticed that the expression of MTHFD1L was significantly higher in all the analyzed 24 subtypes of human cancers as compared with the normal controls. Moreover, MTHDF1L overexpression was also found to be significantly associated with the reduced overall survival (OS) duration of Bladder urothelial cancer (BLCA), Head and neck cancer (HNSC), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that MTHFD1L plays a significant role in the development and progression of these cancers. We further noticed that MTHFD1L was also overexpressed in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of MTHFD1L-associated genes in five diverse pathways. We also explored few interesting correlations between MTHFD1L expression and its promoter methylation, genetic alterations, CNVs, and between CD8+ T immune cells level. Conclusion: In conclusion, our results elucidated that MTHFD1L can serve as a shared diagnostic and prognostic biomarker in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features.     

Optimum leaf excision increases the biomass accumulation and seed yield of maize plants under different planting patterns

Without developing new agronomic practices, present rates of improvement in seed yields of cereal crops globally are insufficient to fulfil the estimated increasing food demand for 2050 and beyond. Intercropping is one of the agricultural practices that can lead to greater crop yields. However, there exists leaf redundancy for maize in intercropping systems, and the top canopy leaves shade more competent leaves at middle strata of maize plants. Therefore, this work aimed to elucidate the effect of leaf excision treatments in maize to understand the optimum leaf area of maize plants under a maize–soybean relay‐intercropping system (MS_R) and a sole cropping system (SM). The effects of four‐leaf excision treatments (T₁, 0; T₂, 2; T₃, 4; T₄, 6 leaves excised from the top of maize plants until 7 days after silking) on light interception, leaf area index (LAI), photosynthetic characteristics, total biomass accumulation at blistering stage (BS), dough stage (DS) and physiological maturity (PM), and seed yield of maize were investigated through field experiments for 2 years under MS_R and SM. Results showed that, under MS_R and SM, as compared to control (T₁), optimum excision of leaves (T₂) from the top of maize plants significantly improved the light interception (by 25, 18 and 16% at BS, DS and PM, respectively) to lower strata leaves and accelerated the biomass partitioning to maize seeds (by 13 and 12% at DS and PM, respectively). Importantly, plants under T₂ exhibited higher green leaf area than control, that is, excision the top two leaves led to an increase in LAI at PM by 10%, suggesting that leaf senescence under T₂ was delayed which enhanced the photosynthetic rate at PM by 7% in 2017 and 6% in 2018. Relative to T₁, maize under T₂ produced 19 and 13% higher maize yield under MS_R and SM, respectively, and relay‐cropped maize had 90% of SM seed yield. These results suggest that by manipulating the canopy structure of maize plants we can enhance the biomass accumulation and seed yield of maize crops under MS_R and SM.     

Lethal and sub‐lethal effects of spinosad on the life‐history traits of army worm,Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), and its fitness cost of resistance

Spodoptera litura is one of the most destructive polyphagous insect pests, with more than 120 host‐plant species. In our present study, a field‐collected population of S. litura when selected with spinosad for 11 consecutive generations resulted in the development of 3921‐fold resistance to spinosad as compared to the susceptible strain. The spinosad‐resistant strain of S. litura had a relatively high fitness cost (0.17) as compared to the susceptible strain. Furthermore, the lethal and sub‐lethal effects of different concentrations of spinosad were checked on the susceptible strain at different levels; i.e., LC₄₀, LC₃₀, LC₂₀ and LC₁₀, which revealed that the impact of spinosad on the life‐history traits of S. litura increased with the increase in concentration of spinosad. A significant impact of spinosad was recorded on the larval duration, pre‐pupal weight, pupal duration, pupal weight, reproductive potential and adult emergence. The outcomes of the current research clearly indicate that fitness cost of spinosad and its sub‐lethal effects have a significant impact on population dynamics of S. litura, for which it can be incorporated in integrated pest management.     

Single or Combined Applications of Zinc and Multi-strain Probiotic on Intestinal Histomorphology of Broilers Under Cyclic Heat Stress

Two-hundred-eighty-day-old broiler chicks were divided into seven groups. The groups were designated as T1, thermoneutral zone; T2, heat stressed (HS); T3,     

Genetic and environmental influences on oxidative damage assessed in elderly Danish twins

Previous studies have shown an association between oxidative stress and various diseases in humans including cancer, cardiovascular disease, diabetes, and chronic respiratory disease. To what extents this damage is determined by genetic and environmental factors is unknown. In a classical twin study with 198 elderly twins we examined the contributions of genetic versus environmental factors to nucleic acid oxidation and lipid peroxidation. Urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and dinor,dihydro F₂-isoprostane metabolites (F₂-IsoP-M) was measured using liquid chromatography–tandem mass spectrometry. The environmental influence on nucleic acid oxidation and lipid peroxidation was predominant, leaving only little influence from genetic factors, as evidenced by no differences in intraclass correlations between monozygotic (MZ) and dizygotic (DZ) twins, neither for 8-oxodG (r_MZ = 0.55, r_DZ = 0.47; P = 0.43), F₂-IsoP-M (r_MZ = 0.33, r_DZ = 0.22; P = 0.42), nor 8-oxoGuo (r_MZ = 0.45, r_DZ = 0.58; P = 0.21). Accordingly, heritability estimates for the three markers of oxidative damage were low (h² = 0.17–0.22). The three urinary markers of oxidative stress were closely correlated (r = 0.60–0.84). In conclusion, we demonstrated in a large population of elderly Danish twins that “whole-body” oxidative damage to nucleic acids and lipids is predominantly determined by potentially modifiable nongenetic factors.