Aurora kinase-C-T191D is constitutively active mutant

Background

Autophagy is a ubiquitous cellular process responsible for the bulk degradation of cytoplasmic components through the autophagosomal-lysosomal pathway. In skeletal muscle, autophagy has been regarded as a key regulator for muscle mass maintenance, and its imbalance leads to sarcopenia. However, the underlying mechanism is poorly understood.

Results

In this study, we demonstrate that ceMTM3, a FYVE-domain containing myotubalarin family phosphatase, is required for the maintenance of muscle fibers by preventing excessive autophagy in Caenorhabditis elegans. Knockdown of ceMTM3 by using feeding-based RNA interference caused loss of muscle fibers accompanied by shortening of muscle cell and body size in aged C. elegans worms. This was preceded by the occurrence of excessive autophagy in the muscle and other tissues, which subsequently resulted in increased lysosomal activity and necrotic cell death. However, knockdown of ceMTM3 did not aggravate the abnormalities of muscle wasting in autophagy-deficient atg-18 mutant worms.

Conclusions

Our data suggest an important role of ceMTM3 in regulating autophagy and maintaining muscle fibers. This study may have clinical implications for prevention and treatment of sarcopenia.     

Kinetics of beta-glucosidase production by Saccharomyces cerevisiae recombinants harboring heterologous bgl genes

The maximum productivity of -glucosidase by Saccharomyces cerevisiaerecombinants under the control of GALI promoter was 100 IU l^–1 h^–1. The highest productivity of -glucosidase by a S. cerevisiae recombinant was 16-fold more than that supported by Cellulomonas biazotea. The recombinants also co-produced ethanol from cellobiose: maximum product yield and productivity were 0.5 and 1.1 g ethanol g^–1 cellobiose and g ethanol l^–1 h^–1, respectively.     

High Fat Feeding in Mice Is Insufficient to Induce Cardiac Dysfunction and Does Not Exacerbate Heart Failure

Preclinical studies of animals with risk factors, and how those risk factors contribute to the development of cardiovascular disease and cardiac dysfunction, are clearly needed. One such approach is to feed mice a diet rich in fat (i.e. 60%). Here, we determined whether a high fat diet was sufficient to induce cardiac dysfunction in mice. We subjected mice to two different high fat diets (lard or milk as fat source) and followed them for over six months and found no significant decrement in cardiac function (via echocardiography), despite robust adiposity and impaired glucose disposal. We next determined whether antecedent and concomitant exposure to high fat diet (lard) altered the murine heart’s response to infarct-induced heart failure; high fat feeding during, or before and during, heart failure did not significantly exacerbate cardiac dysfunction. Given the lack of a robust effect on cardiac dysfunction with high fat feeding, we then examined a commonly used mouse model of overt diabetes, hyperglycemia, and obesity (db/db mice). db/db mice (or STZ treated wild-type mice) subjected to pressure overload exhibited no significant exacerbation of cardiac dysfunction; however, ischemia-reperfusion injury significantly depressed cardiac function in db/db mice compared to their non-diabetic littermates. Thus, we were able to document a negative influence of a risk factor in a relevant cardiovascular disease model; however, this did not involve exposure to a high fat diet. High fat diet, obesity, or hyperglycemia does not necessarily induce cardiac dysfunction in mice. Although many investigators use such diabetes/obesity models to understand cardiac defects related to risk factors, this study, along with those from several other groups, serves as a cautionary note regarding the use of murine models of diabetes and obesity in the context of heart failure.     

Plant‐based oral vaccines against zoonotic and non‐zoonotic diseases

The shared diseases between animals and humans are known as zoonotic diseases and spread infectious diseases among humans. Zoonotic diseases are not only a major burden to livestock industry but also threaten humans accounting for >60% cases of human illness. About 75% of emerging infectious diseases in humans have been reported to originate from zoonotic pathogens. Because antibiotics are frequently used to protect livestock from bacterial diseases, the development of antibiotic‐resistant strains of epidemic and zoonotic pathogens is now a major concern. Live attenuated and killed vaccines are the only option to control these infectious diseases and this approach has been used since 1890. However, major problems with this approach include high cost and injectable vaccines is impractical for >20 billion poultry animals or fish in aquaculture. Plants offer an attractive and affordable platform for vaccines against animal diseases because of their low cost, and they are free of attenuated pathogens and cold chain requirement. Therefore, several plant‐based vaccines against human and animals diseases have been developed recently that undergo clinical and regulatory approval. Plant‐based vaccines serve as ideal booster vaccines that could eliminate multiple boosters of attenuated bacteria or viruses, but requirement of injectable priming with adjuvant is a current limitation. So, new approaches like oral vaccines are needed to overcome this challenge. In this review, we discuss the progress made in plant‐based vaccines against zoonotic or other animal diseases and future challenges in advancing this field.     

Accuracy checks of physical beam modifier factors algorithm used in computerized treatment planning system for a 15 MV photon beam

In order to optimize the tumour dose by using wedge filters, systematic studies were carried out to investigate the accuracy of the beam modifier algorithm in a computerized treatment planning system (Theraplan plus, version 3.8). The effect of different parameters such as beam hardening and softening coefficients on the wedge factor was also studied. A 15 MV photon beam obtained from a linear accelerator was used throughout the experiments. Normalized wedge factors were determined experimentally as well as with the Theraplan plus system as a function of field size and depth in a water phantom for 15°, 30°, 45°, and 60° wedge filters. The attenuation coefficients, beam hardening coefficient, and beam softening coefficients were also determined experimentally using the 15 MV photon beam for each wedge angle. The measured normalized wedge factor was found to increase with increasing depth and field size for the 15 MV beam. The Theraplan plus calculated normalized wedge factor was found to be in good agreement with the experimental values. This study indicated that ignoring the dependence of the wedge factor on depth and field size will result in underexposure of the tumour.     

Serum organochlorine pesticides residues and risk of cancer: A case-control study

Organochlorine pesticides (OCPs) are frequently used worldwide as insecticides, fungicides, herbicides and termiticides and have been associated with a variety of cancers in animal and human studies. In the present study, we examined residues of fourteen OCPs in the serum samples of diagnosed cancer patients and healthy residents of Karachi, Pakistan. A random collection of fasting blood samples was carried out from the donors with informed consent. Serum was separated within 2?h of blood collection and was then subjected to extraction with organic solvents followed by purification with florisil column. The final organic extract of each serum sample was processed with Gas Chromatograph coupled with Electron Capture Detector (GC-ECD). OCPs were detected in 97.59% of the cancer cases and 93.75% of the healthy subjects. Mean concentrations of total OCPs (ΣOCPs) was found elevated in the cancer group (0.606?mg/kg) compared with the control group (0.322?mg/kg). Endosulfan was the highest prevalent OCP with a mean concentration of 0.214?mg/kg in the cancer group and 0.166?mg/kg in the control group. The second most prevalent OCP was 4,4-DDE with a mean concentration of 0.131?mg/kg in the cancer group and 0.019?mg/kg in the control group. Highest level of ΣOCPs was detected in the breast cancer cases (20.411?mg/kg) with a mean level of (2.041?mg/kg). In light of the obtained results and available literature on the subject, it has been concluded that OCPs are positively associated with the risk of various cancers in humans.     

Sugar beet extract acts as a natural bio-stimulant for physio-biochemical attributes in water stressed wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.)

The present study investigated the role of sugar beet extract (SBE) as a bio-stimulant to ameliorate the adverse effects of drought on seed germination and growth of wheat (Triticum aestivum L.). Different concentrations of SBE (0, 10, 20, 30, 40 and 50%) were used for priming the wheat seeds. The experiment was conducted in laboratory (PEG-8000 was used to create water stress) as well as under natural environmental conditions (using soil with 100 and 60% field capacity). Significant ameliorating effects of seed priming with SBE were recorded on different germination attributes, i.e., time to 50% emergence (E₅₀), germination index (GI), mean emergence time (MET), germination percentage (G%), coefficient of uniformity of emergence (CUE) and germination energy (GE) under water stress. Without priming, the plants exhibited symptoms of water stress like decreased biomass, reduction in photosynthetic pigments, e.g., chlorophyll, carotenoids. Seed pre-conditioning with SBE improved the plant growth, photosynthetic pigments, antioxidants’ activities and nutrient homeostasis of plants facing water deficit and grown under well-watered conditions. The maximum increase in biomass, content of chlorophyll, carotenoids and activities of superoxide dismutase (SOD) and peroxidase (POD) was 13.4, 8.5, 11.9, 7.6, 13.6, 42.0, 19.8%, respectively, with SBE seed priming under water stress. In conclusion, SBE seed priming effectively reduced the negativities of water stress on seed germination which resulted in better plant growth in terms of enhanced biomass, photosynthetic pigments, antioxidant defense mechanism and better nutrient homeostasis. Overall, the findings suggest that seed pre-conditioning with SBE as a bio-stimulant will be helpful for better crop stand establishment under low field capacity, especially in semi-arid and arid agricultural fields.     

Novel Changes in NF-κB Activity during Progression and Regression Phases of Hyperplasia: ROLE OF MEK,ERK, AND p38*

Utilizing the Citrobacter rodentium-induced transmissible murine colonic hyperplasia (TMCH) model, we measured hyperplasia and NF-κB activation during progression (days 6 and 12 post-infection) and regression (days 20–34 post-infection) phases of TMCH. NF-κB activity increased at progression in conjunction with bacterial attachment and translocation to the colonic crypts and decreased 40% by day 20. NF-κB activity at days 27 and 34, however, remained 2–3-fold higher than uninfected control. Expression of the downstream target gene CXCL-1/KC in the crypts correlated with NF-κB activation kinetics. Phosphorylation of cellular IκBα kinase (IKK)α/β (Ser^176/180) was elevated during progression and regression of TMCH. Phosphorylation (Ser^32/36) and degradation of IκBα, however, contributed to NF-κB activation only from days 6 to 20 but not at later time points. Phosphorylation of MEK1/2 (Ser^217/221), ERK1/2 (Thr²⁰²/Tyr²⁰⁴), and p38 (Thr¹⁸⁰/Tyr¹⁸²) paralleled IKKα/β kinetics at days 6 and 12 without declining with regressing hyperplasia. siRNAs to MEK, ERK, and p38 significantly blocked NF-κB activity in vitro, whereas MEK1/2-inhibitor (PD98059) also blocked increases in MEK1/2, ERK1/2, and IKKα/β thereby inhibiting NF-κB activity in vivo. Cellular and nuclear levels of Ser⁵³⁶-phosphorylated (p65⁵³⁶) and Lys³¹⁰-acetylated p65 subunit accompanied functional NF-κB activation during TMCH. RSK-1 phosphorylation at Thr³⁵⁹/Ser³⁶³ in cellular/nuclear extracts and co-immunoprecipitation with cellular p65-NF-κB overlapped with p65⁵³⁶ kinetics. Dietary pectin (6%) blocked NF-κB activity by blocking increases in p65 abundance and nuclear translocation thereby down-regulating CXCL-1/KC expression in the crypts. Thus, NF-κB activation persisted despite the lack of bacterial attachment to colonic mucosa beyond peak hyperplasia. The MEK/ERK/p38 pathway therefore seems to modulate sustained activation of NF-κB in colonic crypts in response to C. rodentium infection.     

Some Biochemical Abnormalities Caused by Cypermethrin in Adults of Tribolium castaneum (Herbst.)

Biochemical effects of sub lethal doses LC₁₀ and LC₂₀ of cypermethrin were studied on some enzymes and macromolecule activities of adult beetles of Tribolium castaneum (Herbst.). Cypermethrin caused disturbances in levels of all biochemical components under study. The dose of 0.78 ppm caused abnormalities in α‐amylase and FAA by increasing their activities i.e., 45.45% and 21.97% significantly. The higher sub lethal dose of 2.62 ppm disturbed all the parameters (AcP, α‐amylase, soluble protein and FAA) except AkP, which was decreased by 93.06%. Moreover, sub lethal doses either increased or decreased the levels of all parameters non‐significantly except AkP and FAA which were effected significantly by 87.92% and 14.29% at lower and higher doses, respectively. In the present studies, cypermethrin significantly enhanced the activity of AkP in both susceptible and resistant strains of T. castaneum adult beetles while FAA contents were increased significantly in resistant strain only. The activity of α‐amylase was significantly lowered in susceptible strain only.