In vivo lung morphometry with hyperpolarized 3He diffusion MRI in canines with induced emphysema: disease progression and comparison with computed tomography.

Despite a long history of development, diagnostic tools for in vivo regional assessment of lungs in patients with pulmonary emphysema are not yet readily available. Recently, a new imaging technique, in vivo lung morphometry, was introduced by our group. This technique is based on MRI measurements of diffusion of hyperpolarized (3)He gas in lung air spaces and provides quantitative in vivo tomographic information on lung microstructure at the level of the acinar airways. Compared with standard diffusivity measurements that strongly depend on pulse sequence parameters (mainly diffusion time), our approach evaluates a "hard number," the average acinar airway radius. For healthy dogs, we find here a mean acinar airway radius of approximately 0.3 mm compared with 0.36 mm in healthy humans. The purpose of the present study is the application of this technique for quantification of emphysema progression in dogs with experimentally induced disease. The diffusivity measurements and resulting acinar airway geometrical characteristics were correlated with the local lung density and local lung-specific air volume calculated from quantitative computed tomography data obtained on the same dogs. The results establish an important association between the two modalities. The observed sensitivity of our method to emphysema progression suggests that this technique has potential for the diagnosis of emphysema and tracking of disease progression or improvement via a pharmaceutical intervention.     

Hexose monophosphate shunt,the role of its metabolites and associated disorders: A review

The hexose monophosphate (HMP) shunt acts as an essential component of cellular metabolism in maintaining carbon homeostasis. The HMP shunt comprises two phases viz. oxidative and nonoxidative, which provide different intermediates for the synthesis of biomolecules like nucleotides, DNA, RNA, amino acids, and so forth; reducing molecules for anabolism and detoxifying the reactive oxygen species during oxidative stress. The HMP shunt is significantly important in the liver, adipose tissue, erythrocytes, adrenal glands, lactating mammary glands and testes. We have researched the articles related to the HMP pathway, its metabolites and disorders related to its metabolic abnormalities. The literature for this paper was taken typically from a personal database, the Cochrane database of systemic reviews, PubMed publications, biochemistry textbooks, and electronic journals uptil date on the hexose monophosphate shunt. The HMP shunt is a tightly controlled metabolic pathway, which is also interconnected with other metabolic pathways in the body like glycolysis, gluconeogenesis, and glucuronic acid depending upon the metabolic needs of the body and depending upon the biochemical demand. The HMP shunt plays a significant role in NADPH₂ formation and in pentose sugars that are biosynthetic precursors of nucleic acids and amino acids. Cells can be protected from highly reactive oxygen species by NADPH ₂. Deficiency in the hexose monophosphate pathway is linked to numerous disorders. Furthermore, it was also reported that this metabolic pathway could act as a therapeutic target to treat different types of cancers, so treatments at the molecular level could be planned by limiting the synthesis of biomolecules required for proliferating cells provided by the HMP shunt, hence, more experiments still could be carried out to find additional discoveries.     

A cell surface protein controls endocrine ring gland morphogenesis and steroid production

Identification of signals for systemic adaption of hormonal regulation would help to understand the crosstalk between cells and environmental cues contributing to growth, metabolic homeostasis and development. Physiological states are controlled by precise pulsatile hormonal release, including endocrine steroids in human and ecdysteroids in insects. We show in Drosophila that regulation of genes that control biosynthesis and signaling of the steroid hormone ecdysone, a central regulator of developmental progress, depends on the extracellular matrix protein Obstructor-A (Obst-A). Ecdysone is produced by the prothoracic gland (PG), where sensory neurons projecting axons from the brain integrate stimuli for endocrine control. By defining the extracellular surface, Obst-A promotes morphogenesis and axonal growth in the PG. This process requires Obst-A-matrix reorganization by Clathrin/Wurst-mediated endocytosis. Our data identifies the extracellular matrix as essential for endocrine ring gland function, which coordinates physiology, axon morphogenesis, and developmental programs. As Obst-A and Wurst homologs are found among all arthropods, we propose that this mechanism is evolutionary conserved.     

Efficient directional cloning of recombinant adenovirus vectors using DNA-protein complex.

We describe an efficient cloning system utilizing adenoviral DNA-protein complexes which allows the directional cloning of genes into adenoviral expression vectors in a single step. DNA-protein complexes derived from a recombinant adenovirus (AVC2.null) were isolated by sequential use of CsCl step gradients followed by isopycnic centrifugation in a mixture of CsCl and guanidine HCl. AVC2.null is an adenoviral expression vector containing unique restriction sites between the human CMV-IE promoter and the SV40 intron/polyadenylation site. Transgenes were prepared for cloning into this vector by introduction of compatible restriction sites by PCR. A vector expressing rat granulocyte-macrophage colony-stimulating factor (GM-CSF) was constructed using DNA-protein complex as well as by traditional recombination techniques. The efficacy of our adenoviral cloning system utilizing DNA-protein complex was two logs higher than that seen using homologous recombination. All viruses generated by directional ligation of the insert into the vector DNA-protein complexes contained the desired transgene in the correct orientation. This technique greatly simplifies and accelerates the generation of recombinant adenoviral vectors.     

Using flowering times and leaf numbers to model the phases of photoperiod sensitivity in Antirrhinum majus L

A model has been developed that can be used to determine the phases of sensitivity to photoperiod for seedlings subjected to reciprocal transfers at regular intervals between long (LD) and short day (SD) conditions. The novel feature of this approach is that it enables the simultaneous analysis of the time to flower and number of leaves below the inflorescence. A range of antirrhinum cultivars were grown, all of which were shown to be quantitative long-day plants. Seedlings were effectively insensitive to photoperiod when very young (juvenile). However, after the end of the juvenile phase, SD delayed flowering and increased the number of leaves below the inflorescence. Plants transferred from LD to SD showed a sudden hastening of flowering and a decrease in leaf number once sufficient LD had been received for flower commitment. Photoperiod had little effect on the rate of flower development. The analysis clearly identified major cultivar differences in the length of the juvenile phase and the photoperiod-sensitive inductive phase in both LD and SD.     

Screening of Trace Metals in the Plasma of Breast Cancer Patients in Comparison with a Healthy Population

The plasmas of breast cancer patients and healthy donors were analyzed for selected trace metals by a flame atomic absorption spectrophotometric method. In the plasma of breast cancer patients, mean concentrations of macronutrients/essential metals, Na, K, Ca, Mg, Fe, and Zn were 3584, 197.0, 30.80, 6.740, 5.266, and 6.170 ppm, respectively, while the mean metal levels in the plasma of healthy donors were 3908, 151.0, 72.40, 17.70, 6.613, and 2.461 ppm, respectively. Average concentrations of Cd, Cr, Cu, Mn, Ni, Pb, Sb, Sr, and Zn were noted to be significantly higher in the plasma of breast cancer patients compared with healthy donors. Very strong mutual correlations (r > 0.70) in the plasma of breast cancer patients were observed between Cd–Pb, Cr–Li, Li–K, Li–Cd, K–Cr, Li–Pb, Cr–Co, Cu–Ni, Co–K, Cd–K, and K–Pb, whereas, Al–Cr, Ca–Zn, Cd–Sb, Cd–Zn, Ca–Mg, Fe–Zn, and Na–Mn exhibited strong relationships (r > 0.60) in the plasma of healthy donors. The cluster analysis revealed considerably different apportionment of trace metals in the two groups of donors. The average metal concentrations of different age groups of the two donor categories were also evaluated, which showed the build-up of Al, Cd, Co, Cr, Mn, Li, Pb, Sb, and Zn in the plasma of breast cancer patients. The role of some trace metals in carcinogenesis is also discussed. The study indicated appreciably different patterns of metal distribution and correlation in the plasma of breast cancer patients in comparison with the healthy population.