OxymiRs in cutaneous development,wound repair and regeneration

The state of tissue oxygenation is widely recognized as a major microenvironmental cue that is known to regulate the expression of coding genes. Recent works have extended that knowledge to demonstrate that the state of tissue oxygenation may potently regulate the expression of microRNAs (miRs). Collectively, such miRs that are implicated in defining biological outcomes in response to a change in the state of tissue oxygenation may be referred to as oxymiRs. Broadly, oxymiRs may be categorized into three groups: (A) the existence (expression and/or turnover) of which is directly influenced by changes in the state of tissue oxygenation; (B) the existence of which is indirectly (e.g. oxygen-sensitive proteins, metabolites, pH, etc.) influenced by changes in the state of tissue oxygenation; and (C) those that modify biological outcomes to changes in the state of tissue oxygenation by targeting oxygen sensing pathways. This work represents the first review of how oxymiRs may regulate development, repair and regeneration. Currently known oxymiRs may affect the functioning of a large number of coding genes which have hitherto fore never been linked to oxygen sensing. Many of such target genes have been validated and that number is steadily growing. Taken together, our understanding of oxymiRs has vastly expanded the implications of changes in the state of tissue oxygenation. This emerging paradigm has major implications in untangling the complexities underlying diseases associated with ischemia and related hypoxic insult such as chronic wounds.     

Decay of inspiratory muscle pressure during expiration in conscious humans

In eight conscious spontaneously breathing adults we studied the decay of pressure developed by the inspiratory muscles during expiration (PmusI). PmusI was obtained according to the following equation: PmusI(t) = Ers X V(t) - Rrs X V(t), where V is volume and V is flow at any instant t during spontaneous expiration, and Ers and Rrs are, respectively, the passive elastance and resistance of the total respiratory system. Ers was determined with the relaxation method, and resistance with the interrupter method. All subjects showed marked braking of expiratory flow by PmusI. The mean time for PmusI to reduce to 50 and 0% amounted, respectively, to 23 and 79% of expiratory time. During expiration, 24-55% of the elastic energy stored during inspiration was used as resistive work and the remainder (45-76%) as negative work.     

Sex-dependent structural asymmetry of the medial habenular nucleus of the chicken brain

Summary An investigation of structural asymmetry in the avian brain was conducted on the epithalamic medial habenular nucleus of the chicken. Twelve male and ten female two-day-old chickens were used for a morphometric evaluation of asymmetry. The medial habenular nucleus was measured from paraffin-wax-embedded, 8 m-thick sections by use of a semiautomatic image analyser. The volumes of the right and left medial habenula of each animal were statistically analysed (within animal experimental design). The right medial habenula in males showed significant group asymmetry. In contrast, females failed to demonstrate group bias in favour of either hemisphere. However, individual females were lateralised, with either a larger right or left medial habenula. Although individuals of both sexes were lateralised, there was no significant sex difference in volume in either the right or left medial habenula.We propose that sex-linked structural asymmetry may be influenced by steroid hormonal effects in the central nervous system, and that such asymmetry could be more prevalent in the non-mammalian vertebrate brain than previously considered.     

Dietary Spectrum of Two Sympatric Canid Species in Ladakh,India

We have conducted a study between May and August 2013 to understand the dietary spectrum of two canid species: Tibetan wolf (Canis lupus chanco) and Red fox (Vulpes vulpes) in one of the most inhospitable landscape of the world. Ladakh is characterized by harsh environmental conditions and low primary productivity and therefore animal populations, particularly of large and medium sized herbivores are also low and sparsely distributed. This in turn poses a challenge to the survival of predators. We have attempted to investigate the ways by which the two sympatric canid species are optimizing feeding for their survival in an environment where there is scarcity of wild prey base. Scats of the two species were collected from Chiktan and Rangdum valleys and undigested food remnants were identified. The dietary spectrum of Tibetan wolf was composed of six prey species (2 wild and 4 livestock species). The share of livestock species in the diet was maximum (RO: 62.0%). The Red fox being an opportunistic feeder consumed 19 forgeable items, including small and medium sized mammals, birds, reptiles, insects, plant material, eggs, stones and debris. The livestock species contributed maximum to the diet of Red fox (RO: 22.9%). The dietary niche breadths of both species were more or less similar (0.53 and 0.58) and indicating a generalist feeding behavior. Both the species are surviving in the same environment with a dietary overlap of 0.60. The given information is expected to aid further studies in Indian Trans-Himalaya.     

Probing the ATP-induced conformational flexibility of the PcrA helicase protein using molecular dynamics simulation

Helicases are enzymes that unwind double-stranded DNA (dsDNA) into its single-stranded components. It is important to understand the binding and unbinding of ATP from the active sites of helicases, as this knowledge can be used to elucidate the functionality of helicases during the unwinding of dsDNA. In this work, we investigated the unbinding of ATP and its effect on the active-site residues of the helicase PcrA using molecular dynamic simulations. To mimic the unbinding process of ATP from the active site of the helicase, we simulated the application of an external force that pulls ATP from the active site and computed the free-energy change during this process. We estimated an energy cost of ~85 kJ/mol for the transformation of the helicase from the ATP-bound state (1QHH) to the ATP-free state (1PJR). Unbinding led to conformational changes in the residues of the protein at the active site. Some of the residues at the ATP-binding site were significantly reoriented when the ATP was pulled. We observed a clear competition between reorientation of the residues and energy stabilization by hydrogen bonds between the ATP and active-site residues. We also checked the flexibility of the PcrA protein using a principal component analysis of domain motion. We found that the ATP-free state of the helicase is more flexible than the ATP-bound state.     

Methyl Anthranilate, an Inhibitor for the Germination of Spores of Aerobic Bacilli

Methylanthranilate inhibited the germination of spores of aerobic bacilli without affecting growth and sporulation. The inhibition of germination could not be reversed by removal of methylanthranilate.     

Relationship Between [3H]Mazindol Binding to Dopamine Uptake Sites and [3H]Dopamine Uptake in Rat Striatum During Aging

Certain drugs exhibit a remarkable correlation between their ability to inhibit synaptosomal uptake of dopamine and the binding of [3H]mazindol to striatal membranes. To investigate the role of mazindol binding sites in the dopamine uptake process and the fate of these sites (labeling dopaminergic neurons) during aging, we have examined the properties of mazindol binding and dopamine uptake in individual young and old rats. There was a 48% decrease (p = 0.0001) in the Bmax of mazindol binding and a 23% decrease (p = 0.0166) in the Vmax of dopamine uptake with no apparent change in their affinities with age. Regression analysis of the relationship between Bmax and Vmax exhibited a significant correlation in old (p = 0.0156) but not young rats (p = 0.1398). These data suggest that the number of mazindol binding sites decreases with age and that the number of sites on the dopamine transporter complex far exceeds the number required to elicit maximal dopamine uptake.     

Characterization and subcellular distribution of specific thyrotropin-releasing hormone binding sites in rat cerebellum

The specific binding of thyrotropin-releasing hormone (TRH) by 30,000g pellet fraction was ubiquitously distributed throughout various rat brain regions including cerebellum. Although the cerebellum had the lowest apparent density of specific TRH binding sites found in any of the brain regions studied, it represented a single class of high afinity receptor (K _D=37.73±4.88 nM,B _max=156.0±5.7 fmol/mg protein,n=4). Furthermore, the cerebellar synaptic plasma membrane fractions were richly endowed with TRH-binding, two other membrane fractions (light-synaptic plasma membrane and microsomal) exhibited high TRH-binding whereas nuclear, mitochondrial or myelin fractions were devoid of significant binding activity. These data show for the first time the existence of specific TRH-binding in cerebellum, and thus suggest that TRH may modulate cerebellar synaptic functions by acting through a specific high affinity-receptor.     

Chronic Alcohol Consumption Increases Cyclo (His-Pro)-Like Immunoreactivity in the Rat Brain

Abstract: Administration of histidyl-proline diketopiperazine (cyclo (HisPro)) to rats attenuates ethanol-induced sleep. To understand the role played by cyclo (His-Pro) in the pathophysiology of prolonged alcohol consumption, we have measured the distribution of this peptide in brains of control and alcohol-treated rats. The data show that prolonged alcohol consumption increases the concentration of cyclo (His-Pro) in hypothalamic as well as extrahypothalamic brain. These changes may reflect a physiologic adaptation of the brain during alcohol consumption.