an experience of urban transformation in multan pakistani punjab

This publication concerns studies, programmes and designs for the project Sustainable Social Economic and Environmental Revitalization in the historic core of Multan City in Pakistani Punjab developed by several Politecnico di Milano Departments and Fondazione Politecnico di Milano, an institution that cooperates with Politecnico di Milano in the research fields of architecture, engineering and industrial design. The activities are part of the Debt Swap Agreement signed in 2006 between the governments of Italy and Pakistan for development in the social sectors. Besides the extraordinarily valuable architecture of the Walled City of Multan and its dense and hard-working population, there is a physical and environmental condition that is extremely problematic and that may threaten the continuity of life in the historic part of a city, well known for being among the world's most ancient settlements. The social and cultural interest and the academic challenge of a new opportunity to deal with great traditions pushed the researchers to face the urgency and delicacy of a very complex theme. After the analysis, the surveys and the proposals, the Politecnico group completed the first operational phase reorganizing one of the main City Gate Place, building a new open pavilion and restoring a huge public building and the Gate. The last activity, planned and not yet implemented, refers to the Sarafa Bazaar Project, an integrated system for the urban arrangement through infrastructures systems as sewerage, public lighting and shading, new paving and conservation of historic building's facades

Tracing exogenous surfactant in vivo in rabbits by the natural variation of 13C

BACKGROUND: Respiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by 13C variation and estimate the amount reaching the lungs at different doses of the drug. METHODS: Forty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA) 13C/12C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn's multiple comparison were used to assess differences among experimental groups. RESULTS: Based on DSPC-PA 13C/12C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p < 0.0001) in animals treated with 25 up to 200 mg/kg. Surfactant administration stimulated endogenous surfactant secretion. The percentage of drug recovered from lungs did not depend on the administered dose and accounted for 31% [24-40] of dose. CONCLUSIONS: We reported a risk-free method to trace exogenous surfactant in vivo. It could be a valuable tool for assessing, alongside the physiological response, the delivery efficiency of surfactant administration techniques

Y-chromosome descent clusters and male differential reproductive success: young lineage expansions dominate Asian pastoral nomadic populations

International audienceHigh-frequency microsatellite haplotypes of the male-specific Y-chromosome can signal past episodes of high reproductive success of particular men and their patrilineal descendants. Previously, two examples of such successful Y-lineages have been described in Asia, both associated with Altaic-speaking pastoral nomadic societies, and putatively linked to dynasties descending, respectively, from Genghis Khan and Giocangga. Here we surveyed a total of 5321 Y-chromosomes from 127 Asian populations, including novel Y-SNP and microsatellite data on 461 Central Asian males, to ask whether additional lineage expansions could be identified. Based on the most frequent eight-microsatellite haplotypes, we objectively defined 11 descent clusters (DCs), each within a specific haplogroup, that represent likely past instances of high male reproductive success, including the two previously identified cases. Analysis of the geographical patterns and ages of these DCs and their associated cultural characteristics showed that the most successful lineages are found both among sedentary agriculturalists and pastoral nomads, and expanded between 2100 BCE and 1100 CE. However, those with recent origins in the historical period are almost exclusively found in Altaic-speaking pastoral nomadic populations, which may reflect a shift in political organisation in pastoralist economies and a greater ease of transmission of Y-chromosomes through time and space facilitated by the use of horses

Astrocytic Ca2+ Waves Guide CNS Growth Cones to Remote Regions of Neuronal Activity

Activity plays a critical role in network formation during developmental, experience-dependent, and injury related remodeling. Here we report a mechanism by which axon trajectory can be altered in response to remote neuronal activity. Using photoconductive stimulation to trigger high frequency action potentials in rat hippocampal neurons in vitro, we find that activity functions as an attractive cue for growth cones in the local environment. The underlying guidance mechanism involves astrocyte Ca2+ waves, as the connexin-43 antagonist carbenoxolone abolishes the attraction when activity is initiated at a distance greater than 120 µm. The asymmetric growth cone filopodia extension that precedes turning can be blocked with CNQX (10 µM), but not with the ATP and adenosine receptor antagonists suramin (100 µM) and alloxazine (4 µM), suggesting non-NMDA glutamate receptors on the growth cone mediate the interaction with astrocytes. These results define a potential long-range signalling pathway for activity-dependent axon guidance in which growth cones turn towards directional, temporally coordinated astrocyte Ca2+ waves that are triggered by neuronal activity. To assess the viability of the guidance effect in an injury paradigm, we performed the assay in the presence of conditioned media from lipopolysaccharide (LPS) activated purified microglial cultures, as well as directly activating the glia present in our co-cultures. Growth cone attraction was not inhibited under these conditions, suggesting this mechanism could be used to guide regeneration following axonal injury

Nonlinear gap junctions enable long-distance propagation of pulsating calcium waves in astrocyte networks

A new paradigm has recently emerged in brain science whereby communications between glial cells and neuron-glia interactions should be considered together with neurons and their networks to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, have been shown to communicate with neurons and with each other. They are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating Ca2+ waves. An identified mode of propagation is based on cytoplasm-to-cytoplasm transport of inositol trisphosphate (IP3) through gap junctions that locally trigger Ca2+ pulses via IP3-dependent Ca2+-induced Ca2+ release. It is, however, currently unknown whether this intracellular route is able to support the propagation of long-distance regenerative Ca2+ waves or is restricted to short-distance signaling. Furthermore, the influence of the intracellular signaling dynamics on intercellular propagation remains to be understood. In this work, we propose a model of the gap-junctional route for intercellular Ca2+ wave propagation in astrocytes showing that: (1) long-distance regenerative signaling requires nonlinear coupling in the gap junctions, and (2) even with nonlinear gap junctions, long-distance regenerative signaling is favored when the internal Ca2+ dynamics implements frequency modulation-encoding oscillations with pulsating dynamics, while amplitude modulation-encoding dynamics tends to restrict the propagation range. As a result, spatially heterogeneous molecular properties and/or weak couplings are shown to give rise to rich spatiotemporal dynamics that support complex propagation behaviors. These results shed new light on the mechanisms implicated in the propagation of Ca2+ waves across astrocytes and precise the conditions under which glial cells may participate in information processing in the brain.Comment: Article: 30 pages, 7 figures. Supplementary Material: 11 pages, 6 figure

A Microsatellite Guided Insight into the Genetic Status of Adi, an Isolated Hunting-Gathering Tribe of Northeast India

Tibeto-Burman populations of India provide an insight into the peopling of India and aid in understanding their genetic relationship with populations of East, South and Southeast Asia. The study investigates the genetic status of one such Tibeto-Burman group, Adi of Arunachal Pradesh based on 15 autosomal microsatellite markers. Further the study examines, based on 9 common microsatellite loci, the genetic relationship of Adi with 16 other Tibeto-Burman speakers of India and 28 neighboring populations of East and Southeast Asia. Overall, the results support the recent formation of the Adi sub-tribes from a putative ancestral group and reveal that geographic contiguity is a major influencing factor of the genetic affinity among the Tibeto-Burman populations of India

Apnea of prematurity: from cause to treatment

Apnea of prematurity (AOP) is a common problem affecting premature infants, likely secondary to a “physiologic” immaturity of respiratory control that may be exacerbated by neonatal disease. These include altered ventilatory responses to hypoxia, hypercapnia, and altered sleep states, while the roles of gastroesophageal reflux and anemia remain controversial. Standard clinical management of the obstructive subtype of AOP includes prone positioning and continuous positive or nasal intermittent positive pressure ventilation to prevent pharyngeal collapse and alveolar atelectasis, while methylxanthine therapy is a mainstay of treatment of central apnea by stimulating the central nervous system and respiratory muscle function. Other therapies, including kangaroo care, red blood cell transfusions, and CO2 inhalation, require further study. The physiology and pathophysiology behind AOP are discussed, including the laryngeal chemoreflex and sensitivity to inhibitory neurotransmitters, as are the mechanisms by which different therapies may work and the potential long-term neurodevelopmental consequences of AOP and its treatment

Regulation of cell-to-cell communication mediated by astrocytic ATP in the CNS

It has become apparent that glial cells, especially astrocytes, not merely supportive but are integrative, being able to receive inputs, assimilate information and send instructive chemical signals to other neighboring cells including neurons. At first, the excitatory neurotransmitter glutamate was found to be a major extracellular messenger that mediates these communications because it can be released from astrocytes in a Ca2+-dependent manner, diffused, and can stimulate extra-synaptic glutamate receptors in adjacent neurons, leading to a dynamic modification of synaptic transmission. However, recently extracellular ATP has come into the limelight as an important extracellular messenger for these communications. Astrocytes express various neurotransmitter receptors including P2 receptors, release ATP in response to various stimuli and respond to extracellular ATP to cause various physiological responses. The intercellular communication “Ca2+ wave” in astrocytes was found to be mainly mediated by the release of ATP and the activation of P2 receptors, suggesting that ATP is a dominant “gliotransmitter” between astrocytes. Because neurons also express various P2 receptors and synapses are surrounded by astrocytes, astrocytic ATP could affect neuronal activities and even dynamically regulate synaptic transmission in adjacent neurons as if forming a “tripartite synapse” In this review, we summarize the role of astrocytic ATP, as compared with glutamate, in gliotransmission and synaptic transmission in neighboring cells, mainly focusing on the hippocampus. Dynamic communication between astrocytes and neurons mediated by ATP would be a key event in the processing or integration of information in the CNS

Glutamate regulation of calcium and IP3 oscillating and pulsating dynamics in astrocytes

Recent years have witnessed an increasing interest in neuron-glia communication. This interest stems from the realization that glia participates in cognitive functions and information processing and is involved in many brain disorders and neurodegenerative diseases. An important process in neuron-glia communications is astrocyte encoding of synaptic information transfer: the modulation of intracellular calcium dynamics in astrocytes in response to synaptic activity. Here, we derive and investigate a concise mathematical model for glutamate-induced astrocytic intracellular Ca2+ dynamics that captures the essential biochemical features of the regulatory pathway of inositol 1,4,5-trisphosphate (IP3). Starting from the well-known two-state Li-Rinzel model for calcium-induced-calcium release, we incorporate the regulation of the IP3 production and phosphorylation. Doing so we extended it to a three-state model (referred as the G-ChI model), that could account for Ca2+ oscillations triggered by endogenous IP3 metabolism as well as by IP3 production by external glutamate signals. Compared to previous similar models, our three-state models include a more realistic description of the IP3 production and degradation pathways, lumping together their essential nonlinearities within a concise formulation. Using bifurcation analysis and time simulations, we demonstrate the existence of new putative dynamical features. The cross-couplings between IP3 and Ca2+ pathways endows the system with self-consistent oscillator properties and favor mixed frequency-amplitude encoding modes over pure amplitude modulation ones. These and additional results of our model are in general agreement with available experimental data and may have important implications on the role of astrocytes in the synaptic transfer of information.Comment: 42 pages, 16 figures, 1 table. Figure filenames mirror figure order in the paper. Ending "S" in figure filenames stands for "Supplementary Figure". This article was selected by the Faculty of 1000 Biology: "Genevieve Dupont: Faculty of 1000 Biology, 4 Sep 2009" at http://www.f1000biology.com/article/id/1163674/evaluatio