CA3–CA3 recurrent excitatory synapses are thought to play a key role in memory storage and pattern completion. Whether the plasticity properties of these synapses are consistent with their proposed network functions remains unclear. Here, we examine the properties of spike timing-dependent plasticity (STDP) at CA3–CA3 synapses. Low-frequency pairing of excitatory postsynaptic potentials (EPSPs) and action potentials (APs) induces long-term potentiation (LTP), independent of temporal order. The STDP curve is symmetric and broad (half-width ∼150 ms). Consistent with these STDP induction properties, AP–EPSP sequences lead to supralinear summation of spine [Ca2+] transients. Furthermore, afterdepolarizations (ADPs) following APs efficiently propagate into dendrites of CA3 pyramidal neurons, and EPSPs summate with dendritic ADPs. In autoassociative network models, storage and recall are more robust with symmetric than with asymmetric STDP rules. Thus, a specialized STDP induction rule allows reliable storage and recall of information in the hippocampal CA3 network.
Psoriasis is a chronic inflammatory skin disease clinically characterized by the appearance of red colored, well-demarcated plaques with thickened skin and with silvery scales. Recent studies have established the involvement of a complex signalling network of interactions between cytokines, immune cells and skin cells called keratinocytes. Keratinocytes form the cells of the outermost layer of the skin (epidermis). Visible plaques in psoriasis are developed due to the fast proliferation and unusual differentiation of keratinocyte cells. Despite that, the exact mechanism of the appearance of these plaques in the cytokine-immune cell network is not clear. A mathematical model embodying interactions between key immune cells believed to be involved in psoriasis, keratinocytes and relevant cytokines has been developed. The complex network formed of these interactions poses several challenges. Here, we choose to study subnetworks of this complex network and initially focus on interactions involving $$\hbox {TNF}_{\alpha }$$ TNF α , IL-23/IL-17, and IL-15. These are chosen based on known evidence of their therapeutic efficacy. In addition, we explore the role of IL-15 in the pathogenesis of psoriasis and its potential as a future drug target for a novel treatment option. We perform steady state analyses for these subnetworks and demonstrate that the interactions between cells, driven by cytokines could cause the emergence of a psoriasis state (hyper-proliferation of keratinocytes) when levels of $$\hbox {TNF}_{\alpha }$$ TNF α , IL-23/IL-17 or IL-15 are increased. The model results explain and support the clinical potentiality of anti-cytokine treatments. Interestingly, our results suggest different dynamic scenarios underpin the pathogenesis of psoriasis, depending upon the dominant cytokines of subnetworks. We observed that the increase in the level of IL-23/IL-17 and IL-15 could lead to psoriasis via a bistable route, whereas an increase in the level of $$\hbox {TNF}_{\alpha }$$ TNF α would lead to a monotonic and gradual disease progression. Further, we demonstrate how this insight, bistability, could be exploited to improve the current therapies and develop novel treatment strategies for psoriasis.
In less than ten years, India has launched colossal biometric databases. One among them is related to the first ‘free’ health coverage scheme offered by the government of India: the Rashtriya Swasthya Bima Yojna (RSBY). Based on a public–private partnership between government and private companies, RSBY national scheme was launched in 2008, as a first step towards universal health coverage in a country where households endorse 70% of health expenses. The first phase of RSBY offers to cover ₹30,000 ($600) of inpatient expenses per year for five members of a below poverty line household and is now piloted in several Indian States to include outpatient expenses and above poverty line families too. RSBY relies exclusively on a centralised digital artefact to function, made visible by the ‘RSBY Smart Card’, a chip enabled plastic card containing personal data of individual and their family counting and conditioning the granting of health services to them; thus, no smart card means no health coverage. Till date 120 million Indians have been registered in the RSBY database. This article analyses how health accessibility is crafted under the RSBY scheme by questioning two central dimensions of this data-driven digital health scheme: the smart card technology and the public–private partnership, whereas RSBY scheme promises health coverage for all, its digital infrastructures may complicate access to health services, and reveal new patterns of exclusion of individuals. Thus, we will detail how smartcards technologies and private providers condition access to health care in India.
The sheer size of the Indian population and its presence in a gigantic biometrics database has made possible the appropriation and control of millions of bodies on an everyday basis. It is being done at different levels by players operating the Digital State, with a markets‐based approach aiming to provide governance and development entitlements, healthcare being one among them. However, at the receiving end of this appropriative force are the 22 percent below poverty line (BPL) population, accounting for around 300 million people living at less than 1.25 dollars per day. These tend to be bodies facing a double jeopardy of historical‐social‐economic inequalities and negotiating the biometric means of accessing healthcare entitlements. Specifically, this refers to an arduous process of proving one's 'mistrusted' self to be able to enter the process of availing medical treatment. Based on qualitative fieldwork in Jharkhand and Delhi, the paper argues that the very process of biometrics‐based access to healthcare appropriates the bodies of BPL families even before they get any medical treatment. Findings reflect that the biometrics (technological) means for identifying the mistrusted bodies of BPL populations adds to the existing social inequalities.
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