Autism Research and Treatment and other meaningful terms linking the literature on autism with the literature on NF-kappaB (see Table 2). 4. Discussion Using the literature mining method, RaJoLink, we aimed to uncover hidden connections that may provide additional clues about autism. In the ﬁrst part of the study, calcineurin was identiﬁed as a possible important factor in the devel- opment of the disorder. The Ca2+/calmodulin-dependent phosphatase calcineurin has been shown to be involved in numerous diverse functions, both at the cellular and organism level. Its name is based on its calcium-binding properties as well as its abundant expression in the nervous system [16]. Several studies have supported the crucial role of calcineurin in modifying animal behaviours, predominantly by regulating cellular responses for timing and concentration of calcium in cells [17]. For example, it was shown that a reduction in function of calcineurin in mice resulted in defects in working/episodic like memory, hyperactive movement, social withdrawal, and defects in latent and prepulse inhibition [18]. In Table 1, literature on autism and calcineurin converge on the term synaptic plasticity (SP). This is a process that refers speciﬁcally to the activity-dependent modiﬁcation of the eﬃcacy in synaptic transmission at pre-existing synapses. For over a century, SP has been proposed as playing a central role in the capacity of the brain to incorporate transient experiences into persistent memory traces. Synaptic plasticity is also thought to play a key role in the early development of neural circuitry. Evidence is accumulating that impairment in SP mechanisms may contribute to several prominent neurodevelopmental disorders and among them is autism [19]. While so-called short-term plasticity is thought to play an important role in short-term adaptations to sensory imputes, transient changes in behavioural states, and short-lasting forms of memory, the “long-term” synaptic plasticity, in the form of long-term potentiation (LTP) and long-term depression (LTD), is thought to be, at least in part, the mechanism behind how an experience may modify a behaviour. Fragile X syndrome (FXS), the most common single gene cause of autism [4], linked to synaptic plasticity on the autism side of Table 1. FXS is caused by loss of function of fragile X mental retardation 1 gene (FMR1) resulted in absence of associated protein—FMRP, which is a RNA binding protein regulating translation of many target mRNAs. Most of the targets mRNAs studied so far have been linked to the regulation of synaptic function [20, 21], therefore we focused more closely on the correlation between calcineurin and FXS. Calcineurin is thought to be involved in N-methyl-D- aspartate receptors (NMDAR-) dependent LTD. This has mostly been studied in hippocampal cells, but was also found in neocortical synapses [22]. FXS, on the other hand has been linked to metabotropic glutamate receptor-(mGluR-) dependent LTD, particularly in the hippocampus and cere- bellum [14, 23]. This potential link between an mGluR- triggered form of SP and FXS has focused attention on 5 mGluR antagonists as possible therapeutic agents for this and other developmental disorders [4, 24]. The fact that two diﬀerent mechanisms of LTD involved in FXS and calcineurin action might be explained by an additive eﬀect that both mechanisms have in children with FXS and autism compared to those with FXS without autism. At present, there is no direct evidence reported on the role calcineurin plays in autism. Recently, however, evidence on the signiﬁcant associations of a calcineurin isoform located at the chromosome 8p21.3 region and the subgroup of schizophrenia patients with deﬁcits of sustained attention and executive functioning [25]. The second most important term found in our study was NF-kappaB. This transcription factor was ﬁrst discovered by Sen and Baltimore [26] through its interaction with the immunoglobulin kappa light enhancer sequences. They referred to the binding site for this nuclear factor as the B site and therefore called the factor NF-κB (nuclear factor-kappa B). Our results showed two points of convergences in the literature on both calcineurin and NF-κB with autism. The ﬁrst is Bcl-2, antiapoptotic protein, that works mainly at the level of mitochondria [27]. Fatemi and colleagues [28] reported a 34% to 51% reduction in Bcl-2 levels in the cerebellum of autistic patients compared with controls. Their experiments showed that deregulation of Bcl-2 may result in some of the structural brain and behavioural abnormalities in patients with autism. On one hand, it has been shown that activation of NF-kappaB in neurons can promote their survival by inducing the expression of genes encoding Bcl-2 [29] and on the other, that calcineurin occurred as a complex with Bcl-2 in various regions of rat and mouse brains, in particular during times of cellular stress and damage [30]. More speciﬁcally the protective role of Bcl-2 in metabolic oxidative stress-induced cell death was showed by Lee and colleagues [31]. The problem of oxidative stress in autism has been extensively studied [32]. Also, over the last decade there has been increasing evidence about the association between autism and mitochondrial dysfunction [33, 34]. As Bcl-2 works as an antiapoptotic agent mainly at the level of mitochondria, we may propose that its downregulation is one of the mechanisms related to increase of oxidative stress and mitochondrial dysfunction in autism. Additionally, it has been shown that FMRP expression is, among other functions, an essential part of cellular survival mechanisms, at least partly through modulation of Bcl-2 signal pathways [35]. The second point of convergence was a possible immun- omodulatory role of both substances, calcineurin, and NF- kappaB. Neuroimmune abnormalities in the brain of patients with autism have recently become objects of growing scien- tiﬁc interest [36–38]. It has been proposed that abnormalities in innate as well as in adaptive immune responses play a potentially important role in the development of autism [36, 37]. NF-kappa B has been shown to have a crucial and multifaceted role in innate immune responses [39]. Further, it has been speciﬁed that, on activation, NF-kappaB regulates the expression of almost 400 diﬀerent genes, which