Polypyrimidine Tract Binding Protein (PTB) is an intensely studied RNA binding protein involved in several post-transcriptional regulatory events of gene expression. Initially described as a pre-mRNA splicing regulator, PTB is now widely accepted as a multifunctional protein shuttling between nucleus and cytoplasm. Accordingly, PTB can interact with selected RNA targets, structural elements and proteins. There is increasing evidence that PTB and its paralog PTBP2 play a major role as repressors of alternatively spliced exons, whose transcription is tissue-regulated. In addition to alternative splicing, PTB is involved in almost all steps of mRNA metabolism, including polyadenylation, mRNA stability and initiation of protein translation. Furthermore, it is well established that PTB recruitment in internal ribosome entry site (IRES) activates the translation of picornaviral and cellular proteins. Detailed studies of the structural properties of PTB have contributed to our understanding of the mechanism of RNA binding by RNA Recognition Motif (RRM) domains. In the present review, we will describe the structural properties of PTB, its paralogs and co-factors, the role in post-transcriptional regulation and actions in cell differentiation and pathogenesis. Defining the multifunctional roles of PTB will contribute to the understanding of key regulatory events in gene expression.

Human T cell leukemia viruses (HTLVs) are complex human retroviruses of the Deltaretrovirus genus. Four types have been identified thus far, with HTLV-1 and HTLV-2 much more prevalent than HTLV-3 or HTLV-4. HTLV-1 and HTLV-2 possess strictly related genomic structures, but differ significantly in pathogenicity, as HTLV-1 is the causative agent of adult T cell leukemia and of HTLV-associated myelopathy/tropical spastic paraparesis, whereas HTLV-2 is not associated with neoplasia. HTLVs code for a protein named Tax that is responsible for enhancing viral expression and drives cell transformation. Much effort has been invested to dissect the impact of Tax on signal transduction pathways and to identify functional differences between the HTLV Tax proteins that may explain the distinct oncogenic potential of HTLV-1 and HTLV-2. This review summarizes our current knowledge of Tax-1 and Tax-2 with emphasis on their structure, role in activation of the NF-κB (nuclear factor kappa-B) pathway, and interactions with host factors.

Autosomal dominant lateral temporal epilepsy (ADLTE) (OMIM 600512), or autosomal dominant partial epilepsy with auditory features, is an inherited epileptic syndrome characterized by focal seizures with ictal auditory phenomena or other symptoms suggesting a lateral temporal lobe onset of discharge.^1-3 Seizures may be triggered by environmental sounds or noises, and secondarily generalized tonic-clonic seizures (TCSs) are almost invariably present but occur sporadically. The evolution of the condition is relatively benign because seizures are usually well controlled with standard antiepileptic drugs.^3,4 Conventional brain magnetic resonance imaging results are normal and electroencephalograms (EEGs) frequently show mild temporal abnormalities. Mutations in the leucine-rich, glioma-inactivated 1 (LGI1) gene (GenBank 9211), also named Epitempin, are found in about 50% of the families, compatible with autosomal dominant inheritance with reduced penetrance and suggesting that ADLTE is genetically heterogeneous.^3-5 The LGI1 gene is mainly expressed in brain tissues and shows no homology with known ion channel genes. It encodes a protein whose predicted structure consists of 4 LRR repeats⁶ in the N-terminal portion and 7 EPTP repeats⁷ in the C-terminal region, each domain defining a distinct family of proteins exerting a variety of functions. The function of LGI1 is unclear. Recent in vitro experiments have shown that the Lgi1 protein produced by transfected cells is secreted.^8,9

The emergence of antimicrobial resistance represents a serious threat to public health and for infections due to multidrug-resistant (MDR) microorganisms, representing one of the most important causes of death worldwide. The renewal of old antimicrobials, such as colistin, has been proposed as a valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to present several adverse toxic effects, its usage in clinical practice has been reconsidered due to its broad spectrum of activity against Gram-negative (GN) bacteria and its important role of “last resort” agent against MDR-GN. Despite the revolutionary perspective of treatment with this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In last years, several forward steps have been made in the understanding of the resistance determinants, clinical usage, and pharmacological dosage of this molecule; however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not yet well defined. In this review, we summarize the mode of action, the emerging resistance determinants, and its optimal administration in the treatment of infections that are difficult to treat due to MDR Gram-negative bacteria.