Processing abstract auditory features in the human auditory cortex

Using electric and magnetic brain responses we tested whether violations of an abstract auditory regularity are processed in auditory cortex and whether abstract auditory regularities are retained for at least 10 s. The mismatch negativity (MMN) event-related potential and its magnetic counterpart (MMNm) were recorded to infrequent tone pairs of descending pitch (the second tone having a lower frequency than the first one) embedded in a sequence of tone pairs of ascending pitch, whereas the absolute frequency of both ascending and descending tone pairs varied on seven levels. Results showed that the dominant generators of the electromagnetic activity elicited by violations of the pitch-ascension rule lie within auditory cortex. We also found that the memory representation of pitch-ascension is retained for at least 10 s. When short trains of ascending-pitched tone pairs were followed by a silent period of 8-12 s, descending-pitched probe tone pairs elicited the MMN component when a single reminding pair with ascending pitch was presented before the probe. The reactivating effect of the reminder was similar to what has been previously shown for concrete auditory regularities, such as the constancy of tone pitch. The present results support the view that auditory cortical functions can process sensory and categorical information in a similar manner.     

Targeting of biotinylated compounds to its target tissue using a low-density lipoprotein receptor-avidin fusion protein

The very high binding affinity of avidin to biotin is one of the highest to occur in nature. We constructed a fusion protein composed of avidin and the endocytotic LDL receptor in order to target biotinylated molecules to cells of the desired tissues. In addition to the native avidin, charge-mutated and nonglycosylated avidins were utilized as part of the fusion proteins, in order to modify its properties. All of the fusion protein versions retained the biotin-binding capacity. Although the specificity was not increased, however, fusion proteins composed of natural avidin and nonglycosylated avidin bound most efficiently to the biotinylated ligands. Fluorescence microscopy and atomic force microscopy studies revealed the expression of the fusion protein on cell membranes, and demonstrated specific and high-affinity binding of biotin to the low-density lipoprotein receptor (LDLR)-avidin fusion protein in vitro. Additionally, systemically administered biotinylated ligand targeted with high specificity the intracerebral tumors of rats that were expressing fusion protein after the virus-mediated gene transfer. These results suggest that local gene transfer of the fusion protein to target tissues may offer a novel tool for the delivery of biotinylated molecules in vitro and in vivo for therapeutic and imaging purposes.     

Hospitalized burns in Finland: 36 305 cases from 1980–2010

To analyse the epidemiology of burns in Finland, a comprehensive study was conducted among all hospitalized burn patients between 1980 and 2010. All patients with burn injury as the main diagnosis, 36 305 cases in total, treated in the public and private sectors, were included.Patient data were obtained from the Finnish Hospital Discharge Register (FHDR). The incidence of hospitalized injuries declined from over 30 to 17 per 100 000 persons. Men were at higher risk than women in all age groups. Children aged under ten years were overrepresented throughout the period and the highest incidence was found among one year old boys. The median total length of stay shortened from seven days in 1980–1995 to five days in 1996–2010. The annual number of hospitalized patients is recently under 1000 cases (17/100 000). The male predominance (70%) did not change but the age group with the most injuries shifted from 20–39 years to 40–59 years. Injuries were most common during the summer months.This study of all hospitalized burn injuries of one entire country shows similar tendency of diminishing numbers and rising age of burn victims as in other western countries. The FHDR is a reliable source of data in epidemiological studies but precise recording of E- and N-codes in the registry would enable the accurate analysis of types and extent of injury.     

The dorsal raphe nucleus--from silver stainings to a role in depression

Over a hundred years ago, Santiago Ramón y Cajal used a new staining method developed by Camillo Golgi to visualize, among many other structures, what we today call the dorsal raphe nucleus (DRN) of the midbrain. Over the years, the DRN has emerged as a multifunctional and multitransmitter nucleus, which modulates or influences many CNS processes. It is a phylogenetically old brain area, whose projections reach out to a large number of regions and nuclei of the CNS, particularly in the forebrain. Several DRN-related discoveries are tightly connected with important events in the history of neuroscience, for example the invention of new histological methods, the discovery of new neurotransmitter systems and the link between neurotransmitter function and mood disorders. One of the main reasons for the wide current interest in the DRN is the nucleus' involvement in depression. This involvement is particularly attributable to the main transmitter of the DRN, serotonin. Starting with a historical perspective, this essay describes the morphology, ascending projections and multitransmitter nature of the DRN, and stresses its role as a key target for depression research.     

Oncolytic adenovirus based on serotype 3

Oncolytic adenoviruses have been safe in clinical trials but the efficacy has been mostly limited. All published trials have been performed with serotype 5 based viruses. The expression level of the Ad5 receptor CAR may be variable in advanced tumors. In contrast, the Ad3 receptor remains unclear, but is known to be abundantly expressed in most tumors. Therefore, we hypothesized that a fully serotype 3 oncolytic adenovirus might be useful for treating cancer. Patients exposed to adenoviruses develop high titers of serotype-specific neutralizing antibodies, which might compromise re-administration. Thus, having different serotype oncolytic viruses available might facilitate repeated dosing in humans. Ad3-hTERT-E1A is a fully serotype 3 oncolytic adenovirus controlled by the promoter of the catalytic domain of human telomerase. It was effective in vitro on cell lines representing seven major cancer types, although low toxicity was seen in non-malignant cells. In vivo, the virus had anti-tumor efficacy in three different animal models. Although in vitro oncolysis mediated by Ad3-hTERT-E1A and wild-type Ad3 occurred more slowly than with Ad5 or Ad5/3 (Ad3 fiber knob in Ad5) based viruses, in vivo the virus was at least as potent as controls. Anti-tumor efficacy was retained in presence of neutralizing anti-Ad5 antibodies whereas Ad5 based controls were blocked. In summary, we report generation of a non-Ad5 based oncolytic adenovirus, which might be useful for testing in cancer patients, especially in the context of high anti-Ad5 neutralizing antibodies.