Sex-specific regulation of neuronal functions in Caenorhabditis elegans: the sex-determining protein TRA-1 represses goa-1/Gα(i/o).

Females and males differ substantially in various neuronal functions in divergent, sexually dimorphic animal species, including humans. Despite its developmental, physiological and medical significance, understanding the molecular mechanisms by which sex-specific differences in the anatomy and operation of the nervous system are established remains a fundamental problem in biology. Here, we show that in Caenorhabditis elegans (nematodes), the global sex-determining factor TRA-1 regulates food leaving (mate searching), male mating and adaptation to odorants in a sex-specific manner by repressing the expression of goa-1 gene, which encodes the Gα(i/o) subunit of heterotrimeric G (guanine-nucleotide binding) proteins triggering physiological responses elicited by diverse neurotransmitters and sensory stimuli. Mutations in tra-1 and goa-1 decouple behavioural patterns from the number of X chromosomes. TRA-1 binds to a conserved binding site located in the goa-1 coding region, and downregulates goa-1 expression in hermaphrodites, particularly during embryogenesis when neuronal development largely occurs. These data suggest that the sex-determination machinery is an important modulator of heterotrimeric G protein-mediated signalling and thereby various neuronal functions in this organism and perhaps in other animal phyla.

xol-1, the master sex-switch gene in C. elegans, is a transcriptional target of the terminal sex-determining factor TRA-1.

In the nematode Caenorhabditis elegans, sex is determined by the ratio of X chromosomes to sets of autosomes: XX animals (2X:2A=1.0) develop as hermaphrodites and XO animals (1X:2A=0.5) develop as males. TRA-1, the worm ortholog of Drosophila Cubitus interruptus and mammalian Gli (Glioma-associated homolog) proteins, is the terminal transcription factor of the C. elegans sex-determination pathway, which specifies hermaphrodite fate by repressing male-specific genes. Here we identify a consensus TRA-1 binding site in the regulatory region of xol-1, the master switch gene controlling sex determination and dosage compensation. xol-1 is normally expressed in males, where it promotes male development and prevents dosage compensation. We show that TRA-1 binds to the consensus site in the xol-1 promoter in vitro and inhibits the expression of xol-1 in XX animals in vivo. Furthermore, inactivation of tra-1 enhances, whereas hyperactivation of tra-1 suppresses, lethality in animals with elevated xol-1 activity. These data imply the existence of a regulatory feedback loop within the C. elegans sex-determination and dosage-compensation cascade that ensures the accurate dose of X-linked genes in cells destined to adopt hermaphrodite fate.

Identification of burglars using foil impressioning based on tool marks and DNA evidence.

In burglary cases, the skeleton keys used by burglars often leave tool marks that can not be identified. Hence, forensic trace experts can only provide investigating authorities with useful information by categorizing the lock opening method of pin tumbler lock cylinders and defining the class characteristics of the tool used. It is important to note that as per the standard processes, expensive and more time consuming DNA-tests may not be applied to this evidence type. During the past few years, more and more dimple locks were documented by the police being removed from security doors at burglary scenes and sent to the Hungarian Institute for Forensic Sciences. These dimple locks were made in China with no brand mark, with 6-8 pin tumblers. We noticed previously unknown tool marks on the horizontal keyway, on the face and on the side of the tumblers of most of these dimple locks. We also found fragments of aluminium foil in the bottom of the plugs. Based on this, we came to the conclusion that the burglars work with a new method when opening this type of locks, which required forensic trace experts to introduce a new way of examination. In this study specific data is meant to be presented supporting the observations above. This paper is presenting a new lock opening method and the tool marks left behind. Our purpose was to develop a new method which takes the benefit of a new type of evidence: foil fragments noticed in the cylinder with possible DNA evidence, which was previously unknown by the police. This goes beyond the scope of general investigative findings, allowing a more effective identification of the burglars. We are also going to explicate the results of our DNA tests. Foil fragments having been recorded under sterile conditions brought searchable DNA-profiles in 52 % of the cases. In 55 % of these cases DNA-profiles were matched with suspects' and a series of crimes and groups of criminals were explored. Examining the DNA-profiles that did not match suspects' profiles revealed the presence of victims' DNA in certain cases. The outcomes of our study highlight that collecting victim DNA-samples should be implemented as a default process in cases where a DNA-test is required.