A Normative Theory of Forgetting: Lessons from the Fruit Fly

Recent experiments revealed that the fruit fly Drosophila melanogaster has a dedicated mechanism for forgetting: blocking the G-protein Rac leads to slower and activating Rac to faster forgetting. This active form of forgetting lacks a satisfactory functional explanation. We investigated optimal decision making for an agent adapting to a stochastic environment where a stimulus may switch between being indicative of reward or punishment. Like Drosophila, an optimal agent shows forgetting with a rate that is linked to the time scale of changes in the environment. Moreover, to reduce the odds of missing future reward, an optimal agent may trade the risk of immediate pain for information gain and thus forget faster after aversive conditioning. A simple neuronal network reproduces these features. Our theory shows that forgetting in Drosophila appears as an optimal adaptive behavior in a changing environment. This is in line with the view that forgetting is adaptive rather than a consequence of limitations of the memory system.

Distance-based kriging relying on proxy simulations for inverse conditioning

Let us consider a large set of candidate parameter fields, such as hydraulic conductivity maps, on which we can run an accurate forward flow and transport simulation. We address the issue of rapidly identifying a subset of candidates whose response best match a reference response curve. In order to keep the number of calls to the accurate flow simulator computationally tractable, a recent distance-based approach relying on fast proxy simulations is revisited, and turned into a non-stationary kriging method where the covariance kernel is obtained by combining a classical kernel with the proxy. Once the accurate simulator has been run for an initial subset of parameter fields and a kriging metamodel has been inferred, the predictive distributions of misfits for the remaining parameter fields can be used as a guide to select candidate parameter fields in a sequential way. The proposed algorithm, Proxy-based Kriging for Sequential Inversion (ProKSI), relies on a variant of the Expected Improvement, a popular criterion for kriging-based global optimization. A statistical benchmark of ProKSI’s performances illustrates the efficiency and the robustness of the approach when using different kinds of proxies.

Computed tomography (CT) virtual autopsy and classical autopsy discrepancies: radiologist's error or a demonstration of post-mortem multi-detector computed tomography (MDCT) limitation?

Modern imaging technologies, such as computed tomography (CT) techniques, represent a great challenge in forensic pathology. The field of forensics has experienced a rapid increase in the use of these new techniques to support investigations on critical cases, as indicated by the implementation of CT scanning by different forensic institutions worldwide. Advances in CT imaging techniques over the past few decades have finally led some authors to propose that virtual autopsy, a radiological method applied to post-mortem analysis, is a reliable alternative to traditional autopsy, at least in certain cases. The authors investigate the occurrence and the causes of errors and mistakes in diagnostic imaging applied to virtual autopsy. A case of suicide by a gunshot wound was submitted to full-body CT scanning before autopsy. We compared the first examination of sectional images with the autopsy findings and found a preliminary misdiagnosis in detecting a peritoneal lesion by gunshot wound that was due to radiologist's error. Then we discuss a new emerging issue related to the risk of diagnostic failure in virtual autopsy due to radiologist's error that is similar to what occurs in clinical radiology practice.

Contiguous ∼16 Mb 1p36 deletion: Dominant features of classical distal 1p36 monosomy with haplo-lethality

Monosomy 1p36 results from heterozygous deletions of the terminal short chromosome 1 arm, the most common terminal deletion in humans. The microdeletion is split in two usually non-overlapping and clinically distinct classical distal and proximal 1p36 monosomy syndromes. Using comparative genome hybridization, MLPA and qPCR we identified the largest contiguous ∼16 Mb terminal 1p36 deletion reported to date. It covers both distal and proximal regions, causes a neonatally lethal variant with virtually exclusive features of distal 1p36 monosomy, highlighting the key importance of the gene-rich distal region for the "compound" 1p36 phenotype and a threshold deletion-size effect for haplo-lethality.

Distinct proteinase K-resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak

Considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (BSE). Here we report the in-depth molecular analysis of the proteinase K-resistant prion protein core fragment (PrP(res)) in a highly scrapie-affected goat flock in Greece. The PrP(res) profile by Western immunoblotting in most animals was that of classical scrapie in sheep. However, in a series of clinically healthy goats we identified a unique C- and N-terminally truncated PrP(res) fragment, which is akin but not identical to that observed for atypical scrapie. These findings reveal novel aspects of the nature and diversity of the molecular PrP(res) phenotypes in goats and suggest that these animals display a previously unrecognized prion protein disorder.

Caprine PRNP polymorphisms at codons 171, 211, 222 and 240 in a Greek herd and their association with classical scrapie

The association between PRNP variation and scrapie incidence was investigated in a highly affected Greek goat herd. Four mutations were identified at codons 171Q/R, 211R/Q, 222Q/K and 240P/S. Lysine at codon 222 was found to be associated with the protection from natural scrapie (P=0.0111). Glutamine at codon 211 was observed in eight animals, all of them being scrapie-negative, indicating a possible protective role of this polymorphism although statistical analysis failed to support it (P=0.1074). A positive association (P=0.0457) between scrapie-affected goats and the wild-type Q(171)R(211)Q(222)S(240) allele is presented for the first time. In addition, a novel R(171)RQS allele, which is identical to the A(136)R(154)R(171) allele that has been associated with resistance to classical scrapie in sheep, was observed in low frequency. Resistant alleles that include K(222) and Q(211) are absent or rare in sheep and can provide the basis for the development of a feasible breeding programme for scrapie eradication in goats.