NOTCH, a new signaling pathway implicated in holoprosencephaly

Genetics of Holoprosencephaly (HPE), a congenital malformation of the developing human forebrain, is due to multiple genetic defects. Most genes that have been implicated in HPE belong to the sonic hedgehog signaling pathway. Here we describe a new candidate gene isolated from array comparative genomic hybridization redundant 6qter deletions, DELTA Like 1 (DLL1), which is a ligand of NOTCH. We show that DLL1 is co-expressed in the developing chick forebrain with Fgf8. By treating chick embryos with a pharmacological inhibitor, we demonstrate that DLL1 interacts with FGF signaling pathway. Moreover, a mutation analysis of DLL1 in HPE patients revealed a three-nucleotide deletion. These various findings implicate DLL1 in early patterning of the forebrain and identify NOTCH as a new signaling pathway involved in HPE.     

“Michael's Game,” a card game for the treatment of psychotic symptoms

Objective

“Michael's Game” is a card game which aims at familiarizing healthcare professionals and patients with cognitive therapy of psychotic symptoms. The present study tests the feasibility and the impact of the intervention in naturalistic settings.

Methods

135 patients were recruited in 11 centres. They were assessed pre- and post-tests with the Beck Cognitive Insight Scale (BCIS) and the Peters Delusion Inventory-21 items (PDI-21).

Results

Data about 107 patients were included in the entire analyses. Significant improvements were observed on BCIS subscales as well as a reduction of severity of conviction and preoccupation scores on the PDI-21. The intervention has a moderate effect on the PDI-21 preoccupation and conviction as well as the BCIS subscales. Patients who benefit the most from the program are patients who have a low degree of self-reflectiveness and patients who are concomitantly preoccupied by their symptoms.

Conclusion

The present study supports the feasibility and effectiveness of “Michael's Game” in naturalistic settings.

Practical implications

The game seems to be a useful tool for patients with psychotic disorders.     

Identification of a major pathogenicity determinant and suppressors of RNA silencing encoded by a South Pacific isolate of <Emphasis Type="Italic">Banana bunchy top virus</Emphasis> originating from Pakistan

Five genes encoded by Banana bunchy top virus (BBTV) originating from Pakistan were expressed in Nicotiana benthamiana using a Potato virus X (PVX) vector. Expression of the master replication-associated protein (mRep) and movement protein (MP) resulted in necrotic cell death of inoculated tissues, as well as leaf curling and necrosis along the veins in newly emerging leaves. The systemic necrosis induced by the expression of MP was discolored (dark) in comparison to that induced by mRep. Expression of the cell-cycle link protein (Clink), the coat protein (CP), and the nuclear shuttle protein from the PVX vector induced somewhat milder symptoms, consisting of mild leaf curling and mosaic, although expression of the CP caused a necrotic response in inoculated leaf. The accumulation of viral RNA was enhanced by MP, Clink, and CP. Of the five BBTV-encoded gene products two, the MP and Clink, stabilized GFP-specific mRNA and reduced GFP-specific small interfering RNA in N. benthamiana line 16c when expressed under the control of the 35S promoter and co-inoculated with a construct for the expression of GFP hairpin RNA construct. These results identified MP and Clink as suppressors of RNA silencing. Taken together the ability of MP to induce severe symptoms in plants and suppress RNA silencing implicates this product as a major pathogenicity determinant of BBTV.     

Temporal attention facilitates short-term consolidation during a rapid serial auditory presentation task

Attentional blink (AB) refers to a phenomenon where the correct identification of a first target (i.e., target) impairs the processing of a second target (i.e., probe) nearby in time. In the present study, we investigate the influence of temporal attention on auditory AB by means of scalp-recorded event-related potentials. Participants were instructed to focus their attention on a particular time interval following the target (i.e., short, middle, or long temporal position) in order to detect the occurrence of the probe in a rapid series of distractor sounds. We found a large probe processing deficit when the probe occurred immediately after the target. This AB decreased as the time interval between the target and the probe increased and coincided with the generation of a positive wave at parietal sites (i.e., P3b). The P3b elicited by the probe peaked earlier when the probe occurred at the designated time than when it occurred at another position in time. The results indicate that temporal attention can be deployed to a particular time, which facilitates short-term consolidation of the probe.     

Diversity, geographic distribution, and habitat-specific variations of microbiota in natural populations of the chicken mite, Dermanyssus gallinae

Dermanyssus gallinae is considered to be the most economically significant ectoparasite to affect egg-laying poultry in Europe. This mite can also act as a vector for a number of pathogens. The array of bacteria associated with D. gallinae mites could provide insight into the biology and population dynamics of arthropods, but at the present time little information is available. To understand the intra- and interpopulation diversity of its associated microbiota, we analyzed the whole internal bacterial community of natural populations of D. gallinae originating from two types of poultry farm habitats (standard and free-range) in two regions of France (Brittany and the Rhone-Alpes). Total DNA was extracted from individual or pooled mites, and polymerase chain reaction temporal temperature gradient gel electrophoresis of 16S rRNA was then done to separate bacterial DNA fragments associated with the host arthropod. A large diversity of bacteria was detected, but principally firmicutes and gamma-Proteobacteria. Between-group analyses of temporal temperature gradient gel electrophoresis-banding patterns revealed that bacterial populations clustered into categories according to their geographic origin and the habitat specifics of the farms. Some degree of stability of bacterial populations was observed within a specific time scale. These results suggest that environmental factors either recent (e.g., poultry farming practices) or long-standing (e.g., geographic isolation) may affect the bacterial communities present in D. gallinae. Further knowledge of the microbiota associated with D. gallinae and its variation would indeed offer new perspectives for biological control methods to prevent the establishment, proliferation, and transmission of pathogenic bacteria.     

The co-occurrence of multisensory facilitation and cross-modal conflict in the human brain

Perceptual objects often comprise a visual and auditory signature that arrives simultaneously through distinct sensory channels, and cross-modal features are linked by virtue of being attributed to a specific object. Continued exposure to cross-modal events sets up expectations about what a given object most likely "sounds" like, and vice versa, thereby facilitating object detection and recognition. The binding of familiar auditory and visual signatures is referred to as semantic, multisensory integration. Whereas integration of semantically related cross-modal features is behaviorally advantageous, situations of sensory dominance of one modality at the expense of another impair performance. In the present study, magnetoencephalography recordings of semantically related cross-modal and unimodal stimuli captured the spatiotemporal patterns underlying multisensory processing at multiple stages. At early stages, 100 ms after stimulus onset, posterior parietal brain regions responded preferentially to cross-modal stimuli irrespective of task instructions or the degree of semantic relatedness between the auditory and visual components. As participants were required to classify cross-modal stimuli into semantic categories, activity in superior temporal and posterior cingulate cortices increased between 200 and 400 ms. As task instructions changed to incorporate cross-modal conflict, a process whereby auditory and visual components of cross-modal stimuli were compared to estimate their degree of congruence, multisensory processes were captured in parahippocampal, dorsomedial, and orbitofrontal cortices 100 and 400 ms after stimulus onset. Our results suggest that multisensory facilitation is associated with posterior parietal activity as early as 100 ms after stimulus onset. However, as participants are required to evaluate cross-modal stimuli based on their semantic category or their degree of congruence, multisensory processes extend in cingulate, temporal, and prefrontal cortices.     

Laparoscopic versus open right hepatectomy: a comparative study

Background

The safety of laparoscopic major liver resections is still uncertain. The aim of this study was to compare our results for laparoscopic right hepatectomy (LRH) with those for open right hepatectomy (ORH).

Methods

Patients undergoing LRH were compared with retrospectively selected patients from our ORH database. The 2 groups were well matched for sex, age, American Society of Anesthesiologists score, body mass index, liver disease, and tumor size. Surgical and postsurgical outcomes were compared.

Results

Seventy-two patients were analyzed: 22 in the LRH group and 50 in the ORH group. Operating time was similar. Blood loss was significantly less in laparoscopic resections (P = .038). Specific morbidity rates were not different, general morbidity was lower after laparoscopy (P = .04), and the severity of postsurgical complications was not different. Mean hospital stay was significantly shorter after laparoscopy (P = .009).

Comments

Laparoscopy improved surgical and postsurgical outcomes for ORH in selected patients. This is the first comparative study to demonstrate an advantage of laparoscopy for a major liver resection. Prospective randomized studies with a greater number of cases are needed to confirm the role of laparoscopy in major liver resections.