Do the rat anterior thalamic nuclei contribute to behavioural flexibility?

The rodent anterior thalamic nuclei (ATN) are vital for spatial memory. A consideration of their extensive frontal connections suggests that these nuclei may also subserve non-spatial functions. The current experiments explored the importance of the ATN for different aspects of behavioural flexibility, including their contribution to tasks typically associated with frontal cortex. In Experiment 1, rats with ATN lesions were tested on a series of response and visual discriminations in an operant box and, subsequently, in a water tank. The tasks included assessments of reversal learning as well switches between each discrimination dimension. Results revealed a mild and transient deficit on the operant task that was not specific to any stage of the procedure. In the water tank, the lesion animals were impaired on the reversal of a spatial discrimination but did not differ from controls on any other measure. Experiment 2 examined the impact of ATN damage on a rodent analogue of the ‘Stroop’, which assesses response choice during stimulus conflict. The lesion animals successfully acquired this task and were able to use contextual information to disambiguate conflicting cue information. However, responding during the initial presentation of conflicting cue information was affected by the lesion. Taken together, these results suggest that the ATN are not required for aspects of behavioural flexibility (discrimination learning, reversals or high-order switches) typically associated with the rat medial prefrontal cortex. The results from Experiment 2 suggest that the non-spatial functions of the ATN may be more aligned with those of the anterior cingulate cortex

The Therapeutic Interview Process in Qualitative Research Studies

The purpose of this paper is to describe the systemic strategies used in marriage and family therapy relevant to interviews, via what we call the therapeutic interview process, that expand the meaning of a research study for both the counselor researcher and the participant(s). We outline the therapeutic interview process for conducting transformative - based interviews via similar strategies from a family systems perspective conceptualized by Charlés (2007). The central core of the interview process is the therapeutic conversation itself that involves the systemic whole. This therapeutic conversation is facilitated by debriefing interviews, whereby the counselor researcher is interviewed to promote reflexivit

Collateral projections innervate the mammillary bodies and retrosplenial cortex: A new category of hippocampal cells

To understand the hippocampus it is necessary to understand the subiculum. Unlike other hippocampal subfields, the subiculum projects to almost all distal hippocampal targets, highlighting its critical importance for external networks. The present studies, in male rats and mice, reveal a new category of dorsal subiculum neurons that innervate both the mammillary bodies and the retrosplenial cortex. These bifurcating neurons comprise almost half of the hippocampal cells that project to retrosplenial cortex. The termination of these numerous collateral projections was visualized within the medial mammillary nucleus and the granular retrosplenial cortex (area 29). These collateral projections included subiculum efferents that cross to the contralateral mammillary bodies. Within the granular retrosplenial cortex, the collateral projections form a particularly dense plexus in deep layer II and layer III. This retrosplenial termination site co-localized with markers for VGluT2 and neurotensin. While efferents from the hippocampal CA fields standardly collateralize, subiculum projections often have only one target site. Consequently, the many collateral projections involving the retrosplenial cortex and the mammillary bodies present a relatively unusual pattern for the subiculum, which presumably relates to how both targets have complementary roles in spatial processing. Furthermore, along with the anterior thalamic nuclei, the mammillary bodies and retrosplenial cortex are key members of a memory circuit, which is usually described as both starting and finishing in the hippocampus. The present findings reveal how the hippocampus simultaneously engages different parts of this circuit, so forcing an important revision of this networ

Effects of P-MAPA Immunomodulator on Toll-Like Receptors and p53: Potential Therapeutic Strategies for Infectious Diseases and Cancer

BACKGROUND: Compounds that can act as agonists for toll-like receptors (TLRs) may be promising candidates for the development of drugs against infectious diseases and cancer. The present study aimed to characterize the immunomodulatory effects of P-MAPA on TLRs in vitro and in vivo, as well as to investigate its potential as adjuvant therapy in infectious diseases and cancer. METHODS: For these purposes, the activity of P-MAPA on TLRs was assayed in vitro through NF-κB activation in HEK293 cells expressing a given TLR, and using an in vivo animal model for bladder cancer (BC). The antimicrobial activity of P-MAPA was tested against Mycobacterium tuberculosis (TB) in vitro in an MIC assay, and in vivo using an aerosol infection model of murine tuberculosis. Antitumor effects of P-MAPA were tested in an animal model with experimentally induced BC. Moxifloxacin (MXF) and Bacillus Calmette-Guerin (BCG) were used as positive controls in the animal models. RESULTS: The results showed that P-MAPA, administered alone or in combination with MXF, induced significant responses in vivo against TB. In contrast, the compound did not show antimicrobial activity in vitro. P-MAPA showed a significant stimulatory effect on human TLR2 and TLR4 in vitro. In BC, TLR2, TLR4 and p53 protein levels were significantly higher in the P-MAPA group than in the BCG group. The most common histopathological changes in each group were papillary carcinoma in BC group, low-grade intraepithelial neoplasia in BCG group and simple hyperplasia in P-MAPA group. Concerning the toxicological analysis performed during BC treatment, P-MAPA did not show evidence for hepatotoxicity and nephrotoxicity. CONCLUSIONS: In conclusion, P-MAPA acted as TLR ligand in vitro and improved the immunological status in BC, increasing TLR2 and TLR4 protein levels. P-MAPA immunotherapy was more effective in restoring p53 and TLRs reactivities and showed significantly greater antitumor activity than BCG. The activation of TLRs and p53 may provide a hypothetical mechanism for the therapeutic effects in both cancer and infectious diseases. Taken together data obtained will encourage the further investigation of P-MAPA as a potential candidate for the treatment of cancer and infectious diseases

The syncytial Drosophila embryo as a mechanically excitable medium

Mitosis in the early syncytial Drosophila embryo is highly correlated in space and time, as manifested in mitotic wavefronts that propagate across the embryo. In this paper we investigate the idea that the embryo can be considered a mechanically-excitable medium, and that mitotic wavefronts can be understood as nonlinear wavefronts that propagate through this medium. We study the wavefronts via both image analysis of confocal microscopy videos and theoretical models. We find that the mitotic waves travel across the embryo at a well-defined speed that decreases with replication cycle. We find two markers of the wavefront in each cycle, corresponding to the onsets of metaphase and anaphase. Each of these onsets is followed by displacements of the nuclei that obey the same wavefront pattern. To understand the mitotic wavefronts theoretically we analyze wavefront propagation in excitable media. We study two classes of models, one with biochemical signaling and one with mechanical signaling. We find that the dependence of wavefront speed on cycle number is most naturally explained by mechanical signaling, and that the entire process suggests a scenario in which biochemical and mechanical signaling are coupled

Insomnia, Psychiatric Disorders and Suicidal Ideation in a National Representative Sample of Active Canadian Forces Members

Background Past research on the association between insomnia and suicidal ideation (SI) has produced mixed findings. The current study explored the relationship between insomnia, SI, and past-year mental health status among a large Canadian Forces (CF) sample. Method Data was obtained from the 2013 Canadian Forces Mental Health Survey (CFMHS), and included a large representative sample of Canadian Regular Forces personnel (N = 6700). A series of univariate logistic regressions were conducted to test individual associations between past-year mental health status, insomnia, and potential confounds and SI. Mental health status included three groups: 0, 1, or two or more probable diagnoses of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder (PD) and alcohol abuse/dependence. Stepwise multivariate logistic regression was used to assess the relationship between insomnia and SI with mental health status as a moderator. Results 40.8% of respondents reported experiencing insomnia. Both insomnia and number of mental health conditions incrementally increased the risk of SI. However, past-year mental health status was a significant moderator of this relationship, such that for CF personnel with either no (AOR = 1.61, 1.37–1.89) or only one past-year mental health condition (AOR = 1.39, 1.12–1.73), an incremental increase in insomnia was associated with an increased likelihood of SI. However, in personnel with two or more past-year mental health disorders, insomnia was no longer significantly associated with SI (AOR = 1.04, 0.81–1.33). Conclusions Insomnia significantly increased the odds of SI, but only among individuals with no or one mental health condition. Findings highlight the importance of assessing insomnia among CF members in order to further suicide prevention efforts

Acute Liver Failure (ALF) in Pregnancy: How Much Is Pregnancy Related?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163471/1/hep31144.pd

The minimal computational substrate of fluid intelligence

The quantification of cognitive powers rests on identifying a behavioural task that depends on them. Such dependence cannot be assured, for the powers a task invokes cannot be experimentally controlled or constrained a priori, resulting in unknown vulnerability to failure of specificity and generalisability. Evaluating a compact version of Raven's Advanced Progressive Matrices (RAPM), a widely used clinical test of fluid intelligence, we show that LaMa, a self-supervised artificial neural network trained solely on the completion of partially masked images of natural environmental scenes, achieves human-level test scores a prima vista, without any task-specific inductive bias or training. Compared with cohorts of healthy and focally lesioned participants, LaMa exhibits human-like variation with item difficulty, and produces errors characteristic of right frontal lobe damage under degradation of its ability to integrate global spatial patterns. LaMa's narrow training and limited capacity -- comparable to the nervous system of the fruit fly -- suggest RAPM may be open to computationally simple solutions that need not necessarily invoke abstract reasoning.Comment: 26 pages, 5 figure

Osteoblast Differentiation and Bone Matrix Formation In Vivo and In Vitro

We review the characteristics of osteoblast differentiation and bone matrix synthesis. Bone in air breathing vertebrates is a specialized tissue that developmentally replaces simpler solid tissues, usually cartilage. Bone is a living organ bounded by a layer of osteoblasts that, because of transport and compartmentalization requirements, produce bone matrix exclusively as an organized tight epithelium. With matrix growth, osteoblasts are reorganized and incorporated into the matrix as living cells, osteocytes, which communicate with each other and surface epithelium by cell processes within canaliculi in the matrix. The osteoblasts secrete the organic matrix, which are dense collagen layers that alternate parallel and orthogonal to the axis of stress loading. Into this matrix is deposited extremely dense hydroxyapatite-based mineral driven by both active and passive transport and pH control. As the matrix matures, hydroxyapatite microcrystals are organized into a sophisticated composite in the collagen layer by nucleation in the protein lattice. Recent studies on differentiating osteoblast precursors revealed a sophisticated proton export network driving mineralization, a gene expression program organized with the compartmentalization of the osteoblast epithelium that produces the mature bone matrix composite, despite varying serum calcium and phosphate. Key issues not well defined include how new osteoblasts are incorporated in the epithelial layer, replacing those incorporated in the accumulating matrix. Development of bone in vitro is the subject of numerous projects using various matrices and mesenchymal stem cell-derived preparations in bioreactors. These preparations reflect the structure of bone to variable extents, and include cells at many different stages of differentiation. Major challenges are production of bone matrix approaching the in vivo density and support for trabecular bone formation. In vitro differentiation is limited by the organization and density of osteoblasts and by endogenous and exogenous inhibitors