Assessment of Oxidative Stress in the Livers of Rats Exposed to 2-Aminoanthracene for Twelve Weeks

Diabetes is a chronic illness that affects many people, and it’s thought that environmental exposure to certain compounds may increase its proliferation. In this study, we examine the dietary effects of 2-aminoanthracene (2AA), a polycyclic aromatic hydrocarbon (PAH), in rats, specifically as it relates to oxidative stress. Oxidative stress refers to the imbalance of reactive oxygen species (ROS) and antioxidants in living systems; it has been shown to contribute to type-1 diabetes. To accomplish the study objectives rats were divided into three dietary treatment groups, control (0 mg/kg-2AA), low dose (50 mg/kg-2AA) and high dose (100 mg/kg-2AA). Rats were fed 2AA for three months, and then euthanized using carbon dioxide. Various tissues including the liver and were flash-frozen in liquid nitrogen. To determine 2AA effects in the liver, a portion of the liver was homogenized in phosphate buffered saline solution. The supernatant was analyzed for serum albumin, aspartate aminotransferase (AST), IgA protein, and antioxidants. Furthermore, genes such as Pdx1, Sod1, Gpx1, Prdx6, Ncf2, Duox1 and Ptgs2 typically used to measure cellular oxidative stress were quantified. The expressions of these genes in the liver show the upregulation of Sod1 and Prdx6, and downregulation of Ptgs2 in treated groups. AST activity was marginally increased in treated groups while the albumin concentration was elevated in the 50 mg/kg group and reduced in the 100 mg/kg-2AA animals. IgA levels were slightly elevated while antioxidant levels were reduced in treated groups. Taken together, these results show that ingestion of 2AA may produce hepatic oxidative stress

The double-edge sword effect of anti-CD73 cancer therapy

We and others have identified CD73 as a new cancer target. I hereafter discuss that targeted blockade of CD73 has the effect of a “double-edge sword,” able on the one hand to rescue endogenous adaptive anti-tumor immune responses, and on the other hand, inhibit the metastatic potential of tumor cells

Are medical students influenced by preceptors in making career choices, and if so how? A systematic review

Author version made available in accordance with the publisher's policy.Introduction: Increasingly medical students undertake clinical training in distributed learning environments. The driving factor for this is predominantly to address medical workforce shortages. In these environments students are often taught by private practitioners, residents, house staff and registrars, as well as faculty. Through a mix of short- and long-term preceptorships, clerkships and rotations, medical students are exposed to a wider range of preceptors, mentors and role models than has traditionally been the case. The aim of this systematic review was to understand if and how medical students’ career choices are influenced by their interactions with preceptors. Method: A search of Ovid Medline, Scopus, ISI Web of Science, PubMed, Eric and CIHNAL was undertaken. The search was structured around the key terms: Medical Student, Career Choice and Preceptor, and variants of these terms. Search limits were set to English-language publications between 1995 and 2010. Results: A total of 36 articles met the selection criteria from the 533 citations sourced from the search. Required preceptorships as short as 3 weeks’ duration influence the career choice of students when they rate the preceptor as a high quality teacher. Preceptors who are judged (by students) as high quality teachers have the greatest influence on student career choice by up to four-fold. When students judged a preceptor as being a negative role model, a poor teacher or lacking discipline specific knowledge they will turn away from that field. The positive influence of relationships between preceptors and students on career choice is strongest where there is continuity of preceptors, continuity of care, and continuity of patient interactions. The longer the duration of the preceptorship the greater the influence on student career choice, particularly in primary cares environments. Conclusion: This review adds to the literature by identifying how differing components and combinations of components of a preceptorship influence medical student career choices. Multiple components of the preceptorship combined have a greater influence. In free choice, longitudinal integrated clerkships’ duration of placement and continuity relationships with preceptors have the greatest influence on medical students in pursuing a primary care career. This information informs medical schools, curriculum designers and policy-makers in reforming medical education to address workforce shortages

The role of ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation

Extracellular adenosine is a potent immunomodulatory molecule that accumulates in states of inflammation. Nucleotides such as adenosine triphosphate and adenosine diphosphate are release from injured and necrotic cells and hydrolyzed to adenosine monophosphate and adenosine by the concerted action of the ectonucleotidases CD39 and CD73. Accumulating evidence suggest that purinergic signaling is involved in the inflammatory response that accompanies acute rejection and chronic allograft dysfunction. Modification of the purinergic pathway has been shown to alter graft survival in a number of solid organ transplant models and the response to ischemia–reperfusion injury (IRI). Furthermore, the purinergic pathway is intrinsically involved in B and T cell biology and function. Although T cells have traditionally been considered the orchestrators of acute allograft rejection, a role for B cells in chronic allograft loss is being increasingly appreciated. This review focuses on the role of the ectonucleotidases CD39 and CD73 and adenosine signaling in solid organ transplantation including the effects on IRI and T and B cell biology

Modulation of Long-Range Connectivity Patterns via Frequency-Specific Stimulation of Human Cortex

There is increasing interest in how the phase of local oscillatory activity within a brain area determines the long-range functional connectivity of that area. For example, increasing convergent evidence from a range of methodologies suggests that beta (20 Hz) oscillations may play a vital role in the function of the motor system [1-5]. The "communication through coherence" hypothesis posits that the precise phase of coherent oscillations in network nodes is a determinant of successful communication between them [6, 7]. Here we set out to determine whether oscillatory activity in the beta band serves to support this theory within the cortical motor network in vivo. We combined non-invasive transcranial alternating-current stimulation (tACS) [8-12] with resting-state functional MRI (fMRI) [13] to follow both changes in local activity and long-range connectivity, determined by inter-areal blood-oxygen-level-dependent (BOLD) signal correlation, as a proxy for communication in the human cortex. Twelve healthy subjects participated in three fMRI scans with 20 Hz, 5 Hz, or sham tACS applied separately on each scan. Transcranial magnetic stimulation (TMS) at beta frequency has previously been shown to increase local activity in the beta band [14] and to modulate long-range connectivity within the default mode network [15]. We demonstrated that beta-frequency tACS significantly changed the connectivity pattern of the stimulated primary motor cortex (M1), without changing overall local activity or network connectivity. This finding is supported by a simple phase-precession model, which demonstrates the plausibility of the results and provides emergent predictions that are consistent with our empirical findings. These findings therefore inform our understanding of how local oscillatory activity may underpin network connectivity

Perceptually relevant remapping of human somatotopy in 24 hours

Experience-dependent reorganisation of functional maps in the cerebral cortex is well described in the primary sensory cortices. However, there is relatively little evidence for such cortical reorganisation over the short-term. Using human somatosensory cortex as a model, we investigated the effects of a 24 hr gluing manipulation in which the right index and right middle fingers (digits 2 and 3) were adjoined with surgical glue. Somatotopic representations, assessed with two 7 tesla fMRI protocols, revealed rapid off-target reorganisation in the non-manipulated fingers following gluing, with the representation of the ring finger (digit 4) shifted towards the little finger (digit 5) and away from the middle finger (digit 3). These shifts were also evident in two behavioural tasks conducted in an independent cohort, showing reduced sensitivity for discriminating the temporal order of stimuli to the ring and little fingers, and increased substitution errors across this pair on a speeded reaction time task

Macromolecular crowding modulates folding mechanism of alpha/beta protein apoflavodoxin

Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.Comment: to appear in Biophysical Journal (2009). to appear in Biophysical Journal (2009