Spleen Volume Variation in Patients with Locally Advanced Non-Small Cell Lung Cancer Receiving Platinum-Based Chemo-Radiotherapy.

There is renewed interest in the immune regulatory role of the spleen in oncology. To date, very few studies have examined macroscopic variations of splenic volume in the setting of cancer, prior to or during therapy, especially in humans. Changes in splenic volume may be associated with changes in splenic function. The purpose of this study was to investigate variations in spleen volume in NSCLC patients during chemo-radiotherapy. Sixty patients with stage I-IIIB NSCLC underwent radiotherapy (60Gy/30 fractions) for six weeks with concomitant carboplatin/paclitaxel (Ca/P; n = 32) or cisplatin/etoposide (Ci/E; n = 28). A baseline PET/CT scan was performed within 2 weeks prior to treatment and during Weeks 2 and 4 of chemo-radiotherapy. Spleen volume was measured by contouring all CT slices. Significant macroscopic changes in splenic volume occurred early after the commencement of treatment. A significant decrease in spleen volume was observed for 66% of Ca/P and 79% of Ci/E patients between baseline and Week 2. Spleen volume was decreased by 14.2% for Ca/P (p<0.001) and 19.3% for Ci/E (p<0.001) patients. By Week 4, spleen volume was still significantly decreased for Ca/P patients compared to baseline, while for Ci/E patients, spleen volume returned to above baseline levels. This is the first report demonstrating macroscopic changes in the spleen in NSCLC patients undergoing radical chemo-radiotherapy that can be visualized by non-invasive imaging.

Blurred pictures from the crime scene: the growing case for a function of Chlamydiales in plastid endosymbiosis.

A number of recent papers have brought suggestive evidence for an active role of Chlamydiales in the establishment of the plastid. Chlamydiales define a very ancient group of obligate intracellular bacterial pathogens that multiply in vesicles within eukaryotic phagotrophic host cells such as animals, amoebae or other protists, possibly including the hypothetical phagotroph that internalized the cyanobacterial ancestor of the plastid over a billion years ago. We briefly survey the case for an active role of these ancient pathogens in plastid endosymbiosis. We argue that a good understanding of the Chlamydiales infection cycle and diversity may help to shed light on the process of metabolic integration of the evolving plastid.

Extracellular Subunit Interactions Control Transitions between Functional States of Acid-sensing Ion Channel 1a.

Acid-sensing ion channels (ASICs) are neuronal, voltage-independent Na(+) channels that are transiently activated by extracellular acidification. They are involved in pain sensation, the expression of fear, and in neurodegeneration after ischemic stroke. Our study investigates the role of extracellular subunit interactions in ASIC1a function. We identified two regions involved in critical intersubunit interactions. First, formation of an engineered disulfide bond between the palm and thumb domains leads to partial channel closure. Second, linking Glu-235 of a finger loop to either one of two different residues of the knuckle of a neighboring subunit opens the channel at physiological pH or disrupts its activity. This suggests that one finger-knuckle disulfide bond (E235C/K393C) sets the channel in an open state, whereas the other (E235C/Y389C) switches the channel to a non-conducting state. Voltage-clamp fluorometry experiments indicate that both the finger loop and the knuckle move away from the β-ball residue Trp-233 during acidification and subsequent desensitization. Together, these observations reveal that ASIC1a opening is accompanied by a distance increase between adjacent thumb and palm domains as well as a movement of Glu-235 relative to the knuckle helix. Our study identifies subunit interactions in the extracellular loop and shows that dynamic changes of these interactions are critical for normal ASIC function.

The Impact of Supervisor's Advice, Codes of Conduct, Accountability and Moral Attentiveness of Individuals on Discriminatory Behaviour Against Immigrants.

Past studies on the personnel selection demonstrated that a supervisor's advice to discriminate can lead to compliant behaviours. This study had the aim to extend past findings by examining what can overcome the powerful influence of the hierarchy. 50 Swiss managers participated to an in-basket exercise. The main task was to evaluate Swiss candidates (in-group) and foreigners (out-groups: Spanish and Kosovo Albanians) and to select two applicants for a job interview. Main results were the effect of codes of conduct to prevent discrimination against out-group applicants in the presence of a supervisor's advice to prefer in-group members. But, when participants were accountable to an audience, this beneficial effect disappears because participants followed the supervisor's advice. The second aim was to assess if the difference in responses between participants was related to their difference in moral attentiveness. Results showed some significant relationships but not always in the direction expected.