κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

Structural Aspects and Prediction of Calmodulin-Binding Proteins

Calmodulin (CaM) is an important intracellular protein that binds Ca²⁺ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca²⁺ concentration through interactions with CaM.     

Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe³⁺ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe³⁺ was adsorbed in PDA NPs at pH values close to which Fe(OH)₃ begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe³⁺. Otherwise, it was demonstrated that Fe³⁺ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca²⁺ content, and that when Fe³⁺ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe³⁺ and doxorubicin may constitute a good approach to target breast tumors.     

Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus was investigated in the semen of 99 human immunodeficiency virus (HIV)-infected men (median CD4 cell count, 357/mm3) by use of a polymerase chain reaction (PCR) assay capable of detecting <10 copies of HHV-8 DNA. Of the subjects, 95 (96%) self-identified as men who have sex with men (MSM), and 3 had a history of clinical KS. Seminal cell specimens were negative for HHV-8 in 98 subjects. None of the 26 without KS (27.1% of 96 tested) who were seropositive for HHV-8 by IFA for latency-associated nuclear antigens had HHV-8 detected in their semen. The only subject with any evidence for seminal HHV-8 DNA was seropositive for HHV-8 and had active KS. HHV-8 was detected in 10 (10.4%) of 96 peripheral blood mononuclear cell specimens. The prevalence of HHV-8 DNA by PCR in semen of HIV-infected MSM without KS is low.     

Control strategies for reactive batch distillation

A batch reactor may be combined directly with a distillation column by distilling off the light component product in order to increase the reactor temperature or to improve the product yield of an equilibrium reaction. The same amount of the light product should be removed as the amount being formed by the reaction at any time. A linearized model has been developed which describes the process behaviour satisfactorily for control analysis purposes. The controllability of a combined batch reactor/batch distillation column is found to depend strongly on the operating conditions and on the time during the run. In general, controlling only the reactor temperature (one-point bottom control) is difficult since the set-point has to be specified below a maximum value in order to avoid break-through of an intermediate component in the ditillate. This maximum value may be difficult to know a priori. For the example considered in this study, control of both reactor temperature and distillate composition (two-point control) is also found to be difficult due to large interactions in the column. As with one-point bottom control, the reactor temperature has to be specified below a maximum value. However, energy can be saved since the heat duty can be decreased with time. Controlling the temperature on a tray in the column (one-point column control) is found to give good performance for the given process with no loss of reactant and a high reactor temperature, although no direct control of the reactor temperature is obtained.     

A new method for manufacturing nanostructured electrodes on glass substrates

The present paper describes a new method for manufacturing a nanostructured porous layer of TiO₂ on a conducting glass substrate for use in a dye-sensitized photoelectrochemical cell. The method involves deposition of a layer of semiconductor particles onto a conducting substrate and compression of the particle layer to form a mechanically stable, electrically conducting, and porous nanostructured film at room temperature. Photoelectrochemical characteristics and morphology of the resulting nanostructured films are presented. The potential use of the new manufacturing method in the future applications of nanostructured systems is discussed.     

Effectiveness of spatial representation in the formation of network communities: experimental study on community organizer

In this paper, we present and discuss Community Organizer, a system designed to support network communities. The main characteristic of Community Organizer is the use of spatial representations for the relationships among community members including the communications exchanged among these members. These spatial representations reflect the degree of closeness of interests and concerns among the members, and are intended to provide users with clues on how to form network communities. In order to investigate the effectiveness of the proposed spatial representations, we conducted experiments with two different versions of the software. One version offered meaningful spatial representations while the other version did not. The subjects who used the former software version felt a greater sense of ‘community’, enjoyed using the software more, and actively used it longer than the subjects using the latter software version (control condition). These results indicated that the proposed spatial representations are effective in supporting network community formation.