Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner

Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, residente-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants

Tetra-μ-benzoato-bis­{[4-(pyrrolidin-1-yl)pyridine]zinc(II)}

The central part of the title centrosymmetric dinuclear complex, [Zn2(C7H5O2)4(C9H12N2)2], has a paddle-wheel conformation with four benzoate ligands bridging two symmetry-related ZnII ions. The distorted square-pyramidal coordination environment around the ZnII ion is completed by an N atom from a 4-(pyrrolidin-1-yl)pyridine ligand. The Zn⋯Zn separation of 2.9826 (12) Å does not represent a formal direct metal–metal bond. The ZnII ion is displaced by 0.381 (1) Å from the mean plane of the four basal O atoms. Two of the C atoms of the pyrrolidine ring are disordered over two sites with refined occupancies of 0.53 (2) and 0.47 (2)

Development of pericardial fat count images using a combination of three different deep-learning models

Rationale and Objectives: Pericardial fat (PF), the thoracic visceral fat surrounding the heart, promotes the development of coronary artery disease by inducing inflammation of the coronary arteries. For evaluating PF, this study aimed to generate pericardial fat count images (PFCIs) from chest radiographs (CXRs) using a dedicated deep-learning model. Materials and Methods: The data of 269 consecutive patients who underwent coronary computed tomography (CT) were reviewed. Patients with metal implants, pleural effusion, history of thoracic surgery, or that of malignancy were excluded. Thus, the data of 191 patients were used. PFCIs were generated from the projection of three-dimensional CT images, where fat accumulation was represented by a high pixel value. Three different deep-learning models, including CycleGAN, were combined in the proposed method to generate PFCIs from CXRs. A single CycleGAN-based model was used to generate PFCIs from CXRs for comparison with the proposed method. To evaluate the image quality of the generated PFCIs, structural similarity index measure (SSIM), mean squared error (MSE), and mean absolute error (MAE) of (i) the PFCI generated using the proposed method and (ii) the PFCI generated using the single model were compared. Results: The mean SSIM, MSE, and MAE were as follows: 0.856, 0.0128, and 0.0357, respectively, for the proposed model; and 0.762, 0.0198, and 0.0504, respectively, for the single CycleGAN-based model. Conclusion: PFCIs generated from CXRs with the proposed model showed better performance than those with the single model. PFCI evaluation without CT may be possible with the proposed method

Interactions of a j=1j=1 boson in the 2(2j+1)2(2j+1) component theory

The amplitudes for boson-boson and fermion-boson interactions are calculated in the second order of perturbation theory in the Lobachevsky space. An essential ingredient of the used model is the Weinberg's $2(2j+1)$ component formalism for describing a particle of spin $j$, recently developed substantially. The boson-boson amplitude is then compared with the two-fermion amplitude obtained long ago by Skachkov on the ground of the hamiltonian formulation of quantum field theory on the mass hyperboloid, $p_0^2 -{\bf p}^2=M^2$, proposed by Kadyshevsky. The parametrization of the amplitudes by means of the momentum transfer in the Lobachevsky space leads to same spin structures in the expressions of $T$ matrices for the fermion and the boson cases. However, certain differences are found. Possible physical applications are discussed.Comment: REVTeX 3.0 file. 12pp. Substantially revised version of IFUNAM preprints FT-93-24, FT-93-3

Median raphe serotonergic neurons projecting to the interpeduncular nucleus control preference and aversion

不快感を誘発するセロトニン神経を発見 --セロトニン神経の多様性が明らかに--. 京都大学プレスリリース. 2022-12-23.Appropriate processing of reward and aversive information is essential for survival. Although a critical role of serotonergic neurons in the dorsal raphe nucleus (DRN) in reward processing has been shown, the lack of rewarding effects with selective serotonin reuptake inhibitors (SSRIs) implies the presence of a discrete serotonergic system playing an opposite role to the DRN in the processing of reward and aversive stimuli. Here, we demonstrated that serotonergic neurons in the median raphe nucleus (MRN) of mice process reward and aversive information in opposite directions to DRN serotonergic neurons. We further identified MRN serotonergic neurons, including those projecting to the interpeduncular nucleus (5-HTMRN→IPN), as a key mediator of reward and aversive stimuli. Moreover, 5-HT receptors, including 5-HT2A receptors in the interpeduncular nucleus, are involved in the aversive properties of MRN serotonergic neural activity. Our findings revealed an essential function of MRN serotonergic neurons, including 5-HTMRN→IPN, in the processing of reward and aversive stimuli

A new conventional regression model to estimate hourly photosynthetic photon flux density under all sky conditions

"This is the pre-peer reviewed version of the following article: Foyo-Moreno, I., Alados, I. and Alados-Arboledas, L. (2017), A new conventional regression model to estimate hourly photosynthetic photon flux density under all sky conditions. Int. J. Climatol.. doi:10.1002/joc.5063, which has been published in final form at hppt://dx.doi.org/10.1002/joc.5063 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."In this work we propose a new and simple empirical model to estimate photosynthetic photon flux density under all sky conditions, developed using experimental measurements carried out at Granada, an urban site in Southeastern Spain during two recent years (2014-2015). The model uses the solar zenith angle and clearness index as input parameters, and thus needs only global irradiance measurements usually registered in most radiometric networks. Five stations located in the northern and southern hemisphere with different climatological characteristics at Europe, Asia and America (Spain, Japan and Argentina) were used to validate the model. The model provides satisfactory results, giving low mean bias error for all stations, particularly Mean Bias Error, MBE, being less than 1% in absolute values in three stations and Root Mean Square Error, RMSE, below 6% for all stations except one with 6.1%. These results show better accuracy in comparison to other earlier empirical models and suggest the effectiveness of the model by its general applicability.Andalusia Regional Government. Grant Numbers: P11-RNM-7186, P12-RNM-2409Spanish Ministry of Economy and Competitiveness. Grant Numbers: CGL2016-81092-R, CGL2013-45410-R, CGL2014-52838-C2-1-REuropean Union's Horizon 2020 Research And Innovation Programme. Grant Number: 65410

Specific Myosins Control Actin Organization, Cell Morphology, and Migration in Prostate Cancer Cells

We investigated the myosin expression profile in prostate cancer cell lines and found that Myo1b, Myo9b, Myo10, and Myo18a were expressed at higher levels in cells with high metastatic potential. Moreover, Myo1b and Myo10 were expressed at higher levels in metastatic tumors. Using an siRNA-based approach, we found that knockdown of each myosin resulted in distinct phenotypes. Myo10 knockdown ablated filopodia and decreased 2D migration speed. Myo18a knockdown increased circumferential non-muscle myosin 2A-associated actin filament arrays in the lamella and reduced directional persistence of 2D migration. Myo9b knockdown increased stress fiber formation, decreased 2D migration speed, and increased directional persistence. Conversely, Myo1b knockdown increased numbers of stress fibers but did not affect 2D migration. In all cases, the cell spread area was increased and 3D migration potential was decreased. Therefore, myosins not only act as molecular motors but also directly influence actin organization and cell morphology, which can contribute to the metastatic phenotype

Diabetes status and post-load plasma glucose concentration in relation to site-specific cancer mortality: findings from the original Whitehall study

ObjectiveWhile several studies have reported on the relation of diabetes status with pancreatic cancer risk, the predictive value of this disorder for other malignancies is unclear. Methods: The Whitehall study, a 25year follow-up for mortality experience of 18,006 men with data on post-challenge blood glucose and self-reported diabetes, allowed us to address these issues. Results: There were 2158 cancer deaths at follow-up. Of the 15 cancer outcomes, diabetes status was positively associated with mortality from carcinoma of the pancreas and liver, while the relationship with lung cancer was inverse, after controlling for a range of potential covariates and mediators which included obesity and socioeconomic position. After excluding deaths occurring in the first 10years of follow-up to examine the effect of reverse causality, the magnitude of the relationships for carcinoma of the pancreas and lung was little altered, while for liver cancer it was markedly attenuated. Conclusions: In the present study, diabetes status was related to pancreatic, liver, and lung cancer risk. Cohorts with serially collected data on blood glucose and covariates are required to further examine this area

Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target

Since reprogramming energy metabolism is considered a new hallmark of cancer, tumor metabolism is again in the spotlight of cancer research. Many studies have been carried out and many possible therapies have been developed in the last years. However, tumor cells are not alone. A series of extracellular components and stromal cells, such as endothelial cells, cancer-associated fibroblasts, tumor-associated macrophages and tumor-infiltrating T cells, surround tumor cells in the so-called tumor microenvironment. Metabolic features of these cells are being studied in deep in order to find relationships between metabolism within the tumor microenvironment and tumor progression. Moreover, it cannot be forgotten that tumor growth is able to modulate host metabolism and homeostasis, so that tumor microenvironment is not the whole story. Importantly, the metabolic switch in cancer is just a consequence of the flexibility and adaptability of metabolism and should not be surprising. Treatments of cancer patients with combined therapies including anti-tumor agents with those targeting stromal cell metabolism, anti-angiogenic drugs and/or immunotherapy are being developed as promising therapeutics.Mª Carmen Ocaña is recipient of a predoctoral FPU grant from the Spanish Ministry of Education, Culture and Sport. Supported by grants BIO2014-56092-R (MINECO and FEDER), P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript

Sun exposure to the eyes: predicted UV protection effectiveness of various sunglasses.

The aim of this study was to assess solar ultraviolet radiation (UVR) doses received by the eyes in different exposure situations, and to predict the sun protection effectiveness provided by various styles of sunglasses at facial, periorbital, and ocular skin zones including the cornea and accounting for different head positions. A 3D numeric model was optimized to predict direct, diffuse and reflected erythemally weighted UVR doses received at various skin zones. Precisely defined facial, periorbital, and ocular skin zones, sunglasses (goggles, medium-, and large-sized sunglasses) and three head positions were modeled to simulate daily (08:00-17:00) and midday (12:00-14:00) UVR doses. The shading from sunglasses' frame and lenses' UVR transmission were used to calculate a predictive protection factor (PPF [%]). Highest ocular daily UVR doses were estimated at the uncovered cornea (1718.4 J/m <sup>2</sup> ). Least sun protection was provided by middle-sized sunglasses with highest midday dose at the white lateral (290.8 J/m <sup>2</sup> ) and lateral periorbital zones (390.9 J/m <sup>2</sup> ). Goggles reached almost 100% protection at all skin zones. Large-sized sunglasses were highly effective in winter; however, their effectiveness depended on diffuse UVR doses received. In "looking-up" head positions highest midday UVR doses were received at the unprotected cornea (908.1 J/m <sup>2</sup> ), totally protected when large-sized sunglasses are used. All tested sunglass lenses fully blocked UVR. Sunglasses' protection effectiveness is strongly influenced by geometry, wearing position, head positions, and exposure conditions. Sunglasses do not totally block UVR and should be combined with additional protection means. 3D modeling allows estimating UVR exposure of highly sensitive small skin zones, chronically exposed and rarely assessed