The legacy of translocations among populations of the Ibizan Wall Lizard, Podarcis pityusensis (Squamata: Lacertidae)

The Ibizan wall lizard, Podarcis pityusensis, was the subject of several documented 25 translocations by the German herpetologist Martin Eisentraut, in 1930. He aimed to initiate 26 long-term experiments into the evolution of melanism and other morphological traits and 27 accordingly reported introductions into five islets that (he believed) contained no lizards. In 28 this study, we analysed the genetics and morphological characteristics of individuals we found 29 there. We found no lizards on two of the islets, namely Escull de Tramuntana or Galera, but 30 for the first time, detected a large population on a third, Es Vaixell. Analyses of microsatellite 31 DNA placed individuals from a fourth islet, Dau Gran, with those from the islet of Escull 32 Vermell. They are also morphologically close to individuals from Escull Vermell. This 33 suggests that selection pressures could have favoured the Escull Vermell phenotype following 34 introduction. Eisentraut founded the Es Vaixell population with non- melanic Ibizan 35 specimens, but the present day population of Es Vaixell was found to be fully melanic. Genetic 36 markers support a strong similarity between Es Vaixell and Na Gorra, and indicate that, in all 37 likelihood, the individuals introduced by Eisentraut have left no descendants. It is likely that 38 Es Vaixell already contained lizards prior to this introduction. For reasons which we discuss, 39 the translocations have revealed less than Eisentraut would have originally hoped for, although 40 they do provide some potential insights into lizard morphological evolution following 41 colonization

Nephroprotective Effect of the Virgin Olive Oil Polyphenol Hydroxytyrosol in Type 1-like Experimental Diabetes Mellitus: Relationships with Its Antioxidant Effect

The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67–73%), calculated creatinine clearance was significantly increased (26–38%), and the glomerular volume and glomerulosclerosis index were decreased (20–30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production

Combination Atezolizumab, Cobimetinib, and Vemurafenib as a Treatment Option in BRAF V600 Mutation–Positive Melanoma: Patient Selection and Perspectives

Michelle M Dugan,1 Matthew C Perez,1 Lilit Karapetyan,1,2 Jonathan S Zager1,2 1Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA; 2Department of Oncologic Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USACorrespondence: Jonathan S Zager, Chief Academic Officer, Directory of Regional Therapies, Senior Member, Department of Cutaneous Oncology, Moffitt Cancer Center, McKinley Drive Room 4123, Tampa, FL, 33612, USA, Tel +1-813-745-1085, Fax +1-813-745-5725, Email [email protected]: The treatment landscape for advanced and metastatic melanoma has drastically changed in recent years, with the advent of novel therapeutic options such as immune checkpoint inhibitors and targeted therapies offering remarkable efficacy and significantly improved patient outcomes compared to traditional approaches. Approximately 50% of melanomas harbor activating BRAF mutations, with over 90% resulting in BRAF V600E. Tumors treated with BRAF inhibitor monotherapy have a high rate of developing resistance within six months. Combination therapy with MEK inhibitors helped to mitigate this treatment resistance and led to improved outcomes. Due to the up-regulation of PD-1/PD-L1 receptors in tumors treated with BRAF/MEK inhibitor therapy, further studies included a third combination agent, anti-PD-1/PD-L1 inhibitors. This triple combination therapy may have superior efficacy and a manageable safety profile when compared with single or double agent therapy regimens.Plain Language Summary: Effective treatment of advanced and metastatic melanoma can be challenging. Newer treatment methods for patients with BRAF-mutated tumors include a combination of drugs with different complementary mechanisms. These drugs include BRAF-inhibitors, MEK-inhibitors, and PD-1/PD-L1 inhibitors. When these three medications are used in combination, patients may have better response rates and survival outcomes, when compared to using just one or two of these medications together. Toxicity rates are higher with a triple-medication regimen, so careful patient selection is important to consider.Keywords: BRAF inhibitor, MEK inhibitor, metastatic melanoma, BRAF-mutant melanoma, combination BRAF therapy, triple therap

Shoulder pain due to cervical radiculopathy: an underestimated long-term complication of herpes zoster virus reactivation?

Purpose To evaluate if herpes zoster virus (HZV) reactivation may be considered in the aetiology of cervical radiculopathy. Methods The study group was composed of 110 patients (52 M-58F;mean age ± SD:46.5 ± 6.12; range:40-73) with a clinical diagnosis of cervical radiculopathy. Patients with signs of chronic damage on neurophysiological studies were submitted to an X-ray and to an MRI of the cervical spine in order to clarify the cause of the cervical radiculopathy and were investigated for a possible reactivation of HZV; HZV reactivation was considered as “recent” or “antique” if it occurs within or after 24 months from the onset of symptoms, respectively. Data were submitted to statistics. Results Thirty-eight patients (34,5%,16 M-22F) had a history of HZV reactivation: four (2 M-2F) were “recent” and 34 (14 M-20F) were “antique”. In 68 of 110 participants (61,8%,30 M-38F), pathological signs on X-ray and/or MRI of the cervical spine appeared; in the remaining 42 (38,2%,22 M-20F) X-ray and MRI resulted as negative. Among patients with HZV reactivation, seven (18,4%) had a “positive” X-ray-MRI while in 31 (81,6%) the instrumental exams were considered as negative. The prevalence of “antique” HZV reactivations was statistically greater in the group of patients with no pathological signs on X-ray/MRI of the cervical spine with respect to the group with a pathological instrumental exam (p < 0.01). Conclusions It may be useful to investigate the presence of a positive history of HZV reactivation and to consider it as a long-term complication of a cervical root inflammation especially in patients in which X-ray and MRI of the cervical spine did not show pathological findings

Deployment of spatial attention towards locations in memory representations: an EEG study

Recalling information from visual short-term memory (VSTM) involves the same neural mechanisms as attending to an actually perceived scene. In particular, retrieval from VSTM has been associated with orienting of visual attention towards a location within a spatially-organized memory representation. However, an open question concerns whether spatial attention is also recruited during VSTM retrieval even when performing the task does not require access to spatial coordinates of items in the memorized scene. The present study combined a visual search task with a modified, delayed central probe protocol, together with EEG analysis, to answer this question. We found a temporal contralateral negativity (TCN) elicited by a centrally presented go-signal which was spatially uninformative and featurally unrelated to the search target and informed participants only about a response key that they had to press to indicate a prepared target-present vs. -absent decision. This lateralization during VSTM retrieval (TCN) provides strong evidence of a shift of attention towards the target location in the memory representation, which occurred despite the fact that the present task required no spatial (or featural) information from the search to be encoded, maintained, and retrieved to produce the correct response and that the go-signal did not itself specify any information relating to the location and defining feature of the target

Synergistic Effect of 3 ',4 '-Dihidroxifenilglicol and Hydroxytyrosol on Oxidative and Nitrosative Stress and Some Cardiovascular Biomarkers in an Experimental Model of Type 1 Diabetes Mellitus

The objective of this study was to assess a possible synergistic effect of two extra-virgin olive oil polyphenols, 3,4,-dyhydroxyphenylglycol (DHPG) and hydroxytyrosol (HT), in an experimental model of type 1 diabetes. Seven groups of animals were studied: (1) Nondiabetic rats (NDR), (2) 2-month-old diabetic rats (DR), (3) DR treated with 5 mg/kg/day p.o. HT, (4) DR treated with 0.5 mg/kg/day p.o. DHPG, (5) DR treated with 1 mg/kg/day p.o. DHPG, (6) DR treated with HT + DHPG (0.5), (7) DR treated with HT + DHPG (1). Oxidative stress variables (lipid peroxidation, glutathione, total antioxidant activity, 8-isoprostanes, 8-hydroxy-2-deoxyguanosine, and oxidized LDL), nitrosative stress (3-nitrotyrosine), and some cardiovascular biomarkers (platelet aggregation, thromboxane B2, prostacyclin, myeloperoxidase, and vascular cell adhesion protein 1 (VCAM-1)) were analyzed. The diabetic animals showed an imbalance in all of the analyzed variables. HT exerted an antioxidant and downregulatory effect on prothrombotic biomarkers while reducing the fall of prostacyclin. DHPG presented a similar, but quantitatively lower, profile. HT plus DHPG showed a synergistic effect in the reduction of oxidative and nitrosative stress, platelet aggregation, production of prostacyclin, myeloperoxidase, and VCAM-1. This synergism could be important for the development of functional oils enriched in these two polyphenols in the proportion used in this study

Size-driven quantum phase transitions

Can the properties of the thermodynamic limit of a many-body quantum system be extrapolated by analyzing a sequence of finite-size cases? We present models for which such an approach gives completely misleading results: translationally invariant, local Hamiltonians on a square lattice with open boundary conditions and constant spectral gap, which have a classical product ground state for all system sizes smaller than a particular threshold size, but a ground state with topological degeneracy for all system sizes larger than this threshold. Starting from a minimal case with spins of dimension 6 and threshold lattice size 15×1515×15, we show that the latter grows faster than any computable function with increasing local spin dimension. The resulting effect may be viewed as a unique type of quantum phase transition that is driven by the size of the system rather than by an external field or coupling strength. We prove that the construction is thermally robust, showing that these effects are in principle accessible to experimental observation

The programming of sequences of saccades

Saccadic eye movements move the high-resolution fovea to point at regions of interest. Saccades can only be generated serially (i.e., one at a time). However, what remains unclear is the extent to which saccades are programmed in parallel (i.e., a series of such moments can be planned together) and how far ahead such planning occurs. In the current experiment, we investigate this issue with a saccade contingent preview paradigm. Participants were asked to execute saccadic eye movements in response to seven small circles presented on a screen. The extent to which participants were given prior information about target locations was varied on a trial-by-trial basis: participants were aware of the location of the next target only, the next three, five, or all seven targets. The addition of new targets to the display was made during the saccade to the next target in the sequence. The overall time taken to complete the sequence was decreased as more targets were available up to all seven targets. This was a result of a reduction in the number of saccades being executed and a reduction in their saccade latencies. Surprisingly, these results suggest that, when faced with a demand to saccade to a large number of target locations, saccade preparation about all target locations is carried out in paralle

Nestedness across biological scales

This is the final published version. Available from Public Library of Science via the DOI in this record.All data sets are available for download in the repository https:// bitbucket.org/maucantor/unodf_analyses/src.Biological networks pervade nature. They describe systems throughout all levels of biological organization, from molecules regulating metabolism to species interactions that shape ecosystem dynamics. The network thinking revealed recurrent organizational patterns in complex biological systems, such as the formation of semi-independent groups of connected elements (modularity) and non-random distributions of interactions among elements. Other structural patterns, such as nestedness, have been primarily assessed in ecological networks formed by two non-overlapping sets of elements; information on its occurrence on other levels of organization is lacking. Nestedness occurs when interactions of less connected elements form proper subsets of the interactions of more connected elements. Only recently these properties began to be appreciated in one-mode networks (where all elements can interact) which describe a much wider variety of biological phenomena. Here, we compute nestedness in a diverse collection of one-mode networked systems from six different levels of biological organization depicting gene and protein interactions, complex phenotypes, animal societies, metapopulations, food webs and vertebrate metacommunities. Our findings suggest that nestedness emerge independently of interaction type or biological scale and reveal that disparate systems can share nested organization features characterized by inclusive subsets of interacting elements with decreasing connectedness. We primarily explore the implications of a nested structure for each of these studied systems, then theorize on how nested networks are assembled. We hypothesize that nestedness emerges across scales due to processes that, although system-dependent, may share a general compromise between two features: specificity (the number of interactions the elements of the system can have) and affinity (how these elements can be connected to each other). Our findings suggesting occurrence of nestedness throughout biological scales can stimulate the debate on how pervasive nestedness may be in nature, while the theoretical emergent principles can aid further research on commonalities of biological networks.Conselho Nacional de Desenvolvimento Científico e TecnológicoSão Paulo Research FoundationKillam TrustsThe Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of BrazilFundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarin