Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum)

Significance Lampreys and hagfishes (cyclostomes) are the only living group of jawless vertebrates and therefore are important for the study of vertebrate evolution. We have characterized Hox clusters in the Japanese lamprey (Lethenteron japonicum), and shown that it contains at least six Hox clusters as compared with four Hox clusters in tetrapods. This suggests that the lamprey lineage has undergone an additional round of genome duplication compared with tetrapods. Several conserved noncoding elements (CNEs) were predicted in the Hox clusters of lamprey, elephant shark, and human. Transgenic assay of CNEs demonstrated their potential to function as cis-regulatory elements. Thus, these CNEs may represent part of the core set of cis-regulatory elements that were present in the common ancestor of vertebrates. Cyclostomes, comprising jawless vertebrates such as lampreys and hagfishes, are the sister group of living jawed vertebrates (gnathostomes) and hence an important group for understanding the origin and diversity of vertebrates. In vertebrates and other metazoans, Hox genes determine cell fate along the anteroposterior axis of embryos and are implicated in driving morphological diversity. Invertebrates contain a single Hox cluster (either intact or fragmented), whereas elephant shark, coelacanth, and tetrapods contain four Hox clusters owing to two rounds of whole-genome duplication (“1R” and “2R”) during early vertebrate evolution. By contrast, most teleost fishes contain up to eight Hox clusters because of an additional “teleost-specific” genome duplication event. By sequencing bacterial artificial chromosome (BAC) clones and the whole genome, here we provide evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron japonicum). This suggests that the lamprey lineage has experienced an additional genome duplication after 1R and 2R. The relative age of lamprey and human paralogs supports this hypothesis. Compared with gnathostome Hox clusters, lamprey Hox clusters are unusually large. Several conserved noncoding elements (CNEs) were predicted in the Hox clusters of lamprey, elephant shark, and human. Transgenic zebrafish assay indicated the potential of CNEs to function as enhancers. Interestingly, CNEs in individual lamprey Hox clusters are frequently conserved in multiple Hox clusters in elephant shark and human, implying a many-to-many orthology relationship between lamprey and gnathostome Hox clusters. Such a relationship suggests that the first two rounds of genome duplication may have occurred independently in the lamprey and gnathostome lineages.
Caracterização das alterações estruturais e de matriz extracelular de pequenas vias aéreas em pacientes com síndrome do desconforto respiratório agudo

A disfuncao de vias aereas em pacientes com Sindrome do Desconforto Respiratoria Agudo (SDRA) e caracterizada por limitacao do fluxo expiratorio e hiperinsuflacao dinâmica. As alteracoes morfologicas possivelmente associadas com tais alteracoes funcionais tem sido investigadas em modelos experimentais de lesao pulmonar aguda, que mostram necrose e descamacao epitelial em vias aereas distais. Entretanto, ate o momento, essa avaliacao nao foi realizada em humanos. O objetivo deste estudo foi investigar as alteracoes estruturais e inflamatorias nas pequenas vias aereas de pacientes com SDRA. Com este proposito, estudamos, retrospectivamente, o tecido pulmonar de 31 pacientes com SDRA (A: PaO2/FIO2 Airway dysfunction in patients with acute respiratory distress syndrome (ARDS) is evidenced by expiratory flow limitation and dynamic hyperinflation. The morphological alterations potentially associated with these functional changes have been investigated in experimental models of Acute Lung Injury, which show epithelial necrosis and denudation in distal airways. To date, however, no study has focused on the morphological airway changes in lungs from human subjects with ARDS. Objective: To evaluate structural and inflammatory changes in distal airways in ARDS patients. Methods and Results: We retrospectively studied autopsy lung tissue from 31 ARDS patients (A: PaO2/FIO2
Characteristic aspects of alveolar proteinosis diagnosis

Alveolar proteinosis is an uncommon pulmonary disease characterized by an accumulation of surfactant in terminal airway and alveoli, thereby impairing gas exchange and engendering respiratory insufficiency in some cases. Three clinically and etiologically distinct forms of pulmonary alveolar proteinosis are recognized: congenital, secondary and idiopathic, the latter corresponding to 90% of the cases. In this case report we present a young male patient that was diagnosed with alveolar proteinosis. Computed tomography of the thorax, bronchoscopy and transbronchial biopsy were performed. The histopathologic aspect was characteristic. The patient was discharged in good health conditions and remains asymptomatic to date.
Visuospatial selective attention in chickens

Significance Top-down selective attention, which is fundamental to cognition, has been studied extensively in humans and nonhuman primates. Here we report the behavioral hallmarks of selective attention in a nonprimate species, the domestic chicken. When provided with a spatial cue, birds exhibited dramatic improvements in accuracy, faster reaction times, and higher choice certainty in a target localization task. Our results reveal that chickens shift spatial attention rapidly and dynamically following principles remarkably similar to those documented in primates. Given the evolutionary distance (>250 million years) and enormous ethological differences between chickens and primates, our findings suggest that neural mechanisms mediating selective attention appeared early in vertebrate evolution and that they are conserved across phylogeny. Voluntary control of attention promotes intelligent, adaptive behaviors by enabling the selective processing of information that is most relevant for making decisions. Despite extensive research on attention in primates, the capacity for selective attention in nonprimate species has never been quantified. Here we demonstrate selective attention in chickens by applying protocols that have been used to characterize visual spatial attention in primates. Chickens were trained to localize and report the vertical position of a target in the presence of task-relevant distracters. A spatial cue, the location of which varied across individual trials, indicated the horizontal, but not vertical, position of the upcoming target. Spatial cueing improved localization performance: accuracy (d′) increased and reaction times decreased in a space-specific manner. Distracters severely impaired perceptual performance, and this impairment was greatly reduced by spatial cueing. Signal detection analysis with an “indecision” model demonstrated that spatial cueing significantly increased choice certainty in localizing targets. By contrast, error-aversion certainty (certainty of not making an error) remained essentially constant across cueing protocols, target contrasts, and individuals. The results show that chickens shift spatial attention rapidly and dynamically, following principles of stimulus selection that closely parallel those documented in primates. The findings suggest that the mechanisms that control attention have been conserved through evolution, and establish chickens—a highly visual species that is easily trained and amenable to cutting-edge experimental technologies—as an attractive model for linking behavior to neural mechanisms of selective attention.
Discovering the genetics underlying foetal haemoglobin production in adults

Sickle cell disease (SCD) and β thalassaemia, caused by lesions that affect the HBB (β globin gene), form the most common human genetic disorders world‐wide, and represent a major public health problem. Inter‐individual variation in foetal haemoglobin (HbF) expression is a known and heritable disease modifier; high HbF levels are correlated with reduced morbidity and mortality in both diseases. This review traces our progress in the understanding of the persistence of HbF in adults as a quantitative trait and the genetic approaches used in teasing out the loci contributing to its variability in normal populations and in patients with haemoglobinopathies. Three major loci – Xmn1‐HBG2 single nucleotide polymorphism, HBS1L‐MYB intergenic region on chromosome 6q, and BCL11A– contribute 20–50% of the trait variance in patients with sickle cell anaemia and healthy European Caucasians. It is likely that the remaining trait variance is due to numerous other loci, many contributing modest effects. Identification of the three major loci has not yet been translated into new therapeutic approaches for HbF reactivation but an immediate application would be an improved prediction of one’s ability to produce HbF, which in turn, may improve prediction of disease severity.
Advanced concepts in multiple sclerosis nursing care

The nurse plays a vital role as an educator, care provider, and advocate for patients and families affected by multiple sclerosis (MS). The companion book to an earlier work, "Comprehensive Nursing Care in Multiple Sclerosis," "Advanced Concepts in Multiple Sclerosis Nursing Care, 2nd Edition" examines complex issues in MS management and reflects a new philosophy of MS care: one of empowerment. The focus is on the numerous settings in which MS nurses practice, as well as their many roles and responsibilities in managing this highly variable disease. It will provide the reader with an updated view of MS along with a greater understanding of its lifelong impact. Special features of the second edition include: A new chapter on sustaining hope in MS patients A new chapter on treatment of acute exacerbations A new chapter on emerging intravenous therapies Expanded sections on pain, depression, and skin care with frequent injections The book is divided into sections dealing with the disease itself, advanced practice requirements for nurses, and advanced symptom management. Contributors to "Advanced Concepts in Multiple Sclerosis Nursing Care, 2nd Edition" are nurse clinicians and researchers who work in geographically diverse practice settings throughout North America and Europe. The book will provide nurses with tools and strategies to improve the lives affected by multiple sclerosis and to reinforce the role of the nurse in managing it. "
New Developments in Smart Bandage Technologies for Wound Diagnostics

The pH of wound fluid has long been recognized as an important diagnostic for assessing wound condition, but as yet there are few technological options available to the clinician. The availability of sensors that can measure wound pH, either in the clinic or at home could significantly improve clinical outcome – particularly in the early identification of complications such as infection. New material designs and electrochemical research strategies that are being targeted at wound diagnostics are identified and a critical overview of emerging research that could be pivotal in setting the direction for future devices is provided.
A thinker's guide to ultrasonic imaging

Bridging the gap between elementary physics and advanced ultrasonographic theory, this book provides the clinician with an indispensable tool for the most effective use of ultrasound equipment. It is directed to every individual who must take a transducer in hand, make an ultrasonic study, and interpret the visual results. It stands between the very rudimentary texts that provide simple basics and texts in advanced ultrasound science and applications. It is designed to provide an intermediate step in the continuing education of both physician and sonographer. Each chapter stands alone, yet is connected with the others by reference and suggested readings.
MinCDE exploits the dynamic nature of FtsZ filaments for its spatial regulation

Significance Although the mechanisms of microtubule depolymerization are relatively well understood, those of the tubulin homologue FtsZ have been difficult to understand owing to differences in its filament architecture and dynamics compared with those of microtubules. MinC, an important negative regulator of FtsZ and a component of the Min oscillatory system in Escherichia coli, positions the Z-ring to the midcell. With single-molecule fluorescence imaging in a cell-free minimal system on supported lipid bilayers, in which a network of FtsZ bundles assemble in a chemically well-defined system, the dynamic nature of the FtsZ bundles and the mechanism of disassembly by MinC is elucidated. In Escherichia coli, a contractile ring (Z-ring) is formed at midcell before cytokinesis. This ring consists primarily of FtsZ, a tubulin-like GTPase, that assembles into protofilaments similar to those in microtubules but different in their suprastructures. The Min proteins MinC, MinD, and MinE are determinants of Z-ring positioning in E. coli. MinD and MinE oscillate from pole to pole, and genetic and biochemical evidence concludes that MinC positions the Z-ring by coupling its assembly to the oscillations by direct inhibitory interaction. The mechanism of inhibition of FtsZ polymerization and, thus, positioning by MinC, however, is not understood completely. Our in vitro reconstitution experiments suggest that the Z-ring consists of dynamic protofilament bundles in which monomers constantly are exchanged throughout, stochastically creating protofilament ends along the length of the filament. From the coreconstitution of FtsZ with MinCDE, we propose that MinC acts on the filaments in two ways: by increasing the detachment rate of FtsZ-GDP within the filaments and by reducing the attachment rate of FtsZ monomers to filaments by occupying binding sites on the FtsZ filament lattice. Furthermore, our data show that the MinCDE system indeed is sufficient to cause spatial regulation of FtsZ, required for Z-ring positioning.
Immunotherapeutic Strategies for Brain Tumors

Cancer immunotherapy is the use of the immune system to reject cancers. The main premise is to harness the patient's immune system to attack the malignant tumor cells. This area of research has made tremendous progresses, and the United States Food and Drug Administration recently approved a vaccine for prostate cancers as the first approval for vaccines against non-viral cancers (Kantoff et al., 2010). However, when it comes to central nervous system (CNS) tumors, while early phase immunotherapy trials showed encouraging outcomes, the immunological microenvironment of the CNS and tumors arising in the CNS is still believed to be suboptimal for sufficient antitumor immune responses to mediate clinically-meaningful changes in situ (Okada, H. et al., 2009; Walker, P. R. et al., 2003). In this chapter, we first discuss recent advances in the CNS and CNS tumor immunology. We address factors that may promote immune escape of gliomas. We also review advances in passive and active immunotherapy strategies for glioma, with an emphasis on lessons learned from recent early phase clinical trials. We also discuss novel immunotherapy strategies that have been recently tested in non-CNS tumors with great potential for application to CNS tumors. We will finally discuss how each of these promising strategies can be combined to achieve clinical benefit for patients with CNS tumors.
Biological functions and therapeutic use of erythropoiesis‐stimulating agents: perplexities and perspectives

Randomized clinical studies, carried out in patients with haematological malignancies and with solid tumours, have consistently demonstrated that treatment with recombinant human erythropoietin (Epo) increases haemoglobin levels, reduces blood transfusion requirements, and improves the quality of life. In addition, identification of erythropoietin receptor (EpoR) expression on many types of non‐erythroid and cancer cells has spurred an interest in the extra‐haematological activities of Epo itself and other erythropoiesis‐stimulating agents (ESAs). Epo and its derivatives have emerged as major tissue‐protective cytokines in ischaemic and degenerative damage of cardiovascular, neurological and renal diseases, while their angiogenetic and immunomodulatory properties indicate that their therapeutic potential may extend well beyond erythropoiesis alone. Both preclinical and clinical data, however, have suggested that they may contribute to tumour progression and prejudice survival when administered to anaemic cancer patients, though the results are equivocal and the assumed mechanisms by which tumour growth could be promoted are not fully understood. While these findings offer new perspectives, they nonetheless demand caution in the employment of ESAs. Further, well‐designed experimental and clinical studies are warranted.
Rapid upslope shifts in New Guinean birds illustrate strong distributional responses of tropical montane species to global warming

Significance Montane species may respond to global warming by shifting their distributions upslope in response to warming temperatures. Such shifts are well documented in the temperate zone, but the situation in the tropics, where species are predicted to be more sensitive to altered temperatures, remains unclear. We found strong upslope shifts in the bird species found on two independent New Guinean mountains originally surveyed in the 1960s. Moreover, we incorporated our results into a metaanalysis that suggests tropical montane species are responding more strongly to climate change than temperate-zone species. Though the magnitude of climate change is higher in the temperate zone, both overall biodiversity and distributional shifts due to warming temperatures are greater in the tropics. Temperate-zone species have responded to warming temperatures by shifting their distributions poleward and upslope. Thermal tolerance data suggests that tropical species may respond to warming temperatures even more strongly than temperate-zone species, but this prediction has yet to be tested. We addressed this data gap by conducting resurveys to measure distributional responses to temperature increases in the elevational limits of the avifaunas of two geographically and faunally independent New Guinean mountains, Mt. Karimui and Karkar Island, 47 and 44 y after they were originally surveyed. Although species richness is roughly five times greater on mainland Mt. Karimui than oceanic Karkar Island, distributional shifts at both sites were similar: upslope shifts averaged 113 m (Mt. Karimui) and 152 m (Karkar Island) for upper limits and 95 m (Mt. Karimui) and 123 m (Karkar Island) for lower limits. We incorporated these results into a metaanalysis to compare distributional responses of tropical species with those of temperate-zone species, finding that average upslope shifts in tropical montane species match local temperature increases significantly more closely than in temperate-zone montane species. That tropical species appear to be strong responders has global conservation implications and provides empirical support to hitherto untested models that predict widespread extinctions in upper-elevation tropical endemics with small ranges.
Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease

Significance Understanding loci nominated by genome-wide association studies (GWASs) is challenging. Here, we show, using the specific example of Parkinson disease, that identification of protein–protein interactions can help determine the most likely candidate for several GWAS loci. This result illustrates a significant general principle that will likely apply across multiple diseases. Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein–protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G–associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy–lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.
Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology

Significance The identification of molecular subtype heterogeneity in breast cancer has allowed a deeper understanding of breast cancer biology. We present evidence that there are two intrinsic subtypes of high-grade bladder cancer, basal-like and luminal, which reflect the hallmarks of breast biology. Moreover, we have developed an accurate gene set predictor of molecular subtype, the BASE47, that should allow the incorporation of subtype stratification into clinical trials. Further clinical, etiologic, and therapeutic response associations will be of interest in future investigations. We sought to define whether there are intrinsic molecular subtypes of high-grade bladder cancer. Consensus clustering performed on gene expression data from a meta-dataset of high-grade, muscle-invasive bladder tumors identified two intrinsic, molecular subsets of high-grade bladder cancer, termed “luminal” and “basal-like,” which have characteristics of different stages of urothelial differentiation, reflect the luminal and basal-like molecular subtypes of breast cancer, and have clinically meaningful differences in outcome. A gene set predictor, bladder cancer analysis of subtypes by gene expression (BASE47) was defined by prediction analysis of microarrays (PAM) and accurately classifies the subtypes. Our data demonstrate that there are at least two molecularly and clinically distinct subtypes of high-grade bladder cancer and validate the BASE47 as a subtype predictor. Future studies exploring the predictive value of the BASE47 subtypes for standard of care bladder cancer therapies, as well as novel subtype-specific therapies, will be of interest.
Fatores relacionados com as respostas da testosterona e do cortisol ao treinamento de força

This study aims to review the results found in the literature concerning a variety of factors related to the acute and chronic hormonal response to strength training. It has been observed that there is a close relationship between the trainability of individuals submitted to strength training and the circulating testosterone levels in these subjects. Moreover, other hormonal parameters, such as the ratios between testosterone and its binding protein and between testosterone and cortisol, were also related to the ability to increase strength. Besides the characteristics of the population investigated, several factors associated with the training session affect the acute and chronic hormonal response to training. Among them, volume and intensity are the main variables associated with the magnitude of this response. Determining which factors might be closely related to the hormonal response to strength training may be important to establish a training session and a periodization that optimize the anabolic environment determined by the testosterone and cortisol concentrations, and thus enhance the neuromuscular adaptations resulting from this type of training.