Miracle-dz/UniFAR-FTUs huggingface dataset:
Electrophysiological and Morphological Evidence for Synchronized GnRH Pulse Generator Activity Among Kisspeptin/Neurokinin B/Dynorphin A (KNDy) Neurons in Goats

Abstract Neurons in the arcuate nucleus (ARC) that concomitantly express kisspeptin, neurokinin B (NKB) and dynorphin A are termed KNDy neurons and are likely candidates for the intrinsic gonadotropin-releasing hormone (GnRH) pulse generator. Our hypothesis is that KNDy neurons are functionally and anatomically interconnected to generate discrete neural signals that govern pulsatile GnRH secretion. Our goal was to address this hypothesis using electrophysiological and anatomical experiments in goats. Bilateral electrodes targeting KNDy neurons were implanted into ovariectomized goats, and GnRH pulse generator activity, represented by characteristic increases in multiple-unit activity (MUA volleys), was measured. Spontaneous and pheromone- or senktide (an NKB receptor agonist)-induced MUA volleys were simultaneously recorded from both sides of the ARC. An anterograde tracer, biotinylated dextran amine (BDA), was also injected unilaterally into the ARC of castrated male goats, and the distribution of fibers containing both BDA and NKB was examined using dual-labeling histochemistry. The results showed that MUA volleys, regardless of origin (spontaneous or experimentally induced), occur simultaneously between the right and left sides of the ARC. Tract tracing indicated that axons projecting from NKB neurons in the ARC were directly apposed to other NKB neuronal cells located bilaterally in the ARC. These results demonstrate that GnRH pulse generator activity occurs synchronously between both sides of the ARC in goats and that KNDy neurons are bilaterally interconnected in the ARC via NKB-containing fibers. Taken together, the results suggest that KNDy neurons form a neuronal circuit to synchronize burst activity among KNDy neurons and thereby generate discrete neural signals that govern pulsatile GnRH secretion.
Semantic Video Classification Based on Subtitles and Domain Terminologies

In this paper we explore an unsupervised approach to classify video content by analyzing the corresponding subtitles. The proposed method is based on the WordNet lexical database and the WordNet domains and applies natural language processing techniques on video subtitles. The method is divided into several steps. The first step includes subtitle text preprocessing. During the next steps, a keyword extraction method and a word sense disambiguation technique are applied. Subsequently, the WordNet domains that correspond to the correct word senses are identified. The final step assigns category labels to the video content based on the extracted domains. Experimental results with documentary videos show that the proposed method is quite effective in discovering the correct category for each video.
Three-dimensional architecture of murine rod outer segments determined by cryoelectron tomography

The rod outer segment (ROS) of photoreceptor cells houses all components necessary for phototransduction, a set of biochemical reactions that amplify and propagate a light signal. Theoretical approaches to quantify this process require precise information about the physical boundaries of the ROS. Dimensions of internal structures within the ROS of mammalian species have yet to be determined with the precision required for quantitative considerations. Cryoelectron tomography was utilized to obtain reliable three-dimensional morphological information about this important structure from murine retina. Vitrification of samples permitted imaging of the ROS in a minimally perturbed manner and the preservation of substructures. Tomograms revealed the characteristic highly organized arrangement of disc membranes stacked on top of one another with a surrounding plasma membrane. Distances among the various membrane components of the ROS were measured to define the space available for phototransduction to occur. Reconstruction of segments of the ROS from single-axis tilt series images provided a glimpse into the three-dimensional architecture of this highly differentiated neuron. The reconstructions revealed spacers that likely maintain the proper distance between adjacent discs and between discs and the plasma membrane. Spacers were found distributed throughout the discs, including regions that are distant from the rim region of discs.
PAI‐1 promotes the accumulation of exudate macrophages and worsens pulmonary fibrosis following type II alveolar epithelial cell injury

Fibrotic disorders of the lung are associated with perturbations in the plasminogen activation system. Specifically, plasminogen activator inhibitor‐1 (PAI‐1) expression is increased relative to the plasminogen activators. A direct role for this imbalance in modulating the severity of lung scarring following injury has been substantiated in the bleomycin model of pulmonary fibrosis. However, it remains unclear whether derangements in the plasminogen activation system contribute more generally to the pathogenesis of lung fibrosis beyond bleomycin injury. To answer this question, we employed an alternative model of lung scarring, in which type II alveolar epithelial cells (AECs) are specifically injured by administering diphtheria toxin (DT) to mice genetically engineered to express the human DT receptor (DTR) off the surfactant protein C promoter. This targeted AEC injury results in the diffuse accumulation of interstitial collagen. In the present study, we found that this targeted type II cell insult also increases PAI‐1 expression in the alveolar compartment. We identified AECs and lung macrophages to be sources of PAI‐1 production. To determine whether this elevated PAI‐1 concentration was directly related to the severity of fibrosis, DTR+ mice were crossed into a PAI‐1‐deficient background (DTR+: PAI‐1−/−). DT administration to DTR+: PAI‐1−/− animals caused significantly less fibrosis than was measured in DTR+ mice with intact PAI‐1 production. PAI‐1 deficiency also abrogated the accumulation of CD11b+ exudate macrophages that were found to express PAI‐1 and type‐1 collagen. These observations substantiate the critical function of PAI‐1 in pulmonary fibrosis pathogenesis and provide new insight into a potential mechanism by which this pro‐fibrotic molecule influences collagen accumulation. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Acquisition versus Retention : Competitive Customer Relationship Management

Customer relationship management suggests that sellers identify their most valuable customers and provide special products/services to them, either immediately in an effort to build a sense of commitment to the firm (an acquisition strategy) or just as they are thinking of leaving (a retention strategy). While a monopolist profits most from an acquisition CRM strategy, assuming costs are held constant, the main result of our analytic model is that in a competitive marketplace one firm pursues an acquisition strategy and its rival uses a retention strategy. A critical ingredient in this finding is exogenous and identical customer churn rates. A retention strategy leads to a relatively smaller committed “buyer club,” so it leads to a net windfall gain from customer churn. While a monopolist should choose acquisition CRM, when there is competition a first mover should choose retention CRM. The rival firm is forced to differentiate by choosing the less profitable acquisition strategy. Further, a retention strategy asks the customers to trust that special services will be provided eventually. We find that both the firm pursuing a retention strategy and its customers are better off when the churn rate is lower, so this trust is rewarded. Finally, if acquisition CRM eliminates customer churn by creating early feelings of delight, then an all-acquisition outcome can be the competitive equilibrium.
GMATA: An Integrated Software Package for Genome-Scale SSR Mining, Marker Development and Viewing

Simple sequence repeats (SSRs), also referred to as microsatellites, are highly variable tandem DNAs that are widely used as genetic markers. The increasing availability of whole-genome and transcript sequences provides information resources for SSR marker development. However, efficient software is required to efficiently identify and display SSR information along with other gene features at a genome scale. We developed novel software package Genome-wide Microsatellite Analyzing Tool Package (GMATA) integrating SSR mining, statistical analysis and plotting, marker design, polymorphism screening and marker transferability, and enabled simultaneously display SSR markers with other genome features. GMATA applies novel strategies for SSR analysis and primer design in large genomes, which allows GMATA to perform faster calculation and provides more accurate results than existing tools. Our package is also capable of processing DNA sequences of any size on a standard computer. GMATA is user friendly, only requires mouse clicks or types inputs on the command line, and is executable in multiple computing platforms. We demonstrated the application of GMATA in plants genomes and reveal a novel distribution pattern of SSRs in 15 grass genomes. The most abundant motifs are dimer GA/TC, the A/T monomer and the GCG/CGC trimer, rather than the rich G/C content in DNA sequence. We also revealed that SSR count is a linear to the chromosome length in fully assembled grass genomes. GMATA represents a powerful application tool that facilitates genomic sequence analyses. GAMTA is freely available at http://sourceforge.net/projects/gmata/? source=navbar.
Health service utilization for eating disorders: findings from a community-based study.

BACKGROUND Prior use of health services was examined in a community sample of women with bulimic-type eating disorders. METHOD Participants (n = 159) completed a structured interview for the assessment of eating disorder psychopathology as well as questions concerning treatment-seeking and type of treatment received. RESULTS Whereas a minority (40.3%) of participants had received treatment for an eating problem, most had received treatment for a general mental health problem (74.2%) and/or weight loss (72.8%), and all had used one or more self-help treatments. Where treatment was received for an eating or general mental health problem, this was from a primary care practitioner in the vast majority of cases. Only half of those participants who reported marked impairment associated with an eating problem had ever received treatment for such a problem and less than one in five had received such treatment from a mental health professional. CONCLUSION Women with bulimic-type eating disorders rarely receive treatment for an eating problem, but frequently receive treatment for a general mental health problem and/or for weight loss. The findings underscore the importance of programs designed to improve the detection and management of eating disorders in primary care.
Stereotactic body radiation therapy in pancreatic cancer: the new frontier

Pancreatic cancer (PCA) remains a disease with a poor prognosis. The majority of PCA patients are unable to undergo surgical resection, which is the only potentially curative option at this time. A combination of chemotherapy and chemoradiation (CRT) are standard options for patients with locally advanced, unresectable disease, however, local control and patient outcomes remains poor. Stereotactic body radiation therapy (SBRT) is an emerging treatment option for PCA. SBRT delivers potentially ablative doses to the pancreatic tumor plus a small margin over a short period of time. Early studies with single-fraction SBRT demonstrated excellent tumor control with high rates of toxicity. The implementation of SBRT (3–5 doses) has demonstrated promising outcomes with favorable tumor control and toxicity rates. Herein we discuss the evolving role of SBRT in PCA treatment.
Effects of the Δ67 Complex of Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase on Nucleoside Analog Excision

ABSTRACT Long-term use of combination therapy against human immunodeficiency virus type (HIV-1) provides strong selective pressure on the virus, and HIV-1 variants that are resistant to multiple inhibitors have been isolated. HIV-1 variants containing amino acid substitutions within the coding region of HIV-1 reverse transcriptase (RT), such as the 3′-azido-3′-deoxythymidine (AZT)-resistant variant AZT-R (M41L/D67N/K70R/T215Y/K219Q) and a variant containing an insertion in the fingers domain (S69SGR70/T215Y), are resistant to the nucleoside RT inhibitor (NRTI) AZT because of an increase in the level of excision of AZT monophosphate (AZTMP) from the primer. While rare, variants have also been isolated which contain deletions in the RT coding region. One such virus, described by Imamichi et al. (J. Virol 74:10958-10964, 2000; J. Virol. 74:1023-1028, 2000; J. Virol. 75:3988-3992, 2001), contains numerous amino acid substitutions and a deletion of codon 67, which we have designated the Δ67 complex of mutations. We have expressed and purified HIV-1 RT containing these mutations. We compared the polymerase and pyrophosphorolysis (excision) activity of an RT with the Δ67 complex of mutations to wild-type RT and the two other AZT-resistant variants described above. All of the AZT-resistant variants we tested excise AZTMP and 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA [tenofovir]) from the end of a primer more efficiently than wild-type RT. Although the variant RTs excised d4TMP less efficiently than AZTMP and PMPA, they were able to excise d4TMP more efficiently than wild-type RT. HIV-1 RT containing the Δ67 complex of mutations was not able to excise as broad a range of NRTIs as the fingers insertion variant SSGR/T215Y, but it was able to polymerize efficiently with low concentrations of deoxynucleoside triphosphates and seems to be able to excise AZTMP and PMPA at lower ATP concentrations than AZT-R or SSGR/T215Y, suggesting that a virus containing the Δ67 complex of mutations would replicate reasonably well in quiescent cells, even in the presence of AZT.
Even if they are not aware of it, general practitioners improve well-being in their adolescent patients

Abstract Background: Most adolescents consult their general practitioner (GP) for common reasons, somatic or administrative but many of them have hidden feelings of distress. Objectives: To assess the immediate impact of ‘ordinary’ consultations on feelings of distress among adolescents and to compare adolescents experiencing difficulties (D) to those with no difficulties (N). To analyse how accurately GPs assess the impact of their consultation on adolescents’ feelings. Methods: GPs were randomly selected from two non-contiguous French administrative areas between April and June 2006. Fifty-three GPs gave two questionnaires to the first 10 to 15 adolescents aged 12 to 20 seen in consultation. One questionnaire was issued before the consultation and the other one afterwards. Adolescents had to position themselves about different aspects of well-being and say where they would seek help if they had problems. A GP questionnaire assessed how well they estimated their impact on the adolescent’s feeling of well-being. Results: Six hundred and sixty-five adolescents were assessed. They reported feeling better about their health, being able to talk, having someone to talk to or to confide in and on feeling understood. The D group (n = 147) felt significantly better compared to the N group (n = 518). GPs tended to underestimate this improvement, especially regarding adolescents in the D group feeling better about their health. Conclusions: Consulting a GP generates increased well-being among adolescents, especially for those experiencing difficulties. GPs tend to underestimate the positive impact they may have. Further studies are needed to explore if this benefit is permanent over time.
The Pea Nodule Environment Restores the Ability of a Rhizobium leguminosarum Lipopolysaccharide acpXL Mutant To Add 27-Hydroxyoctacosanoic Acid to Its Lipid A

ABSTRACT Members of the Rhizobiaceae contain 27-hydroxyoctacosanoic acid (27OHC28:0) in their lipid A. A Rhizobium leguminosarum 3841 acpXL mutant (named here Rlv22) lacking a functional specialized acyl carrier lacked 27OHC28:0 in its lipid A, had altered growth and physiological properties (e.g., it was unable to grow in the presence of an elevated salt concentration [0.5% NaCl]), and formed irregularly shaped bacteroids, and the synchronous division of this mutant and the host plant-derived symbiosome membrane was disrupted. In spite of these defects, the mutant was able to persist within the root nodule cells and eventually form, albeit inefficiently, nitrogen-fixing bacteroids. This result suggested that while it is in a host root nodule, the mutant may have some mechanism by which it adapts to the loss of 27OHC28:0 from its lipid A. In order to further define the function of this fatty acyl residue, it was necessary to examine the lipid A isolated from mutant bacteroids. In this report we show that addition of 27OHC28:0 to the lipid A of Rlv22 lipopolysaccharides is partially restored in Rlv22 acpXL mutant bacteroids. We hypothesize that R. leguminosarum bv. viciae 3841 contains an alternate mechanism (e.g., another acp gene) for the synthesis of 27OHC28:0, which is activated when the bacteria are in the nodule environment, and that it is this alternative mechanism which functionally replaces acpXL and is responsible for the synthesis of 27OHC28:0-containing lipid A in the Rlv22 acpXL bacteroids.
Synthetic “smart gel” provides glucose-responsive insulin delivery in diabetic mice

A synthetic polymer gel–based insulin delivery device provides an artificial pancreas–like function in healthy and diabetic mice. Although previous studies have attempted to create “electronics-free” insulin delivery systems using glucose oxidase and sugar-binding lectins as a glucose-sensing mechanism, no successful clinical translation has hitherto been made. These protein-based materials are intolerant of long-term use and storage because of their denaturing and/or cytotoxic properties. We provide a solution by designing a protein-free and totally synthetic material–based approach. Capitalizing on the sugar-responsive properties of boronic acid, we have established a synthetic polymer gel–based insulin delivery device confined within a single catheter, which exhibits an artificial pancreas–like function in vivo. Subcutaneous implantation of the device in healthy and diabetic mice establishes a closed-loop system composed of “continuous glucose sensing” and “skin layer”–regulated insulin release. As a result, glucose metabolism was controlled in response to interstitial glucose fluctuation under both insulin-deficient and insulin-resistant conditions with at least 3-week durability. Our “smart gel” technology could offer a user-friendly and remarkably economic (disposable) alternative to the current state of the art, thereby facilitating availability of effective insulin treatment not only to diabetic patients in developing countries but also to those patients who otherwise may not be strongly motivated, such as the elderly, infants, and patients in need of nursing care.
Cost-Effective Screening for Breast Cancer Worldwide: Current State and Future Directions

Affordability of healthcare is highly limited by its skyrocketing cost. Access to screening and diagnostic medical equipment and medicine in developing countries is inadequate for the majority of the population. There is a tremendous worldwide need to detect breast cancer at its earliest stage. These needs must be balanced by the ability of countries to provide breast cancer screening technology to their populations. We reviewed the diagnostic accuracy, procedure cost and cost-effectiveness of currently available technique for breast screening and diagnosis including clinical breast examination, mammography, ultrasound, magnetic resonance imaging, biopsy and a new modality for cancer diagnostics termed elasticity imaging that has emerged in the last decade. Clinical results demonstrate that elasticity imaging even in its simplest and least sophisticated versions, like tactile imaging, has significant diagnostic potential comparable and exceeding that of conventional imaging techniques. In view of many countries with limited resources, effective yet less expensive modes of screening must be considered worldwide. The tactile imaging is one method that has the potential to provide cost-effective breast cancer screening and diagnostics.
Complex Social Structure of an Endangered Population of Bottlenose Dolphins (Tursiops truncatus) in the Aeolian Archipelago (Italy)

We investigated social structure and association patterns for a small population of Mediterranean bottlenose dolphins, Tursiops truncatus, inhabiting the Aeolian Archipelago (southern Italy). Specifically we evaluate the role of sex and age composition, residency patterns and interaction with trammel nets on this social organization. Association data for 23 regularly sighted individuals were obtained from summer photoidentification surveys collected from 2005–2012. Using a combined cluster and social network analysis approach, we found associations between dolphins were hierarchically structured, where two mixed-sex social units were subdivided into smaller temporarily dynamic groups. We found non-random and long-term preferred associations in the population; however, the degree of social cohesion, residence pattern and interaction with trammel nets differed considerably between the two social units. Six of eight females occurred in the more resident social unit-1; in addition, social unit-1 individuals had significantly stronger associations, higher preferred associates, lived in larger groups and occurred less frequently with trammel nets. Nine of eleven males were clustered in social unit-2 and five of these males, interacting with trammel nets, formed small groups and preferred associations. We propose that female and male groups associate in the study area during the breeding season and that some males choose to interact with reproductive females forming a distinct but interrelated social unit. Other males may be associating in a larger fission-fusion network, which consists of dolphins that appear to temporarily join the network from the coastal population. We cannot exclude that some males specialized in trammel net foraging, suggesting that this foraging technique may favor a solitary lifestyle. Large group sizes and high degree of social cohesion for females could be an indication of greater protection and more efficiency in detecting, deterring or repelling anthropogenic pressures. Most likely dolphins' social organization depends on a combination of socio-ecological, demographic and anthropogenic factors.