Miracle-dz/UniFAR-FTUs huggingface dataset:
Ihha induces hybrid cartilage-bone cells during zebrafish jawbone regeneration

The healing of bone often involves a cartilage intermediate, yet how such cartilage is induced and utilized during repair is not fully understood. By studying a model of large-scale bone regeneration in the lower jaw of adult zebrafish, we show that chondrocytes are crucial for generating thick bone during repair. During jawbone regeneration, we find that chondrocytes co-express genes associated with osteoblast differentiation and produce extensive mineralization, which is in marked contrast to the behavior of chondrocytes during facial skeletal development. We also identify the likely source of repair chondrocytes as a population of Runx2+/Sp7− cells that emanate from the periosteum, a tissue that normally contributes only osteoblasts during homeostasis. Analysis of Indian hedgehog homolog a (ihha) mutants shows that the ability of periosteal cells to generate cartilage in response to injury depends on a repair-specific role of Ihha in the induction as opposed to the proliferation of chondrocytes. The large-scale regeneration of the zebrafish jawbone thus employs a cartilage differentiation program distinct from that seen during development, with the bone-forming potential of repair chondrocytes potentially due to their derivation from osteogenic cells in the periosteum. Highlighted article: The analysis of zebrafish jawbone regeneration reveals important differences between how the skeleton is formed in the embryo and repaired in adults.
Activation of Superficial Dorsal Horn Neurons in the Mouse by a PAR-2 Agonist and 5-HT: Potential Role in Itch

Itch, an unpleasant sensation associated with the desire to scratch, is symptomatic of dermatologic and systemic disorders that often resist antihistamine treatment. Histamine-independent itch mediators include serotonin (5-HT) and agonists of the protease-activated receptor-2 (PAR-2). We used behavior, Fos immunohistochemistry, and electrophysiology to investigate if these mediators activate spinal dorsal horn neurons in a manner consistent with itch. Intradermal (id) injection of the PAR-2 agonist SLIGRL-NH2 in the rostral back evoked bouts of directed hindlimb scratches over 20–30 min. Hindpaw injection of SLIGRL-NH2 produced Fos staining in superficial dorsal horn which was then targeted for single-unit recording. Small id microinjections of SLIGRL-NH2 or 5-HT identified responsive single units in the superficial dorsal horn of mice anesthetized with pentobarbital. Thirty-eight units characterized as wide dynamic range, nociceptive specific, or mechanically insensitive exhibited significantly increased firing after id SLIGRL-NH2 for 9 min, to partial (25%) tachyphylaxis with repeated injection. A majority additionally responded to 5-HT (70%), mustard oil (79%), and capsaicin (71%). Seven units isolated with the 5-HT search stimulus exhibited significant and prolonged responses to 5-HT with tachyphylaxis to repeated injections. The majority also responded to SLIGRL-NH2, mustard oil, and capsaicin. The prolonged responses of superficial dorsal horn neurons to SLIGRL-NH2 and 5-HT suggest a role in signaling itch. However, their responsiveness to algogens is inconsistent with itch specificity. Alternatively, such neurons may signal itch, whereas noxious stimulus levels recruit these and a larger population of pruritogen-insensitive cells to signal pain which masks or occludes the itch signal.
Direct inhibition of P/Q-type voltage-gated Ca2+ channels by Gem does not require a direct Gem/Cavβ interaction

The Rem, Rem2, Rad, and Gem/Kir (RGK) family of small GTP-binding proteins potently inhibits high voltage-activated (HVA) Ca2+ channels, providing a powerful means of modulating neural, endocrine, and muscle functions. The molecular mechanisms of this inhibition are controversial and remain largely unclear. RGK proteins associate directly with Ca2+ channel β subunits (Cavβ), and this interaction is widely thought to be essential for their inhibitory action. In this study, we investigate the molecular underpinnings of Gem inhibition of P/Q-type Ca2+ channels. We find that a purified Gem protein markedly and acutely suppresses P/Q channel activity in inside-out membrane patches, that this action requires Cavβ but not the Gem/Cavβ interaction, and that Gem coimmunoprecipitates with the P/Q channel α1 subunit (Cavα1) in a Cavβ-independent manner. By constructing chimeras between P/Q channels and Gem-insensitive low voltage-activated T-type channels, we identify a region encompassing transmembrane segments S1, S2, and S3 in the second homologous repeat of Cavα1 critical for Gem inhibition. Exchanging this region between P/Q and T channel Cavα1 abolishes Gem inhibition of P/Q channels and confers Cavβ-dependent Gem inhibition to a chimeric T channel that also carries the P/Q I-II loop (a cytoplasmic region of Cavα1 that binds Cavβ). Our results challenge the prevailing view regarding the role of Cavβ in RGK inhibition of high voltage-activated Ca2+ channels and prompt a paradigm in which Gem directly binds and inhibits Cavβ-primed Cavα1 on the plasma membrane.
Varying expectancies and attention bias in phobic and non-phobic individuals

Phobic individuals display an attention bias to phobia-related information and biased expectancies regarding the likelihood of being faced with such stimuli. Notably, although attention and expectancy biases are core features in phobia and anxiety disorders, these biases have mostly been investigated separately and their causal impact has not been examined. We hypothesized that these biases might be causally related. Spider phobic and low spider fearful control participants performed a visual search task in which they specified whether the deviant animal in a search array was a spider or a bird. Shorter reaction times (RTs) for spiders than for birds in this task reflect an attention bias toward spiders. Participants' expectancies regarding the likelihood of these animals being the deviant in the search array were manipulated by presenting verbal cues. Phobics were characterized by a pronounced and persistent attention bias toward spiders; controls displayed slower RTs for birds than for spiders only when spider cues had been presented. More important, we found RTs for spider detections to be virtually unaffected by the expectancy cues in both groups, whereas RTs for bird detections showed a clear influence of the cues. Our results speak to the possibility that evolution has formed attentional systems that are specific to the detection of phylogenetically salient stimuli such as threatening animals; these systems may not be as penetrable to variations in (experimentally induced) expectancies as those systems that are used for the detection of non-threatening stimuli. In sum, our findings highlight the relation between expectancies and attention engagement in general. However, expectancies may play a greater role in attention engagement in safe environments than in threatening environments.
Safety of the Use of Blood Salvage and Autotransfusion During Liver Transplantation for Hepatocellular Carcinoma

Objective: To determine whether autotransfusion of red blood cells (RBCs) salvaged during liver transplantation is associated with the recurrence of hepatocellular carcinoma (HCC). Background: Blood salvage is widely used during liver transplantation to reinfuse salvaged autologous RBCs and reduce allogeneic transfusion. However, the reintroduction of cancer cells via autotransfusion is a major concern in HCC patients. Methods: Among 397 patients who underwent living-donor liver transplantation for HCC, 97 of 114 recipients without intraoperative autotransfusion were matched with 222 of 283 recipients with intraoperative autotransfusion with unfixed matching ratio using the propensity score based on age, sex, allogeneic transfusion, immunosuppression, tumor biology, and others. Competing risks Cox regression was used to compare HCC recurrence risk of the 2 paired groups. Results: Recipients in autotransfusion group received 1177 ± 1318 mL of salvaged RBCs during surgery. A leukocyte depletion filter was used for all autotransfused RBCs. Cumulative HCC recurrence rate at 1, 2, and 5 years after transplantation were 10.4% (5.3%–17.6%), 19.1% (11.6%–28.0%), and 24.1% (15.2%–34.0%) for nonautotransfusion group and 10.8% (7.2%–15.4%), 14.9% (10.5%–20.0%), and 20.3% (14.9%–26.4%) for autotransfusion group, respectively. Autotransfusion versus nonautotransfusion group was not significantly different in overall recurrence [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.47–1.53, P = 0.579] and intrahepatic recurrence (HR 0.75, 95% CI 0.36–1.56) or extrahepatic recurrence (HR 1.00, 95% CI 0.49–2.04). Conclusions: We found no evidence of a significant impact of autotransfusion on posttransplant HCC recurrence. Thus, salvaged and filtered RBCs could be used in HCC patients undergoing liver transplantation with potential benefits from avoiding allogeneic RBCs transfusion and its complications.
Unforeseen Costs of Cutting Mosquito Surveillance Budgets

A budget proposal to stop the U.S. Centers for Disease Control and Prevention (CDC) funding in surveillance and research for mosquito-borne diseases such as dengue and West Nile virus has the potential to leave the country ill-prepared to handle new emerging diseases and manage existing ones. In order to demonstrate the consequences of such a measure, if implemented, we evaluated the impact of delayed control responses to dengue epidemics (a likely scenario emerging from the proposed CDC budget cut) in an economically developed urban environment. We used a mathematical model to generate hypothetical scenarios of delayed response to a dengue introduction (a consequence of halted mosquito surveillance) in the City of Cairns, Queensland, Australia. We then coupled the results of such a model with mosquito surveillance and case management costs to estimate the cumulative costs of each response scenario. Our study shows that halting mosquito surveillance can increase the management costs of epidemics by up to an order of magnitude in comparison to a strategy with sustained surveillance and early case detection. Our analysis shows that the total costs of preparedness through surveillance are far lower than the ones needed to respond to the introduction of vector-borne pathogens, even without consideration of the cost in human lives and well-being. More specifically, our findings provide a science-based justification for the re-assessment of the current proposal to slash the budget of the CDC vector-borne diseases program, and emphasize the need for improved and sustainable systems for vector-borne disease surveillance.
The Gondwana Breakup and the History of the Atlantic and Indian Oceans Unveils Two New Clades for Early Neobatrachian Diversification

The largest anuran diversity belongs to the Neobatrachia, which harbor more than five thousand extant species. Here, we propose a new hypothesis for the historical aspects of the neobatrachian evolution with a formal biogeographical analysis. We selected 12 genes for 144 neobatrachian genera and four archaeobatrachian outgroups and performed a phylogenetic analysis using a maximum likelihood algorithm with the rapid bootstrap test. We also estimated divergence times for major lineages using a relaxed uncorrelated clock method. According to our time scale, the diversification of crown Neobatrachia began around the end of the Early Cretaceous. Our phylogenetic tree suggests that the first split of Neobatrachia is related to the geological events in the Atlantic and Indian Oceans. Hence, we propose names for these clades that indicate this connection, i.e., Atlanticanura and Indianura. The Atlanticanura is composed of three major neobatrachian lineages: Heleophrynidae, Australobatrachia and Nobleobatrachia. On the other hand, the Indianura consists of two major lineages: Sooglossoidea and Ranoides. The biogeographical analysis indicates that many neobatrachian splits occurred as a result of geological events such as the separation between South America and Africa, between India and the Seychelles, and between Australia and South America.
Polymorphism in vitamin D-binding protein as a genetic risk factor in the pathogenesis of endometriosis.

CONTEXT Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated. OBJECTIVE Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis. DESIGN AND SETTING This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center. PATIENTS Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded. INTERVENTION Blood was collected preoperatively. MAIN OUTCOME MEASURE Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis. RESULTS We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P < 0.02). Analysis of specific allele products using nano-scale liquid chromatography-electrospray ionization-mass spectrometry indicated that it was the GC*2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC*1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion. CONCLUSIONS We speculate that the inability to sufficiently activate macrophages' phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.
Landmark Selection in the Environment: Relationships with Object Characteristics and Sense of Direction

Abstract This study examined the types and locations of objects selected as landmarks by people walking unfamiliar routes, and the effects of people's sense of direction. Selected landmarks comprised various types of objects, including buildings, signage, street furniture, or trees, and were located at intersections and nonintersections depending on the structures of routes. People with a better sense of direction tended to select fewer landmarks, focusing on commonly recognized landmarks. For buildings, the physical properties of facade area, color saturation, and age-affected selection frequencies, but different effects of physical properties were observed for individual routes, indicating the importance of context.
Further Dissociating the Processes Involved in Recognition Memory: An fMRI Study

Based on an event-related potential study by Rugg et al. [Dissociation of the neural correlates of implicit and explicit memory. Nature, 392, 595-598, 1998], we attempted to isolate the hemodynamic correlates of recollection, familiarity, and implicit memory within a single verbal recognition memory task using event-related fMRI. Words were randomly cued for either deep or shallow processing, and then intermixed with new words for yes/no recognition. The number of studied words was such that, whereas most were recognized (hits), an appreciable number of shallow-studied words were not (misses). Comparison of deep hits versus shallow hits at test revealed activations in regions including the left inferior parietal gyrus. Comparison of shallow hits versus shallow misses revealed activations in regions including the bilateral intraparietal sulci, the left posterior middle frontal gyrus, and the left frontopolar cortex. Comparison of hits versus correct rejections revealed a relative deactivation in an anterior left medial-temporal region (most likely the perirhinal cortex). Comparison of shallow misses versus correct rejections did not reveal response decreases in any regions expected on the basis of previous imaging studies of priming. Given these and previous data, we associate the left inferior parietal activation with recollection, the left anterior medial-temporal deactivation with familiarity, and the intraparietal and prefrontal responses with target detection. The absence of differences between shallow misses and correct rejections means that the hemodynamic correlates of implicit memory remain unclear.
Correlation and causation between the UN Human Development Index and national and personal wealth and resource exploitation

Abstract Human development is increasingly on global policy agendas, in particular related to the Sustainable Development Goals. Here, the UN Human Development Index is analysed for correlation and causation with economic and resource parameters using novel quantitative techniques. Global datasets at national resolution are used to explore correlation and causation with the HDI. The whole HDI is not correlated to national totals of wealth or resource use, but is strongly correlated to personal wealth and resource use. The multi-spatial convergence cross mapping method is adapted to shed light on causation in this system. It is shown that the HDI is tightly linked to the economy and to personal resource use. Analysis of the HDI sub-indices reveals subtleties easily overlooked. For example, it is shown that access to water and electricity strongly influence GNI. It is shown that simple resource accumulation/exploitation is less important in determining HDI growth than personal wealth and access to resources. That is, equitable distribution is more effective than gross accumulation in influencing the HDI. Strong feedback means that investments in water treatment and distribution networks, for example, will have strong effects on HDI change, a conclusion that may play an important role in national developmental policy debate.
Effect of transportation stress on heat shock protein 70 concentration and mRNA expression in heart and kidney tissues and serum enzyme activities and hormone concentrations of pigs.

OBJECTIVE To determine the enzymatic and hormonal responses, heat shock protein 70 (Hsp70) production, and Hsp70 mRNA expression in heart and kidney tissues of transport-stressed pigs. ANIMALS 24 pigs (mean weight, 20 +/- 1 kg). PROCEDURES Pigs were randomly placed into groups of 12 each. One group was transported for 2 hours. The other group was kept under normal conditions and used as control pigs. Sera were used to detect triiodothyronine, thyroxine, and cortisol concentrations and alanine aminotransferase, aspartate aminotransferase, and creatine kinase activities. The heart and kidneys of anesthetized pigs were harvested and frozen in liquid nitrogen for quantification of Hsp70 and Hsp70 mRNA. RESULTS No significant differences were detected in serum alanine aminotransferase activity and triiodothyronine and cortisol concentrations between groups; however, the serum creatine kinase and aspartate aminotransferase activities and thyroxine concentrations were higher in transported pigs. Densitometric readings of western blots revealed that the amount of Hsp70 in heart and kidney tissues was significantly higher in transported pigs, compared with control pigs. Results of fluorescence quantitative real-time PCR assay revealed that the Hsp70 mRNA transcription in heart tissue, but not kidney tissue, was significantly higher in transported pigs, compared with control pigs. CONCLUSIONS AND CLINICAL RELEVANCE Transportation imposed a severe stress on pigs that was manifested as increased serum activities of aspartate aminotransferase and creatine kinase and increased amounts of Hsp70 and Hsp70 mRNA expression in heart and kidney tissues. Changes in serum enzyme activities were related to the tissue damage of transport-stressed pigs.
Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach

Objective: To investigate the heterogeneity of idiopathic Parkinson’s disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established diagnostic criteria. Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I–III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored. Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment. Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson’s disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment.