Miracle-dz/UniFAR-FTUs huggingface dataset:
Hormonal Control of Cell Proliferation Requires PASTICCINO Genes

PASTICCINO (PAS) genes are required for coordinated cell division and differentiation during plant development. In loss-of-function pas mutants, plant aerial tissues showed ectopic cell division that was specifically enhanced by cytokinins, leading to disorganized tumor-like tissue. To determine the role of the PAS genes in controlling cell proliferation, we first analyzed the expression profiles of several genes involved in cell division and meristem function. Differentiated and meristematic cells of the pas mutants were more competent for cell division as illustrated by the ectopic and enlarged expression profiles of CYCLIN-DEPENDENT KINASE A and CYCLIN B1. The expression of meristematic homeobox genes KNOTTED-LIKE IN ARABIDOPSIS (KNAT2, KNAT6), and SHOOT MERISTEMLESS was also increased in pas mutants. Moreover, the loss of meristem function caused by shoot meristemless mutation can be suppressed by pas2. The KNAT2 expression pattern defines an enlarged meristematic zone in pas mutants that can be mimicked in wild type by cytokinin treatment. Cytokinin induction of the primary cytokinin response markers, ARABIDOPSIS RESPONSE REGULATOR (ARR5 and ARR6), was enhanced and lasted longer in pas mutants, suggesting that PAS genes in wild type repress cytokinin responses. The expression of the cytokinin-regulated cyclin D, cyclin D3.1, was nonetheless not modified in pas mutants. However, primary auxin response genes were down-regulated in pas mutants, as shown by a lower auxin induction of IAA4 and IAA1 genes, demonstrating that the auxin response was also modified. Altogether, our results suggest that PAS genes are involved in the hormonal control of cell division and differentiation.
Role of the Endogenous Antioxidant System in the Protection of Schistosoma mansoni Primary Sporocysts against Exogenous Oxidative Stress

Antioxidants produced by the parasite Schistosoma mansoni are believed to be involved in the maintenance of cellular redox balance, thus contributing to larval survival in their intermediate snail host, Biomphalaria glabrata. Here, we focused on specific antioxidant enzymes, including glutathione-S-transferases 26 and 28 (GST26 and 28), glutathione peroxidase (GPx), peroxiredoxin 1 and 2 (Prx1 and 2) and Cu/Zn superoxide dismutase (SOD), known to be involved in cellular redox reactions, in an attempt to evaluate their endogenous antioxidant function in the early-developing primary sporocyst stage of S. mansoni. Previously we demonstrated a specific and consistent RNA interference (RNAi)-mediated knockdown of GST26 and 28, Prx1 and 2, and GPx transcripts, and an unexpected elevation of SOD transcripts in sporocysts treated with gene-specific double-stranded (ds)RNA. In the present followup study, in vitro transforming sporocysts were exposed to dsRNAs for GST26 and 28, combined Prx1/2, GPx, SOD or green-fluorescent protein (GFP, control) for 7 days in culture, followed by assessment of the effects of specific dsRNA treatments on protein levels using semi-quantitative Western blot analysis (GST26, Prx1/2 only), and larval susceptibility to exogenous oxidative stress in in vitro killing assays. Significant decreases (80% and 50%) in immunoreactive GST26 and Prx1/2, respectively, were observed in sporocysts treated with specific dsRNA, compared to control larvae treated with GFP dsRNA. Sporocysts cultured with dsRNAs for GST26, GST28, Prx1/2 and GPx, but not SOD dsRNA, were significantly increased in their susceptibility to H2O2 oxidative stress (60–80% mortalities at 48 hr) compared to GFP dsRNA controls (∼18% mortality). H2O2-mediated killing was abrogated by bovine catalase, further supporting a protective role for endogenous sporocyst antioxidants. Finally, in vitro killing of S. mansoni sporocysts by hemocytes of susceptible NMRI B. glabrata snails was increased in larvae treated with Prx1/2, GST26 and GST28 dsRNA, compared to those treated with GFP or SOD dsRNAs. Results of these experiments strongly support the hypothesis that endogenous expression and regulation of larval antioxidant enzymes serve a direct role in protection against external oxidative stress, including immune-mediated cytotoxic reactions. Moreover, these findings illustrate the efficacy of a RNAi-type approach in investigating gene function in larval schistosomes.
Productivity and the Role of Complementary Assets in Firms’ Demand for Technology Innovations

This paper uses data on transactions in the pharmaceutical industry to examine the demand-side of technology outsourcing. By integrating a transaction-cost economics perspective with the analysis of internal R&D capabilities, we find that firms with relatively more cospecialized complementary assets or relatively strong internal R&D productivity have a lower propensity to source a technology from outside the firm. We show, however, that since downstream capabilities and internal R&D are complementary activities in the presence of asset specificity and transaction costs, a decrease in internal R&D productivity reduces the marginal vale of the downstream assets within firm boundaries, thus stimulating the demand for external technology.
The Molecular Phenotype of Heparan Sulfate in theHs2st −/− Mutant Mouse*

Heparan sulfate (HS) is a co-receptor for a number of growth factors, morphogens, and adhesion proteins. HS biosynthetic modifications may determine the strength and outcome of HS-ligand interactions. We previously described the phenotype of mice with a gene-trap mutation inHs2st, encoding the key HS 2-O-sulfotransferase enzyme in HS polymer modification. In contrast to the early developmental failure of embryos lacking HS, the onset of abnormalities in the Hs2st −/− mice occurs only after midgestation, the most dramatic being the complete failure of kidney development. Uronate 2-O-sulfates were not detected in the mutant HS, indicating a complete loss of function of Hs2st. However, the domain structure of the mutant HS is conserved, and compensatory increases in N- and 6-O-sulfation maintain the overall charge density. The apparent affinities of the mutant HS for hepatocyte growth factor/scatter factor and fibronectin were unchanged but were reduced for fibroblast growth factor-1 and -2. Surprisingly, theHs2st −/− cells were able to mount an apparently normal signaling response to fibroblast growth factor-1 and -2 as well as to hepatocyte growth factor/scatter factor.
Preventing Over-Fitting during Model Selection via Bayesian Regularisation of the Hyper-Parameters

While the model parameters of a kernel machine are typically given by the solution of a convex optimisation problem, with a single global optimum, the selection of good values for the regularisation and kernel parameters is much less straightforward. Fortunately the leave-one-out cross-validation procedure can be performed or a least approximated very efficiently in closed form for a wide variety of kernel learning methods, providing a convenient means for model selection. Leave-one-out cross-validation based estimates of performance, however, generally exhibit a relatively high variance and are therefore prone to over-fitting. In this paper, we investigate the novel use of Bayesian regularisation at the second level of inference, adding a regularisation term to the model selection criterion corresponding to a prior over the hyper-parameter values, where the additional regularisation parameters are integrated out analytically. Results obtained on a suite of thirteen real-world and synthetic benchmark data sets clearly demonstrate the benefit of this approach.
The evolutionary history of Stomatopoda (Crustacea: Malacostraca) inferred from molecular data

The crustacean order Stomatopoda comprises seven superfamilies of mantis shrimps, found in coastal waters of the tropics and subtropics. These marine carnivores bear notable raptorial appendages for smashing or spearing prey. We investigated the evolutionary relationships among stomatopods using phylogenetic analyses of three mitochondrial and two nuclear markers. Our analyses recovered the superfamily Gonodactyloidea as polyphyletic, with Hemisquilla as the sister group to all other extant stomatopods. A relaxed molecular clock, calibrated by seven fossil-based age constraints, was used to date the origin and major diversification events of stomatopods. Our estimates suggest that crown-group stomatopods (Unipeltata) diverged from their closest crustacean relatives about 340 Ma (95% CRI [401–313 Ma]). We found that the specialized smashing appendage arose after the spearing appendage ∼126 Ma (95% CRI [174–87 Ma]). Ancestral state reconstructions revealed that the most recent common ancestor of extant stomatopods had eyes with six midband rows of hexagonal ommatidia. Hexagonal ommatidia are interpreted as plesiomorphic in stomatopods, and this is consistent with the malacostracan ground-plan. Our study provides insight into the evolutionary timescale and systematics of Stomatopoda, although further work is required to resolve with confidence the phylogenetic relationships among its superfamilies.
The Basolateral Nucleus of the Amygdala Is Necessary to Induce the Opposing Effects of Stressful Experience on Learning in Males and Females

The basolateral nucleus of the amygdala (BLA) has been implicated in the modulation of learning after stress. Acute inescapable stress enhances classical eyeblink conditioning in male rats, whereas the same stressor impairs eyeblink conditioning in female rats. The experiments here directly assessed whether inactivation of the BLA during stress exposure would block both the stress-induced facilitation in males and the retardation of eyeblink conditioning in females. To this end, the BLA was temporarily inactivated by infusion of the GABA agonist muscimol before acute stressor exposure. All rats were trained in a different context 24 h later. Males infused with muscimol before the stressful event did not exhibit facilitated eyeblink conditioning, whereas those infused with the vehicle emitted more conditioned responses than unstressed males. Females infused with muscimol before stress did not express a deficit in conditioning, whereas those infused with vehicle and stressed emitted fewer conditioned responses than unstressed vehicle controls. These data demonstrate that neuronal activity within the BLA during stress exposure is necessary to modulate learning 24 h later in a new context. Thus, the BLA is necessary to induce the long-term effect of stressful experience on conditioning regardless of sex and direction of modulation.
Glutathione Ethyl Ester Supplementation during Pancreatic Islet Isolation Improves Viability and Transplant Outcomes in a Murine Marginal Islet Mass Model

Background The success of pancreatic islet transplantation still faces many challenges, mainly related to cell damage during islet isolation and early post-transplant. The increased generation of reactive oxygen species (ROS) during islet isolation and the consumption of antioxidant defenses appear to be an important pathway related to islet damage. Methodology/Principal Findings In the present study we evaluated whether supplementation of glutathione-ethyl-ester (GEE) during islet isolation could improve islet viability and transplant outcomes in a murine marginal islet mass model. We also cultured human islets for 24 hours in standard CMRL media with or without GEE supplementation. Supplementation of GEE decreased the content of ROS in isolated islets, leading to a decrease in apoptosis and maintenance of islet viability. A higher percentage of mice transplanted with a marginal mass of GEE treated islets became euglycemic after transplant. The supplementation of 20 mM GEE in cultured human islets significantly reduced the apoptosis rate in comparison to untreated islets. Conclusions/Significance GEE supplementation was able to decrease the apoptosis rate and intracellular content of ROS in isolated islets and might be considered a potential intervention to improve islet viability during the isolation process and maintenance in culture before islet transplantation.
Survival Benefit of Adding Chemotherapy to Intensity Modulated Radiation in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

Background To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity modulated radiotherapy (IMRT) and to identify the optimal combination treatment strategy. Patients and Methods Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. Results With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS), metastasis-free survival (MFS), relapse-free survival (RFS), and disease-free survival (DFS) were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12−6.22; P = 0.03), patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35−12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09−5.44; P = 0.03), neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. Conclusions Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.
DRUG RESISTANCE IN HELICOBACTER PYLORI.

Background Helicobacter pylori has a worldwide distribution and is associated with the pathogenesis of various diseases of the digestive system. Treatment to eradicate this microorganism involves the use of a combination of antimicrobials, such as amoxicillin, metronidazole, clarithromycin, and levofloxacin, combined with proton pump inhibitors. Although the current therapy is effective, a high rate of treatment failure has been observed, mainly because of the acquisition of point mutations, one of the major resistance mechanisms developed by H. pylori. This phenomenon is related to frequent and/or inappropriate use of antibiotics. Conclusion This review reported an overview of the resistance to the main drugs used in the treatment of H. pylori, confirming the hypothesis that antibacterial resistance is a highly local phenomenon and genetic characteristics of a given population can influence which therapy is the most appropriate.
A complete and decidable logic for resource-bounded agents

We propose a context-logic style formalism, Timed Reasoning Logics (TRL), to describe resource-bounded reasoners who take time to derive consequences of their knowledge. The semantics of TRL is grounded in the agentýs computation, allowing an unambiguous ascription of the set of formulas which the agent actually knows at time t. We show that TRL can capture various rule application and conflict resolution strategies that a rule-based agent may employ, and analyse two examples in detail: TRL(STEP) which models an all rules at each cycle strategy similar to that assumed in step logic [5], and TRL(CLIPS) which models a single rule at each cycle strategy similar to that employed by the CLIPS [22] rule based system architecture.We prove a general completeness and decidability results for TRL(STEP).
Phyllocarid crustaceans from the Late Devonian of the Kowala quarry (Holy Cross Mountains, central Poland)

Phyllocarida (Crustacea, Malacostraca) are among the most diversified and widespread Late Devonian arthropods. Although previous studies mention phyllocarid fossils from Late Devonian (Frasnian and Famennian) deposits of the Holy Cross Mountains of south‐central Poland, phyllocarids from the Kowala quarry have not been systematically described. Two new species are described from Kowala strata: Echinocaris bisulcata sp. nov. characterized by oval carapace valves with a short hinge line, cone‐like tubercules on the carapace anterior lobe, two pronounced lateral sulci (ventral and median) and two pairs of short spines on every abdominal segment; and Montecaris marynowskii sp. nov. characterized by two pairs of robust abdominal spines, a telson that is shorter than furcal rami, distal parts of which are parallel to the telson, and a body length approximately four times longer than the telson length. Additionally, an isolated furca identified as Dithyrocaris sp. is described herein. Damage observed in the holotype specimen of Montecaris marynowski sp. nov. is consistent with a healed injury, possibly caused by predatory fish. Notes concerning the global occurrences of montecaridids, echinocaridids and the genus Dithyrocaris in the Late Devonian are also provided.
Preservation of femoral bone thickness in middle age predicts survival in genetically heterogeneous mice

To see whether age‐related changes in bone could predict subsequent lifespan, we measured multiple aspects of femur size and shape at 4, 15, and 24 months of age in genetically heterogeneous mice. Mice whose cortical bone became thicker from 4 to 15 months, associated with preservation of the endosteal perimeter, survived longer than mice whose endosteal cavity expanded, at the expense of cortical bone, over this age range. Femur size at age 4 months was also associated with a difference in life expectancy: mice with larger bones (measured by length, cortical thickness, or periosteal perimeter) had shorter lifespans. Femur length, midlife change in cortical bone thickness, and midlife values of CD8 T memory cells each added significant power for longevity prediction. Mice in the upper half of the population for each of these three endpoints lived, on average, 103 days (12%) longer than mice with the opposite characteristics. Thus, measures of young adult bone dimensions, changes as a result of bone remodeling in middle age, and immunological maturation provide partially independent indices of aging processes that together help to determine lifespan in genetically heterogeneous mice.
Detection of human interchromosomal trans-splicing in sequence databanks

Trans-splicing is a common phenomenon in nematodes and kinetoplastids, and it has also been reported in other organisms, including humans. Up to now, all in silico strategies to find evidence of trans-splicing in humans have required that the candidate sequences follow the consensus splicing site rules (spliceosome-mediated mechanism). However, this criterion is not supported by the best human experimental evidence, which, except in a single case, do not follow canonical splicing sites. Moreover, recent findings describe a novel alternative tRNA mediated trans-splicing mechanism, which prescinds the spliceosome machinery. In order to answer the question, 'Are there hybrid mRNAs in sequence databanks, whose characteristics resemble those of the best human experimental evidence? ', we have developed a methodology that successfully identified 16 hybrid mRNAs which might be instances of interchromosomal trans-splicing. Each hybrid mRNA is formed by a trans-spliced region (TSR), which was successfully mapped either onto known genes or onto a human endogenous retrovirus (HERV-K) transcript which supports their transcription. The existence of these hybrid mRNAs indicates that trans-splicing may be more widespread than believed. Furthermore, non-canonical splice site patterns suggest that infrequent splicing sites may occur under special conditions, or that an alternative trans-splicing mechanism is involved. Finally, our candidates are supposedly from normal tissue, and a recent study has reported that trans-splicing may occur not only in malignant tissues, but in normal tissues as well. Our methodology can be applied to 5'-UTR, coding sequences and 3'-UTR in order to find new candidates for a posteriori experimental confirmation.
The Diagnostic Performance of the GenoType MTBDRplus Version 2 Line Probe Assay Is Equivalent to That of the Xpert MTB/RIF Assay

ABSTRACT Molecular diagnostics for Mycobacterium tuberculosis have recently been endorsed by the World Health Organization. The Xpert MTB/RIF assay was endorsed for use on patient material, regardless of smear gradation, while the GenoType MTBDRplus (version 1) has been limited for use on smear-positive patient material. In this study, we evaluated the diagnostic performance of the Xpert MTB/RIF and GenoType MTBDRplus (version 2) assays on smear-positive and smear-negative patient specimens submitted to a high-throughput diagnostic laboratory. A total of 282 consecutive specimens were subjected to the two new molecular assays, and their performance characteristics were assessed relative to the routine diagnostic standard. Both assays showed similar diagnostic performance characteristics. The sensitivities of the GenoType MTBDRplus (v2.0) and Xpert MTB/RIF assays for the detection of culture-positive M. tuberculosis were 73.1% and 71.2%, respectively, while the specificities of both assays were 100%. Both assays were able to diagnose the presence of M. tuberculosis in 57 to 58% of smear-negative cases, suggesting that the performance characteristics were dependent on bacillary load. The detection of M. tuberculosis in culture-negative specimens confirmed that molecular assays should not be used for treatment monitoring. The sensitivity and specificity for rifampin resistance detection were 100% in both assays; however, the GenoType MTBDRplus (v2.0) assay provided additional information on isoniazid susceptibility. The GenoType MTBDRplus (v2.0) assay will complement the Xpert MTB/RIF screening assay by validating rifampin susceptibility and providing information on isoniazid susceptibility. In addition, the GenoType MTBDRplus (v2.0) assay will provide pharmacogenetic information that may be critical in guiding appropriate treatment.
Meanings and aspects of quality of life for cancer patients: A descriptive exploratory qualitative study

Abstract Given the importance of quality of life (QoL) for cancer patients, it is important to work out what this concept means not only for cancer patients, and for the nurses who care for them, but also the aspects of which it is composed. Therefore, an interpretive research study was conducted to explore in-depth meanings and aspects of QoL as expressed by cancer nurses. Participants were selected from different inpatient and outpatient oncology services and a palliative setting in Adelaide, South Australia. Results showed that many aspects contribute to an individual’s QoL. These include the physical, the psychological, the spiritual, and both environmental and social interactions. More importantly, participants stated that spirituality is multifaceted and that there may be aspects in life that may be taken for granted. The meaning of patients’ QoL was viewed by nurses as a patient’s overall happiness and satisfaction. Also, nurses identified that providing choices to patients made an important contribution to a patient’s QoL. Therefore, this exploration into the in-depth meanings and aspects of QoL for cancer patients from nurses’ perspectives identifi ed that, in addition to the aspects related to QoL that have been identified previously in the literature, aspects related to spirituality would need to be extensively covered, and providing choices to patients would be important in patients’ QoL in an Australian setting.