Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mitochondrial Control Region of Blowflies (Diptera: Calliphoridae): A Hot Spot for Mitochondrial Genome Rearrangements

Abstract The family Calliphoridae consists of myiasis-causing flies, including species of economic, forensic, and medical importance. In this study, the complete control regions (CRs) of mitochondrial DNA from 15 calliphorid species were sequenced and structurally characterized. The CRs had a high content of adenines (A) and thymines (T) and varied in length from 854 to 2,018 bp, showing intraspecific variations in sequence and length. Two major domains were identified: the conserved domain containing conserved sequence blocks and cis-regulatory structures that may be related to the transcription and the origin of replication of mitochondrial DNA, and the variable domain, containing high sequence and length variation. Within the variable domain, duplication of the tRNAIle gene, previously reported for three Chrysomya species, was identified in two more species of this genus and in two species of two other genera. The structural characterization shows the plasticity of the mitochondrial genome in dipterans. The organizational similarities of the duplicated region found in different species and the possible origin of the duplicated genes are discussed.
Haemodynamics and fluid balance after intravenous infusion of 1.5% glycine in sheep

With the aim of studying the pathophysiological background of the “TUR syndrome”, we gave six conscious ewes an intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min. Isotonic saline infusions served as controls. Central haemodynamics were monitored. The plasma concentrations of protein, K, Na and vasopressin, and plasma osmolality were measured repeatedly for up to 4 h. The urinary excretions of Na, K and osmoles were also followed. Both infusions caused an elevation of the mean arterial pressure. With glycine, the pressure increased from 93 ± 4 to 112 ± 12 mmHg (12.4 ± 0.5 to 14.9 ± 1.6 kPa) (mean ± s.d.). The pulmonary capillary wedge pressure increased from 7±3 to 16±3 mmHg (0.9 ± 0.4 to 2.1 ± 0.4 kPa) and remained slightly elevated. The central venous pressure rose from 2 ± 3 to 11 ± 3 mmHg (0.3 ± 0.4 to 1.5 ± 0.4 kPa) but returned to baseline within 30 min after the infusion. Infusion of glycine resulted in a decrease in the plasma Na concentration from 144 ± 3 to 114 ± 4 mmol/l. The plasma osmolality decreased from 290 ± 2 to 280 ± I mosmol/l, and remained low. There was a median 6‐fold increase in plasma vasopressin concentration, while saline did not elicit vasopressin release. Despite the absence of electrolytes in glycine solution, the urinary excretion of sodium amounted to 106 ± 40 mmol. We conclude that i.v. infusion of 1.5% glycine solution in sheep causes a transient circulatory strain and natriuresis. Moreover, a vasopressin‐mediated reduction of maximal water excretion contributes to persisting hypoosmolality.
Prediction of high-pressure polymorphism in NiS2 at megabar pressures

A sequence of pressure-induced phase transitions of vaesite, NiS2, with pyrite structure, has been established from static LDA calculations. A dozen AX2 candidate structures have been studied at high pressures including cotunnite (α-PbCl2), which is commonly observed in other AX2 compounds at high pressures. At 150 GPa, vaesite transforms to a tetragonal phase (P42/n) rather than cotunnite. This tetragonal structure is characterized by layers of Ni atoms in eight-fold coordination with S atoms rather than the nine-fold coordination observed in cotunnite. With further compression to about 7.5 Mbar, the tetragonal phase transforms into a hexagonal AlB2-type structure (P6/mmm) which is characterized by planar hexagonal layers of S intercalated by Ni atoms where each Ni atom is 12-fold coordinated by S atoms. Calculated band structures and valence electron density maps show S–S and Ni–S bonded interactions for NiS2 under these extremely compressed conditions. The tetragonal phase may have geophysical implications if present in the Earth’s core.
Simulating the Greenland ice sheet under present-day and palaeo constraints including a new discharge parameterization

Abstract. In this paper, we propose a new sub-grid scale parameterization for the ice discharge into the ocean through outlet glaciers and inspect the role of different observational and palaeo constraints for the choice of an optimal set of model parameters. This parameterization was introduced into the polythermal ice-sheet model SICOPOLIS, which is coupled to the regional climate model of intermediate complexity REMBO. Using the coupled model, we performed large ensemble simulations over the last two glacial cycles by varying two major parameters: a melt parameter in the surface melt scheme of REMBO and a discharge scaling parameter in our parameterization of ice discharge. Our empirical constraints are the present-day Greenland ice sheet surface elevation, the surface mass balance partition (ratio between total ice discharge and total precipitation) and the Eemian interglacial elevation drop relative to present day in the vicinity of the NEEM ice core. We show that the ice discharge parameterization enables us to simulate both the correct ice-sheet shape and mass balance partition at the same time without explicitly resolving the Greenland outlet glaciers. For model verification, we compare the simulated total and sectoral ice discharge with other estimates. For the model versions that are consistent with the range of observational and palaeo constraints, our simulated Greenland ice sheet contribution to Eemian sea-level rise relative to present-day amounts to 1.4 m on average (in the range of 0.6 and 2.5 m).
Indications for corneal grafting in Zimbabwe.

OBJECTIVE To assess the indications for corneal grafting in Zimbabwe. DESIGN Hospital based retrospective study. SETTING The study was conducted at Sekuru Kaguvi Eye Hospital. METHODS Data were collected for patients who had corneal grafts performed at Sekuru Kaguvi Eye Hospital during the period January 1992 to March 1998. RESULTS The leading indications for penetrating keratoplasty were keratoconus (26.8%), presumed post measles scarring (17.8%), pseudophakic bullous keratopathy (12.5%), corneal scarring due to Herpes simplex keratitis (10.7%) and corneal scarring due to trauma (10.7%). A change in the indications was observed during the study period. The outcome of corneal grafting was favourable with more than 75% experiencing significant improvement in vision. CONCLUSION Indications for penetrating keratoplasty in Zimbabwe show a pattern different from those for the developed world. A change in the indications during the study reflects changes in local ophthalmic practice.
Gastrointestinal hormonal dysfunction in gastroparesis and functional dyspepsia

Background Numerous hormones secreted by the gut, during both the fasted state and in response to a meal, influence gastrointestinal motor and/or sensory function, and appear to contribute to the pathogenesis of delayed gastric emptying associated with gastroparesis, functional dyspepsia (FD) and feed intolerance in critical illness. Gut hormones are, accordingly, potential targets for the management of these patients.
Critical role of the N‐terminal cyclic AMP‐binding domain of Epac2 in its subcellular localization and function

cAMP is a well‐known regulator of exocytosis, and cAMP‐GEFII (Epac2) is involved in the potentiation of cAMP‐dependent, PKA‐independent regulated exocytosis in secretory cells. However, the mechanisms of its action are not fully understood. In the course of our study of Epac2 knockout mice, we identified a novel splicing variant of Epac2, which we designate Epac2B, while renaming the previously identified Epac2 Epac2A. Epac2B, which lacks the first cAMP‐binding domain A in the N‐terminus but has the second cAMP‐binding domain B of Epac2A, possesses GEF activity towards Rap1, as was found for Epac2A. Immunocytochemical analysis revealed that exogenously introduced Epac2A into insulin‐secreting MIN6 cells was localized near the plasma membrane, while Epac2B was found primarily in the cytoplasm. Interestingly, cAMP‐binding domain A alone introduced into MIN6 cells was also localized near the plasma membrane. In MIN6 cells, Epac2A was involved in triggering hormone secretion by stimulation with 5.6 mM glucose plus 1 mM 8‐Bromo‐cAMP, but Epac2B was not. The addition of a membrane‐targeting signal to the N‐terminus of Epac2B was able to mimic the effect of Epac2A on hormone secretion. Thus, the present study indicates that the N‐terminal cAMP‐binding domain A of Epac2A plays a critical role in determining its subcellular localization and potentiating insulin secretion by cAMP. J. Cell. Physiol. 219: 652–658, 2009. © 2009 Wiley‐Liss, Inc.
SPATA18, a Spermatogenesis-Associated Gene, Is a Novel Transcriptional Target of p53 and p63

ABSTRACT The transcription factor p53 functions not only to suppress tumorigenesis but also to maintain normal development and homeostasis. Although p53 was implicated in different aspects of fertility, including spermatogenesis and implantation, the mechanism underlying p53 involvement in spermatogenesis is poorly resolved. In this study we describe the identification of a spermatogenesis-associated gene, SPATA18, as a novel p53 transcriptional target and show that SPATA18 transcription is induced by p53 in a variety of cell types of both human and mouse origin. p53 binds a consensus DNA motif that resides within the first intron of SPATA18. We describe the spatiotemporal expression patterns of SPATA18 in mouse seminiferous tubules and suggest that SPATA18 transcription is regulated in vivo by p53. We also demonstrate the induction of SPATA18 by p63 and suggest that p63 can compensate for the loss of p53 activity in vivo. Our data not only enrich the known collection of p53 targets but may also provide insights on spermatogenesis defects that are associated with p53 deficiency.
Packages of Participation: Swedish Employees’ Experience of Lean Depends on How They Are Involved

OCCUPATIONAL APPLICATIONS The results presented here show that active and continuous employee participation in organizational change programs, e.g., the implementation of Lean, can have several positive employee effects. However, the benefit of participation may depend on “what is inside the package,” which is important for practitioners to know as they decide both whether and how to involve workers in implementing Lean. Structured and continuous “packages” of participation, such as improvement groups, may provide the most positive employee experience, whereas temporary packages, such as intermittent change projects, may provide the least positive. Packages combining both continuous and temporary participation may even diminish some of the positive effects of continuous participation, while also possibly being the most costly approach. Just as Lean interventions strive to maximize value and minimize waste, so must organizations planning organizational change identify the participatory approaches that will yield the highest value without excess waste. TECHNICAL ABSTRACT Background: Lean production is a dominant approach in Swedish and global manufacturing and service industries. Studies of Lean's employee effects are few and contradictory. Purpose: Employee effects from Lean are likely not uniform. This article investigates the effect of employees’ participation on their experiences of Lean. Method: This study investigated how different packages of employee participation in Lean affected manufacturing workers’ experiences of Lean. During 2008–2011, qualitative and quantitative data were collected from Swedish manufacturing companies participating in the national Swedish Lean production program Produktionslyftet. Data from 129 surveys (28 companies), 39 semi-structured interviews, and 30 reports were analyzed. In the main analysis, comparisons were made of the survey-reported Lean experiences of employees in three groups: temporary group employees (N = 36), who participated in Lean mostly through intermittent projects; continuous group employees (N = 69), who participated through standing improvement groups; and combined group employees (N = 24), who participated in both ways. Results: Continuous group employees had the most positive experience of Lean, followed by the combined group. Temporary group employees had the least positive experiences, being less likely than their counterparts to report that Lean improved teamwork; occupational safety; and change-related learning, decision making, and authority. Conclusions: These findings support the importance of continuous, structured opportunities for participation but raise the possibility that more participation may result in greater workload and role overload, mitigating some benefits of employee involvement. Consequently, companies should consider involving employees in change efforts but should attend to the specific design of participation activities.
Distinct mechanisms of internalization of Neisseria gonorrhoeae by members of the CEACAM receptor family involving Rac1‐ and Cdc42‐dependent and ‐independent pathways

Opa adhesins of pathogenic Neisseria species target four members of the human carcinoembryonic antigen‐related cellular adhesion molecule (CEACAM) family. CEACAM receptors mediate opsonization‐independent phagocytosis of Neisseria gonorrhoeae by human granulocytes and each receptor individually can mediate gonococcal invasion of epithelial cells. We show here that gonococcal internalization occurs by distinct mechanisms depending on the CEACAM receptor expressed. For the invasion of epithelial cell lines via CEACAM1 and CEACAM6, a pathogen‐directed reorganization of the actin cytoskeleton is not required. In marked contrast, ligation of CEACAM3 triggers a dramatic but localized reorganization of the host cell surface leading to highly efficient engulfment of bacteria in a process regulated by the small GTPases Rac1 and Cdc42, but not Rho. Two tyrosine residues of a cytoplasmic immune receptor tyrosine‐based activating motif of CEACAM3 are essential for the induction of phagocytic actin structures and subsequent gonococcal internalization. The granulocyte‐specific CEACAM3 receptor has properties of a single chain phagocytic receptor and may thus contribute to innate immunity by the elimination of Neisseria and other CEACAM‐binding pathogens that colonize human mucosal surfaces.
Working height, block mass and one- vs. two-handed block handling: the contribution to low back and shoulder loading during masonry work

The goal of this study was to compare the effects of the task variables block mass, working height and one- vs. two-handed block handling on low back and shoulder loading during masonry work. In a mock-up of a masonry work site, nine masonry workers performed one- and two-handed block-lifting and block-placing tasks at varying heights (ranging from floor to shoulder level) with blocks of varying mass (ranging from 6 to 16 kg). Kinematics and ground reaction forces were measured and used in a 3-D linked segment model to calculate low back and shoulder loading. Increasing lifting height appeared to be the most effective way to reduce low back loading. However, working at shoulder level resulted in relatively high shoulder loading. Therefore, it was recommended to organise masonry work in such a way that blocks are handled with the hands at about iliac crest height as much as possible.
Interactive effect of foliarly applied ascorbic acid and salt stress on wheat (Triticum aestivum L.) at the seedling stage

A hypdoponic experiment was conducted to assess the role of ascorbic acid in alleviation of the adverse effects of salt stress on growth of two wheat cultivars, S-24 (salt tolerant) and MH-97 (moderately salt sensitive). Seven-day old plants were subjected to normal or saline conditions (0 and 150 mM) for four weeks. Ascorbic acid was exogenously applied as foliar spray with varying levels (0, 50, 100 mg L-1) in hydroponics. Salt stress severely reduced growth of both wheat cultivars. Foliar spray with AsA improved the growth of non-stressed plants of both cultivars, but did not alleviate the adverse effects of salt stress on plants. However, salt-induced reduction in leaf chlorophyll 'a' was improved with AsA application. Salt-induced enhanced activities of all antioxidant enzymes were not substantially changed with AsA application. However, AsA application enhanced the Na+ accumulation in the leaves of salt stressed plants of both cultivars, but it did not change the K+ accumulation in the leaves and roots of the salt stressed plants of both cultivars. Furthermore, AsA applied as a foliar spray did not induce substantial changes and hence salt tolerance of both wheat cultivars. Thus, it can be concluded that though foliar spray with applied ascorbic acid protected the photosynthetic machinery from the damaging effects of salt stress, it did not improve growth of the two wheat cultivars under saline conditions.
Introducing the postoperative care team

It is amazing how after years of scientific research and therapeutic progress many simple and basic questions about the epilepsies remain unanswered. Even the natural course of epilepsy is not well known because of the widespread use of antiepileptic drugs. Gowers suspected that seizures trigger subsequent seizures or, in other words, that there is a facilitation phenomenon.1 This idea still survives but has yet to be substantiated. We also do not know if antiepileptic drugs alter the natural course of epilepsy and prevent chronicity and intractability developing. Are the risks of further seizures in newly diagnosed patients (especially children) worth the side effects associated with antiepileptic drugs? What is the optimum time to begin treatment? Clinical studies have produced diverging and sometimes conflicting views on these problems. In this week's BMJ , van Donselaar et al (p 401) followed 204 untreated children aged 1 month to 16 years who experienced one (123 patients) or more idiopathic or “remote symptomatic” tonic-clonic seizures (including seizures with partial onset). 2 They analysed the time between seizures until the start of treatment, the fourth untreated seizure, or the end …
Stereotactic Body Radiotherapy of Bone Metastases in Oligometastatic Disease: Prognostic Factors of Oncologic Outcomes

Background To evaluate the safety of stereotactic body radiotherapy (SBRT) of bone metastases in oligometastatic disease and to investigate prognostic factors of local control (LC), progression/disease-free survival (PDFS), and overall survival (OS). Methods Eligibility criteria were number of metastates ≤5, controlled primary tumor without evidence of progression under systemic therapy, exclusion of surgery, and no previous radiotherapy of the lesion of interest. Oligometastatic status was classified into only bone (BOD) and outside bone disease (OBOD), whereas SBRT was delivered to bone lesions using 2 different schedules: 24 Gy/1 fraction or 27 Gy/3 fractions. A positron emission tomography study of the lesion of interest was performed at baseline and at 3 months after SBRT to evaluate metabolic response according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A Cox regression model was used for univariate and multivariate analysis. Results Between January 2010 and December 2013, 40 patients were enrolled. Only 1 patient experienced severe late toxicity (radiation-related fracture). Local control was longer among responders’ than nonresponders’ lesions (94.2% and 91.2% versus 63% and 35% at 1 and 2 years, respectively) (p = 0.004; hazard ratio = 9.958). The multivariate analysis of PDFS showed a significant correlation with planning target volume (PTV) size (p = 0.003) and oligometastatic status (p = 0.002). The multivariate analysis of OS confirmed a statistically significant value of the oligometastatic status (p = 0.002) and a significant trend for PTV size (p = 0.065). Conclusions Stereotactic body radiotherapy is safe with a low incidence of severe toxicity. Positron emission tomography response was a strong prognostic factor of LC whereas BOD status and small PTV size could identify a subset of oligometastatic patients at better prognosis.
Reply to Mendall

We thank Dr. Mendall for his comments about our study describing the increasing average weight of patients with Crohn’s disease in clinical trials over the years and the significant correlation between this novel finding and disease activity. This was a hypothesis-generating study of the data published in connection with previous clinical trials. The author states that fecal calprotectin is a useful surrogate marker for Crohn’s disease risk and could thus be useful in future epidemiological studies. The role of fecal calprotectin in the association between obesity and Crohn’s disease is a valid one. It was not possible to address this in our study of previous clinical trials of therapeutic agents. The associations ascribed to obesity, such as decreased physical activity and a high-fat diet, are ecological and do not impute causality with Crohn’s disease. Adiposity in general may be proinflammatory as a result of multiple adipokine and cytokine effects. We agree that obesity might have a causal effect in Crohn’s disease and could possibly affect its clinical outcome. Even in the absence of adiposity, a high-fat diet might accelerate disease pathogenesis in Crohn’s disease, and alteration of the microbiome and barrier function could underlie this association. Unfortunately, body mass index, which is the most routinely used clinical weight measurement, is a very insensitive marker of adiposity. A large proportion of malnourished patients with Crohn’s disease have a normal body mass index, despite having an abnormal body composition and muscle function. This observation might explain the discrepancy in the findings between the European Prospective Cohort Study and the Nurses’ Health study. A bimodal distribution in the incidence of Crohn’s disease based on obesogenic factors is a contentious issue. The present data do not suggest that the incidence of obesity is higher in pediatric Crohn’s disease, but surgical risk is significantly associated with an obese status, possibly indicating more aggressive disease in this cohort. The observed difference, when compared with the adult data, could be explained by the confounders of reduced disease duration, less life-years exposure to the proinflammatory obese state, and a tendency to a different disease phenotype in the pediatric Crohn’s cohort. Further work needs to be undertaken to investigate the association between adiposity and its effects on the incidence and severity of Crohn’s disease both in adult and pediatric population.
Genetic interactions underlying otic placode induction and formation

The formation of the otic placode is a complex process requiring multiple inductive signals. In zebrafish, fgf3 and fgf8, dlx3b and dlx4b, and foxi1 have been identified as the earliest‐acting genes in this process. fgf3 and fgf8 are required as inductive signals, whereas dlx3b, dlx4b, and foxi1 appear to act directly within otic primordia. We have investigated potential interactions among these genes. Depletion of either dlx3b and dlx4b or foxi1 leads to a delay of pax2a expression in the otic primordia and reduction of the otic vesicle. Depletion of both foxi1 and dlx3b results in a complete ablation of otic placode formation. A strong synergistic interaction is also observed among foxi1, fgf3, and fgf8, and a weaker interaction among dlx3b, fgf3, and fgf8. Misexpression of foxi1 can induce expression of pax8, an early marker for the otic primordia, in embryos treated with an inhibitor of fibroblast growth factor (FGF) signaling. Conversely, morpholino knockdown of foxi1 blocks ectopic pax8 expression and otic vesicle formation induced by misexpression of fgf3 and/or fgf8. The observed genetic interactions suggest a model in which foxi1 and dlx3b/dlx4b act in independent pathways together with distinct phases of FGF signaling to promote otic placode induction and development. Developmental Dynamics 230:419–433, 2004. © 2004 Wiley‐Liss, Inc.