Miracle-dz/UniFAR-FTUs huggingface dataset:
COMPLEXITY, PLEIOTROPY, AND THE FITNESS EFFECT OF MUTATIONS

One of the assumptions underlying many theoretical predictions in evolutionary biology concerns the distribution of the fitness effect of mutations. Approximations to this distribution have been derived using various theoretical approaches, of which Fisher's geometrical model is among the most popular ones. Two key concepts in this model are complexity and pleiotropy. Recent studies have proposed different methods for estimating how complexity varies across species, but their results have been contradictory. Here, we show that contradictory results are to be expected when the assumption of universal pleiotropy is violated. We develop a model in which the two key parameters are the total number of traits and the mean number of traits affected by a single mutation. We derive approximations for the distribution of the fitness effect of mutations when populations are either well‐adapted or away from the optimum. We also consider drift load in a well‐adapted population and show that it is independent of the distribution of the fitness effect of mutations. We show that mutation accumulation experiments can only measure the effect of the mean number of traits affected by mutations, whereas drift load only provides information about the total number of traits. We discuss the plausibility of the model.
Wastewater from Mexico City contains organotin compounds and organotin-resistant bacteria

Abstract Organotin compounds are man-made chemicals used worldwide for diverse applications. These organometallic compounds may be released from antifouling paints, polyvinyl chloride and other materials into terrestrial and aquatic environments. Mexico City is a highly populated and industrialized city with many potential sources of environmental pollution. We evaluated the content of butyltins, triphenyltin and bacteria in water from various sites with different water quality in Mexico City, Pachuca City and two towns located between these two cities. Butyltins and/or triphenyltin were detected by gas chromatography and mass spectrometry analysis in samples from 4/4 sites containing wastewater, 1/2 sites containing reclaimed water and 2/5 sites holding accumulated water in open-air deposits. Neither organotin compounds nor bacteria were found in household water samples. However, 80 bacterial strains were isolated from partially treated or untreated wastewater and 72 of them were identified at the genus and species levels by the automated Mass Spectrometry Identification System VITEK MS. In vitro growth of 16 of 28 tested strains was not inhibited by 1 mM tributyltin or triphenyltin, indicating that many environmental bacteria are highly tolerant to organotin compounds.
Study on black gram (vignamungo)/ vegetable amaranthus (amaranthustricolor l.) intercropping in sandy regosol

Intercropping is the practice of growing more than one crop in the same field simultaneously and considered for increasing and stability of yield per unit. In this regard, a field experiment was conducted at Crop farm, Eastern University, Sri Lanka during yala 2014 to study the effect of black gram/vegetable amaranthus intercropping system in sandy regosol. The experiment was laid out in Randomized Complete Block Design with four replicates and five treatments; monocropping black gram (T1), monocropping vegetable amaranthus (T2), black gram intercropped with one row of vegetable amaranthus (T3), black gram intercropped with two rows of vegetable amaranthus (T4) and black gram intercropped with three rows of vegetable amaranthus (T5). All the agronomic practices for cultivation were done according to the department of agriculture, Sri Lanka recommendation. The measurements were recorded at the harvesting stage of vegetable amaranthus and harvesting stage of black gram at thirty and sixty days after sowing of crops, respectively. The results showed that black gram/vegetable amaranthus intercropping system had significant (p<0.05) influenced on tested parameters of vegetable amaranthus such as fresh leaf weight, fresh stem weight along with marketable yield. In which highest marketable yield was recorded in monocropping amaranthus followed by T3 and T4 and lowest in T5. In the meantime there were significant differences on tested parameters including plant height and total plant fresh weight of black gram compare to monocropping while yield per hectare of black gram did not change significantly by intercropped vegetable amaranthus (p<0.05). Therefore it can be concluded that vegetable amaranthus and black gram are compatible crops and can be recommended for intercropping in sandy regosol.
Ryanodine Receptor Blockade Reduces Amyloid-β Load and Memory Impairments in Tg2576 Mouse Model of Alzheimer Disease

In Alzheimer disease (AD), the perturbation of the endoplasmic reticulum (ER) calcium (Ca2+) homeostasis has been linked to presenilins, the catalytic core in γ-secretase complexes cleaving the amyloid precursor protein (APP), thereby generating amyloid-β (Aβ) peptides. Here we investigate whether APP contributes to ER Ca2+ homeostasis and whether ER Ca2+ could in turn influence Aβ production. We show that overexpression of wild-type human APP (APP695), or APP harboring the Swedish double mutation (APPswe) triggers increased ryanodine receptor (RyR) expression and enhances RyR-mediated ER Ca2+ release in SH-SY5Y neuroblastoma cells and in APPswe-expressing (Tg2576) mice. Interestingly, dantrolene-induced lowering of RyR-mediated Ca2+ release leads to the reduction of both intracellular and extracellular Aβ load in neuroblastoma cells as well as in primary cultured neurons derived from Tg2576 mice. This Aβ reduction can be accounted for by decreased Thr-668-dependent APP phosphorylation and β- and γ-secretases activities. Importantly, dantrolene diminishes Aβ load, reduces Aβ-related histological lesions, and slows down learning and memory deficits in Tg2576 mice. Overall, our data document a key role of RyR in Aβ production and learning and memory performances, and delineate RyR-mediated control of Ca2+ homeostasis as a physiological paradigm that could be targeted for innovative therapeutic approaches.
Sex Differences in Cardiovascular Mortality in Diabetics and Nondiabetic Subjects: A Population-Based Study (Italy)

The objective of this study is to assess the impact of diabetes on cardiovascular mortality, focusing on sex differences. The inhabitants of Reggio Emilia province on December 31, 2009, aged 20–84 were followed up for three years for mortality. The exposure was determined using Reggio Emilia diabetes register. The age-adjusted death rates were estimated as well as the incidence rate ratios using Poisson regression model. Interaction terms for diabetes and sex were tested by the Wald test. People with diabetes had an excess of mortality, compared with nondiabetic subjects (all cause: IRR = 1.68; 95%CI 1.60–1.78; CVD: IRR = 1.61; 95%CI 1.47–1.76; AMI: IRR = 1.59; 95%CI 1.27–1.99; renal causes: IRR = 1.71; 95%CI 1.22–2.38). The impact of diabetes is greater in females than males for all causes (P = 0.0321) and for CVD, IMA, and renal causes. Further studies are needed to investigate whether the difference in cardiovascular risk profile or in the quality of care delivered justifies the higher excess of mortality in females with diabetes compared to males.
Molecular and Clinical Studies in 138 Japanese Patients with Silver-Russell Syndrome

Background Recent studies have revealed relative frequency and characteristic phenotype of two major causative factors for Silver-Russell syndrome (SRS), i.e. epimutation of the H19-differentially methylated region (DMR) and uniparental maternal disomy 7 (upd(7)mat), as well as multilocus methylation abnormalities and positive correlation between methylation index and body and placental sizes in H19-DMR epimutation. Furthermore, rare genomic alterations have been found in a few of patients with idiopathic SRS. Here, we performed molecular and clinical findings in 138 Japanese SRS patients, and examined these matters. Methodology/Principal Findings We identified H19-DMR epimutation in cases 1–43 (group 1), upd(7)mat in cases 44–52 (group 2), and neither H19-DMR epimutation nor upd(7)mat in cases 53–138 (group 3). Multilocus analysis revealed hyper- or hypomethylated DMRs in 2.4% of examined DMRs in group 1; in particular, an extremely hypomethylated ARHI-DMR was identified in case 13. Oligonucleotide array comparative genomic hybridization identified a ∼3.86 Mb deletion at chromosome 17q24 in case 73. Epigenotype-phenotype analysis revealed that group 1 had more reduced birth length and weight, more preserved birth occipitofrontal circumference (OFC), more frequent body asymmetry and brachydactyly, and less frequent speech delay than group 2. The degree of placental hypoplasia was similar between the two groups. In group 1, the methylation index for the H19-DMR was positively correlated with birth length and weight, present height and weight, and placental weight, but with neither birth nor present OFC. Conclusions/Significance The results are grossly consistent with the previously reported data, although the frequency of epimutations is lower in the Japanese SRS patients than in the Western European SRS patients. Furthermore, the results provide useful information regarding placental hypoplasia in SRS, clinical phenotypes of the hypomethylated ARHI-DMR, and underlying causative factors for idiopathic SRS.
miR128-1 inhibits the growth of glioblastoma multiforme and glioma stem-like cells via targeting BMI1 and E2F3

MicroRNA128-1 (miR128-1), as a brain-specific miRNA, is downregulated in glioblastoma multiforme (GBM) and closely associated with the progression of GBM. However, the underlying molecular mechanism of the downregulation and its role in the regulation of tumorigenesis and anticancer drug resistance in GBM remains largely unknown. In the current study,we found that miR128-1 was downregulated in GBM and glioma stem-like cells (GSCs). Intriguingly, treatment with the DNA methylation inhibitors 5-Aza-CdR (Aza) and 4-phenylbutyric acid (PBA) resulted in miR128-1 upregulation in both GBM cells and GSCs. Either forced expression of miR128-1 or Aza/PBA treatment inhibited tumor cell proliferation, migration and invasion in vitro. Moreover, overexpression of miR128-1 inhibited the growth of transplant tumor in vivo. BMI1 and E2F3 were found to be direct targets of miR128-1 and downregulated by miR128-1 in vitro and in vivo. Our results revealed a mechanism of methylation that controls miR128-1 expression in GBM cells and GSCs and indicate miR128-1 could function as a tumor suppressor in GBM by negatively regulating tumor cell proliferation, invasion and self-renewal through direct targeting BMI1 and E2F3. Our findings suggest that DNA methylation inhibitors are potential agents for GBM treatment by upregulating miR-128-1.
Prediction of lymph node metastasis in patients with apparent early endometrial cancer

Objective The purpose of this study is to investigate the incidence of lymph node metastasis in early endometrial cancer patients and to evaluate preoperative clinicopathological factors predicting lymph node metastasis. Methods We identified 142 patients with endometrial cancer between January 2000 and February 2013. All patients demonstrated endometrioid adenocarcinoma with grade 1 or 2 on preoperative endometrial biopsy. Preoperative magnetic resonance imaging showed that tumors were confined to the uterine corpus with superficial myometrial invasion (less than 50%), and there were no lymph nodes enlargements. All patients had complete staging procedures and were surgically staged according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) staging system. Clinical and pathological data were obtained from medical records and statistically analyzed. Results Of the 142 patients, 127 patients (89.4%) presented with stage 1A, 8 (5.6%) with stage IB, 3 (2.1%) with stage II, and 4 (2.8%) with stage III disease. Three patients (2.1%) had lymph node metastasis-2 IIIC1 and 1 IIIC2 disease. Age, preoperative tumor grade, and myometrial invasion less than 50% on preoperative MRI were not associated with lymph node metastasis. A high preoperative serum CA-125 level (>35 IU/mL) was a statistically significant factor for predicting lymph node metastasis on univariate and multivariate analyses. Lymph node metastasis was only found in patients with preoperative grade 2 tumors or a high serum CA-125 level. Conclusion Preoperative tumor grade and serum CA-125 level can predict lymph node metastasis in apparent early endometrial cancer patients.
Estimating sand concentrations using ADCP‐based acoustic inversion in a large fluvial system characterized by bi‐modal suspended‐sediment distributions

Quantifying sediment flux within rivers is a challenge for many disciplines due, mainly, to difficulties inherent to traditional sediment sampling methods. These methods are operationally complex, high cost, and high risk. Additionally, the resulting data provide a low spatial and temporal resolution estimate of the total sediment flux, which has impeded advances in the understanding of the hydro‐geomorphic characteristics of rivers. Acoustic technologies have been recognized as a leading tool for increasing the resolution of sediment data by relating their echo intensity level measurements to suspended sediment. Further effort is required to robustly test and develop these techniques across a wide range of conditions found in natural river systems. This article aims to evaluate the application of acoustic inversion techniques using commercially available, down‐looking acoustic Doppler current profilers (ADCPs) in quantifying suspended sediment in a large sand bed river with varying bi‐modal particle size distributions, wash load and suspended‐sand ratios, and water stages. To achieve this objective, suspended sediment was physically sampled along the Paraná River, Argentina, under various hydro‐sedimentological regimes. Two ADCPs emitting different sound frequencies were used to simultaneously profile echo intensity level within the water column. Using the sonar equation, calibrations were determined between suspended‐sand concentrations and acoustic backscatter to solve the inverse problem. The study also analyzed the roles played by each term of the sonar equation, such as ADCP frequency, power supply, instrument constants, and particle size distributions typically found in sand bed rivers, on sediment attenuation and backscatter. Calibrations were successfully developed between corrected backscatter and suspended‐sand concentrations for all sites and ADCP frequencies, resulting in mean suspended‐sand concentration estimates within about 40% of the mean sampled concentrations. Noise values, calculated using the sonar equation and sediment sample characteristics, were fairly constant across evaluations, suggesting that they could be applied to other sand bed rivers. © 2018 John Wiley & Sons, Ltd.
Effect of Membrane Type for the Treatment of Organized Industrial Zone (OIZ) Wastewater with a Membrane Bioreactor (MBR): Batch Experiments

Organized industrial zone (OIZ) wastewater is a mixed wastewater that is contributed by both municipal use and from different industrial sectors. Since MBR has advantages over conventional treatment plants, membrane types and fouling become the most important parameters in the treatment of this kind of wastewater. In this study, six different membrane types were used to find the most suitable membrane with the least resistivity to fouling. Three different microfiltration (MF) and ultrafiltration (UF) membranes were operated to estimate their (i) membrane, (ii) cake, (iii) pore, and (iv) total resistances. The highest total resistance was observed in a polyethersulfone (PES) membrane (3.8 × 1010 m−1), while the lowest one was a UF polyvinylidene fluoride (PVDF) membrane with approximately 20 times lower resistance than the highest one. PVDF membranes showed lower total resistances than PES membranes. An MF or a 250 kDa UF membrane could be operated long-term in a membrane bioreactor with the least fouling potential.
Study of large bowel peristalsis.

Spontaneous colonic peristalsis inman occurs infrequently and,therefore, hasproved difficult to investigate; radiological studies havebeenlimited because ofthedangers ofirradiation, andobservations ofintraluminal pressure change havebeen mainly confined totherectumandlowersigmoid colon (Connell, 1961; Ritchie, Ardran, andTruelove, 1962). Progressive wavesofcontraction whichempty longsegments ofcolon can,however, bestimulated byanenema; suchactivity isusually called astrippingwaveandcanberegarded asaformofinduced peristalsis1 (Williams, 1967). Inthepresent study, bothspontaneous andinducedperistalsis ofthecolon havebeenstudied by balloon kymography andcomparisons havebeen madewithrectal activity. (Whenever possible, cineradiology hasbeenusedtoconfirm thefindings obtained withballoon kymography.) Thestudy was conducted intwoparts. balloons (5mm x 8mm),placed 5cmapart, connected byfinepolythene tubing totransducers, anda direct writing recorder, theunit being similar tothat described byAtkinson, Edwards, Honour, andRowlands (1957). Theunits wereintroduced into thecolon orrectum with asigmoidoscope withaslittle distension ofthebowel as possible. Access wasgained tothetransverse anddescending colon viawellestablished healthy colostomies, theunits being placed asfarfromthecolostomy opening aspossible. After introduction ofthepressure recording unit, thebowelwasleft undisturbed foratleast 30 minutes before astudy wasstarted. Thesensitivity ofthe recorder wasadjusted sothatachange ofpressure of 10cm ofwaterwasrepresented byadeflection ofapproximately 1cm.Incertain studies, thepressure changes werealsomonitored bywater-filled opentiptubes (internal diameter 1mm),inaddition totheballoon system. Bisacodyl wasusedeither assuppositories (10mg)or asasolution inethylene glycol. Oxyphenisatin wasdissolved inwater. Inseven patients, colonic peristalsis wasrecorded by simultaneous cineradiology andpressure recording. PARTI COLONICSTUDIES Spontaneous andstimulated peristalsis hasbeeninvestigated inpatients withwellestablished colostomies, accessbeing thereby gained totheright andleft colon. Bisacodyl andOxyphenisatin, drugs which areknownto increase thefrequency ofstripping waves(Schlegel, 1954; McLaren, King, andCopland, 1955, andWilliams, 1967), wereusedtostimulate colonic emptying. Afterestablishing thatthestripping waves excited bythese drugs wereperistaltic innatureandsimilar tothoseoccurring naturally, Bisacodyl wasused toinduce peristalsis, sothat further studies couldbe madeoftheunderlying mechanism. Theresults oftheseinvestigations are reported.
Life expectancy, mortality and elections: their association during elections in Malta

Introduction: While life expectancy has increased over the past thirty years, such increases have not been constant around election times in Malta. This study seeks to explore the relationship between the time of elections in Malta and specific mortality rates. Aim: To determine if there is an association between mortality and elections in Malta. Method: Yearly age specific death rates for all-cause mortality, mortality from ischaemic heart disease, cerebrovascular disease, other heart diseases and all circulatory diseases as well as suicides were calculated from the Malta National Mortality Register for the period between 1985 and 2013. Years when elections and referenda were held between 1985 and 2013 were obtained from the Electoral Commission.1 The years 1985 – 2013 were coded using dummy variables to categorise them into pre-election, post-election, election year or any other year. Data was analysed usingPoisson’s regression technique in STATA withMortality Rate Ratio (MRR) presented as the outcome measure. Results: A significant increase in overall mortality during election years resulted for circulatory disease MRR 1.058 (p<0.001; 95% CI 1.029-1.087), cerebrovascular disease MRR 1.09 (p=0.002; 95% CI 1.032-1.155) and other heart diseases MRR 1.36 (p<0.001; 95% CI 1.276-1.449). A significant increase was also noted during pre- election years in circulatory disease MRR 1.046 (p=0.002; 95% CI 1.017-1.075) and other heart diseases MRR 1.33 (p<0.001; 95% CI 1.248-1.422) and post-election years for cerebrovascular disease MRR 1.08 (p=0.009; 95% CI 1.020-1.150) and other heart diseases MRR 1.19 (p<0.001; 95% CI 1.108-1.273)) relative to the other years. Conclusion: This ecological study provides an indication that mortality patterns may be associated with the electoral cycle in Malta. Further research on individual physical and psychological responses to political events, particularly around election time is warranted.
Evoked and Spontaneous Purinergic Junctional Ca2+ Transients (jCaTs) in Rat Small Arteries

Confocal microscopy of fluo-4 fluorescence in pressurized rat mesenteric small arteries subjected to low-frequency electrical field stimulation revealed Ca2+ transients in perivascular nerves and novel, spatially localized Ca2+ transients in adjacent smooth muscle cells. These muscle Ca2+ transients occur with a very brief latency to the stimulus pulse (most <3 ms). They are wider (≈5 &mgr;m) and last longer (t1/2, 145 ms) than Ca2+ sparks. They are abolished by the purinergic receptor (P2X) antagonist suramin, but they are totally unaffected by the &agr;1-adrenoceptor antagonist prazosin or by capsaicin (which inhibits the function of perivascular sensory nerves). We conclude that these novel Ca2+ transients represent Ca2+ entering smooth muscle cells through P2X receptors activated by ATP released from sympathetic nerves, and we therefore call them “junctional Ca2+ transients” or jCaTs. As expected from spontaneous neurotransmitter release, jCaTs also occur spontaneously, with characteristics identical to evoked jCaTs. Visualization of sympathetic neurotransmission shows that purinergic components dominate at low frequencies of sympathetic nerve fiber activation.
ESAIM: Control, Optimisation and Calculus of Variations

We study an initial boundary-value problem for a wave equation with time-dependent sound speed. In the control problem, we wish to determine a sound-speed function which damps the vibration of the system. We consider the case where the sound speed can take on only two values, and propose a simple control law. We show that if the number of modes in the vibration is finite, and none of the eigenfrequencies are repeated, the proposed control law does lead to energy decay. We illustrate the rich behavior of this problem in numerical examples. Mathematics Subject Classification. 35K35, 35B37, 49J15, 49J20. Received January 14, 2002. Revised February 15, 2002.