Miracle-dz/UniFAR-FTUs huggingface dataset:
SUMOylation Targets Adeno-associated Virus Capsids but Mainly Restricts Transduction by Cellular Mechanisms

Host factors within the cell are the major mode of restriction of adeno-associated virus (AAV) and keep it from fulfilling its maximum potential as a gene therapy vector. A better understanding of the intricacies of restriction would enable the engineering of better vectors. Via a genome-wide short interfering RNA screen, we identified that proteins of the small ubiquitin-like modifier (SUMO) pathway play an important role in AAV restriction. In this study, we investigate whether this restriction is targeted to the AAV directly or indirectly through host cell factors. The results indicate that both targets act in concert to restrict AAV. ABSTRACT Adeno-associated virus (AAV) has proven to be a promising candidate for gene therapy due to its nonpathogenic nature, ease of production, and broad tissue tropism. However, its transduction capabilities are not optimal due to the interaction with various host factors within the cell. In a previous study, we identified members of the small ubiquitin-like modifier (SUMO) pathway as significant restriction factors in AAV gene transduction. In the present study, we explored the scope of this restriction by focusing on the AAV capsid and host cell proteins as targets. We show that during vector production, the capsid protein VP2 becomes SUMOylated, as indicated by deletion and point mutations of VP2 or the obstruction of its N terminus via the addition of a tag. We observed that SUMOylated AAV capsids display higher stability than non-SUMOylated capsids. Prevention of capsid SUMOylation by VP2 mutations did not abolish transduction restriction by SUMOylation; however, it reduced activation of gene transduction by shutdown of the cellular SUMOylation pathway. This indicates a link between capsid SUMOylation and SUMOylation of cellular proteins in restricting gene transduction. Infection with AAV triggers general SUMOylation of cellular proteins. In particular, the DAXX protein, a putative host cell restriction factor that can become SUMOylated, is able to restrict AAV gene transduction by reducing the intracellular accumulation of AAV vectors. We also observe that the coexpression of a SUMOylation inhibitor with an AAV2 reporter gene vector increased gene transduction significantly. IMPORTANCE Host factors within the cell are the major mode of restriction of adeno-associated virus (AAV) and keep it from fulfilling its maximum potential as a gene therapy vector. A better understanding of the intricacies of restriction would enable the engineering of better vectors. Via a genome-wide short interfering RNA screen, we identified that proteins of the small ubiquitin-like modifier (SUMO) pathway play an important role in AAV restriction. In this study, we investigate whether this restriction is targeted to the AAV directly or indirectly through host cell factors. The results indicate that both targets act in concert to restrict AAV.
Bayesian analysis in expert systems

We review recent developments in applying Bayesian probabilistic and statistical ideas to expert systems. Using a real, moderately complex, medical example we illustrate how qualitative and quantitative knowledge can be represented within a directed graphical model, generally known as a belief network in this context. Exact probabilistic inference on individual cases is possible using a general propagation procedure. When data on a series of cases are available, Bayesian statistical techniques can be used for updating the original subjective quantitative inputs, and we present a sets of diagnostics for identifying conflicts between the data and the prior specification. A model comparison procedure is explored, and a number of links made with mainstream statistical methods. Details are given on the use of Dirichlet prior distributions for learning about parameters and the process of transforming the original graphical model to a junction tree as the basis for efficient computation.
Conceptual mechanical design of antagonistic variable stiffness joint based on equivalent quadratic torsion spring

The variable stiffness joint is a kind of flexible actuator with variable stiffness characteristics suitable for physical human–robot interaction applications. In the existing variable stiffness joints, the antagonistic variable stiffness joint has the advantages of simple implementation of variable stiffness mechanism and easy modular design of the nonlinear elastic element. The variable stiffness characteristics of antagonistic variable stiffness joints are realized by the antagonistic actuation of two nonlinear springs. A novel design scheme of the equivalent nonlinear torsion spring with compact structure, large angular displacement range, and desired stiffness characteristics is presented in this article. The design calculation for the equivalent quadratic torsion spring is given as an example, and the actuation characteristics of the antagonistic variable stiffness joint based on the equivalent quadratic torsion spring are illustrated. Based on the design idea of constructing the antagonistic variable stiffness joint with compact structure and high compliance, as well as the different design requirements of the joints at different positions of the multi–degrees of freedom robot arm, nine types of mechanical schemes of antagonistic variable stiffness joint with the open design concept are proposed in this article. Finally, the conceptual joint configuration schemes of the robot arm based on the antagonistic variable stiffness joint show the application scheme of the designed antagonistic variable stiffness joint in the multi–degrees of freedom robot.
Identificação de polimorfismos em região do cromossomo 3 da galinha associado ao desempenho de deposição de gordura

Identification of polymorphisms in a region of chicken chromosome 3 associated with the performance of the fat deposition Eighteen chickens from a parental generation used in a reciprocal cross with broiler and layer lines were sequenced by new generation technology with an average of 10fold coverage. The DNA sequencing was performed by Illumina next generation platform. The genetic variants discovery was performed in a quantitative trait loci (QTL) region which was previously associated with abdominal fat weight and percentage in chicken chromosome 3 (GGA3) between the microsatellite markers LEI0161 and ADL0371 (33,595,706-42,632,651 bp). SAMtools software was used to detect 136,054 unique SNPs and 15,496 unique INDELs for the 18 chickens, and after quality filtration 92,518 unique SNPs and 9,298 unique INDELs were retained. One list of 77 genes was analised and genes related to lipid metabolism were searched. Variants located in coding region (386 SNPs and 15 INDELs) were identified and associated with important metabolic pathways. Loss of functional variants in the genes LOC771163, EGLN1, GNPAT, FAM120B, THBS2 and GGPS1 may be responsible for the QTL associated with fat deposition in chicken.
Forage selection of sable antelope in Pilanesberg Game Reserve, South Africa

Concern about the habitat requirements of sable antelope (Hippotragus niger) has increased due to population declines shown in some protected areas. Our study was prompted by the lack of initial increase by the sable antelope introduced into the Pilanesberg Game Reserve in North West Province, South Africa; 67 animals released between 1979 and 1983 had only grown to approximately 70 animals by 1988. We recorded forage selection by sable antelope within the context of the landscape units favoured in different seasons. Chrysopogon serrulatus, Panicum maximum, Heteropogon contortus, and Themeda triandra contributed most to the diet of sable antelope. Faecal crude protein content did not drop below 6.6% of dry matter during the dry season, with use of burnt grassland by sable contributing to an elevation in faecal protein levels at the beginning of the wet season. The sable population had increased to 127 animals by 1991, suggesting that the earlier lack of population growth had been due to below-average rainfall, lack of burns providing green regrowth during the dry season, or a delay in learning to exploit available forage resources efficiently.
Seasonal, Spatial, and Postharvest Variability in the Survival of Repeatedly Discarded Saucer Scallops in Shark Bay, Western Australia

ABSTRACT Saucer scallops, Amusium balloti, are targeted by Shark Bay prawn and scallop trawl fisheries where regulatory discarding can occur during summer and winter months that may adversely impact the recruitment of this resource. Survival of repeatedly discarded saucer scallops was thus estimated for the Shark Bay trawl fisheries using short-term tag—recapture experiments under various fishing and environmental conditions. Estimates of apparent survival of discarded scallops was significantly higher during the postspawning winter period (>90%) than during the prespawning summer period (20–90%), but no differences in survival between fishing grounds or between postcapture treatment groups (air exposed vs. those kept in a holding tank) were observed. This suggests that thermal stress from large differences in seasonal temperatures was more critical to scallop survival than differences in scallop reproductive condition. Thus past (pre-2004) management regulations that imposed regulatory discarding during the warmer summer months would have incurred high discard mortalities. Under current management measures, however, regulatory discarding is predominantly during winter months, when scallops exhibit higher resilience to trawlinduced stress. The results support the current management strategy of fishing during the warmer prespawning summer months when the amount of discards is less. Regulatory discarding during the winter spawning period may generate a higher discard rate but the associated discard mortality is at its minimum.
The effect of diapause, cold acclimation and ice-nucleating bacteria on the cold-hardiness of Plodia interpunctella

Laboratory tests showed that over 50 d at 0°C, over 10 d at -5°C or 1 d at -10°C were required to control non cold-acclimated 5 th instar larvae of Plodia interpunctella (Lepidoptera: Prylidae) (Indian meal moth). To control the most cold-hardy stage, diapausing cold-acclimated 5 th instar larvae over 14 d at -10°C or 1 d at -15°C were required. A freeze-out of a single floor of a seed warehouse was carried out from 23 December 1993 until 2 January 1994 by shutting off the heat and opening the windows. The lowest temperatures achieved varied with the size and location of the seed bulk. Seed packets, that had a few grams of seed, reached -17°C, whereas, the middle of a bag stack with forty 50-kg bags of maize only reached -9°C. By the end of the 10-d freeze-out all non cold-acclimated P. interpunctella larvae were killed in the packets, 90% of the diapausing cold-acclimated larvae were killed in a single bag and 65% were killed middle of the stack. Mortality in the freeze-out was higher than we would have predicted from the laboratory data. The supercooling points (temperature at which freezing begins) of the P. interpunctella larvae range from -7°C for the non-diapausing non-acclimated to -13°C for the diapausing acclimated.
The effects of prolonged fasting of the body composition and reproductive success of female polar bears (Ursus maritimus)

1. In total, pregnant Polar Bears that enter maternity dens in late summer/autumn may fast for up to 8 months in addition to meeting the nutritional demands of gestation and lactation. We quantified the nutritional costs of this prolonged 'reproductive fast' and examined the effect of variation in maternal body condition on reproductive success. 2. Prior to entering dens, pregnant females were obese, containing as much as 1 kg of fat/kg of lean body mass (LBM). Among bears, LBM increased with body fat mass. This accumulation of LBM may be necessary in order to transport the large fat stores required for fasting, and may also provide a pool of protein essential for reproduction. 3. While fasting, bears lost 43% of body mass. Of the total energy expended on maintenance and reproduction, 93% was drawn from fat stores. This dependency upon fat conforms to the pattern of nutrient metabolism seen among other species adapted to prolonged fasting. Maternal metabolic rate was less than the predicted resting metabolic rate which illustrates the effectiveness of denning as an energy-conserving strategy. 4. Body fat was critically important for reproductive success. In particular, offspring body weight was very strongly related to the size of maternal fat stores before denning. Fatter bears produced heavier cubs which would be more likely to survive. 5. Among bears, pre-denning body condition was positively associated with age. Within the observed range (4-21 years), age-specific reproductive success should thus be highest among older bears. Such an effect could arise if : (1) the body condition of individual bears tends to improve with age and experience or (2) animals of poorer quality and condition die at a younger age.
BLOOD VOLUMES

Background The volume of blood collected for research purposes from most mammals is generally not a problem. However, repeated blood sample collection in mice, rats, hamsters, guinea pigs, small cats, birds and some fish can be problematic because of their small body size. In order to prevent anemia, electrolyte imbalance, hypovolemic shock or other complications, the following guidelines should be followed:
Editorial

research programme. The Journal has been particularly receptive to studies which compare organizational life in different societies. This is also part of the particularly European identity of O. S. , constituted when scholars began to question the wisdom of the universalistic organizational mainstream of the time. This had neglected the differences in organization between societies, and it was challenged by findings that demonstrated the importance of locally specific organization practice and theory. To be sure, we have been alerted to the growing internationalization of organizational activity; but we have also become increasingly aware that,
Inter-Tumor Heterogeneity—Melanomas Respond Differently to GM-CSF-Mediated Activation

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. Whereas cells of one melanoma acquired pro metastatic features following exposure to GM-CSF, cells from another melanoma either did not respond or became less malignant. We propose that inter-melanoma heterogeneity as manifested by differential responses of melanoma cells (and perhaps also of other tumor) to GM-CSF may be developed into a predictive marker providing a tool to segregate melanoma patients who will benefit from GM-CSF therapy from those who will not.
Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study

Abstract Background: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. Methods: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. Results: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004). Conclusions: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. Policy Significance Statement: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination.
Effect of differently coated silver nanoparticles on hemostasis

Abstract With the emergence of nano-enabled medical devices (MDs) for the use in human medicine, ensuring their safety becomes of crucial importance. Hemocompatibility is one of the major criteria for approval of all MDs in contact with blood (e.g. vascular grafts, stents, or valves). Silver nanoparticles (AgNPs) are among the most used nanomaterials for MDs due to their biocidal activity; however, detailed knowledge on their hemostatic effects is still lacking. This study aimed to evaluate comprehensively AgNPs effects on hemostasis in human blood by exploiting combination of affordable and clinically relevant techniques. Differently stabilized AgNPs were prepared using sodium bis(2-ethylhexyl)sulphosuccinate (AOT), polyvinylpyrrolidone (PVP), poly-L-lysine (PLL), and bovine serum albumin (BSA) as coating agents. They were tested for hemolytic activity, induction of platelet aggregation, plasmatic coagulation, thrombin generation, and hemostasis in whole blood. All AgNPs were found to cause dose-dependent hemolysis. The BSA-, AOT-, and PVP-coated AgNPs delayed plasmatic coagulation, while only PLL-AgNPs inhibited plasmatic coagulation, induced platelet activation, and interfered with hemostasis by delaying clotting time and decreasing clot firmness in whole blood. Obtained results demonstrate that a combination of different techniques should be used for reliable assessment of AgNPs hemostatic effects highlighting the need for a standardized approach in sampling and experimental protocols.
Nematicidal Activity of Some Biocontrol Agents against Root-Knot Nematodes In-Vitro.

Nineteen rhizospheric bacterial isolates and three biocontrol agents (Serratia marcescens, Pseudomonas fluorescens and Bacillus thuringiensis BT14) were evaluated against root-knot nematodes (Meloidogyne incognita). The obtained data revealed that, five bacterial isolates (B38, B39, B78, B91 and B103) and S. marcescens strain were the most effective bacteria against the J2s of M. incognita whereas, these bacteria achieved the highest mortality percentages by more than 94%. Results also indicated that isolate B38 showed the highest mortality percentage of nematicidal volatile activity by 70.3%, followed by S. marcescens and isolate B103. Moreover, isolate B38 succeeded to record maximum hydrolysis zone values of gelatinase, protease and chitinase (4.27, 5.55 and 4.33 cm, respectively). The most potent isolates for bioagent production were chosen and these isolates were identified as Pseudomonas fluorescens B103 and Bacillus subtilis B38. In addition, poly agar medium recorded the highest values for nematicidal activities by B. subtilis B38, Ps. fluorescens B103 and S. marcescens, while Emerson's agar medium lowest one. Bacterial cells suspension showed more efficient mortality on nematode M. incognita compared with their cultural filtrates. The highest mortality percentages were recorded at dilutions 10
Five Degree Internal Conical Connection and Marginal Bone Stability around Subcrestal Implants: A Retrospective Analysis

Background: There is limited information on the effect of the connection between subcrestally placed implants and abutments on marginal bone levels. The aim of the present retrospective study was to evaluate marginal bone levels after definitive prosthesis delivery around implants with an internal 5° conical connection placed in a subcrestal position. Materials and methods: Patients treated with fixed prostheses supported by implants placed at a subcrestal level between 2012 and 2018 were recalled for a follow-up examination. All implants had 5° internal conical connection with platform switching. Radiographic marginal bone level (MBL) was measured. MBL change between prosthetic delivery (t0) and follow-up examination (t1) was calculated. A multiple regression model was performed to identify the most significant predictors on MBL change. Results: Ninety-three patients and 410 implants, with a mean follow-up of 2.72 ± 1.31 years, were examined. Mean MBL was −1.09 ± 0.65 mm and −1.00 ± 0.37 mm at t0 and t1, respectively, with a mean bone remodeling of 0.09 ± 0.68 mm. An implant’s vertical position in relation to the bone crest, the year of follow up and the presence of type-2 controlled diabetes were demonstrated to be influencing factors for MBL modifications. Conclusions: Subcrestally placed implants with platform switching and internal conical connection maintained stable bone levels over a mean follow-up of more than 2 years. How a tight internal conical connection between abutment and implant may contribute to this clinical evidence should be more deeply investigated. MBL variations seem to be mostly influenced by an implant’s vertical position and presence of type-2 controlled diabetes.