Miracle-dz/UniFAR-FTUs huggingface dataset:
Model-driven engineering of N-linked glycosylation in Chinese Hamster Ovary cells.

Chinese Hamster Ovary (CHO) cells are used for industrial production of protein-based therapeutics (i.e. 'biologics'). Here we describe a method for combining systems-level kinetic models with a synthetic biology platform for multi-gene overexpression to rationally perturb N-linked glycosylation. Specifically, we sought to increase galactose incorporation on a secreted Immunoglobulin G (IgG) protein. We rationally design, build, and test a total of 23 transgenic cell pools that express single or three-gene glycoengineering cassettes comprising a total of 100 kilobases of engineered DNA sequence. Through iterative engineering and model refinement, we rationally increase the fraction of bi-galactosylated glycans five-fold from 11.9% to 61.9% and simultaneously decrease the glycan heterogeneity on the secreted IgG. Our approach allows for rapid hypothesis testing and identification of synergistic behavior from genetic perturbations by bridging systems and synthetic biology.
The Relationship Between Angular Osteologic and Radiographic Measurements of the Human Talus and Calcaneus.

BACKGROUND Radiographic imaging of the foot is commonly performed when medical evaluation is indicated. Angular measurements between bones may be assessed as part of the examination for trauma and foot biomechanics. However, angular relationships between surfaces of the physical bone as they compare with the bone's radiographic image has had limited investigation. METHODS For this study, 54 human feet from amputated limbs were imaged in standard radiographic views and skeletonized. Selected angular measurements were taken on each skeletonized talus and calcaneus and were compared with those taken from radiographic images using paired Student t tests and linear regression analysis. RESULTS Transverse plane measurements of the talus were not significantly different (P ≥ .05), associating strongly (r2 = 0.67-0.75; all P < .001). Most transverse and sagittal plane measurements of the calcaneus were not significantly different (P ≥ .05), with transverse plane measurements more strongly associated (r2 = 0.70-0.77; all P < .001) than sagittal plane measurements (r2 = 0.35-0.78; all P < .001). CONCLUSIONS Selected angular measurements of the talus and calcaneus taken from radiographic images can be compared quantitatively with the physical bone, demonstrating that angular measurements from radiographic images provide useful information concerning both of these bones. This knowledge can be applied to the understanding of the morphology of the calcaneus and talus as it relates to human foot biomechanics and should also be of use in the interpretation of the human fossil pedal record.
Murine Model of Maternal Immunization Demonstrates Protective Role for Antibodies that Mediate Antibody Dependent Cellular Cytotoxicity in Protecting Neonates from Herpes Simplex Virus Type 1 and Type 2.

BACKGROUND Neonatal herpes simplex virus (HSV) disease results in unacceptable morbidity and mortality. The primary humoral immune response to natural infection is neutralizing antibodies (Abs). However, Abs that activate Fc gama receptors (FcγRs) and mediate antibody-dependent cellular cytolysis (ADCC) may play a dominant role in protection. In adult mice, a single-cycle HSV candidate vaccine deleted in glycoprotein-D (ΔgD-2) that induces ADCC provided complete protection against HSV disease and prevented the establishment of latency. Passive transfer studies showed that Abs were sufficient for protection. The current study tested the hypothesis that maternal immunization with ΔgD-2 would protect neonates. METHODS C57Bl/6 female mice were vaccinated 3 weeks apart with ΔgD-2 and pups were challenged at different times postnatally with lethal doses of HSV-1 or HSV-2. Concentration and functionality of Abs and immune cells were assessed. RESULTS Maternal ΔgD-2 immunization provided significant protection and reduced viral dissemination following lethal challenge with HSV-1 or HSV-2. Protection correlated with Abs acquired transplacentally or from breastmilk that mediated ADCC. Protection was reduced when pups were challenged on Day 1 of life and this was associated with decreased ability of newborn cells to mediate antibody-dependent cell killing. CONCLUSIONS Abs mediating ADCC provide significant protection against neonatal HSV.
Effectiveness of Insulin Degludec in Thai Patients with Diabetes Mellitus: Real-World Evidence From a Specialized Diabetes Center

Background Insulin degludec, an ultra-long-acting insulin analogue, has been available in Thailand since October 2016. Although clinical trial results revealed less hypoglycemia, data from real-world settings is limited especially in Asian patients. This study aimed to evaluate prospectively the real-world effectiveness, safety, quality of life (QOL) and patient satisfaction with insulin degludec among Thai patients with diabetes mellitus (DM). Methods From October 2016 to September 2017, all patients who had started insulin degludec for at least 3 months were observed and evaluated at baseline, 3, 6, and 12 months. QOL was assessed using WHOQOL-BREF-THAI and level of satisfaction was measured by 7-point Likert scale. Glycemic fluctuation from paired iPro2 continuous glucose monitoring (CGM) obtained 4–6 weeks apart were also evaluated from a subset of patients with T1DM who switched from insulin glargine to insulin degludec. Results A total of 55 patients (T2DM 76.4%, females 54.5%, mean age 57.1±16.1 years, duration of diabetes 16.7±8.8 years, BMI 27.3±5.5 kg/m 2 , baseline A1C 9.3±2.3%, median duration of treatment 8 months) were included in the study. In T1DM patients (n=13), the overall mean A1C reduction at 12 months was 0.5% with minimal weight gain of 0.9 kgs at 12 months. In T2DM patients (n=42), the overall mean A1C reduction at 12 months was 0.8% with minimal weight loss of 0.4 kgs at 12 months. The proportion of T1DM patients who could achieve optimal glycemic control increased slightly from 14.3 to 18.2% but the proportion of T2DM patients who could achieve optimal glycemic control increased from 30.8 to 53.8%. Patient satisfaction showed a sustained improvement throughout the duration of study. In four T1DM patients who had paired CGM data, insulin degludec provided greater reductions in glycemic variability endpoints with increased time-in-range when compared with previous insulin glargine. Discussion Our data suggested that the effectiveness of insulin degludec was consistent with the results seen in clinical trials with lower risk of patients-reported hypoglycemia, and a significant improvement in glycemic control. Patients also reported higher treatment satisfaction. More long-term and cost-effectiveness data are needed to establish the role of this ultra-long-acting insulin in real-world settings.
Long-Term Glucose Forecasting Using a Physiological Model and Deconvolution of the Continuous Glucose Monitoring Signal

(1) Objective: Blood glucose forecasting in type 1 diabetes (T1D) management is a maturing field with numerous algorithms being published and a few of them having reached the commercialisation stage. However, accurate long-term glucose predictions (e.g., >60 min), which are usually needed in applications such as precision insulin dosing (e.g., an artificial pancreas), still remain a challenge. In this paper, we present a novel glucose forecasting algorithm that is well-suited for long-term prediction horizons. The proposed algorithm is currently being used as the core component of a modular safety system for an insulin dose recommender developed within the EU-funded PEPPER (Patient Empowerment through Predictive PERsonalised decision support) project. (2) Methods: The proposed blood glucose forecasting algorithm is based on a compartmental composite model of glucose–insulin dynamics, which uses a deconvolution technique applied to the continuous glucose monitoring (CGM) signal for state estimation. In addition to commonly employed inputs by glucose forecasting methods (i.e., CGM data, insulin, carbohydrates), the proposed algorithm allows the optional input of meal absorption information to enhance prediction accuracy. Clinical data corresponding to 10 adult subjects with T1D were used for evaluation purposes. In addition, in silico data obtained with a modified version of the UVa-Padova simulator was used to further evaluate the impact of accounting for meal absorption information on prediction accuracy. Finally, a comparison with two well-established glucose forecasting algorithms, the autoregressive exogenous (ARX) model and the latent variable-based statistical (LVX) model, was carried out. (3) Results: For prediction horizons beyond 60 min, the performance of the proposed physiological model-based (PM) algorithm is superior to that of the LVX and ARX algorithms. When comparing the performance of PM against the secondly ranked method (ARX) on a 120 min prediction horizon, the percentage improvement on prediction accuracy measured with the root mean square error, A-region of error grid analysis (EGA), and hypoglycaemia prediction calculated by the Matthews correlation coefficient, was 18.8%, 17.9%, and 80.9%, respectively. Although showing a trend towards improvement, the addition of meal absorption information did not provide clinically significant improvements. (4) Conclusion: The proposed glucose forecasting algorithm is potentially well-suited for T1D management applications which require long-term glucose predictions.
Survey of Leptospira spp. and Brucella abortus in Free-Ranging Armadillos from Pantanal, Brazil

Abstract: Out of the 20 recognized species of armadillos in the world, 11 are found in Brazil, and five of them are found in Pantanal, one of the world's largest wetlands. Beef cattle (Bos taurus) farming is the main economic activity in this region, which promotes intense wildlife-livestock contact and increases the likelihood of pathogen exposure, including to agents with zoonotic and economic relevance. Previous studies demonstrated that several wildlife species in Pantanal have been exposed to Brucella abortus and Leptospira spp. ; however, little is known regarding the exposure and/or prevalence of zoonotic pathogens in armadillos. We used conventional PCR, the rose Bengal test (RBT), and the microscopic agglutination test (MAT) to investigate the exposure to and infection by Brucella spp. and Leptospira spp. using blood samples from four species of armadillos: nine-banded armadillo (Dasypus novemcinctus, n=2), southern naked-tailed armadillo (Cabassous unicinctus, n=8), yellow armadillo (Euphractus sexcinctus, n=16), and giant armadillo (Priodontes maximus, n=22), captured in Nhecolândia, Pantanal, Brazil. Samples were PCR- and RBT-negative for Brucella spp. infection and exposure. However, MAT revealed a Leptospira spp. seroprevalence of 31% (5/16; 95% confidence interval [CI]=0.11–0.58) in yellow armadillo and 18% (4/22; 95% CI=0.05–0.40) in giant armadillo specimens to serogroups Autumnalis, Cynopteri, and Pomona, with titers ranging from 200 to 1,600. Our results contribute to the understanding of zoonotic pathogens in armadillos in Pantanal and reinforce the importance of wildlife health surveillance in this area.
Personalized models of personality disorders: using a temporal network method to understand symptomatology and daily functioning in a clinical sample

Abstract Background An ongoing challenge in understanding and treating personality disorders (PDs) is a significant heterogeneity in disorder expression, stemming from variability in underlying dynamic processes. These processes are commonly discussed in clinical settings, but are rarely empirically studied due to their personalized, temporal nature. The goal of the current study was to combine intensive longitudinal data collection with person-specific temporal network models to produce individualized symptom-level structures of personality pathology. These structures were then linked to traditional PD diagnoses and stress (to index daily functioning). Methods Using about 100 daily assessments of internalizing and externalizing domains underlying PDs (i.e. negative affect, detachment, impulsivity, hostility), a temporal network mapping approach (i.e. group iterative multiple model estimation) was used to create person-specific networks of the temporal relations among domains for 91 individuals (62.6% female) with a PD. Network characteristics were then associated with traditional PD symptomatology (controlling for mean domain levels) and with daily variation in clinically-relevant phenomena (i.e. stress). Results Features of the person-specific networks predicted paranoid, borderline, narcissistic, and obsessive-PD symptom counts above average levels of the domains, in ways that align with clinical conceptualizations. They also predicted between-person variation in stress across days. Conclusions Relations among behavioral domains thought to underlie heterogeneity in PDs were indeed associated with traditional diagnostic constructs and with daily functioning (i.e. stress) in person-specific networks. Findings highlight the importance of leveraging data and models that capture person-specific, dynamic processes, and suggest that person-specific networks may have implications for precision medicine.
Kresoxim-methyl and famoxadone as activators of toxigenic potential of Aspergillus carbonarius

ABSTRACT Ochratoxin A (OTA) is a secondary metabolite produced by filamentous fungi species belonging to the genera Penicillium and Aspergillus. The contamination of grapes by ochratoxigenic species occurs worldwide in regions of tropical and temperate climates. Better control of fungal growth is achieved through good cultural practice and proper selection of fungicides. Kresoxim-methyl and famoxadone are the most common fungicides used in vineyards. This study aimed at analysing the OTA production and toxigenic potential of Aspergillus carbonarius under fungicide treatment with famoxadone and kresoxim-methyl. The growth rate of A. carbonarius was evaluated by measuring the glucosamine content and the diameter of the fungal colonies. OTA production was quantified by HPLC analysis. The treatment with fungicides, kresoxim-methyl and famoxadone, significantly reduced the fungal growth, by 76% and 60%, respectively. However, the mycotoxin production was greater in the fungicide-treated groups than the control group, showing that even though the fungicides were effective in controlling fungal growth, they were ineffective against mycotoxin production. Graphical Abstract
Bioguided Purification of Active Compounds from Leaves of Anadenanthera colubrina var. cebil (Griseb.) Altschul

Anadenanthera colubrina var cebil (Griseb.) Altschul is a medicinal plant found throughout the Brazilian semi-arid area. This work performed a bioguided purification of active substances present in ethyl acetate extract from A. colubrina leaves. The anti-Staphylococcus aureus and antioxidant actions were used as markers of bioactivity. The extract was subjected to flash chromatography resulting in five fractions (F1, F2, F3, F4, and F5). The fractions F2 and F4 presented the highest antimicrobial action, with a dose able to inhibit 50% of bacteria growth (IN50) of 19.53 μg/mL for S. aureus UFPEDA 02; whereas F4 showed higher inhibitory action towards DPPH radical (2,2-diphenyl-1-picryl-hydrazyl-hydrate) [dose able to inhibit 50% of the radical (IC50) = 133 ± 9 μg/mL]. F2 and F4 were then subjected to preparative high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR), resulting in the identification of p-hydroxybenzoic acid and hyperoside as the major compounds in F2 and F4, respectively. Hyperoside and p-hydroxybenzoic acid presented IN50 values of 250 μg/mL and 500 μg/mL against S. aureus UFPEDA 02, respectively. However, the hyperoside had an IN50 of 62.5 μg/mL against S. aureus UFPEDA 705, a clinical isolate with multidrug resistant phenotype. Among the purified compounds, the proanthocyanidins obtained from F2 exhibited the higher antioxidant potentials. Taken together, these results highlight the potential of A. colubrina leaves as an alternative source of biomolecules of interest for the pharmaceutical, food, and cosmetic industries.
Dietary Protein, Exercise, and Frailty Domains

Increasing awareness of the impact of frailty on elderly people resulted in research focusing on factors that contribute to the development and persistence of frailty including nutrition and physical activity. Most effort so far has been spent on understanding the association between protein intake and the physical domain of frailty. Far less is known for other domains of frailty: cognition, mood, social health and comorbidity. Therefore, in the present narrative review, we elaborate on the evidence currently known on the association between protein and exercise as well as the broader concept of frailty. Most, but not all, identified studies concluded that low protein intake is associated with a higher prevalence and incidence of physical frailty. Far less is known on the broader concept of frailty. The few studies that do look into this association find a clear beneficial effect of physical activity but no conclusions regarding protein intake can be made yet. Similar, for other important aspects of frailty including mood, cognition, and comorbidity, the number of studies are limited and results are inconclusive. Future studies need to focus on the relation between dietary protein and the broader concept of frailty and should also consider the protein source, amount and timing.
Predicting functional responses in agro-ecosystems from animal movement data to improve management of invasive pests.

Functional responses describe how changing resource availability affects consumer resource use, thus providing a mechanistic approach to prediction of the invasibility and potential damage of invasive alien species (IAS). However, functional responses can be context-dependent, varying with resource characteristics and availability, consumer attributes, and environmental variables. Identifying context-dependencies can allow invasion and damage risk to be predicted across different ecoregions. Understanding how ecological factors shape the functional response in agro-ecosystems can improve predictions of hotspots of highest impact and inform strategies to mitigate damage across locations with varying crop types and availability. We linked heterogeneous movement data across different agro-ecosystems to predict ecologically-driven variability in the functional responses. We applied our approach to wild pigs (Sus scrofa), one of the most successful and detrimental IAS worldwide where agricultural resource depredation is an important driver of spread and establishment. We used continental-scale movement data within agro-ecosystems to quantify the functional response of agricultural resources relative to availability of crops and natural forage. We hypothesized that wild pigs would selectively use crops more often when natural forage resources were low. We also examined how individual attributes such as sex, crop type, and resource stimulus such as distance to crops altered the magnitude of the functional response. There was a strong agricultural functional response where crop use was an accelerating function of crop availability at low density (Type III) and was highly context-dependent. As hypothesized, there was a reduced response of crop use with increasing crop availability when non-agricultural resources were more available, emphasizing that crop damage levels are likely to be highly heterogeneous depending on surrounding natural resources and temporal availability of crops. We found significant effects of crop type and sex - with males spending 20% more time and visiting crops 58% more often than females, and both sexes showing different functional responses depending on crop type. Our application demonstrates how commonly collected animal movement data can be used to understand context-dependencies in resource use to improve our understanding of pest foraging behavior, with implications for prioritizing spatio-temporal hotspots of potential economic loss in agro-ecosystems.
Approaches to denote treatment outcome: Clinical significance and clinical global impression compared

The authors of a previous study proposed a statistically based approach to denote treatment outcome, translating pretest and posttest scores into clinically relevant categories, such as recovery and reliable improvement. We assessed the convergent validity of the Jacobson–Truax (JT) approach, using T‐score based cutoff values, with ratings by an independent evaluator.
PIEZO1 and TRPV4, which Are Distinct Mechano-Sensors in the Osteoblastic MC3T3-E1 Cells, Modify Cell-Proliferation

Mechanical-loading and unloading can modify osteoblast functioning. Ca2+ signaling is one of the earliest events in osteoblasts to induce a mechanical stimulus, thereby demonstrating the importance of the underlying mechanical sensors for the sensation. Here, we examined the mechano-sensitive channels PIEZO1 and TRPV4 were involved in the process of mechano-sensation in the osteoblastic MC3T3-E1 cells. The analysis of mRNA expression revealed a high expression of Piezo1 and Trpv4 in these cells. We also found that a PIEZO1 agonist, Yoda1, induced Ca2+ response and activated cationic currents in these cells. Ca2+ response was elicited when mechanical stimulation (MS), with shear stress, was induced by fluid flow in the MC3T3-E1 cells. Gene knockdown of Piezo1 in the MC3T3-E1 cells, by transfection with siPiezo1, inhibited the Yoda1-induced response, but failed to inhibit the MS-induced response. When MC3T3-E1 cells were transfected with siTrpv4, the MS-induced response was abolished and Yoda1 response was attenuated. Moreover, the MS-induced response was inhibited by a TRPV4 antagonist HC-067047 (HC). Yoda1 response was also inhibited by HC in MC3T3-E1 cells and HEK cells, expressing both PIEZO1 and TRPV4. Meanwhile, the activation of PIEZO1 and TRPV4 reduced the proliferation of MC3T3-E1, which was reversed by knockdown of PIEZO1, and TRPV4, respectively. In conclusion, TRPV4 and PIEZO1 are distinct mechano-sensors in the MC3T3-E1 cells. However, PIEZO1 and TRPV4 modify the proliferation of these cells, implying that PIEZO1 and TRPV4 may be functional in the osteoblastic mechano-transduction. Notably, it is also found that Yoda1 can induce TRPV4-dependent Ca2+ response, when both PIEZO1 and TRPV4 are highly expressed.
Dual regulation of xylem formation by an auxin-mediated PaC3H17-PaMYB199 module in Populus.

• Wood (secondary xylem) formation in tree species is dependent on auxin-mediated vascular cambium activity in stems. However, the complex regulatory networks underlying xylem formation remain elusive. • Xylem development in Populus was characterized based on microscopic observations of stem sections in transgenic plants. Transcriptomic, quantitative real time PCR (qRT-PCR), chromatin immunoprecipitation (ChIP)-PCR and EMSA analyses were conducted to identify target genes involved in xylem development. Yeast two-hybrid (Y2H), pull-down, bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (IP) assays were used to validate protein-protein interactions. • PaC3H17 and its target PaMYB199 were found to be predominantly expressed in the vascular cambium and developing secondary xylem in Populus stems, and play opposite roles in controlling cambial cell proliferation and secondary cell wall (SCW) thickening through an overlapping pathway. Further, PaC3H17 interacts with PaMYB199 to form a complex, attenuating PaMYB199-driven suppression of its xylem targets. Exogenous auxin application enhances the dual control of the PaC3H17-PaMYB199 module during cambium division, thereby promoting SCW deposition. • Dual regulation of xylem formation by an auxin-mediated PaC3H17-PaMYB199 module represents a novel regulatory mechanism in Populus, increasing our understanding of the regulatory networks involved in wood formation.