Exploring the potential of Lactocaseibacillus rhamnosus PMC203 in inducing autophagy to reduce the burden of Mycobacterium tuberculosis.

Mycobacterium tuberculosis, a lethal pathogen in human history, causes millions of deaths annually, which demands the development of new concepts of drugs. Considering this fact, earlier research has explored the anti-tuberculosis potential of a probiotic strain, Lactocaseibacillus rhamnosus PMC203, leading to a subsequent focus on the molecular mechanism involved in its effect, particularly on autophagy. In this current study, immunoblotting-based assay exhibited a remarkable expression of autophagy marker LC3-II in the PMC203 treated group compared to an untreated group. A remarkable degradation of p62 was also noticed within treated cells compared to control. Furthermore, the immunofluorescence-based assay showed significant fold change in fluorescence intensity for alexa-647-LC3 and alexa-488-LC3, whereas p62 was degraded noticeably. Moreover, lysosomal biogenesis generation was elevated significantly in terms of LAMP1 and acidic vesicular organelles. As a result, PMC203-induced autophagy played a vital role in reducing M. tuberculosis burden within the macrophages in treated groups compared to untreated group. A colony -forming unit assay also revealed a significant reduction in M. tuberculosis in the treated cells over time. Additionally, the candidate strain significantly upregulated the expression of autophagy induction and lysosomal biogenesis genes. Together, these results could enrich our current knowledge of probiotics-mediated autophagy in tuberculosis and suggest its implications for innovatively managing tuberculosis.

Correlation analysis between potential hepatotoxicity and ingredient content of polygoni multiflori caulis.

Polygoni Multiflori Caulis (PMC) is commonly used in clinical practice. While the adverse reactions of Polygoni Multiflori Radix (RPM) are well-known, the potential adverse reactions of PMC are often neglected. This article aims to clarify the relationship between hepatotoxic components in PMC and its various producing areas. This study provides a qualitative and quantitative analysis of PMC from various regions, which can serve as a basis for safe usage.

The interdependent transport of yeast vacuole Ca2+ and H+ and the role of phosphatidylinositol 3,5-bisphosphate.

Yeast vacuoles are acidified by the v-type H+-ATPase (V-ATPase) that is comprised of the membrane embedded VO complex and the soluble cytoplasmic V1 complex. The assembly of the V1-VO holoenzyme on the vacuole is stabilized in part through interactions between the VO a-subunit ortholog Vph1 and the lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). PI(3,5)P2 also affects vacuolar Ca2+ release through the channel Yvc1 and uptake through the Ca2+ pump Pmc1. Here, we asked if H+ and Ca2+ transport activities were connected through PI(3,5)P2. We found that overproduction of PI(3,5)P2 by the hyperactive fab1T2250A mutant augmented vacuole acidification, whereas the kinase-inactive fab1EEE mutant attenuated the formation of a H+ gradient. Separately, we tested the effects of excess Ca2+ on vacuole acidification. Adding micromolar Ca2+ blocked vacuole acidification, whereas chelating Ca2+ accelerated acidification. The effect of adding Ca2+ on acidification was eliminated when the Ca2+/H+ antiporter Vcx1 was absent, indicating that the vacuolar H+ gradient can collapse during Ca2+ stress through Vcx1 activity. This, however, was independent of PI(3,5)P2, suggesting that PI(3,5)P2 plays a role in submicromolar Ca2+ flux but not under Ca2+ shock. To see if the link between Ca2+ and H+ transport was bidirectional, we examined Ca2+ transport when vacuole acidification was inhibited. We found that Ca2+ transport was inhibited by halting V-ATPase activity with Bafilomycin or neutralizing vacuolar pH with chloroquine. Together, these data show that Ca2+ transport and V-ATPase efficacy are connected but not necessarily through PI(3,5)P2.

High-resolution multi-shot diffusion-weighted MRI combining markerless prospective motion correction and locally low-rank constrained reconstruction.

PURPOSE: Subject head motion is a major challenge in DWI, leading to image blurring, signal losses, and biases in the estimated diffusion parameters. Here, we investigate a combined application of prospective motion correction and spatial-angular locally low-rank constrained reconstruction to obtain robust, multi-shot, high-resolution diffusion-weighted MRI under substantial motion. METHODS: Single-shot EPI with retrospective motion correction can mitigate motion artifacts and resolve any mismatching of gradient encoding orientations; however, it is limited by low spatial resolution and image distortions. Multi-shot acquisition strategies could achieve higher resolution and image fidelity but increase the vulnerability to motion artifacts and phase variations related to cardiac pulsations from shot to shot. We use prospective motion correction with optical markerless motion tracking to remove artifacts and reduce image blurring due to bulk motion, combined with locally low-rank regularization to correct for remaining artifacts due to shot-to-shot phase variations. RESULTS: The approach was evaluated on healthy adult volunteers at 3 Tesla under different motion patterns. In multi-shot DWI, image blurring due to motion with 20 mm translations and 30° rotations was successfully removed by prospective motion correction, and aliasing artifacts caused by shot-to-shot phase variations were addressed by locally low-rank regularization. The ability of prospective motion correction to preserve the orientational information in DTI without requiring a reorientation of the b-matrix is highlighted. CONCLUSION: The described technique is proved to hold valuable potential for mapping brain diffusivity and connectivity at high resolution for studies in subjects/cohorts where motion is common, including neonates, pediatrics, and patients with neurological disorders.

Coverage of intermittent preventive treatment of malaria in infants after four years of implementation in Sierra Leone.

BACKGROUND: Intermittent Preventive Treatment of malaria in infants (IPTi) is a malaria control strategy consisting of the administration of an anti-malarial drug alongside routine immunizations. So far, this is being implemented nationwide in Sierra Leone only. IPTi has been renamed as Perennial Malaria Chemoprevention -PMC-, accounting for its recently recommended expansion into the second year of life. Before starting a pilot implementation on PMC, the currently implemented strategy and malaria prevalence were assessed in young children in selected areas of Sierra Leone. METHODS: A cross-sectional, community-based, multi-stage cluster household survey was conducted from November to December 2021 in selected districts of the Northern and northwestern provinces of Sierra Leone among 10-23 months old children, whose caretakers gave written informed consent to participate in the survey. Coverage of IPTi and malaria prevalence-assessed with rapid diagnostic tests-were calculated using percentages and 95% confidence intervals weighted for the sampling design and adjusted for non-response within clusters. Factors associated with RDT + and iPTi coverage were also assessed. RESULTS: A total of 720 children were recruited. Coverage of three IPTi doses was 50.57% (368/707; 95% CI 45.38-55.75), while prevalence of malaria infection was 28.19% (95% CI 24.81-31.84). Most children had received IPTi1 (80.26%, 574/707; 95% CI 75.30-84.44), and IPTi2 (80.09%, 577/707; 95% CI 76.30-83.40) and over half of the children also received IPTi3 (57.72%, 420/707; 95% CI 53.20-62.11). The uptake of each IPTi dose was lower than that of the vaccines administered at the same timepoint at all contacts. CONCLUSION: In Sierra Leone, half of the children received the three recommended doses of IPTi indicating an increase in its uptake compared to previous data of just a third of children receiving the intervention. However, efforts need to be made in improving IPTi coverage, especially in the planned expansion of the strategy into the second year of life following recent WHO guidelines.

Prevalence and risk factors associated with malaria infection in children under two years of age in southern Togo prior to perennial malaria chemoprevention implementation.

BACKGROUND: Malaria remains the leading cause of mortality and morbidity in young children in sub-Saharan Africa. To prevent malaria in children living in moderate-to-high malaria transmission areas, the World Health Organization has recommended perennial malaria chemoprevention (PMC). Prior to piloting PMC implementation in southern Togo, a household survey was conducted to estimate malaria infection prevalence in children under 2 years of age (U2). METHODS: A cross-sectional community-based household survey was conducted in the Haho district in the Togo Plateaux region. A three-stage random sampling method was used to select study participants aged 10-23 months whose caretakers gave informed consent. The prevalence of Plasmodium infection, defined as a positive rapid diagnostic test (RDT), was estimated with 95% confidence interval (CI). Clinical malaria was defined as having a positive RDT plus fever (≥ 37.5 °C) or history of fever in the last 24 h. Mixed-effects logistic regression models were used to assess the child's, caretaker's, and household's factors associated with malaria infection. RESULTS: A total of 685 children were included in the survey conducted January-February in 2022 (dry season). Median age was 17 months (interquartile range: 13-21). About 80% of the children slept under a bed net the night before the interview. Malaria infection prevalence was 32.1% (95% CI 27.7-37.0) with significant area variation (cluster range: 0.0-73.3). Prevalence of clinical malaria was 15.4% (95% CI 12.2-19.2). Children whose caretakers were animist (aOR: 1.71, 95% CI 1.19-2.46) and those living in mother-headed households (aOR: 2.39, 95% CI 1.43-3.99) were more likely to have a positive RDT. Living more than 5 km away from the nearest health facility (aOR: 1.60, 95% CI 1.04-2.44) and presence of two or more under-5-years children in the household (aOR: 1.44, 95% CI 1.01-2.07) were also associated with increased risk of infection. CONCLUSION: One-third of the children U2 who participated in this survey had malaria infection, thus PMC could be a promising strategy to reduce malaria burden in young children in Plateaux region. Reinforcement of outreach services and targeting the poorest households should be prioritized to reduce the inequity in malaria prevention in children exposed to the infection.

Perennial malaria chemoprevention with and without malaria vaccination to reduce malaria burden in young children: a modelling analysis.

BACKGROUND: A recent WHO recommendation for perennial malaria chemoprevention (PMC) encourages countries to adapt dose timing and number to local conditions. However, knowledge gaps on the epidemiological impact of PMC and possible combination with the malaria vaccine RTS,S hinder informed policy decisions in countries where malaria burden in young children remains high. METHODS: The EMOD malaria model was used to predict the impact of PMC with and without RTS,S on clinical and severe malaria cases in children under the age of two years (U2). PMC and RTS,S effect sizes were fit to trial data. PMC was simulated with three to seven doses (PMC-3-7) before the age of eighteen months and RTS,S with three doses, shown to be effective at nine months. Simulations were run for transmission intensities of one to 128 infectious bites per person per year, corresponding to incidences of < 1 to 5500 cases per 1000 population U2. Intervention coverage was either set to 80% or based on 2018 household survey data for Southern Nigeria as a sample use case. The protective efficacy (PE) for clinical and severe cases in children U2 was calculated in comparison to no PMC and no RTS,S. RESULTS: The projected impact of PMC or RTS,S was greater at moderate to high transmission than at low or very high transmission. Across the simulated transmission levels, PE estimates of PMC-3 at 80% coverage ranged from 5.7 to 8.8% for clinical, and from 6.1 to 13.6% for severe malaria (PE of RTS,S 10-32% and 24.6-27.5% for clinical and severe malaria, respectively. In children U2, PMC with seven doses nearly averted as many cases as RTS,S, while the combination of both was more impactful than either intervention alone. When operational coverage, as seen in Southern Nigeria, increased to a hypothetical target of 80%, cases were reduced beyond the relative increase in coverage. CONCLUSIONS: PMC can substantially reduce clinical and severe cases in the first two years of life in areas with high malaria burden and perennial transmission. A better understanding of the malaria risk profile by age in early childhood and on feasible coverage by age, is needed for selecting an appropriate PMC schedule in a given setting.

Rare oncology therapeutics: review of clinical pharmacology package of drug approvals (2019-2023) by US FDA, best practices and recommendations.

There are many challenges with rare diseases drug development and rare oncology indications are not different. To understand the regulatory landscape as it relates to application of clinical pharmacology principles in rare oncology product development, we reviewed publicly available information of 39 approvals by US FDA between January 2019 and March 2023. The objective was to understand the expected clinical pharmacology studies and knowledge base in such approvals. Model informed drug development (MIDD) applications were also reviewed, as such approaches are expected to play a critical role in filling clinical pharmacology gaps in rare oncology, where number of clinical trials and size of these trials will perhaps continue to be small. The findings highlighted how clinical pharmacology contributed to the evidence of effectiveness, dose optimization and elucidation of intrinsic and extrinsic factors affecting drug's behavior. Clinical pharmacology studies were often integrated with modeling in many of the NDAs/BLAs. Of the post marketing requirements (PMR) received, 18% were for dose optimization, 49% for DDI, 8% for QTc, 49% for specific population, and 5% for food effect. Two post marketing commitments (PMC) were issued for immunogenicity of the 11 biologics submissions. 15% (6 of 39) of the submissions used maximum tolerated dose (MTD) to advance their molecule into Phase 2 studies. Of them 3 approvals received PMR for dose optimization. 3 + 3 was the most prevalent Phase 1 design with use in 74% of the New Drug Applications (NDA)/Biologic License Applications (BLA) reviewed. Rest used innovative approaches such as BLRM, BOIN or mTPi, with BLRM being the most common. Seamless clinical pharmacology and MIDD approaches are paramount for rare oncology drug development.

Good long-term patients reported outcomes, return-to-work and return-to-sport rate and survivorship after posterior cruciate ligament (PCL)-based multiligament knee injuries (MLKI) with posteromedial corner tears as significant risk factor for failure.

PURPOSE: To assess the survival rate and associated risk factors of a wide cohort of patient's underwent surgical treatment for posterior cruciate ligament (PCL)-based multiligament knee injury (MLKI) at long-term follow-up and to investigate the long-term patient's reported outcomes (PROMS) and functional activity. METHODS: All cases of PCL-based MLKI performed at one single sport-medicine institution were extracted and patient's with a minimum 2 years of follow-up included. VAS, Lysholm, KOOS, Tegner Activity level scores, the incidence and time of return to sport (RTS) and return to work (RTW) were collected before, after surgery and at final follow-up. A multivariate logistic regression was performed to investigate the outcomes associated with the patient's acceptable symptoms state (PASS) for each sub-score of the KOOS. The Kaplan-Meier method with surgical failure (re-operation to one of the reconstructed ligaments) as endpoint was used to perform the survivorship analysis for the entire cohort. RESULTS: Forty-two patients were included and evaluated at an average of 10 years. All PROMS significantly improved from pre- to post-surgery (range ηp2 0.21-0.43, p < 0.05) except for the Tegner score which significantly improved from pre-surgery and to final follow-up (ηp2 = 0.67, p < 0.001). RTW was achieved in the 95.2% after 2.4 ± 1.9 months. RTS was achieved in 78.6% after 6.7 ± 5.0 months. The higher number of surgeries were the significant negative predictors of PASS for the KOOS sub-scales Sport (p = 0.040) and Quality of Life (p = 0.046), while the presence of meniscal lesions was a significant negative predictor of PASS only for the KOOS sub-scale of Sport (p = 0.003). Six patients (14.3%) underwent reoperation and were considered as surgical failures. The global survivorship was 95.2%, 92.6%, 87.1%, and 74.7% at 2, 5, 12, and 15 years, respectively. The survivorship in patient undergoing PMC reconstruction surgery was significantly lower (p = 0.004; HR 7.1) compared to patients without a PMC lesion. CONCLUSION: Good-to-excellent PROMS could be obtained and maintained at long-term follow-up after surgery, with the higher number of surgeries and meniscal lesions as significant negative predictors of the PASS. Moreover, the presence of a PMC lesion significantly increases the risk of the PCL reconstruction failure. LEVEL OF EVIDENCE: III.

Structural Health Monitoring (SHM) Study of Polymer Matrix Composite (PMC) Materials Using Nonlinear Vibration Methods Based on Embedded Piezoelectric Transducers.

Nowadays, nonlinear vibration methods are increasingly used for the detection of damage mechanisms in polymer matrix composite (PMC) materials, which are anisotropic and heterogeneous. The originality of this study was the use of two nonlinear vibration methods to detect different types of damage within PMC through an in situ embedded polyvinylidene fluoride (PVDF) piezoelectric sensor. The two used methods are nonlinear resonance (NLR) and single frequency excitation (SFE). They were first tested on damage introduced during the manufacturing of the smart PMC plates, and second, on the damage that occurred after the manufacturing. The results show that both techniques are interesting, and probably a combination of them will be the best choice for SHM purposes. During the experimentation, an accelerometer was used, in order to validate the effectiveness of the integrated PVDF sensor.

Sorption of Salts of Various Metals by Polyelectrolyte Microcapsules.

Anthropogenic activity negatively affects the environment by polluting it with the salts of various metals. One of the ways to reduce this influence is to use water purification methods for the salts of various metals. Water purification methods based on nanomaterials are promising. In this regard, we proposed to study polyelectrolyte microcapsules (PMC) as a promising sorption agent for the salts of various metals. It was found that the polystyrene sulfonate-polyallylamine (PSS-PAH) polyelectrolyte complex and polyelectrolyte microcapsules of different compositions are not able to adsorb salts CuSO4, Pb(NO)3, FeCl3, and CuCl2. At the same time, it was found that all types of capsules, except for (PSS/PAH)2/PSS, are capable of sorbing about 420 µg of K3[Fe(CN)6] and about 500 µg of K4[Fe(CN)6] from solution. The adsorption of polyelectrolyte microcapsules has an electrostatic nature which is confirmed by increases in the sorption capacity of PMC of K3[Fe(CN)6] and K4[Fe(CN)6] with decreases in the pH of the solution. Also, It was confirmed that the sorption process of PMC of K3[Fe(CN)6] and K4[Fe(CN)6] is concentration dependent and has the limitation of the number of binding sites.

Phosphatidylinositol 3,5-bisphosphate regulates Ca2+ transport during yeast vacuolar fusion through the Ca2+ ATPase Pmc1.

The transport of Ca2+ across membranes precedes the fusion and fission of various lipid bilayers. Yeast vacuoles under hyperosmotic stress become fragmented through fission events that requires the release of Ca2+ stores through the TRP channel Yvc1. This requires the phosphorylation of phosphatidylinositol-3-phosphate (PI3P) by the PI3P-5-kinase Fab1 to produce transient PI(3,5)P2 pools. Ca2+ is also released during vacuole fusion upon trans-SNARE complex assembly, however, its role remains unclear. The effect of PI(3,5)P2 on Ca2+ flux during fusion was independent of Yvc1. Here, we show that while low levels of PI(3,5)P2 were required for Ca2+ uptake into the vacuole, increased concentrations abolished Ca2+ efflux. This was as shown by the addition of exogenous dioctanoyl PI(3,5)P2 or increased endogenous production of by the hyperactive fab1T2250A mutant. In contrast, the lack of PI(3,5)P2 on vacuoles from the kinase dead fab1EEE mutant showed delayed and decreased Ca2+ uptake. The effects of PI(3,5)P2 were linked to the Ca2+ pump Pmc1, as its deletion rendered vacuoles resistant to the effects of excess PI(3,5)P2 . Experiments with Verapamil inhibited Ca2+ uptake when added at the start of the assay, while adding it after Ca2+ had been taken up resulted in the rapid expulsion of Ca2+ . Vacuoles lacking both Pmc1 and the H+ /Ca2+ exchanger Vcx1 lacked the ability to take up Ca2+ and instead expelled it upon the addition of ATP. Together these data suggest that a balance of efflux and uptake compete during the fusion pathway and that the levels of PI(3,5)P2 can modulate which path predominates.

Quantitative evaluation of prospective motion correction in healthy subjects at 7T MRI.

PURPOSE: Quantitative assessment of prospective motion correction (PMC) capability at 7T MRI for compliant healthy subjects to improve high-resolution images in the absence of intentional motion. METHODS: Twenty-one healthy subjects were imaged at 7 T. They were asked not to move, to consider only unintentional motion. An in-bore optical tracking system was used to monitor head motion and consequently update the imaging volume. For all subjects, high-resolution T1 (3D-MPRAGE), T2 (2D turbo spin echo), proton density (2D turbo spin echo), and T2∗ (2D gradient echo) weighted images were acquired with and without PMC. The images were evaluated through subjective and objective analysis. RESULTS: Subjective evaluation overall has shown a statistically significant improvement (5.5%) in terms of image quality with PMC ON. In a separate evaluation of every contrast, three of the four contrasts (T1 , T2 , and proton density) have shown a statistically significant improvement (9.62%, 9.85%, and 9.26%), whereas the fourth one ( T2∗ ) has shown improvement, although not statistically significant. In the evaluation with objective metrics, average edge strength has shown an overall improvement of 6% with PMC ON, which was statistically significant; and gradient entropy has shown an overall improvement of 2%, which did not reach statistical significance. CONCLUSION: Based on subjective assessment, PMC improved image quality in high-resolution images of healthy compliant subjects in the absence of intentional motion for all contrasts except T2∗ , in which no significant differences were observed. Quantitative metrics showed an overall trend for an improvement with PMC, but not all differences were significant.

Globular C1q domain-containing protein from Pinctada fucata martensii participates in the immune defense process.

The globular C1q domain-containing (C1qDC) protein can recognize a variety of ligands, such as pathogen-associated molecular patterns, and plays an important role in the innate immune response. Our previous studies showed that a novel globular C1q domain-containing protein (PmC1qDC-1) is involved in the damage repair process of pearl oyster shells. However, the function of PmC1qDC-1 in pearl oyster innate immunity remains unknown. In the present study, the high-level structural analysis showed that PmC1qDC-1 was a spherical structure composed of 10 strands and was similar to the AiC1qDC-2 of bay scallop (Argopecten irradians). In situ hybridization indicated that PmC1qDC-1 had strong fluorescence signal in gills. Furthermore, the mRNA expression of PmC1qDC-1 was highly induced at 6-48 h in gill after lipopolysaccharide, peptidoglycan and polyinosinic-polycytidylic acid stimulation. Additionally, we obtained the recombinant protein of PmC1qDC-1 (rPmC1qDC-1) and found that rPmC1qDC-1 had antibacterial activity against Gram-negative (i.e., Pseudomonas aeruginosa, Vibrio parahaemolyticus, Escherichia coli, and Aeromonas hydrophila) and Gram-positive (i.e., Staphylococcus aureus and Bacillus subtilis) bacteria. These results indicated that PmC1qDC-1 might play an important role in the immune response against bacteria and viruses. This study provides clues for further studying the immune defense of Pinctada fucata martensii against pathogens and exploring the evolution of the classic pathway of complement system.

How effective is the health promotion policy in Sichuan, China: based on the PMC-Index model and field evaluation.

BACKGROUND: Many countries around the world highlight the health in all policies (HiAP). However, most of the related research focused on the influential factors and implementation strategies, with less concern on the evaluation of HiAP. In response to HiAP's call, the Chinese government has proposed health promotion policies (HPPs) in counties or districts, the evaluation of HPPs in sample counties or districts of Sichuan province in China is an essential basis for optimizing policy content, improving policy implementation, and ensuring health promotion's continuous and efficient operation. METHODS: This paper established an evaluation system for HPPs based on the PMC-Index model and then quantitatively analyzed 37 representative HPPs from the pilot areas in Sichuan province. In addition, a team of experts conducted a field assessment. RESULTS: The results showed that the average PMC index of 37 HPPs was 7.091, and correlation analysis showed that there was a significant correlation between the PMC index and expert score. CONCLUSIONS: This study indicates that the overall consistency of HPPs was good and proves a connection between the formulation and implementation of HPPs.

A Study of the Buffer Capacity of Polyelectrolyte Microcapsules Depending on Their Concentration and the Number of Layers of the Polyelectrolyte Shell.

Polyelectrolyte microcapsules are used in the development of new forms of targeted delivery systems, self-healing materials, sensors, and smart materials. Nevertheless, their buffer capacity has not been practically studied, although that characteristic makes it possible to estimate the change in the state of protonation of the entire polyelectrolyte system. This is necessary both for creating a buffer barrier system for pH-sensitive compounds (metals, enzymes, polyelectrolytes, drugs) and for the correct interpretation of the results of research and studying of the PMC structure. The buffer capacity of a PMC can be affected by the concentration of microcapsules in solution and the number of shell layers since the listed parameters affect other physicochemical properties of the PMC shell. This includes, for example, the electrical conductivity, permeability (of ions), osmotic pressure, charge density, etc. In this regard, we studied the change in the buffer capacity of polyelectrolyte microcapsules depending on their concentration and the number of shell layers. As a result, it was found that with an increasing concentration of microcapsules, the buffering capacity of the PMC increases, but at the same time, in the pH range from 4 to 5.5, the calculated buffering capacity of 1 billion capsules decreases with increasing their concentration. This effect may be associated with a decrease in the available -NH2 groups of the PMC's shell. In addition, it was found that the main contribution to the buffer capacity of a PMC is made by the entire shell of the microcapsule and not just its surface. At the same time, the buffer capacity of the capsules has non-linear growth with an increase in the number of PMC shell layers. It is presumably associated either with a decrease in the polyelectrolyte layer with an increase in their number or with a decrease in the permeability of hydrogen protons.

The relation of meiotic behaviour to hybridity, polyploidy and apomixis in the Ranunculus auricomus complex (Ranunculaceae).

BACKGROUND: Hybridization and polyploidization are powerful evolutionary factors that are associated with manifold developmental changes in plants such as irregular progression of meiosis and sporogenesis. The emergence of apomixis, which is asexual reproduction via seeds, is supposed to be connected to these factors and was often regarded as an escape from hybrid sterility. However, the functional trigger of apomixis is still unclear. Recently formed di- and polyploid Ranunculus hybrids, as well as their parental species were analysed for their modes of mega- and microsporogenesis by microscopy. Chromosomal configurations during male meiosis were screened for abnormalities. Meiotic and developmental abnormalities were documented qualitatively and collected quantitatively for statistical evaluations. RESULTS: Allopolyploids showed significantly higher frequencies of erroneous microsporogenesis than homoploid hybrid plants. Among diploids, F2 hybrids had significantly more disturbed meiosis than F1 hybrids and parental plants. Chromosomal aberrations included laggard chromosomes, chromatin bridges and disoriented spindle activities. Failure of megasporogenesis appeared to be much more frequent in than of microsporogenesis is correlated to apomixis onset. CONCLUSIONS: Results suggest diverging selective pressures on female and male sporogenesis, with only minor effects of hybridity on microsporogenesis, but fatal effects on the course of megasporogenesis. Hence, pollen development continues without major alterations, while selection will favour apomixis as alternative to the female meiotic pathway. Relation of investigated errors of megasporogenesis with the observed occurrence of apospory in Ranunculus hybrids identifies disturbed female meiosis as potential elicitor of apomixis in order to rescue these plants from hybrid sterility. Male meiotic disturbance appears to be stronger in neopolyploids than in homoploid hybrids, while disturbances of megasporogenesis were not ploidy-dependent.

Molecular and functional analysis of PmC1qDC in nacre formation of Pinctada fucata martensii.

The C1q-domain-containing (C1qDC) proteins are a family of proteins characterized by a globular C1q (gC1q) domain in their C-terminus which hold the potential function in the shell formation as shell matrix proteins. In this study, a C1qDC protein was identified and characterized in pearl oyster (Pinctada fucata martensii) (PmC1qDC) to explore its function in nacre formation. The PmC1qDC-deduced protein sequence carried a typical globular C1q (gC1q) domain that possessed the typical 10-stranded ß-sandwich fold with a jelly-roll topology common to all C1qDC family members and shared high homology with other gC1q domains. Homologous analysis of PmC1qDC presented it contained conserved secondary structure and Phe135, Phe155, Tyr166, Phe173, Tyr181, Phe183, and Phe256 amino acid residues. Expression pattern analysis showed that PmC1qDC expressed in all the detected tissues and exhibited a significantly higher expression level in nacre formation-associated tissues. After the shell notching, the expression level of PmC1qDC showed significantly up-regulation after 12 h in the central zone of mantle (MC). PmC1qDC expression significantly decreased in the MC after RNA interference (RNAi). Furthermore, disordered crystals with evident rough surface and irregular crystal tablets were observed in the nacre after RNAi. Results suggested that PmC1qDC affects the shell nacre formation, which is significant to improve the pearl production of pearl oyster.

Relative contribution of individual versus combined functional imaging studies in predicting seizure freedom in pediatric epilepsy surgery: an area under the curve analysis.

OBJECTIVE: The goal of this study was to evaluate the predictive value and relative contribution of noninvasive presurgical functional imaging modalities based on the authors' institutional experience in pursuing seizure-free surgical outcomes in children with medically refractory epilepsy. METHODS: This was a retrospective, single-institution, observational cohort study of pediatric patients who underwent evaluation and surgical treatment for medically refractory partial epilepsy between December 2003 and June 2016. During this interval, 108 children with medically refractory partial epilepsy underwent evaluation for localization and resective epilepsy surgery. Different noninvasive functional imaging modalities, including ictal SPECT, FDG-PET, and magnetoencephalography-magnetic source imaging, were utilized to augment a standardized paradigm (electroencephalography/semiology, MRI, and neuropsychology findings) for localization. Outcomes were evaluated at a minimum of 2 years (mean 7.5 years) utilizing area under the receiver operating characteristic curve analysis. Localizing modalities and other clinical covariates were examined in relation to long-term surgical outcomes. RESULTS: There was variation in the contribution of each test, and no single presurgical workup modality could singularly and reliably predict a seizure-free outcome. However, concordance of presurgical modalities yielded a high predictive value. No difference in long-term outcomes between inconclusive (normal or diffusely abnormal) and abnormal focal MRI results were found. Long-term survival analyses revealed a statistically significant association between seizure freedom and patients with focal ictal EEG, early surgical intervention, and no history of generalized convulsions. CONCLUSIONS: Comprehensive preoperative evaluation utilizing multiple noninvasive functional imaging modalities is not redundant and can improve pediatric epilepsy surgical outcomes.

Inferring parameters of prey switching in a 1 predator-2 prey plankton system with a linear preference tradeoff.

We construct two ordinary-differential-equation models of a predator feeding adaptively on two prey types, and we evaluate the models' ability to fit data on freshwater plankton. We model the predator's switch from one prey to the other in two different ways: (i) smooth switching using a hyperbolic tangent function; and (ii) by incorporating a parameter that changes abruptly across the switching boundary as a system variable that is coupled to the population dynamics. We conduct linear stability analyses, use approximate Bayesian computation (ABC) combined with a population Monte Carlo (PMC) method to fit model parameters, and compare model results quantitatively to data for ciliate predators and their two algal prey groups collected from Lake Constance on the German-Swiss-Austrian border. We show that the two models fit the data well when the smooth transition is steep, supporting the simplifying assumption of a discontinuous prey-switching behavior for this scenario. We thus conclude that prey switching is a possible mechanistic explanation for the observed ciliate-algae dynamics in Lake Constance in spring, but that these data cannot distinguish between the details of prey switching that are encoded in these different models.